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III INTERNATIONAL CONFERENCE ON ACQUIRED
IMMUNODEFICIENCY SYNDROME (AIDS)
June 1-5, 1987
Washington Hilton and Towers
Washington, D.C.
The purpose of the conference is to review and exchange information on AIDS epidemiology, virology,
molecular biology, immunology, serology, hematology, animal models, neurological implications, neu-
ropsychiatric aspects, oncology, diagnostic tests, clinical manifestations, behavioral and addiction
aspects, public health, ethical and psychosocial implications, and prevention and control strategies.
Sponsored by the: U.S. Department of Health and Human Services
Public Health Service
National Institutes of Health
Alcohol, Drug Abuse, and Mental Health Administration
Centers for Disease Control
Food and Drug Administration
Health Resources and Services Administration
and the
World Health Organization
RC
CONFERENCE COMMITTEES
Steering Committee
James B. Wyngaarden, National Institutes of Health
Paul D. Parkman, Food and Drug Administration
David N. Sundwall, Health Resources and Services Administration
James O. Mason, Centers for Disease Control
Donald I. Macdonald, Alcohol, Drug Abuse, and Mental Health Administration
Jonathan Mann, World Health Organization
Organizing Committee
George J. Galasso, Chairman, National Institutes of Health
Kenneth Bridbord, Co-Chairman, Fogarty International Center, National Institutes of Health
Peter J. Fischinger, National Cancer Institute, National Institutes of Health
John R. La Montagne, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Amoz I. Chernoff, National Heart, Lung, and Blood Institute, National Institutes of Health
Gerald V. Quinnan, Food and Drug Administration
Peter Bridge, Alcohol, Drug Abuse, and Mental Health Administration
Samuel C. Matheny, Health Resources and Services Administration
Walter R. Dowdle, Centers for Disease Control
Gary R. Noble, Public Health Service
Scientific Program Committee
H.J. Alter, USA
D. Armstrong, USA
H. Bachmayer, Austria
L. Barbosa, USA
K. Bart, USA
C. Bartholomew, Trinidad
W.A. Blattner, USA .
D.T. Bolognesi, USA
S. Broder, USA
J.B. Brunet, France
A. Burny, Belgium
L. Chieco-Bianchi, Italy
J. Chin, Switzerland
J.W. Curran, USA
G. de The, France
D. Des Jarlais, USA
R.C. Desrosiers, USA
F. Deinhardt, West Germany
M. Donoghue, USA
G.R. Dreesman, USA
P. Ebbesen, Denmark
M. Essex, USA
A.S. Fauci, USA
A. Fisher, USA
R.C. Gallo, USA
A.J. Georges, Central African Republic
G. Giraldo, Italy
J.C. Gluckman, France
C. Grady, USA
J. Graham, USA
I.D. Gust, Australia
J. Harris, USA
W.A. Haseltine, USA
D. Henderson, USA
E.M. Hersh, USA
J.C. Hill, USA
Y. Hinuma, Japan
M.S. Hirsch, USA
C. Hostetter, USA
G. Hunsmann, West Germany
H.W Jaffe, USA
J. Jaffee, USA
W.F.H. Jarrett, Scotland
J.G. Joseph, USA
W Koff, USA
H. Koprowski, USA
K. Krohn, Finland
H.C. Lane, USA
R. Lanman, USA
T. Lee, USA
J. Leikola, Finland
S.J. Lengel, USA
PH. Levine, USA
J. A. Levy, USA
M.A. Martin, USA
H. Masur, USA
C.R. McCarthy, USA
L. Montagnier, France
J. Mosley, USA
T Muyembe, Zaire
G. Nemo, USA
B. Oberg, Sweden
G. Papaevangelou, Greece
J.W. Pape, Haiti
WP Parks, USA
H.G. Pereira, Brazil
P. Piot, Belgium
F Polk, USA
J.D. Porter, USA
R.W Price, USA
R.J. Riseberg, USA
M. Roper, USA
A. Rubinstein, USA
G. Schochetman, USA
N. Schram, USA
WG. Van Acken, The Netherlands
PA. Volberding, USA
D. Volkman, USA
S. Wain-Hobson, France
R. Weiss, UK
W Winkelstein, USA
F Wong-Staal, USA
D. Zagury, France
V.M. Zhdanov, USSR
CONFERENCE COMMITTEES
Education/Service Group Subcommittee
James C. Hill, Chairman, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Stephen Beck, National Association of People with AIDS
Terry Beirn, American Foundation for AIDS Research
Bernard Branson, HERO
James Graham, Whitman-Walker Clinic, Inc.
Paul Kawata, National AIDS Network
Jeffrey Levi, National Gay and Lesbian Task Force
Ann McFarren, AIDS Action Council
Carol Sussman, American Red Cross
Neil Schram, Los Angeles City I County AIDS Task Force
Planning Committee for News Operations
R. Anne Thomas, Chairman, National Institutes of Health
Winifred Austermann, Alcohol, Drug Abuse, and Mental Health Administration
Don Berreth, Centers for Disease Control
Geraldine Blumberg, National Institutes of Health
James A. Bryant, National Institutes of Health
Mary M. Evert, Public Health Service
Jack W. Martin, Food and Drug Administration
Don Ralbovsky, National Institutes of Health
Marc Stern, National Institutes of Health
Conference Management Conference Secretariat
Melissa M. Widerkehr Nancy E. Shapiro
Courtesy Associates, Inc. Fogarty International Center
655 Fifteenth Street, N.W. Building 38A, Room B2N13
Suite 300 National Institutes of Health
Washington, DC 20005 Bethesda, MD 20892
Phone: (202) 347-5900 Phone: (301) 496-2517
The III International Conference on AIDS wishes to express its appreciation to the Agency for
International Development for their important support of the Conference . . . and a special thank
you to:
Abbott Diagnostics Division, Abbott Laboratories for their contribution to Wednesday's Reception/Buffet.
Bio-Data Corporation, publishers of the AIDS Record, for their contribution to the poster session.
Burroughs Wellcome Company for their contribution to the Abstracts Volume.
E.R. Squibb & Sons, Inc. for their contribution to the Abstracts Volume.
Genentech, Inc. for a general contribution to the Conference.
Johnson & Johnson Biotechnology Center, Inc. for a general contribution to the Conference.
Merck Sharp & Dohme Research Laboratories for a general contribution to the Conference.
Merrill Dow Pharmaceuticals, Inc. for their support of the Stone House Committee Event.
Organon Teknika for their contribution to the Final Program.
The Upjohn Company for their contribution to foreign travel.
TABLE OF CONTENTS
M.l Opening Plenary Session 1
M.2 Plenary Session I 1
M.3 Epidemiology — Natural History 1
M.4 Virology — Structure and Function 1 2
M.5 Psychosocial — Behavioral Studies of AIDS 3
M.6 Prevention/Public Health — Impact of HIV Testing on the Behavior of Homosexual Males 4
M.7 Roundtable Discussion — Communicating AIDS Education Across Cultural Barriers 5
M.8 Epidemiology — AIDS in Developing Countries 5
M.9 Virology — Structure and Function II 6
M. 10 Immunology — Viral Proteins and Virus Specific Immune Responses 7
M. 1 1 Clinical Management — Cancer, Hemophilia and Cardiovascular Disease 8
M. 12 Roundtable Discussion — Prevention and Control of AIDS in Developing Countries 9
M. 13 Roundtable Discussion — The Status of Screening: Supplementary Tests for HIV Infections 10
M. 14 Roundtable Discussion — AIDS and the Media 10
MP Monday Poster Session 10
T. 1 Plenary Session II 52
T.2 Plenary Session III 52
T.3 Epidemiology — Serology 53
T.4 Virology — Antivirals 54
T.5 Clinical Management — Neurology 55
T.6 Prevention/Public Health — Reaching the General Public 56
T.7 Epidemiology — Surveillance: Incidence, Prevalence and Trends 57
T.8 Clinical Trials — AZT and Ribavirin 58
T.9 Immunology — HIV-Specific Cytotoxicity 59
T. 10 Psychosocial — Psychosocial Research: At Risk Populations 60
T.ll Roundtable Discussion — Access Issues Associated with AIDS: Discrimination, Services, Care 61
T. 12 Roundtable Discussion — Use of AZT in HIV Infections 61
T. 13 Roundtable Discussion — Encouraging Physician Counseling for AIDS Prevention 61
T. 14 Roundtable Discussion — Legal, Ethical and Public Policy Issues: International Perspective 61
T.15 Roundtable Discussion — Psychological Distress and Maintenance of Behavior Change in HIV
Illness 61
T.16 Biology of HIV 61
TP Tuesday Poster Session 62
W. 1 Plenary Session IV 105
W.2 Epidemiology — Heterosexual Transmission 105
W.3 Virology — Vaccines 106
W.4 Blood and Blood Products — Screening and Donor Characteristics 107
W.5 Clinical Management — Pulmonary, Pediatric and Neurologic Implications 108
W.6 Roundtable Discussion — Hetrosexual Transmission of the AIDS Virus 109
W.7 Roundtable Discussion — Vaccine Related Issues 109
W.8 Roundtable Discussion — Legal, Ethical and Public Policy Issues: The American Perspective 110
W.9 Roundtable Discussion — Assuring an Adequate Blood Supply of Healthy Blood Donors 110
W. 10 Roundtable Discussion — Meeting Gaps in Medical Needs 110
WP Wednesday Poster Session 110
Th.l Plenary Session V 153
Th.2 Virology — Related Viruses 153
Th.3 Health Care — Patient Care, Attitudes, Knowledge, and Risks 154
Th.4 Clinical Studies — Opportunistic Infections 155
TABLE OF CONTENTS
Th.5
Th.6
Th.7
Th.8
Th.9
Th.10
Th.ll
Th.12
Th.13
Th.14
Th.15
Th.16
Th.17
Prevention/Public Health — Drug Users and Other High Risk Groups
Roundtable Discussion — Developing Community-Based Service Organizations
Epidemiology — Perinatal Transmission and AIDS
Clinical Management — Infections I
Immunology — HIV Specific Antibodies
Blood and Blood Products — Transfusion Associated AIDS and Hemophilia
Health Care — Issues in Health Care Delivery
Roundtable Discussion — People Living With AIDS: Personal Perspectives
Roundtable Discussion — Prevention of Perinatal Transmission of HIV Infection
Roundtable Discussion — AIDS Education for the General Public
Roundtable Discussion — AIDS in the Developing World (Social/Economic)
Roundtable Discussion — Hemophilia: Where Should the Preventive Effort Be Placed?.
Roundtable Discussion — Current Issues in Drug Abuse and AIDS
156
157
157
158
159
160
161
162
162
163
163
163
163
THP Thursday Poster Session 163
F.l Epidemiology— HIV- AIDS Cofactors
F.2 Virology — Diagnostics
F.3 Clinical Management — Infections II
F.4 Immunology — Immunopathogenesis
F.5 Legal/Ethics
F.6 Epidemiology — Other Retroviruses
F.7 Virology — Animal Models
F.8 Prevention/Public Health — Monitoring Changes in Sexual Behavior
F.9 Immunology — Viral Replication
F. 10 Closing Plenary Session
206
207
208
209
210
211
212
213
214
215
Authors Index 217
Opening Plenary Session
MONDAY, JUNE 1
M.1
General Introductory, Welcoming and Keynote Remarks
Speakers include:
The Honorable George Bush, Vice President of the United States
Robert E. Windom, Assistant Secretary for Health, U.S. Department of
Health and Human Services, Washington, D.C.
C. Everett Koop, Surgeon General and Director of the International Health
Program Office, U.S. Public Health Service, Washington, D.C.
Lowell T. Harmison, Deputy Assistant Secretary for Health, U.S.
Department of Health and Human Services, Washington, D.C.
Carlyle Guerra de Macedo, Director, Pan American Health Organization,
Washington, D.C.
George J. Galasso, General Chairman, III International Conference on
AIDS and Associate Director for Extramural Affairs, National Institutes
of Health, Bethesda, Maryland.
M.2.3
The natural history and clinical manifestations of HIV-infection
PETER PIOT. Institute of Tropical Medicine, Antwerp, Belgium.
The clinical expression of HIV-infection appears increasingly complexe.
It includes manifestations due to opportunistic diseases, as well as illness
directly caused by HIV itself. Neurological disease may include involvement
of brain, spinal cord and peripheral nerves, and is probably directly caused
by HIV, as is lymphocytic interstitial pneumonia. The etiology of chronic
diarrhea and a papular pruritic skin eruption associated with HIV-infection
is unclear. Several clinical classification systems for HIV-infection have
ben proposed. Between 2 and 8 % of infected individuals per year progress
to AIDS, with no apparent decrease in the rate of disease progression over
time. Within 5 to 10 years of infection the majority of infected persons
develop clinical disease. Reported risk factors and/or predictors of di-
sease progression such as a decreased number of T-helper lymphocytes, an in-
creased number of T-suppressor lymphocytes, a low level of HIV-antibody and
a high titer of CMV-antibody , may be markers or reflect duration of infec-
tion. A chronically activated state secondary to chronic viral and parasi-
tic antigenic exposure may increase both the susceptibility to HIV-infection
and development of disease. Increased HIV gene expression and persistent
antigenemia may also be contributing factors in disease development. Per-
sistent viral production in monocyte/macrophage cells in the brain and
elsewhere may be a source of virus production in other organs. Infection
of the brain implies that HIV may be protected from immune surveillance or
therapeutic intervention.
Plenary Session I
Epidemiology — Natural History
M.2.1
The AIDS Viruses
Robert Gallo, National Cancer Institute, National Institutes of Health,
Washington, D.C.
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
M 3 1 ^ne Natural History of Human Immunodeficiency Virus Infection in a
Cohort of Homosexual and Bisexual Men: a 7-year Prospective Study.
NANCY A. HESSOL*, GM RUTHERFORD*, PM O'MALLEY*, LS DOLL**, WW DARROW**, HW
JAFFE**, et al_. , *Dept.of Public Health, San Francisco, CA, and Centers for
Disease Control, Atlanta, GA.
To determine the natural history of HIV infection, a stratified random sample
of 6,700 homosexual and bisexual men originally recruited between 1978 and 1980
for studies of hepatitis B were evaluated. To date, 662 (9.9%) of these men
have been reported with AIDS, and approximately 70S are estimated to be infect-
ed with HIV. Of the 719 (11%) men randomly chosen from the entire cohort who
participated in AIDS studies, 63 were known to have seroconverted before the
studies began in late 1983. These 63 men have now been followed for a mean of
72 months since their initial seropositive specimen or estimated date of sero-
conversion: 19 (30%) have been reported to have AIDS; 29 (46%) had generalized
lymphadenopathy, oral candidiasis, weight loss, persistent idiopathic fever or
diarrhea; and 15 (24%) were asymptomatic. Additional data were analyzed from
273 men who participated in hepatitis B vaccine trials, for whom multiple serum
specimens were available, and who consented to have their old serum specimens
tested for the presence of HIV antibodies. Of these 273 men, 112 (41%) were
either seropositive on entry into the cohort (18 men) or had known seroconver-
sion dates within a 24 month period (94 men). Combining these 112 men with the
63 men from the random sample, a Kaplan-Meier survival curve of the cumulative
proportion of men without AIDS by duration of HIV infection was constructed.
From analysis of these 155 men, an estimated 15% (95% confidence interval, 9 -
21%) of the HIV infected men in the Clinic cohort will develop AIDS over 60
months of infection, 24% (95% c.i., 17 - 31%) will develop AIDS after 72
months, 31% (95% c.i., 22 - 40%) will develop AIDS after 84 months, and 36%
(95% c.i., 26 - 46%) after 88 months.
M.2.2 Significance of variati
isolates for serology a
ERLING NORRBY*, GUNNEL BIBERFELD,
LJUNGGREN*,****, EVA-MARIA FENYO*.
**Dept. Immunology and *** Dept. V
and ****Dept. Immunology, Karolins
Two groups of HIVs have been ide
West Africans includes the strains
have closely related envelope glyc
corresponding proteins of HIVs rep
difference is reflected in distinc
cytotoxicity of antibodies against
isolates. The internal components
properties, but certain distinguis
occurrence of the two groups of HI
accurate and sensitive serological
immunoprophylactic measures. Site
offers attractive possibilities fo
can distinguish antibody responses
HIVs.
on between human immunodeficiency (HIV)
nd vaccine development.
JAN ALBERT*,***, FRANCESCA CHI0DI*, KRISTINA
*Dept. Virology, Karolinska Institute,
irology, National Bacteriological Laboratory,
ka Institute, Stockholm, Sweden,
ntified. The group of HIVs isolated from
HTLV-4, LAV-2 and SBL-6669. These strains
oproteins, which differ markedly from the
resented by the strain HTLVIIIB. This
tive reactions in antibody-dependent cell
HIV and the HIV-related West African virus
of HIVs of both groups share immunogenic
hing features have been identified. The
Vs need to be considered in development of
tests and in attempts to introduce effective
-directed serology using synthetic peptides
r establishment of serological tests which
to viruses representing the two groups of
U 3 2 In a Cohort of HIV Seropositive Men Followed for 30 Months, Initial
Leu 3a T Lymphocyte Counts Predict Subsequent Declines in T Cell
Counts, Clinical Findings and AIDS
WILLIAM LANG*, R. ANDERSON**, W. WINKELSTEIN, Jr.***, R. ROYCE***,
H. PERKINS****, *Children's Hospital of San Francisco, CA, "California
Department of Health Services, Sacramento, CA, ***UCB School of Public Health,
Berkeley, CA, ****Irwin Memorial Blood Bank, San Francisco, CA.
Fran the San Francisco Men's Health Study, a prospective study of HIV infec-
tion in a population-based probability sample, 370 HIV-infected men were
recruited. A subset of 206 men attended examinations every 6 months from
June 1984 through December 1986. Initial Leu 3a counts were unimcdally
distributed and depressed compared to uninfected men. Over 30 months, the
entire distribution shifted toward lower values. When the group was strati-
fied according to initial Leu 3a count, declines of 18 to 30% occurred in all
quartiles indicating depletion of Leu 3a cells regardless of initial values.
To explore the relationship of initial Leu 3a values to development of
HIV related symptoms and AIDS, all 370 seropositive men were stratified into
groups with less than 500 (n=100) , 500-650 (n=92) , 650-300 (n=01) , and greater
than 800 (n=97) initial Leu 3a cells. Among participants with less than 2
symptoms suggestive of HIV infection at outset, 25% with less than 500 Leu 3a
cells developed increasing symptoms compared to 12% of those with greater
than 800 Leu 3a cells. Twenty-four of the 37 AIDS cases occurred in the
lowest group compared to 5 in the highest.
These findings suggest that HIV infection affects Leu 3a counts progres-
sively in most people and that initial Leu 3a number is strongly predictive
of clinical outcome in the ensuing 30 months.
MONDAY, JUNE 1
M 3 3 Progression to AIDS, predictors of AIDS, and seroconversion in a cohort of homosexual
men: Results of a four year prospective study.
MARTIN T SCHECHTER. WJ BOYKO, MS WEAVER, B DOUGLAS, B WILLOUGHBY, WA MCLEOD,
et al. The Vancouver Lymphadenopathy-AIDS Study, St. Paul's Hospital, University of British
Columbia, Vancouver, BC, Canada.
The Vancouver Lymphadenopathy-AIDS Study is an ongoing prospective study of over 600
homosexual men who were recruited through their GP's beginning in 11/82 and who have been seen since
at roughly six-month intervals. A total of 323 men were seropositive at entry into the study. Through
11/86, a total of 36 cases of AIDS were diagnosed in this group, yielding a Kaplan-Meier (K-M)
estimate for the 48 month cumulative incidence of AIDS of 18.6%. The following are the categories
(and K-M estimates of the four-year incidence of AIDS) for the lab predictors of progression to AIDS:
CD4 count <400(33.6%) CD4/CD8 ratio <.75(36.9%) IgG >1600(26.0%)
>400 (143%) p=.0001 >.75(11.1%) p=.0001 <1600(142%) p=.003
IgA >250(373%) CI q binding >8%(305%) Hbg <1 5.0 (28.4%)
<250 (93%) p=.003 <8% (6.1%) p=.034 >15.0 (72%) p=.029
Cox regression revealed that CD4 cell depletion, IgG elevation, and IgA elevation, were significant
and independent predictors of progression to AIDS in seropositive homosexual men.
Of 345 men who were HIV negative at enrolment, 85 (25%) have seroconverted by the time of this
analysis. The K-M estimate for the risk of seroconverting during 11/82-07/86 was 22.5%. The
seroconversion rates during 5 successive 9 month periods from 11/82 to 07/86 were 4.4%, 9.1%, 5.2%,
4.3%, and 1.7%. Cox regression analysis revealed the following significant risk factors for
seroconversion: number of sexual partners, receptive anal intercourse, history of gonorrhea, use of illicit
drugs, and age below 30 in 11/82. That men under 30 were twice as likely to seroconvert as older men
appears to be due to lesser modification of behavior in the younger group. In fact, the proportions of men
in the age groups <30, 30-34, 35-39, and 40+, reporting a decrease in the annual number of sexual partners
were 49%, 56%, 61 %, and 68% respectively. Additional counselling about safer sexual practices should
therefore be selectively directed to younger members of the gay population.
M 3 6 Continuing Studies on the Natural History of HIV Infection in
Zaire.
BOSENGE NGALY", R.W. RYDER**, B. KAPITA*, H. FRANCIS***, T. QIJINN***, J.M.
MANN** et al. , *Mama Yemo Hospital and Department of Public Health,
Kinshasa, Zaire, **CDC, Atlanta, *** NIH, Bethesda.
In November, 1986 2020 hospital staff members at Mama Yemo Hospital were
re-examined for HIV antibodies. Among the 44 employees who were asymptom-
atically HIV-infected in 1984 and who were followed up in 1986, 2 had
developed AIDS (2.3 cases/person years of observation [PYO]). During the
2-year period, an additional 18 of these 44 patients but only 1 of the 1958
persistently HIV(-) patients developed signs/symptoms consistent with AIDS-
related complex [ARC] (ARC rate of 20.4 cases/100 PYO in seropositives, .05
rate in seronegatives). Nine of 18 HIV(+) symptomatic patients in 1984 had
a marked decline in clinical status when re-seen in 1986. Ten (7.1%) of the
140 1984 HIV(+) employees on whom information could be obtained in 1986 had
died.
There were 41 seroconversions during this period for an infection rate of
1.0/100 PYO. Fifty-eight percent of the new infections were in men. The
average age of patients with new infections was 41.4 years for males and
35.5 years for females. Twenty four percent of new female infections had
had a spontaneous abortion compared with 44 of previously infected and It of
non- infected women. Nine new infections had ARC at the time they were
examined. New infections did not cluster in employee groups having the most
contact with patients or their body fluids.
In this representative urban, middle-class, African population with It
yearly HIV incidence, an important rate of disease progression has been
documented.
Virology — Structure and Function I
M.3.4
ural History of HIV Infection in Intravenous Drug Abusers (IVDAs)
PETER A SELWYN*. EE SCHOENBAUM*, D HARTEL*, T PETERMAN**, RS KLEIN*,
Nat
GH FRIEDLAND*. et al, *Montefiore Medical Center/Albert Einstein College of
Medicine, Bronx, NY, **CDC, Atlanta, GA, USA.
We are prospectively studying patients in a methadone maintenance program in
NYC to characterize the natural history of HIV infection in this group of IVDAs.
Fr,om 7/85-4/86, 498 patients enrolled in an HIV seroprevalence study; we now
present preliminary follow-up data. All subjects had an initial interview regard-
ing drug use and sexual behavior, serum was obtained for HIV antibody (Ab) and a
physicial exam was performed. Rescreening visits are scheduled semi-annually,
with interview, repeat Ab test, and exam. All patients receive on-site primary
care and are monitored by clinical staff for the occurrence of AIDS/HIV disease.
In the original group, there were 169 seropositives (SP) without AIDS, and 329
seronegatives (SN) . 91 (54%) SPs were male; mean age was 33yrs.; 17 (10%) were
white (W), 54 (32%) black (B) , 98 (58%) Hispanic (H) . 5 of 6 SPs with oral thrush
(OT) at study entry developed AIDS at a mean of 4.7 mos. follow-up. 163 SPs with-
out OT have been followed for a median of 15 months (range 10-20). Of these, 6
(3.7%) developed AIDS and 2 (1.2.%) presumptive AIDS at a mean of 12.3 mos. fol-
low-up. Among SPs without OT, cumulative incidence of AIDS was thus ~5%, with
2.7 cases/ 1000 person-months follow-up. Of 13 cases of AIDS/presumptive AIDS, 8
(62%) were male; mean age 34 yrs.; 1 was W (8%), 6 B (46%), 6 H (46%) . Multiple
logistic regression analysis including demographic, drug use, and sexual varia-
bles from initial interview data indicated that black race (p <. 01) , prostitution
(p<.02), and drug use in a "shooting gallery" (p{.03) were all predictive of the
development of AIDS among SPs. 44/169 (26%) original SPs have been formally re-
screened to date. 5/44 (11%) had new generalized lymphadenopathy on exam and
2/44 (5%) had new OT at a median of 14 mos. follow-up.
Results indicate that HIV-infected IVDAs progress to clinical disease at a
substantial rate; AIDS was predicted by certain drug use and sexual behaviors.
The observed association with race requires further explanation.
M d 1 Pathogenesis of HIV Infection - Virus: Host Interactions
JAY A. LEVY, Department of Medicine and Cancer Research Institute,
University of California, School of Medicine, San Francisco, CA, 94143.
The human immunodeficiency virus (HIV) is a human lentivirus that has a
variety of heterogeneous subtypes. They can be distinguished by replicating
properties in different cell types, cytopathology , induction of a latent state,
sensitivity to serum neutralization, restriction enzyme patterns, and nucelo-
tide sequences, particularly in the envelope region. These properties of HIV
contribute to the pathogenicity of some isolates. The immunologic responses
of the host determine whether the infection with HIV progresses to disease,
or whether the virus is kept under control. Strong cell-mediated immune re-
sponses appear responsible for suppression of virus replication and spread.
Other immune reactions may advance the state of the disease, such .as autoanti-
bodies against platelets, helper T lymphocytes and other host cells. The form-
ation of immune complexes containing HIV antigens and viral proteins may com-
promise immune function. The malignancies in AIDS may result from an enhanced
response of certain cells in the immune system. B cell lymphomas may result
from lymphokine or antiidiotype production, and Kaposi's sarcoma may represent
proliferation of endothelial cells responding to enhanced angiogenesis-promot-
ing factors. These malignancies may be linked as well to Epstein-Barr virus,
CMV or papova viruses. The pathogenesis of HIV infection, therefore, is the
end result of an interplay between particular HIV with specific host responses.
An understanding of the factors involved is important in our approaches at
control and prevention of HIV infection.
M 3 5 Risk of Disease In Recipients of Blood from Donors Later Found
Infected With Human Immunodeficiency Virus (HIV)
J.W. WARD*, D. DEPPE*, H. PERKINS**, S. KLEINMAN***, P HOLLAND"*", J Allen*,
*Centers For Disease Control, Atlanta, Ga,** Irwin Memorial Blood Bank, San
Francisco,*** American Red Cross, Los Angeles, + Sacramento Blood Center,
Sacramento CA.
Recipients of blood from donors later found infected with HIV are unique in
that their date of infection is known, and the natural history of HIV
infection may be more easily observed. We have identified 777 recipients of
blood from 131 donors later found to be infected with HIV. Of 457 recipients
investigated, 155 (34%) survived less than 4 months post-transfusion, 249
(54%) survived longer than 4 months, and 53 (12%) were lost to follow-up. Of
those who survived longer than 4 months, 18 (7%) developed AIDS 10 to 63
months after transfusion (median 28 months). Of the 54 HIV-seropositive
recipients followed an average of 46 months after transfusion, 28 (52%) have
remained asymptomatic, 12 (22%) have generalized lymphadenopathy, 9 (17%) have
AIDS-related complex, and 5 (9%) have developed AIDS. Of these 54 recipients,
13 (24%) had an acute illness compatible with acute retroviral syndrome. Of 19
tested asymptomatic seropositive recipients, 14 (74%) had low T-cell
helper:suppressor ratios. The 49 seropositive recipients without AIDS were not
significantly different than the 18 who developed AIDS by sex (47% male vs 39%
male), age at transfusion (49 years vs 52 years), and total blood received (7
units vs 16 units). However, the 18 AIDS patients more frequently had blood
and clotting disorders (usually autoimmune) than did the other seropositive
recipients (28% vs 0%, p<0.001). Blood recipients from infected donors are at
high risk for HIV-related disease. The association of blood and clotting
disorders with the development of AIDS is under investigation.
U A 9 Clonal Analysis of Functional Differences of Human
Immunodeficiency Virus (HIV)
SHINJI HARADA* , N. YAMAMOTO**, Y. HINUMA*, Institute for Virus
Research, Kyoto University, Kyoto 606, **Dept. of Virology and
Parasitology, Yamaguchi University, School of Medicine, Yamaguchi,
755 Japan.
Different isolates (HTLV-IIIB, LAV-1, ARV-2) of HIV were cloned
by a novel plague-forming method using a HTLV-I carrying cell line
MT-4. All viral preparations were titrated by reverse transcrip-
tase (RT) activity and plaque-forming unit (PFU) . PFU/RT values
which indicate the relative proportion of incomplete and infec-
tious viruses were used for the determination of the viral infec-
tivity. High values were obtained mainly from clones of HTLV-IIIB
and LAV-1, while low values were from ARV-2-derived clones,
suggesting that ARV-2 and its clones were genetically less infec-
tive. To assess cytocidal effect of the viruses, we selected and
used 4 clones with similar PFU/RT value (infectivity) for prolife-
ration assay of infected MT-4 cells, one (HTLV-IIIB-C-2) of which
was found to kill more cells than others even at the same doses
(MOIs). Furthermore, plaques induced by the HTLV-IIIB-C-2-iitfected
cell were larger than others, suggesting that release (prolifera-
tion) of the progeny was maximum in HTLV-IIIB-C-2-infected cell.
Among clones tested, three were found to induce strong cytopathic
changes (fusion and ballooning ) selectively to MT-4 cells. Thus,
we concluded that infectivity, proliferation and cytopathic
fusion-effect might be encoded by the viral genome and be separa-
ble by the plaque-cloning method.
MONDAY, JUNE 1
M A Q T4 Glycoprotein and T4 Messenger RNA in Human Immunodeficiency
Virus-Permissive cells
M. MALKOVSKY, KAREN PHILPOTT*. A. MELLOR*. P.J. MADDON**, R. AXEL***,
A.G. DALGLEISH, et al., Retrovirus Research Group and Transplantation
Biology Section, MRC Clinical Research Centre, Watford Road, Harrow,
Middlesex HA1 3UJ, England; Department of Biochemistry and Molecular
Biophysics and Howard Hughes Medical Institute, College of Physicians
and Surgeons, Columbia University, New York, New York 10032, USA.
The mere presence of the T4 molecule on the surface of both human lymphoid
and non-lymphoid cells is sufficient to render the cells susceptible to
human immunodeficiency virus (HIV) infection in vitro (Maddon et al., Cell
47, 333-348, 1986). Recently, we have Identified a B-lymphoblastoid cell
line (Gupta) which expresses neither T4 on the cell surface (FACS analysis)
nor T4 mRNA (Northern blotting, SI nuclease protection assay). However,
Gupta cells can be productively infected with HIV using a relatively low
dose (10 infectious units per ml) of virus. Interestingly, the HIV
infection of Gupta cells is not associated with syncytial formation, which
is typically induced by HIV in T4-posltive cell lines. Also, the CD4
monoclonal antibodies (anti-Leu-3a and DAK0-T4), which block the cytopathic
effect of HIV on T lymphocytes do not inhibit the HIV infection of Gupta
cells. Finally, we have studied several monkey species and found that T
lymphocytes of the olive baboon (Papio anubis) and the common marmoset
(Callithrix jacchus) express certain epitopes pertinent to HIV infection,
suggesting that these species could serve as a model of HIV infection In
vivo.
M 4 6 Structure/Function Relationships of the HIV Envelope Glycoproteins
MARK KOWALSKI, JOSEPH POTZ, WEI CHUN GOH, LADAN BASIRIPOUR, CRAIG
ROSEN, ANDREW DAYTON, ERNEST TERWILLIGER, WILLIAM HASELTINE*, JOSEPH SODROSKI
Dana-Farber Cancer Institute, Dept. of Biochemical Pharmacology, Harvard Med-
ical School, and *Dept. of Cancer Biology, Harvard School of Public Health,
Boston, MASS.
The HIV envelope glycoproteins play a central role in virus entry into the
host cell and in the direct cytopathic effect of HIV Infection on T4 bearing
cells. Plasmids expressing mutant HIV envelope proteins were constructed and
used to transfect human T and B lymphocyte lines. Expression and processing of
the HIV envelope was monitored as well as the ability of the mutant envelope
protein to bind to the T4 receptor and to induce the formation of syncytia by
membrane fusion. Mutations affecting the association of the gpl20 exterior
protein and the gp41 transmembrane protein, mutations affecting the binding of
the gpl20 to the T4 molecule, and mutations affecting post-T4-binding steps in
the process of syncytium formation were defined. The ability of anti-peptide
sera or sera from HIV infected individuals to interfere with the function of
envelope proteins derived from divergent HIV strains was examined.
Psychosocial — Behavioral Studies of AIDS
M 4 4 Delineation of a Region of the HIV gP120 Envelope Protein which
Interacts with the CD4 Antigen of the Helper T Lymphocyte
LAURENCE A. LASKY, T. GREGORY, G. NAKAMURA, C. FENNIE, D. SMITH, P. BERHAN,
et aK , Departments of Molecular Biology, Process Development, and Assay
Development, Genentech, Inc., So. San Francisco, CA, USA.
The most important initial event in the infection of cells by HIV is the
interaction between the virus envelope protein, gP120, and its cellular
receptor, the CD4 antigen. In order to understand this interaction, we have
begun to investigate the regions of the envelope antigen which interact with
the CD4 protein. Previously, we demonstrated that large quantities of a
secreted form of the HIV gPl 20 antigen could be produced in permanent mammalian
cell lines. A radiolabelled form of this envelope protein has been found to
bind to a recombinant CD4 antigen with high affinity, and this binding can be
inhibited by the appropriate 0KT4 monoclonal antibodies as well as human
neutralizing sera. A number of monoclonal antibodies specific for gPl 20 have
been tested for their ability to block this interaction, and one has been found
to be effective. The gP120 epitope which interacts with this blocking
monoclonal antibody has been isolated by passing a mild acid hydrolysate of
gP120 over an immunoaffinity column which utilized the blocking monoclonal
antibody. One peptide specifically bound to the column, and N-terminal
sequencing revealed that it was located in the C-terminal portion of the
envelope protein. In order to further analyze this region, in vitro
mutagenesis of the HIV envelope gene was used to delete a small region of the
envelope protein within the peptide which bound to the blocking monoclonal
antibody. The resultant mutant gPl 20 protein was unable to bind to the CD4
antigen.
M.5.1 Neuropeptides and the HIV receptor: Peptide T. _ and its
Pentapeptide Analogues are Potent CD. Receptor Cigands Present
in env of All HIV Isolates. MR RUFF, J HILL, C SMITH, P
HALLBERG, E STERNBERG, N JELESOFF.JB O'NEILL, CB PERT
Brain Biochemistry, CNB, NIMH, Bethesda, MD 20S92U5A"
We have previously reported on the deduction of peptide T as
the putative attachment sequence by which HIV binds to macro-
phages, T cells, and brain cells (Pert et al PNAS 83, '86). We have obtained
[ H]-D-Ala, -peptide T and developed specific receptor binding assays to the
60 kD T. molecule present on rat, human, and monkey brain membranes as well
as human T cells and mouse macrophages. The core sequence necessary for CD.
receptor activity is the pentapeptide TTNYT whose analogues appear in all HIV
isolates obtained to date as well as HTLV I and II. Pentapeptides have been
synthesized and demonstrated to have potent bioactivity in, human monocyte
chemotaxis (Ruff et al FEBS 211), and in displacement of [ H] peptide T from
human T cells, rat hippocampal membranes, and mouse macrophage membranes. T.
receptor binding can be detected only on T. positive clones, but not on J„
negative clones. D-amino acid Tyr substitution in the critical, highly
conserved 4 position results in a virtual total loss of bioactivity.
Requirements for tertiary structure for bioactivity will be described. The
original anti-viral demonstration has been extended to A3. 01 cells in which
10" to 10" M peptide T and its pentapeptide analogs reduce infectivity of
the entire course of infection by 80-90%. VIP, a neuropeptide enriched in
cortex and sacral autonomic ganglia, shares structural homology since VIP7-11
is TDNYT and this neuropeptide is active at CDa. We hypothesize that the
VIP-mimetic properties of HIV env produce the profound immunological failure
and psychotomimetic disorders chracteristic of AIDS.
M 4 5 Reversion of a Non-infectious Envelope Mutant of the Human
Immunodeficiency Virus in a Tissue Culture System.
RONALD L. WILLEY*, DANIEL J. CAPON**, THEODORE THEODORE , MALCOLM A. MARTIN*.
* Laboratory of Molecular Microbiology, NIAID, NIH, Bethesda, MD 20892; and
Genentech, Inc., South San Francisco, CA.
Site specific mutagenesis has been used to introduce a single amino acid
substitution within the env gene of the human immunodeficiency virus (HIV) .
The substitution of a glutamine for an asparagine codon at a potential N-l inked
glycosylation site within a highly conserved region of env gpl20 resulted in
the production of defective virions. Particles produced following
transfection of the mutant clone into a colon carcinoma cell line were unable
to infect T4+ lymphocytes. However, revertant infectious particles appeared
in long-term cocultures of transfected colon cells and T4+ lymphocytes.
In three of nine experiments, infectious virions were detected at 26, 35, and
35 days after the addition of lymphocytes. Revertant proviral DNAs were
cloned and their env genes sequenced. These results indicate that the HIV
genome can undergo variation during replication in tissue culture in the
absence of any immune pressure.
M.5.2
Carl Eisdorf er , University of Miami, Miami, Florida.
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
MONDAY, JUNE 1
U J 3 PSYCHOIMMUNOLOGIC RESEARCH AND AIDS
T. Peter Bridge, M.D., Intramural Research Program, National Institute
of Mental Health, Bethesda, Maryland 20892
The neurotrophic nature of HIV infection has led to numerous
clinical descriptions of CNS correlates of AIDS, ARC, and HIV infection.
These Include cognitive, motor, and behavioral change believed secondary
to HIV infection itself rather than to the opportunistic CNS infections
consequent to the profound Immunologic dysregulation of AIDS. AIDS
treatments are proposed or being tested that are known to be associated
with demonstrable neuropsychiatric sequelae. Not only the neurotrophic
nature of HIV, but also the increasing documentation of the
Interdigitation of the immune , endocrine , and central nervous systems
predict that an immunologic infection by HIV would have CNS
consequences and that effective treatments will either be active In the
CNS and/or have side effects in the CNS. Data will be reviewed
addressing the biobehavioral basis for AIDS research arising from
the integration of the immune and central nervous systems. Evidence
for the Identity of neurotransmitters and immunotransmitters will be
presented as well as emerging research on the impact of behavior on
Immuno/neuro transmitters and the behavioral sequelae of Immuno/
neurotransmitter modulation. This paper serves both to provide background
for the other papers presented in this session as well as to discuss
a future direction of AIDS research in the near term.
M 5 6 Viral "Plds es B Bl,e ot action lor developing novel entl-vlral agents:
Studies with AL721. A. S. Lippa1, F. T. Crews2, M. H. Grieco3, E. Buimovicl-Klein3. M.
Lange3, D. I. Scheer4, and C. A. Klepner1 ; 1 Praxis Pharmaceuticals Inc., Beverly Hills,
CA , 2Universitv ol Florida Medical School, Gainesville, FLA, 3S1. Luke's/Roosevelt Hospital Center,
New York, NY, 4Yale University School of Medicine, New Haven, CT.
A major underlying theme in biology is the understanding that many Important processes involve the
recognition of biologically relevant substances by specific receptor molecules. This theme can be
observed in such diverse processes as 1)the attachment of neurotransmitters to their appropriate
receptor proteins, 2) the binding of antigens to antibodies and 3) the infection of host celts by viruses.
In these cases, successful receptor binding is highly dependent on the orientation and tertiary
conformation of the interacting molecules, which in the case of membrane proteins is regulated by the
lipid composition of the membrane. Human immunodeficiency virus (HIV), an enveloped retrovirus,
attaches to T4 lymphocyte receptors with high specificity. Based on the high lipid composition (approx.
50%) of HIV, its hyperviscous nature and abnormally high fe1) cholesterol to phospholipid molar ratio
(C/P), we believe that the viral envelope may have an important role in maintaining the structural
integrity and infectivity of the virus by providing a rigid lipid matrix enabling the viral attachment
proteins to maintain the proper conformation/orientation for binding to T4 receptors. AL721 is a
unique mixture of orally active lipids which has been shown previously to modify membrane lipid
composition and to enhance lipid bilayer membrane fluidity by the extraction of cholesterol from cell
membranes with high C/P. Treatment with AL721 decreased the cholesterol content and altered the
biophysical properties of HIV envelope in parallel with its ability to inhibit the infectivity of HIV. In
eight patients presenting with persistent generalized lymphadenopathy and who were seropositive for
antibody and virus, eight weeks treatment with AL721 decreased mean blood levels of reverse
transcriptase activity by 60% and increased the diminished lymphoproliferative responses to both
pokeweed and concanvalin A mitogens. These data support the hypothesis that the HIV membrane is a
major structural component of the virus and that modifications in viral lipid composition by AL721 may
prevent viral infection of host cells.
Prevention/Public Health — Impact of HTV
Testing on the Behavior of Homosexual Males
M.5.4 An unspeakable Disease. Self-Isolation of HIV infected pa=
tients as a result of Conflicting Aspirations
Michael P'll.T.AK*. C . GHARAKHANIANVW . ROZENBAUM'; A . VIALLEFONT", F . AIME ; ' "
•GSPH,CNRS, Par is, "Fac.de Medecine, Univ. Paris ,K''U-19 4 ,INSERM, Paris,
France
104 patients (38 AIDS, 14 ARC, 43 Lymphaden.,9 Asympt.Jof a Paris
hospital were interviewed in March and April 1986 about changes in
their social and work relationships, psychological stress and their
speaking about the diagnosis. Most patients including married men
and gays living in couple relationships speak only with the closest
persons, 501 of L and A a;:d 30% of ARC and AIDS with nobody about
their illness. Except for a drastic decline in sexual activities,
nothing apparently changes in their personal life and work before
longer periods of hospitalisation. Although suffering from insomnia,
deDression and anxieties, only 6% of patients sollicit or accept
psychological and psychiatric help, less than 10% support services
offered by associations. Patients tend to refuse help becouse con=
tinuing a "normal life" symbolizes hope. But this is only possible
by hiding ones diagnosis. This attitude then hinders mobilizing sup=
port around them. This suggests that patients live with contradicto=
ry aspirations that compare to a double bind situation as seeking
help and breakina the silence is easily identified with giving up
one's hone and abandoning one 'self in a situation overdetermined
by the threat of death.
Only wide social acceptance of HIV infection as a "normal diseaee"
can help to solve this psychological dilemma.
M.6.1
Effect of HIVab Serodiagnosis on Sexual Behavior in
Homosexual Men in The Netherlands
GODFRIED J. P. VAN GRIENSVEN, R.A.P. TIELMAN, J. GOUDSMIT, J. VAN DER NOORDAA,
F. DE WOLF, R.A. COUTINHO, et al . , AIDS Study Group Amsterdam/Utrecht, P.O. Box
80140, 3508 TC Utrecht, The Netherlands
Between October 1984 and October 1986, 860 homosexual men, living in and
around Amsterdam, The Netherlands, were surveyed every six months, regarding
sexual behavior. At the start of the study 746 subjects learned their HIVab
status, of whom 234 (31 per cent) were HIVab+ . In addition 114 individuals,
recruited as controls, were not tested on HIVab. Regarding changes in sexual
behavior, data were analysed with analysis of variance in a doubly multivariate
repeated measures design. To improve the comparability between groups (obscured
by pretest differences in group means and a differential "floor" effect)
deviation scores were computed. These express the relative popularity of each
sexual technique in relation to all other techniques.
Reductions were found in the number of sexual partners and the number of
partners on all measured sexual techniques. HIVab tested individuals reported
greater reductions than did controls. Cases who were HIVab+ reported the
greatest reductions. The relative popularity of masturbation active and passive
and anogenital insertive and receptive intercourse remained constant. Oro-oral
sexual contact and orogenital insertive and receptive intercourse became less
popular, while oroanal insertive and receptive intercourse became slightly
more popular. No substantial differences between groups were found in this
respect .
M.5.5 *" Intensive Psychoimmunologic Study of
Long-Surviving Persons with AIDS
LYD1A TEMOSHOK, J. ZICH, G.F. SOLOMON, D.P. STITES, UCSF School Med., CA.
Given the increasing number of studies which link stress and/or behavioral
factors with immune response and disease progression, psychosocial factors might
be expected to play a role in AIDS. While there has been much interest and
speculation about the relationship of psychologic and immunologic factors in AIDS,
there are no completed studies in this area, to date. The present study is con-
cerned with the interactions among psychosocial, immunologic, and psychophysio-
logic parameters in persons with AIDS who have varying durations of survival.
Initially, 5 subjects were diagnosed with AIDS for less than one year (x= 8
months), 8 were diagnosed between 1 and 2 years ago (x= 19.9 months), and 5
"long-surviving" men were diagnosed more than 3 years ago (x= 42.4 months).
Blood was drawn prior to an initial psychosocial interview and 6 weekly interviews
addressing recent emotional experiences and related coping patterns. Blood was
assayed for helper-indueer and suppressor-cytotoxic T cell numbers and ratio,
Natural Killer cell numbers and function, virus "specific" T cells, large granular
lymphocytes, activated suppressor cells, activated helper cells, B cells, and
Cortisol levels. The six emotion-related interviews were videotaped and subjects
were monitored for heart rate, skin temperature, skin conductance, and respiration.
Various psychosocial measures were administered to assess social support, stress,
daily moods, health-promoting activities, and psychological "hardiness."
Relationships among immunologic and Cortisol levels, psychophysiological reactivity,
emotional expressiveness, and stress/coping indices will be presented. The data
analyses focus on within subject patterns of co-variation, as well as differences
across subjects, particularly, patterns that distinguish "long-surviving" persons with
AIDS. Further analyses will investigate factors related to actual duration of
survival from time of diagnosis.
M fi ? Factors Influencing the Decision to Learn HIV Antibody Results in
Gay and Bisexual Men
DAVID W. LYTER, R.O. VALDISERRI, L.A. KINGSLEY, W.P. AMOROSO, C.R. RINALDO, JR,
University of Pittsburgh, Pittsburgh, PA.
During the latter part of 1985, 1809 gay or bisexual men enrolled in the
Pittsburgh cohort of MACS (Multicenter AIDS Cohort Study) were invited by mail
to learn their HIV antibody results. Participants were asked to complete and
return a questionnaire^designed to assess the factors influencing their deci-
sion about learning results, their recent sexual behavior, their knowledge
about AIDS and their attitudes towards AIDS risk reduction. 869 (48%) men ac-
cepted the invitation, 160 (9%) declined and 780 (43%) failed to respond. There
were no significant differences in demographic, behavioral and attitudinal
characteristics or HIV seroprevalence between the men who accepted and those
who declined. However, significant demographic differences were noted between
the men who responded to the invitation versus those who did not., in that the
latter group was comprised of a greater proportion of men who were younger,
non-white or less well-educated. The most frequently cited reason (87%) why
men wanted their results was to determine if they had been infected with HIV.
Of those who declined, 31% cited concerns about the psychologic impact of
learning about a positive antibody result as being the most important reason
for their decision to decline. The most frequently selected contributing rea-
son for declining results (61%) was the belief that the test is not predictive
of the development of AIDS. 24% believed that the test is inaccurate and 19%
expressed concerns about confidentiality. These findings have relevance to the
design and implementation of HIV screening programs.
MONDAY, JUNE 1
u c O Sexual practices and condom use in a cohort of homosexual men: Evidence of differential
modification between seropositive and seronegative men.
BRIAN WILLOUGHBY, MT SCHECHrER, WJ BO^KO, KJP CRA1B, MS WEAVER, B DOUGLAS, et
al. The Vancouver Lymphadenopathy-AIDS Study, St. Paul's Hospital, University of British
Columbia, Vancouver, BC, Canada.
We have been following a cohort of approximately 600 homosexual men recruited through 6 general
practioners with six-monthly questionnaires, physical exams, and lab testing. To assess behavioral
change, we compared sexual practices reported at the earliest visit (EV) during the period [03/84 -
12/&41 with those reported at the latest visit <LV) during the period [05/85 - 09/86] in all 430 members
of our cohort who had complete data for at least 2 visits during the observation period. This included
150 seropositive men with a mean interval between EV and LV of 19.4 months (range=8-28) and 280
seronegative men with a corresponding mean interval of 20.1 months (range=6-29). Overall, the mean
annual number of sex partners declined from 7.7 to 6.4 (p<.001). This was confined primarily to the
seropositives (9.2 to 5.8; p<.001), as compared to the seronegatives (6.9 to 6.7; p=NS). Because the
seropositives had higher levels at EV and thus greater potential to decline, we restricted the analysis
to the upper 50<£ at EV. In this analysis, the seropositives declined from 16.2 to 7.7 (p<.001) while the
seronegatives declined from 15.6 to 10.9 <p<.001), with the decline being significantly greater in the
seropositives (-85 vs -4.7; p=.043).
To study condom use in high risk situations, we analyzed their use during receptive anal intercourse
with casual partners among those men in the upper 50^ of casual sexual contact. At LV, 35% of
seronegatives and 7% of seropositives reported never using condoms during this activity (rx.001) while
only 42% of seronegatives and 44% of seropositives reported ahixtys using condoms during this activity.
These data suggest that the very px-ple at continuing risk, namely seronegatives, may have modified
their behavior to a lesser degree. Even within an AIDS related study with six monthly visits, less
than half of seronegatives reported alzciys using condoms during receptive anal intercourse with
casual partners as of their most recent visit. The data suggest that we need to redouble our efforts at
educating all people 2t risk regardless of their HIV status.
M.6.6 Safer Sex and accentance of testino. Results of the nation^
wide annual servey amonci French Gay Men
Michael POLLAK* M . A . SCHILTZ", B . LE JEUNEV T5SPM , CNRS , Paris , France'/GPH ,
Paris .France.
- An annual nationwide survey among French Gay Men (sample size;
1200) shows considerable chanqes in sexual behavior between 1985
and 1986. Number of partners has decreased, condom use has increased
from 5% to 33%, more than 10% no longer practice anal sex, some
30% never did. At the same time volontary testing is widely accep=
ted, as revealed by more than 30% of the respondents already
tested in 1986. One out of three tested gay men being HIV-positive.
Knowing ones test results does not necessarily translate into safer
sex practices. One can rather say that the same factors are con=
ducive to both safer sex and testing: - Confidence in medical
authorities and past regular STD surveillance; - self confidence
and social acceptance of one's homosexuality; - proximity with
AIDS victims; - existence of a 'privileged' (although not necessa=
rily exclusive) love relationship that provides emotional security.
Roundtable Discussion
M 6 4 "ne HIV Antibody Test: Influence on Sexual Behaviour of Homosexual
CARLES F FARTHING*. V JESSOH**, H-L TAYLOR**, A G LAWRENCE*. B G GAZZARD* .
UK.
•Public Health Laboratory, Collindale
ephens Hospital, London,
Laboratories, London, UK.
There has been debate as to whether patients at risk of HIV infection should
be er.couraged to have an HIV antibody test performed. We therefore conducted
a survey bv anonymous questionnaire which was completed whether or not the
test was eventually carried out. All patients were counselled prior to being
offered the test and a similar questionnaire was completed 3 months after the
initial interview. Of 324 homosexual men offered the test 87% agreed to be
tested although 157 had come to the clinic without this intention. Only 4
patients did not wish to know the results. Sixty five per cent of patients tad
already modified their sexual behaviour but 93;© th-ught they would be more
likely to adhere to safer sexual practices if shown to be positive ».heras 79%
would do so if the test was negative.
Three months later 16% of patients regretted having the test - all had had
a positive result. Half of the 83% of patients practicing safer sex felt they
were doing so as a result of the counselling, but the rest as a result of the
test being positive.
Ovr results suggest that the naiority of gay men (88%) wish to know their
HIV antibody status and that having the test performed encourages the adoDtion
of safer sex practices.
M.7
Communicating AIDS Education Across Cultural Barriers
Panel Organized By: Paul Kawata
National AIDS Network
Washington, D.C.
Panel Moderator:
Gil Gerald
National AIDS Network
Washington, D.C.
Juan Ramos, National Institute of Mental Health, Rockville, Maryland
Carl Bean, Minority AIDS Council of California. Los Angeles. California
Gloria Rodriguez, NJ State Department of Health, East Orange. New Jersey
William Smith, Academy for Educational Developnent, Washington, D.C.
Jaime Sepulveda, Colonia Valle, Mexico
M 6 5 Evaluation of Anti-HIV Testings in Sweden, a Country where HIV In-
fections are Subjected to Legislation
Professor M. BOTTIGER M.D., Nat. Bact. Laboratory, Stockholm, Sweden
In Sweden testings for presence of anti-HIV are encouraged. However, all
physicians earring out the tests must be able to give psychosocial help and
advice both to the afflicted and those who are seronegative but at risk. In
November 1985 the HIV infection was included among the veneral diseases sub-
jected to legislation. The number of tests performed and the number of posi-
tive test results in this country with 8.3 million inhabitants have been re-
ported since then. L'p to 1987 115,000 tests (blood donors excluded) were re-
ported - 10,000 thereof from homosexual men and 13,000 from drug addicts.
Persons at risk were as a rule investigated several times.
The number of tests performed did not decrease significantly during the
period before and after legislation. However the yearly number of new sero-
positive persons diagnosed declined from 356 in 1985 to 570 in 1986. The num-
ber of seropositive blood donors also successively decreased from 13 in the
first 530,000 tested to none of the 200,000 tested the last half of 1986.
HIV-infected persons are reported from the physicians to the central epide-
miological department under a code. The same code is used in reports directly
laboratories. The two report systems are in agreement with each other.
Epidemiology — AIDS in Developing Countries
M 8 1 Infection by mv among populations of six oountries of Central
* Africa. . „
•■■.. :ZRLIK , R. JOSSE , E. DELAPORTE , J. P. DURAN3 , C. HENGY ,
****
A.J. GEORGES , *O.C.E.A.C, Yaounde, Cameroon, **C.I.R.M.F. , Gabon,
*** Pasteur Center, Cameroon, **** Pasteur Institute, Bangui, Central African
Republic.
From 1985 to 1987, O.C.E.A.C. carried out 25 serological cluster sample sur-
veys in joint authorship with Ministries of Health of the six Member-states
of the Organization. More than 9000 randomly selected peoples living in six
countries of Central Africa (Cameroon, Central African Republic, Chad, Congo,
Equatorial Guinea and Gabon) were concerned.
Rural and urban areas were investigated in different climatic zones. Various
group of age were studied. The collected blood samples were first screened by
ELISA test, then positive cases were confirmed by Western Blotting.
Circulation of HIV within some of the populations of the Sub-region is con-
firmed, with seroprevalence rates from 0 to 5 % with Western Blotting.
Heterosexual spread of HIV is the major way of infection. Under the age of
15 seroprevalence rates are significantly (p = 0.01) lower than those observed
in adults. Each sex is equally concerned.
Urban areas are very significantly more affected than rural areas (p = 0.001)
Incidence rates were evaluated by the comparison of the results of several
surveys carried on in the same nlace after intervals of 12 or 24 months.
MONDAY, JUNE 1
U g 2 HIV Antibody Prevalence in Migrant Mineworkers in South Africa
during 1986.
BRIAN A. BRINK*, R. SHER** , L. CLAUSEN*. *Chamber of Mines of South Africa,
Johannesburg, South Africa. **School of Pathology, University of the Wit-
waters rand and South African Institute of Medical Research, Johannesburg,
South Africa.
Some 512 000 employees on the Gold and Platinum Mines of South Africa are
black male migrant workers recruited from various countries in Southern and
Central Africa. They live in male hostels for an average of 12.7 months and
return home for an average of 3.3 months. Concern about a rising incidence
of sexually transmitted diseases in these employees and reports of a high
prevalence of HIV infection in Central Africa prompted this study.
During 1986, 330 000 blood specimens were taken at routine medical examin-
ations from all migrant workers returning to work. A total of 29 961 specimens
were systematically selected for HIV antibody testing, yielding unbiased
samples, stratified according to country of origin. The fresh sera were
screened with Abbott or Wellcozyme EIA tests and positives were confirmed by
other EIA's, indirect flourescence and Western Blotting if necessary.
HIV antibody prevalence was: Malawi 119/3165 (3.76%) , Botswana 7/2063
(0.34%), Mozambique 2/2152 (0.09%), Lesotho 2/2246 (0.09%), Swaziland 1/1885
(0.05%), South Africa 4/18450 (0.02%). These results confirm that there is a
low prevalence of HIV infection in Southern African blacks. Malawian
mineworkers have a higher prevalence of HIV infection which is probably
contracted in Malawi. There is as yet no evidence for spread of HIV infection
in the hostel environment.
M O C The Association between HIV Seropositivity, Blood Transfusions,
and Malaria in a Pediatric Population in Kinshasa, Zaire.
ALAN E. GREENBERG*, P. NGUYEN-DINH* , J.M. MANN******, N. KABOTE****, R.L.
COLEBUNDERS** »*****, T.C. QUINN******, et al., *Malaria Branch, Centers for
Disease Control, Atlanta, GA, **Projet SIDA, Ministry of Health and Social
Affairs, Kinshasa, Zaire, ***AIDS Program, Centers for Disease Control,
Atlanta, GA, ****Mama Yemo Hospital, Kinshasa, Zaire, *****Institute of
Tropical Medicine, Antwerp, Belgium, ******Laboratory of Immunoregulation,
National Institutes of Health, Bethesda, MD.
To investigate the role of blood transfusions in the transmission of HIV
among African children, we studied 1046 pediatric patients presenting to Mama
Yemo Hospital (MYH) in Kinshasa, Zaire. Overall, 147 (14.1%) had histories of
previous transfusion, and 40 (3.8%) were HIV seropositive; there was a strong,
dose-response association between transfusions and HIV seropositivity
(p<10~6). To study the clinical indications for blood transfusions, we
reviewed 1000 MYH Emergency Ward records and found that 332/480 (69.2%) of the
children receiving transfusions had malaria, and 97.3% of all transfusions
were given to patients with pre-transfusion hematocrits of 25% or less. We
then surveyed 167 hospitalized children and found that 21 (12.6%) were HIV
seropositive, 78 (46.7%) had received transfusions during the current
hospitalization, and 112 (67.1%) had malaria. Ten of the 11 HIV seropositive
malaria patients had received transfusions during the current hospitalization,
and four of these children were documented to have been seronegative prior to
transfusion. The treatment of malaria with blood transfusions is an important
factor in the exposure of Kinshasa children to HIV infection.
M 8 3 frisks for Heterosexual Transmission of Hlv in Zimbabwe
David A. KATZENSTEIN*. A. LATIF* ,M. T. BASSETT* ,J.C.
EMMANUEL**. *University of Zimbabwe School of Medicine and
**The Blood Transfusion Service. Harare, Zimbabwe.
In Zimbabwe, interviews with Zlo HIV seropositive patients
showed that contact with prostitutes (80%), multiple sexual
partners (96%) and a history of sexually transmitted disease
(STU) (75%) were the risks identified in 200 men. In women, 18%
admitted to mult iple sexual partners and 51% had a STD history.
We interviewed 75 married couples in whom the husband was
the seropositive index case. In 15 both partners were
seropositive (T+); in 30 the husband was seropositive and the
i>i fe seronegat i ve i T- ) . T+ men had more sexua 1 part ners and
episodes of STI1 in the past two years than T- men. History of
genital ulcer in male partners carried a 3 fold excess risk of
seroposi Livity in t he female partner (T+ 71% vs. T- 27% p <- . 00 1 ) .
Syphy I 1 i s , chancroid, or genital Herpes were separately
associated with transmission (p <-05).
Multiple sexual partners and STDs are the primary risk
factors for Hl\ infection in Zimbabwe. In 60% of couples HIV
transmission had occurred, associated with a history of genital
ulceration in men. Identification of seronegative wives of Hl\
seropositive men presents an opportunity to prevent infection.
M 8 6 Pattern of HIV Infection in Haiti: 1977-1986
JEAN W. PAPE*. M.E. STANBACK*, M. PAMPHILE**, R. VERDIER**,M-M
DESCHAMPS**, W.D. JOHNSON, JR.*, et al. , Cornell Univ. Med. Coll., NY*,
GHESKIO, Port-au-Prince, Haiti**.
The prevalence of antibody to HIV (wv, p24, gpl20) was determined in 2464
Haitians evaluated in Port-au-Prince in 1985-1986 and in 191 Haitians bled dur-
ing a 1977-79 dengue outbreak. Among AIDS contacts, seroprevalence was highest
among heterosexual sex partners (N=174, 55%). Rates in their siblings and
friends were higher in males (N=168, 22%) than in females (N=76, 9%). Among un-
related groups, the seroprevalence was 6% for 329 healthy urban adults - 9% in
129 mothers of sick infants, 6% in 109 hotel and factory workers, and 0 in 91
persons of higher socioeconomic status. The rate was 3% in 130 healthy rural
adults including 97 mothers of sick infants. Rates among urban tbc pts. (37%)
were higher than among rural pts. (15%). 8% of 1037 individuals who had blood
tests performed in 3 commercial labs were seropositive. None of the dengue pts.
bled in 1977-79 were seropositive. This pattern suggests that HIV is of recent
date in Haiti, and is more prevalent in urban areas and in lower socioeconomic
groups .
Groups
AIDS patients
AIDS pts.1 spouses
AIDS pts.' sibs. and friends
Healthy urban adults
Laboratory specimens
Healthy rural adults
Tuberculosis patients
Dengue patients
No. test*
2d
7.
Se
ropositive
384
85
174
55
244
18
329
6
1037
8
130
3
166
22
191
0
M 8 4 Incidence of human immunodeficiency virus (HIV) infection and rel-
ted disease in a cohort of Nairobi prostitutes
FRANCIS A PLUMMER, JN SIMONSEN, EN NGUGI, DW CAMERON, P PIOT, JO NDINYA-ACHOLA
Kenya Medical Research Institute, Univ Nairobi, Ministry of Health, Nairobi,
Univ Manitoba, Winnipeg; Institute of Tropical Medicine, Antwerp
In Africa HIV is a heterosexual sexually transmitted diS^r*. Although there
are many studies reporting the prevalence of HIV inf actio; i in Africa, few
studies of the incidence of HIV infection and the frequency of development of
HIV related illness in Africa are available. We began a study of the epide-
miology of STD in a cohort of Nairobi prostitutes in January 1985. Initially
65 % of 535 women enrolled were seropositive for HIV. All women were asympto-
matic. This cohort has now been followed prospectively for two years for the
development of new HIV infections and illness related to HIV. Among initially
seropositive women persistent generalizd lymphadenopathy was found in 47 % one
year after enrollment. The one year incidence of more severe illness among
298 women evaluated was 5.7 %. These included herpeszoster (8), severe vagi-
nal candidiasis (3), severe weight loss (1), undiagnosed pneumonia (1) and
death (3). Among women who were initially seronegative for HIV the incidence
of new HIV infection was 56 %. HIV infection is epidemic among this group
of Nairobi prostitutes. Illness associated with HIV is developing at rates
similar to those observed in European and North American groups. Urgent
measures to control this epidemic are required.
Virology — Structure and Function II
M 0 1 T-CELL ACTIVATION INCREASES GENE EXPRESSION DIRECTED BY
THE HIV LTR: IMPLICATIONS FOR PATHOGENESIS IN AIDS
1 2 2
Paul A. Luciw , Sandra E. Tong-Sarksen , and B. Matija Peterlin
1 University of California, Davis CA 95616, 2 Howard Hughes Med-
ical Institute, University of California, San Francisco CA 94143
The human immunodeficiency virus (HIV) , a lymphocytopathic
retrovirus, is the causative agent of the acquired immunodefic-
iency syndrome (AIDS) . In tissue culture systems with T4 lymphoid
cells, the amount of HIV replication is related to the extent of
T-cell activation. We have utilized transient expression assays
in the Jurkat T-cell line to investigate the effects of T-cell
activation signals on gene expression directed by the HIV long
terminal repeat (LTR) . Promoter activity of the HIV LTR was about
10-fold greater in activated T-cells (treated with lectin) than
in unstimulated cells. These activation signals are specific for
the HIV LTR since expression directed by the HTLV-I LTR, RSV LTR,
and HSV thymidine kinase promoter is not affected. The region
encompassing the HIV enhancer appears to be the target of T-cell
activation signals. The kinetics of induction of expression di-
rected by the HIV LTR closely parallel those for the 11-2 and
11-2 receptor genes. The affects of of T-cell activation signals
and the HIV coded transactivator (TAT) gene were observed to be
multiplicative. By acting on the HIV LTR, T-cell activation sig-
nals may convert a latent infection to a productive infection;
thus, T-cell activation may be significant with respect to the
onset of clinical AIDS in individuals infected with HIV.
MONDAY, JUNE 1
M Q 9 Mapping of the cis-acting Regulatory Regions Responsive to the HIV
art gene product.
CRAIG ROSEN, ERNEST TERWILLIGER, JOSEPH SODROSKI, and WILLIAM HASELTINE*
Dana-Farber Cancer Institute, Dept. of Biochemical Pharmacology, Harvard Medi-
cal School, and *Dept. of Cancer Biology, Harvard School of Public Health,
Boston, MASS.
The product of the HIV art gene is required in trans for the expression of
virion capsid and envelope proteins. However, the block in expression of virus
encoded protein in virus defective for the art gene is not absoulute as such
mutants can produce a functional tat gene protein. To explain the observed
regulatory effects it would suffice for the repressive sequences to be within
the env gene as all of the mRNA species that encode virion gag and env protein
contain these sequences whereas the mRNA for the tat and art genes does not.
To test this hypothesis we designed a novel transient gene expression assay to
identify the cis-acting determinants necessary for regulation of gene expres-
sion by the art protein. Our results demonstrate that sequences that confer re-
pression of gene expression are dispursed throughout the genome and that these
sequences are distinct from those sequences responsive to the art product.
One art responsive element, designated ARE, is present within a 40 base pair
sequence that contain a highly purine-rich stretch. We propose that the func-
tion of art is to relieve repression of gene expression that results from the
presence of intragenic repressor sequences.
M 9 5 The role of the i°H 9ene 0f HTLV-III/HIV
AMANDA FISHER1, B.Ensoli1, L.Ivanoff^, |_.Ratner3 A F.Wong-Staal 1
1 Laboratory of Tumor Cell Biology, NCI, NIH, Bethesda, MD 20205
2 E.I.Dupont, Willnungton, Delaware
3 Division Hematology & Oncology, Washington University, St. Louis,
MI 63110
The role of the sor gene of HTLV-III/HIV and its product is not known
although initial reports have indicated that it, 1 ike 3'orf is dispensible
for replication (Sodroski, 1986). To investigate this issue we constructed
a series of variants of HTLV-III in which either the entire coding sequences
of sor had been removed or termination codons had been introduced into the
sor reading frame by site directed mutagenesis. These mutants were capable
of generating virus particles upon upon transfection. However, all the mutant
clones were extremely limited in their capaciy to establish stable infection
in vitro ; less than 1% of cells consistently expressed HTLV-III antigen in
cultures infected with sor mutant viruses as opposed to 80-90% of cells in
controls (all cultures were monitored for 8-12 weeks). Analysis of cos-1 cells
transiently transfected with the mutated clones showed no change in either
the quantity or quality of viral RNA, protein or particle expression. Further-
more the ability of these clones to trans-activate remained unaltered when
tested in lymhoid and in nonlymphoid cells. These data argue that (i) the
sor gene has an important biological role modulating virus propagation
and ( i i) that this gene most 1 ikely acts at a post trans! ational level .
M Q O Human Immunodeficiency Virus Protease
S. Oroszlan, T.D. Copeland, L.E. Henderson, Laboratory of Molecular
Virology and Carcinogenesis, BRI-Basic Research Program, NCI-Frederick Cancer
Research Facility, Frederick, MD.
As for other retroviruses the gag and gag-pol polyproteins of human immuno-
deficiency virus (HIV) are processed during virus maturation by the viral
coded protease which together with RT and endonuclease is translated in a -1
frame relative to the open reading frame of the gag gene. We have analyzed
the primary structure of the proteins of human T-lymphotropic virus type-Ill
(HTLV-III) grown in H-9 cells. Proteins were purified from sucrose density
gradient banded virus by reversed phase liquid chromatography. Comparison
of the determined N- and C-terminal sequences with published nucleotide
sequences of proviral DNA identified the proteolytic cleavage products and
their order in the Pr559a9 and Prl709a9-P°l polyproteins. As expected the
amino acid sequences around the maturation cleavage sites were found to show
substantial homology.
A peptide corresponding to the C-terminal sequence of HTLV-III protease was
synthesized. Antibody to this peptide is now being utilized to isolate the
protease in quantities sufficient for further structural and enzymological
studies. HIV protease shows sequence homology to other well characterized
retroviral proteases which have been shown to have an important role in
virus replication and infectivity. Retroviral proteases have conserved in
their sequence one of the active-site sequences of aspartylproteases and
can be inhibited by certain active-site-directed inhibitors of these enzymes.
(Research sponsored by National Cancer Institute, DHHS, under contract No.
NO1-CO-23909 with Bionetics Research Inc.).
M Q fi Direct Mutagenesis Analysis of the Trans-Activator Genes of Human
Ifl.a.u T Cfill LjmphotropiC Virus Type III
M. REZA SADAIE, T. BENTER and F. W0NG-STAAL, Laboratory of Tumor Cell Biology,
National Cancer Institute, NIH, Bethesda, Maryland 20892.
Human T-lynphotropic virus is unique in containing multiple non- structural
genes that are regulatory in function. Two of these { tat- III and trs) have
been shown to be essential for virus replication based on deletion mutant
studies. However, independent roles of these genes in regulation of virus rep-
lication have not been elucidated previously. In this study, we used the ap-
proach of site directed mutagenesis to generate point mutations in desired nu-
leotide positions. We obtaind a panel of tat and trs mutants and evaluated
their functions by the following parameters: transcription, steady-state mRNA
levels, protein synthesis and virus production. The following conclusions
could be drawn: 1) Tat- III has a positive trans-acting role in both transcrip-
tional and post-transcriptional events. 2) A chain terminating mutation in the
trs gene rendered the provirus defective resulting in a grossl y modified viral
spl icing pattern and unusually high levels of the viral 1.8 Kb mRNA species.
Therefore, trs gene product may have a negative trans-acting role in regulat-
ing the level of the 1.8 Kb mRNA species. 3) Point mutant proviruses defective
in tat or trs were complemented by a wild type tat and trs cDNA subclone al-
lowing the mutants to resume the normal transcription pattern and subsequent
virus production. 4) Both tat and trs function in a co-operative manner regu-
lating the virus replication, i .e. ; both gene products are required for optimal
trancription and translation of the viral structural genes.
M Q d Functional Analysis of the HIV A (SOR) Gene Product
3 KLAUS STREBEL*, D.F. DAUGHERTY** , T.M. FOLKS***, K.A. CLOUSE° ,
M.A. MARTIN*. *Laboratory of Molecular Microbiology, and ***Laboratory of
Immunoregulation; National Institute of Allergy and Infectious Diseases, NIH,
Bethesda, MD 20892; **University of Michigan, Ann Arbor, MI.; Georgetown
University , Washington , DC .
We investigated the biological function of the HIV A-gene product by using
a mutant of an infectious clone containing a 620 bp deletion in the A gene
region (pAA) . When the infectious molecular clone of HIV and the AA mutant
were separately transfected into the SW480 colon carcinoma cell line, the
production of virus particles (as monitored by RT) was readily detected, but
a cell-free lysate, containing AA progeny virus, could not be passaged into
T4+ lymphocytes. In contrast, the AA HIV infection could be transferred to
T4+ lymphocytes by cocultivation. To ascertain whether the A gene product
could function in trans, cDNA clones expressing the A protein were
cotransfected with the AA mutant and the resulting filtrates were evaluated
for their infectivity in T4+ lymphocytes. In all cases examined, the AA
mutant could be complemented with constructions expressing the A gene;
however, the progeny virus from these cultures could not be repassaged in T4+
lymphocytes. These observations suggest that deletion of the A-gene results
in the production of particles that are apparently defective at an early step
during their replication.
Immunology — Viral Proteins and Virus
Specific Immune Responses
M 10 1 Analysis with recombinant vaccinia viruses of CD4/HIV gp interaction
within individual cells.
P. SALMON, R.OLIVIER, Y. RIVIERE, M.P.KIENNY(L.HONTAGNIER,J.C.GLUCKMAN,D.KLATZMANN.
UFR Pitie-Salpetriere and Institut Pasteur, Paris, Transgene, Strasbourg, FRANCE.
Interaction between HIV gp and CM occurs during virus-cell contact (tro-
pism) ,during cell-cell fusion (syncitia) and, though less well documented, within
individual cells (cell death?). In infected cells, the selective and progressive
disappearance of CD4 at the membrane, contrasting with conserved CM mRNA levels,
and intracytoplasmic CM/gp complexes have been noted, suggesting their causal
relationship with cell death. We further investigated this point by infecting
CM+ lymphocytes with various recombinant vaccinia viruses that contained normal or nu-
tated, partial or complete, env gene. Expression of various membrane markers, and
gp detection with HAb, was assessed by cytofluorometry on viable cells. Progres-
sive and complete disappearance of Leu 3a staining associated with a 3 to 10
fold decrease of OKT4 fluorescence intensity correlated with increasing expres-
sion of gp, which indicates both reduction in the number of CM molecules at
the membrane and their complexing with gp. Surprisingly, expression of the "na-
tural" HIV gp 110-41 had no effect, and only uncleaved gp 160 or normal gp 110
directly anchored in the membrane through its linkage to a homologous or hetero-
logous transmembrane protein induced such effect. As after "natural" HIV in-
fection, we could immunoprecipitate intracytoplasmic CM/gp complexes and show-
ed unchanged CM mRNA but no cell fusion. Therefore, during "natural" infection
of CM+ lymphocytes, while few cells express viral antigens, complete CM modu-
lation indicates that all cells are finally infected, which directly leads to
their death. Our results are relevant to the selection of the proper recombinant
for vaccination or immune response analysis, and to understand the CM/gp com-
plex formation and cell death.
MONDAY, JUNE 1
M 10 2 Analysis of HIV Protein Presentation on Infected Cell Surfaces:
Evidence for Group, Type, and Host Cell Specificity.
STEPHEN G. CARTER*. W.G. ROBEY**, L.O. ARTHUR*, P.J. FISCHINGER**, AND M.A.
GONDA*, *Program Resources, Inc., NCI-FCRF, Frederick, MD, **Office of
Director, National Cancer Institute, NCI-FCRF, Frederick, MD
Development of a successful vaccine against HIV requires the identification
of proteins on the virus envelope and cell surfaces involved in the immune
recognition process. Antibodies were prepared to purified proteins (core and
envelope) from HIV (strain HTLV-IIIB) and analyzed by flow cytometry. Anti-
bodies to glycosylated or deglycosylated forms of gpl20 bind to HTLV-IIIB-
infected H-9 cells, although those against the deglycosylated gpl20 react to a
lesser degree. Antibodies to gp41, the transmembrane protein, also recognize
small amounts of gp41. A polyvalent, monospecific antiserum to p24, the major
core protein, did not detect any epitopes on HTLV-III-infected H-9 cells.
These results suggest that epitopes of gp41 and glycosylated and nonglycosy-
lated gpl20 are involved in the immune recognition process. Thus, they may be
important in evoking protective antibodies, whereas epitopes of p24 may not.
We also investigated the reactivity of a sequential series of bleeds from a
goat inoculated with HTLV-IIIB gpl20 isolated from infected H-9 cells With
various isolates (envelope strains) of HIV growing in H-9 cells. Both type-
and group-specific antibodies were demonstrated by flow cytometry, with the
type-specific reactivity occurring (early bleeds) prior to the detection of
group-specific (late bleeds) reactivity. Unexpectedly, these antisera showed a
marked reduction in reactivity with HTLV-IIIB grown in Molt-3 cells, another
human lymphocyte. This reduced reactivity could not be attributed to a lack of
production of viral antigen; but rather may reflect cell-specific processing
of gpl20. Cell-specific processing of gpl20 should be investigated further as
it may directly influence the immune recognition of envelope preparations.
M 10 5 Common and Variable Neutralization Antigens of HIV-1 and HIV-2
" " PAUL R. CLAPHAM*, J.N. WEBER*, L. MONTAGNIER**, R.A. WEISS*,
institute of Cancer Research, Chester Beatty Laboratories, London.
** Unite d'Oncologie Virale, Institut Pasteur, 25-28 rue du Dr. Roux, 75724,
Paris Cedex 15.
We have shown that sera from HIV-1 infected individuals are capable of
neutralizing a genetically diverse range of HIV-1 isolates (Nature, 324, 572-
575, 1985). Some HIV-1 isolates (e.g. ARV-2) are far more sensitive to neutra-
lization than others.
Sera from HIV-2 infected individuals will cross-neutralize some isolates
of HIV-1 but the neutralizing titres are significantly lower than those in
the sera of HIV-1 infected individuals. HIV-1 sera fail to cross-neutralize
the LAV-2 isolate of HIV-2. However, this isolate is poorly neutralized by
autologous sera, and low-titre cross-neutralization would be missed. The
identification of common neutralization antigens between diverse HIV strains
is important for vaccine development.
M 1fl 1 Cellular Immune Response to Viral Peptides in Patients Exposed to
IYI.IU.0 HIV_ PAUL M. AHEARNE*, K.J. WEINHOLD*, T.J. MATTHEWS*, S. PUTNEY**,
S. PETTEWAYt, N. Changtt , et al. *Department of Surgery, Duke University
Medical Center, Durham, NC, **Repligen Corporation, Cambridge, MA, tCentral
Research and Development Department, E.I. DuPont de Nemours & Company,
Wilmington, DE, ttCenter for Biotechnology, Baylor College of Medicine,
Houston, TX.
In order to study anti-HIV cellular as well as humoral reactivity in AIDS
patients, we measured the proliferative response of peripheral blood lympho-
cytes to a purified native gag p24 and four recombinant peptides representing
various regions of the env gene. These peptides include Penv3 (gpl20 amino
terminus) , PB1 (gpl20 midportion) , Penv9 (gpl20 carboxy terminus + a portion
of gp41) and pl21 (gp41 subportion). The patients were characterized by their
HIV antibody status and general immunocompetence as reflected by the in vitro
response to tetanus toxoid (TT) .
P24 elicited ±n vitro blastogenesis in seropositive TT responders but not in
TT non-responders nor seronegative controls. Fifty percent of the patients
showed humoral reactivity to p24. All seropositive (Western) patients
expressed strong humoral reactivity to Penv9 and pl21 in contrast to the weak
cellular stimulation to these two peptides. PB1 elicited a variable humoral
response and little if any cellular response. In sharp contrast to the very
weak humoral stimulation, the most impressive cellular response was to Penv3.
This showed good cellular reactivity in TT responders, slightly decreased
reactivity in TT non-responders and poor reactivity in controls. The cellular
response to Penv3 seems to continue after loss of TT reactivity; whereas, the
immune response to the core protein p24 is decreased with loss of TT reactivity.
These results suggest that regions of gpl20 which are recognized by cellular
elements (Penv3) may differ from those that stimulate a humoral response (Penv9).
M 10 6 Antibody-dependent cellular cytotoxicity (ADCC)-inducing antibodies
aqainst human immunodeficiency virus (HIV).
Kristina Ljunggren*, E-M. Fenyb**, B. Bbttiger***, G. Biberfeld*** and
M. Jondal*. Departments of Immunology* and Virology** at Karolinska Institute,
Department of Immunology*** at National Bacteriological Laboratory. Stockholm,
Sweden.
A method to detect antibodies which mediate HIV-specific ADCC was established
using HIV infected monocytoid U937 (clone 2) cells as targets. Simultaneously,
the ADCC efficiency of the allogeneic effectorcells was tested with rabbit-
anti-b2 microglobulin serum against the same U937 cells. It was found that
approximately 40% of all anti-HIV positive sera could induce ADCC killing,
irrespective of the clinical stage of the donor. Quantitative comparison of
ADCC titers of sera from patients with different severity of HIV infection
showed that high HIV specific ADCC titers were more common in symptomfree
patients (75%) than in AIDS patients (42%). When the T4:T8 lymphocyte ratio
was compared to ADCC titers, no correlation was found. Sera from AIDS patients
which had lost antibodies to gag(p!9,p24) and pol (p55) proteins, but which
were still positive for gp!60, 120 and 41, could mediate ADCC.
In further studies, the fine specificity of ADCC active antibodies will be
defined using target cells infected with recombinant virus expressing part of
the envelope antigens. Also, evaluation of the clinical significance of HIV-
specific ADCC antibodies will be needed.
Clinical Management — Cancer, Hemophilia
and Cardiovascular Disease
M 10 4 Cellular immune response and neutralizing antibodies
towards HIV in infected individuals.
SATU MATTINEN*, A. RANKI**, W.G. ROBEY *** , J. ANTONEN* AND
K.J.E. KROHN*,**, xlnstitute of Biomedical Sciences, University
of Tampere, Finland, **Laboratory of Tumor Cell Biology, NCI,
Bethesda, MD, #**FCRF , NCI, Freder i ck ,MD.
To study the relevance of immune response towards HIV to the
progression of the disease we measured neutralizing antibodies
and T cell responses to purified HTLV-III proteins gpl20 and p24
as well as to inactivated whole virions in 28 HIV Infected
individuals. Neutralizing antibodies, capable of preventing the
cytolytic effect of HIV on a sensitive target cell line, ATH-8,
were seen in 66% of the cases. The presence of neutralizing
activity correlated with western blot confirmed antibodies to
gpl20, gp-41 and pl7. In T cell proliferative assays, a few
individuals responded to p24, but no response to the whole
virions or to gpl20 was seen, not even in cases having remained
asymptomatic for 3 years. Prevention of the viral replication
with 2' .S'-dideoxyadenosi ne did not increase responsiveness.
Moreover, in. si tu hybridisation revealed only a few infected
cells (10~^7 10~4), morphologically belonging to the monocyte -
dendritic cell lineage. We have shown that the early anergy to
soluble recall antigens in HIV Infection is due to infection of
the above cells, but in the present material even persons showing
normal PPD response had HIV specific anergy. The possibility,
that man has an inborn tolerance to the T cell epitopes in HIV
external envelope, can be disproved only by direct immunization
exper iments.
M 11 1 Tne Clinical, Research and Public Health Applications of the Walter
IVI.II.I Reed scaglng classification of HIV Infection R REDFIELD WRAIR Wash DC
In 1985, the Walter Reed Staging Classification of HIV Infection was
proposed. This staging scheme recognizes thac HIV infection as an
etiologlc disease process in which the central pathogenic event resulting
in immunodeficiency is the progressive destruction of the T helper cell
population. In addition this scheme recognizes that central nervous
system disease, complicating neoplasms, thrombocytopenia and severe
constitutional symptoms may have pathogenic mechanisms of occurrence
secondary to HIV but independent of functional intregity of the T cell
system. The purpose of this talk Is to describe the proper excecution of
this system, and to demonstrate its multiple applications outlined below.
Data will be provided demonstrating its usefulness for each.
1) ROUTINE CLINICAL: a) uniformity o£ clinical evaluation among health
care system; b) pathogenic based framework to clinically approach, manage
and follow patients; c) prognostic predictor for physician and patient;
2) RESEARCH: a) facilitate an understanding of the natural history of HIV
infection; b) facilitate an understanding of the pathogensls and effect on
outcome of associated disease processes; c) facilitate an understanding
of the Immune response to HIV and its biological significance; d)
facilitate the evaluation of therapeudic modalities; e) facilitate an
understanding of the efficiency of transmission of different modes and
stages of infection;
3) PUBLIC HEALTH: a) facilitate accurate survalence of HIV infection and
disease; b) facilitate accurate determination of the Incidence of
infection; c) facilitate early case identification; d) facilitate the
implimentation of public health control programs; e) facilitate the
evaluation of the effectiveness of public health invention straglties.
MONDAY, JUNE 1
M 11 2 Update on AIDS-Associated Non-Kodgkin ' s Lymphoma ( N'HL)
in San Francisco.
LAWRENCE D. KAPLAN, PA VOLBERDING, DI A3RAMS , Dept of Medicine,
San Francisco General Hospital (SFGK), UCSF Cancer Research
Institute, SF . CA, USA.
Forty homosexual men with NKL were treated at SFGH 10/82-12 '36.
Serologic studies performed in 28 patients reveaied all 2S,
including ail surviving patients, to be HIV seropositive.
Histologic pattern included small noncieaved (52%), large ceil
(45%} ar.c cutaneous 7-ceii (2.5%). Patients presented with Stage
IV disease (75%), Stage III (15%), Stage II (7.5%), and Stage IE
(solitary lung nodule) in 5%. Extranodal sites included bone
marrow (10) meninges (7), liver (5), lung (3), stomach (4),
epidural (2), soft tissue [2), nasopnarynx (1), other GI (3).
Thirty-one were treated with aggressive chemotherapy and 2
received primary radiation therapy. Treated patients without a
prior AIDS diagnosis i25) had a complete response (CR; rate of
56% and a median survival of 16.5 mos . Those with a prior AIDS
diagnosis (10) had a CR=16% and a median survivai=2.9 mos (p=0.04
for survival). There was a direct re_at:onsh:p between relative
dose intensity and freedom from relapse. Significant dose
reductions were required in 6,9 of those with prior AIDS
diagnoses, due to severe marrow suppression, opportunistic
infection, or ootn. Wniie aggressive therapy does prolong
survival in some patients, those with prior AIDS diagnoses are
less likely to tolerate such therapy, to achieve CR , and to
remain disease free.
M 11 5 International Surveillance for HIV Seroconversion In Hemophilia
Patients Receiving Heat-treated Factor Concentrate Therapy.
DALE N LAWRENCE1 , S SCHULMAN2 , C R RIZZA3, T LAMBERT4, E P MAUSER-
BUNSCHOTEN3, K RICKARD6, et al., Centers for Disease Control,
Atlanta, GA, 2Swedish Hemophilia Fdn, Stockholm, ^ Oxford Hemophilia
Ctr, UK, 4Hopital Bicetre, Paris, FR, 5Van Creveldcllnic, Bilthoven,
NL, 6Royal Prince Alfred Hospital, Sydney, AUS, et al.
Scattered reports in 1986 described HIV seroconversions in hemophilia
patients receiving heat-treated factor concentrates (HtFC) produced before
donated plasma was screened for HIV antibody. In late 1986, 14 regional and
national hemophilia treatment centers in 7 countries of Europe and North
America and Australia collaborated to characterize their seroconverters and
to quantitate the risk associated with unscreened and screened HtFC. Most
of the 1300 seronegative patients under periodic serologic surveillance had
previously received unheated FC. Of 450 initially seronegative severe
hemophilia A patients, three children still seronegative 6 months after the
exclusive use of (unscreened) HtFC, seroconverted thereafter (0.7Z of
hemophilia A; 0.2% of total). The latest seroconversion was in November
1985. All 3 are asymptomatic, but at least 1 has severe T cell
abnormalities and at least 1 other was HIV culture-positive. To provide
reliable estimates of the risk of HIV seroconversion associated with
screened HtFC which was introduced in these centers between August
1985-July 1986, continued collaborative surveillance is underway to
accumulate adequate numbers of patient-years of such therapy. To date, no
seroconversions have been noted in nearly 400 patient-years of therapy. By
May 1987, the aggregate total for the centers will exceed 1500
patient-years, allowing analysis by type of hemophilia and severity level.
M.11.3 Clinical Course ar.c Epidemiology of Hodgkin's Disease
IHD) in Homosexual Men in San Francisco (SF).
LAWRENCE D KAPLAN, DI ABRAMS , PA VOLBERDING, Dept of Medicine,
San Francisco General Hospital (SFGH), Cancer Research Institute
UCSF, San Francisco, CA, USA.
Thirteen homosexual men with HD have been diagnosed and treated
at SFGH between 5 33 and 12 86. All 9 patients tested were HIV
seropositive. 9 (70%) had a prior history of generalized
lyir.phadenopathy or thrush and no patient had a prior AIDS
diagnosis. Mixed ceiiularity histology was present in 9 (70%),
nodular sclerosis (NSHD) in 3 (23%) and 1 was unclassified.
Stage III or IV disease was presen* in 12 (92%) with bone marrow
involvement in 9 (70%). Five (38%) were treated witii MO?? and 7
(62%) with MOPP.A3VD. There were 7 (54%) complete responses, and
one of these relapsed. PC? developed in 3 (62*1 , M. avium ir. 1
(8%). Three patients (30%) remain alive with active disease at
1,5, and 15 mos from diagnosis. Only one (5%) is disease-free at
24 mos. We compared this grou.p to 35 cases of HD in never-
married SF males, age 20-49 diagnosed between 1973-1979. 22 (63%)
were NSK0 and 8 (23%) were MCHD . Twenty-five (70%) had Stage III
or IV disease. 21 patients (60%) and i3 (52%) of those with stage
III or IV disease have survived disease free >5 yrs .
The incidence of HD in this SF population has not increased
during the period 1980-1985 (relative risk =1.2,1985), suggesting
a lack of correlation between HIV infection and development of
HD . However, our clinical data suggests a marked alteration in
the natural history of HD in HIV-infected individuals, am" thus,
the importance of serologic testing in this group.
M 11 fi Cardiac Pathology and Cardiovascular Cause of Death in Patients
Dying with the Acquired Immunodeficiency Syndrome (AIDS)
DAVID W. ANDERSON*, R. VIRMANI*, A. M. MACHER* , T. O'LEARY*, M. ROBINOWTTZ* .
W.C. ROBERTS**, et al., *Armed Forces Institute of Pathology, Washington, DC
and **Cardiovascular Pathology, NHLBI, NIH, Bethesda, MD.
The presence of cardiac pathology was retrospectively evaluated at
necropsy in 82 patients dying with AIDS in the USA between 1981 and 1986.
Myocarditis (MYO), defined according to the Dallas criteria as myocardial
necrosis surrounded by inflammatory cells, occurred in 40 (50%) cases.
Opportunistic myocardial pathogens were seen in only 14 cases (T. gondii-3,
H. capsulatum-3 , C. neof grmans-3 , P. _ carinii-1 , Cytcmegalovirus-2 , and
Mycobacteria spp-2). Dilated cardiomyopathy was diagnosed at necropsy in
the presence of biventricular dilatation without significant coronary or
valvular heart disease and occurred in 7 (9%) patients, all of whom
manifested MYO. In contrast, right ventricular dilatation in the absence of
biventricular dilatation was found in 14 (17%) cases and was associated with
right ventricular hypertrophy (p<0.05), pericardial effusion (p<0.01) and
opportunistic pulmonary infections (p<0.05) but not MYO (p>0.05). A
clinical cardiovascular cause of death was established in 7 (9%) cases and
included 6 patients with MYO (refractory ventricular tachycardia-1 , dilated
cardiomyopathy with congestive failure-4 . and sudden death-1).
Epicardial Kaposi's sarcoma occurred in 9 (10%) cases and was generally
not clinically significant. However, in one case extensive pericardial and
periaortic involvement led to hemopericardium and death from cardiac
tamponade .
Conclusion: Myocarditis is a frequent necropsy finding in patients dying
with AIDS and may lead to fatal dilated cardiomyopathy in this population.
Roundtable Discussions
M 11 4 HIV I;iolation from
' " CHARLA ANDREWS , J.
P. Levine. University of Ma
As part of a prospect i
infection in hemophiliacs
cultured for virus. HIV was
were seropositive for HIV
positive hemophiliacs had
he lper/T- suppressor ratios,
platelet count and a higher
compared to virus-negative p
Hemophiliacs: Immunological and Clinical Studies.
Sullivan, D. Bret tier, A. Forsberg, F. Brewster,
ssachusetts Medical Center, Worcester, MA.
ve study of human immunodeficiency virus (HIV)
blood from 72 individuals without AIDS or ARC was
isolated from 15 out of 66 (23%) hemophiliacs who
and none of 6 seronegative patients. Virus
significantly reduced T-helper cell numbers, T-
pokeweed mitogen (PWM) responsiveness, total
ncidence of thrombocytopenia (<150f 000/ul) when
atients.
M.12
Prevention and Control of AIDS in Developing Countries
MEAN DATA FROM SEROPOSITIVE HEMOPHILIACS
HIV T-helper T-helper/ PWM Platelets
isolation n (cells/ul) T-suppressor (cpm) (Pit/til)
+ IU 398 . . 603 7^8 187 ,000
51 768 .806* 12910* 236.137"
*p<.001; # p<.05
The seropositive, virus-positive hemophiliacs also presented
clinical findings than virus isolation negative hemophilia
positive hemophiliac developed AIDS during the study. The
antibody titer did not differ significantly between the v
virus-positive hemophiliacs. HIV was recultured from 5 out
up to 1 year later; 9 virus-negative hemophiliacs remained
when re-cultured. The significant decrease of T-helper cells
of thrombocytopenia in 50% of the virus-positive group may be
a heavier virus load, and might be an early marker of
prognosis.
<150,000{%)
platelet/ul
7/lU (S0%) ,
9/51 (9.8%)"''
with more severe
cs. One virus-
mean neutralizing
rus-negative and
of 6 hemophiliacs
negative for HIV
and the presence
a reflection of
more unfavorable
Panel Moderators: Kenneth Bart
Agency for International Development
Washington, D.C.
M. Mukunyandela
Tropical Diseases Research Centre
Ndola, Zambia
Donald Forthal , Department of State, Washington, D.C.
Anthony Meyer, Agency for International Development, Washington, D.C.
Bahman Habibi, National Center for Blood Transfusion, Paris, France
T. Stephen Jones, Centers for Disease Control, Atlanta, Georgia
King K. Holmes, Harborview Medical Center, Seattle, Washington
James Shelton, Agency for International Development, Washington, D.C.
MONDAY, JUNE 1
M.13
The Status of Screening: Supplementary Tests for HIV Infections
Panel Organized By: Thomas F. Zuck
Food and Drug Administration
Rockville, Maryland
Panel Moderator:
Panel Members:
Ian Gust
Fairfield Hospital
Melbourne, Australia
Experts from the United Kingdom, Europe, North America
and Australia
MR2 AI°S Subacute Encephalitis : Identification of HIV Infected Cells
ROSEMAY VAZEUX', N. BROUSSE", A. JARRY", L MONTAGNIER*. M.BRAHIC*,
'Institut Pasteur, Paris, "Inserm U.239, Faculte Xavier Bichat, Paris, France.
Human immunodeficiency virus (HIV) RNA and proteins were detected in 5 brain
tissues to 12 AIDS patients with subacute encephalitis, using in situ hybridization and
immunohistological labeling with monoclonal antibodies against p18, p25, gp41 and
gp1 10. Staining patterns were superposable with the 2 techniques. A massive and
diffuse HIV infection, with clusters of HIV infected cells present in almost every tissue
block studied, including spinal cord, was correlated with severe demence and was
detected in 3 of these 5 HIV infected patients.
The majority of infected cells were mononucleated and bore processes. Using
single and double immunohistological procedures, we identified these cells as
macrophages Leu M5+, EBM 11+, KB 90+, 9.4+, HLA-DR+, T6-, DRC-. The majority of
them had the phenotype of normal resident brain macrophages/microglial cells (Leu
M3-, CD4-), others were labeled with markers of circulating macrophages (Leu M3+,
CD4+/-), were present in inflammatory infiltrates and microglial nodules, and were
associated with a few infected CD3+/CD8- T cells. We could not detect any infected
astrocytes or neurons, all infected process bearing cells were labelled with
macrophage markers thus it is very unlikely that oligodendrocytes were infected.
M.14
Feline Leukemia Virus
AIDS and the Media
Panel Organized By: Terry Beirn
American Foundation for AIDS Research
New York, New York
Susan Freinkel, Wichita Eagle-Beacon, Wichita, Kansas
Herculamo Siqueira, Denison Advertising, Rio De Janeiro, Brazil
Allen Wurtzel, ABC, New York, New York
Ellen Levine, Women's Day Magazine, New York, New York
Diana Kerew, Diana Kerew Productions Inc., Los Angeles, Californi
J. G. M. Jagwe, Uganda National Committee on Prevention of AIDS,
Entebbe, Uganda
|\||P3 Effect of Di ethyl carbamazine
Infected Cats
LYNN H. .KITCHEN, Harvard School of Public Health, Boston, MA.
Eight cats (2 sets of littermates) testing positive for feline leukemia
virus (FeLV) antigen in peripheral blood leukocytes were entered into
prospective trials to evaluate the therapeutic effect of oral diethyl-
carbamazine citrate (DEC). Twenty-two additional healthy outbred FeLV cats
were also treated with DEC. Pre and post treatment serum viral infectivity
was determined for 24 treated cats. Fourteen of these 24 treated cats
(58%) initially presented with high titers of serum infectious virus by the
assay of Fischinger. Serum viral infectivity became undetectable 1 month
after initiating treatment in 12 cats, after 90 days in 1 cat, and after
300 days in 1 cat. Nine cats initially testing negative (<1:10 dilution)
for antibody to feline oncornavirus associated cell membrane antigen
(F0CMA) tested positive after treatment. Average survival was prolonged by
3 months with DEC treatment in 2 FeLV- inoculated cats in comparison to' 2
untreated controls. Survival among cats treated without prospective
controls was improved in comparison to an historical control study. DEC
treatment has prevented lymphopenia (to date, age 9 months) in 2 naturally-
infected FeLV kittens; 2 untreated littermates have both developed
lymphopenia. Our results may have implications for humans infected with
immunosuppressive retroviruses.
Poster Session
MR1
*Inst
FRG
t ute ,
The
two
been
growt
shown
on t
show
at c
tion ,
ral
in
p24
as j
vity,
of p
perti
activ
high
er .
of a
G. e
Taguc
(3)Mu
INH
W,E
itut f
and #La
Bethes
sesqu
natural
identi
h of
that
he repl
a sign
oncentr
no in
blood o
dose-d
and pl5
udged b
The p
atients
es (3)
ating
therape
A clin
varol i
t al:(
hi.Ys
ller.W.
IBITION OF REPLICATION OF HIV BY AVAROL AND AVARONE
■-G. MiJLLER*, H,C. SCHRODER* and P,S, SARIN*
ogische Chemie, Universitat, D-6500 Mainz,
Tumor Cell Biology, National Cancer Insti-
P
borat
da MD
iterp
pro
fied
T eel
these
icati
if ica
ation
hibit
r spl
epend
in t
y app
otent
with
"T
prope
utic
ical
n pat
1985)
and M
E,G,
hysio
ory o
2089
enoid
ducts
as c
1 lym
comp
on of
nt cy
s as
ory e
een 1
ent m
he in
rox.
ial u
AIDS
-lymp
rty ,
indie
trial
ients
Can
u Her
et al
quinon
from t
ostati
homa 1
unds h
HIV in
oprote
ow as
feet i
mphocy
nner t
ected
0% inh
ef ulne
and AR
otropi
nt imut
s , and
to det
with A
er Re
W , E -. G .
(1986)
e avar
he mar
c agen
ines (
ave a
H9 ce
ctive
0.1 ug
s obse
tes (3
he exp
H9 eel
ibit io
ss of
C is s
c " c y t
agenic
penet
ermine
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_, 45,
(198T>)
EursJ,
one and i
ine spong
ts that
1) . In th
dose-depe
lis in vi
effect on
/ml (0,3
rved in h
) , Both a
ression o
Is , and b
n of reve
these com
upported
ostatic
activity
ration of
the pote
in prepa
4822;
J, Natl,
Cancer CI
ts h
e Dy
pref
e pr
nden
tro
HIV
uM),
uman
varo
f th
lock
rse
poun
by t
acti
lo
the
ntia
rati
(2)
Can
in s0
ydro
side
eren
esen
t in
(2) =
inf
At
or
1 an
e HI
vir
tran
ds i
heir
vity
w to
bio
1 an
on i
Sar
cer
ncol
quinone
avara
tially
t study
hibitory
Both co
ected H9
this con
murine p
d avaron
V gag p
al repl
scriptas
n the tr
f ollowi
B-lym
xicity i
od-brain
tiviral
(1) Mull
in,P;S, ,
Inst ; , in
22,437
avarol ,
, have
inhibit
it is
effect
mpounds
cells
centra-
eriphe-
e block
roteins
ication
e acti-
eatment
ng pro-
phocyte
n mice ,
barri-
ef f ect
er.W.E,
Sun ,D. ,
press ;
|U|P4 Anti-HIV Activity of 3'-Substltuted-2' ,3'-Dideoxythymidine Analo-
gues
RUDI PAUWELS, M. BABA, J. BALZARINI, P. HERDEWIJN, E. DE CLERCQ and J. DESMY-
TER, Rega Institute for Medical Research, Katholleke Unlversltelt Leuven,
B-3000 Leuven, Belgium.
In MT-4 cells 3'-azido-2' ,3'-dldeoxythymldlne (AzddThd, AZT) Inhibits HIV
replication at 0.04 uM, that Is at a dose 50-fold lower than in ATH8 cells
(1-5 uM). No such Increased activity was observed for 2' ,3'-dldeoxycytidine
and 2' ,3' -dideoxyadenosine when evaluated in MT-4 cells. Therefore, this cell
line was used to determine the structure-activity relationship of newly syn-
thesized 2' ,3 '-dideoxy thymidine analogues modified in the 3'-position.
From this study AzddThd, ddThd and its 2 ' ,3 '-unsaturated derivative ddeThd
emerged as the most potent inhibitors of HIV (complete protection at 0.04, 5
and 0.2 uM, respectively) with an almost identical selectivity index. 3'-
Fluoro-ddThd effected 10-40 % protection at 0.008 pM but proved extremely to-
xic. None of the other 3'-halogenated derivatives of ddThd (i.e. 3'-chloro-,
3'-bromo-, 3'-iodo-ddThd) had a significant HIV-inhibitory effect. The 3'-0-
mesyl derivative of ddThd effected 50 % protection against HIV at a concen-
tration of 5 uM without any toxicity at 125 uM, whereas other 3'-0-linked
substituents (i.e. 3'-methoxy, 3'-ethoxy, 3'-0-carboxymethyl) virtually anni-
hilated the antiretroviral effect of ddThd. Substitution of a thiocyano group
at C-3' of ddThd led to a similar protective activity as seen with 3'-0-me-
syl-ddThd, but 3 '-thiocyano-ddThd proved also cytotoxic. 3'-Ethylthio- and
3'-hydroxyethylthio-ddThd were less active than 3 '-thiocyano-ddThd. Our stu-
dies thus revealed that any substituent at the C-3' position of ddThd, with
the exception of azido, considerably decreased the antiretroviral effect of
ddThd, suggesting a critical function of this part of the molecule in its in-
teraction with Its target enzyme(s).
10
MONDAY, JUNE 1
MR5 Mismatched Double-Stranded RNA (Ampligen) Protects Target Cells
from HIV Infection and Reduces the Concentration of 3'-Azido-
3'Deoxythymidine (AZT) Required for Virustatic Activity. WILLIAM M. MITCHELL,
DAVID C. MONTEFIORI, W. EDWARD ROBINSON, and WILLIAM A. CARTER,
Vanderbilt University, Nashville, Tennessee, and Hahnemann School of Medicine,
Philadelphia, Pennsylvania.
The biological response modifier rln-r(Ci 2"U)n. generally referred to as
mismatched double-stranded (ds) RNA or Ampligen*' was able to protect target
lymphoblastoid cells in vitro from infection by the human immunodeficiency virus
(HIV). Significant protection of the highly HIV-permissive T-cell line C3 is observed
with Ampligen in the 10-50 ug/ml concentration range. Similar results are observed
at 50 ug/ml in CEM cells. When administered simultaneously with sub-virustatic
concentrations of azidothymidine (AZT), protection of target cells from HIV
infection is increased. At higher doses of AZT tested, the virustatic activity observed
appeared to be in a synergistic virustatic relationship with Ampligen. Moreover, in
combination with Ampligen at least a five-fold reduction in AZT concentration can
be used in order to obtain equivalent virustatic activities. Thus, combined therapy
with Ampligen and AZT can be expected to be more beneficial to ARC or AIDS
patients since current AZT regimens of apparent clinical effectiveness are associated
with significant toxicities which undermine its therapeutic potential.
MR8
K. SU
CA 90
Angel
The
tence
demen
labor
two r
did n
human
cells
and a
days
Elisa
drama
first
inf ec
HIV a
as we
HI
PAUL
GITA, H.
509 & Ne
es, CA 9
re is ev
i n the
t i a in o
atory un
el a ted a
ot propo
cervix
Howev
tta i ned
pos t- i nf
. After
tic peak
, and la
tion. T
nd may b
11 as fo
V pro
SHAP
LEE
urol o
0073,
idenc
CNS i
rder
derto
nd tw
gate
care i
er, H
pea k
ect io
prol
s of
sting
he ne
e use
ram
poga t
SHAK,
et.a
gy Se
U.S
e tha
s ass
to ch
ok th
o unr
in Af
noma
IV pr
rel ea
n. H
onged
rel ea
from
urobl
ful
odel
es in
D.T.
1 . , Ha
rvi ce ,
A.
t HIV
ociate
arac te
e prop
el ated
ri can
(Hela)
opogat
sed re
IV was
growt
sed RT
36 to
as toma
for HI
relate
human neuroblastoma cells
IMAGAWA, K. SAN0, F. CALLEGARI,
rbor-UCLA Medical Center, Torrance,
VAMC, Wadsworth Division, Los
is neurotropic and that its persis-
d with AIDS encephalopathy and
rize HIV persistence in vitro, this
ogation of HIV in four cell lines,
to the CNS;it was found that HIV
Green monkey kidney (Vero) cells;
cells, and human brain astrocytoma
ed in a neuroblastoma cell line
verse transcriptase activity 10-14
also detected using antigen capture
h in cell culture, there were additional
activity, 20-fold greater than the
74 days and 110 to 140. days post-
cell line used is susceptible to
V replication and isolation studies
d to HIV persistence in CNS cells.
MR6 Modification of HIV N-Glycosylation by the a-Mannosidase
Inhibitor Swainsonine. DAVID C. MONTEFIORI, W. EDWARD
ROBINSON AND WILLIAM M. MITCHELL, Vanderbilt University, School of Medicine,
Nashville, Tennessee.
The two envelope glycoproteins (gp41 and gpl20) of human immunodeficiency
virus (HIV) serve functions obligatory to the pathogenesis of HIV including
attachment of virus to target cells and syncytium formation. Swainsonine is an
indolizidine alkaloid found in certain legumes and molds and alters protein N-
glycosylation through its potent reversible inhibition of a-mannosidase II (Broquist,
H., Ann. Rev. Nutr. 5, 391-409, 1985). Our interest has been to investigate the
significance of N-glycosylation in HIV pathogenesis using swainsonine and other
inhibitors of glycoprotein processing as tools. We have found that swainsonine
affects N-glycosylation of HIV glycoproteins without affecting virus yields. The
concentrations of swainsonine utilized in these studies (1-10 u.g/ml) had no effect on
cell division or RNA and protein synthesis. Synthesis of virus in the presence of
swainsonine was confirmed by reverse transcriptase activity in culture fluids and by
density gradient centrifugation of [35S] methionine labelled virus. Results of [3H]
mannose labelling experiments and SDS-PAGE/fluorography demonstrated that
swainsonine causesa reduction in the molecular weight of the HIV envelope gp120
reducing itto a gpl 10 molecule.
MPQ Early and late IgM response in HIV infection
JOEP M. LANGE*, J.V. Parry**, A. Smith***,
P.P. Mortimer**, R.S. Tedder***, J. Goudsmit*, 'Department of Vi-
rology, University of Amsterdam, The Netherlands, **Virsl Refe-
rence Laboratory, Public Health Laboratory Service, London, UK,
***Middlesex Hospital Medical School, London, UK.
A total of 463 sequential serum samples from 57 homosexual men,
who seroconverted for HIV antibodies (Ab) in IgG ELISA and Western
blot assays, were tested by solid phase IgM antibody capture as-
says. The IgM responses were confirmed by immunoblot, after ab-
sorption of IgG Ab, and shown to be predominantly directed to
core proteins. Samples were obtained approximately every 3 months
and more often in the period following IgG Ab seroconversion. The
mean follow-up time was 21 months (10-25 months).
In 30 people no IgM response was found. In 20 people an IgM res-
ponse, not lasting longer than 3 months, was found approximately
concomitant with IgG Ab seroconversion. In 2 people an IgM respon-
se occurred 5-9 months after IgG Ab seroconversion and persisted
thereafter. In 5 people both a transient early and persisting
late (occurring 5-15 months after IgG Ab seroconversion) IgM
response were found.
There was no relationship between the prssence of "flu-like"
disease at HIV-Ab seroconversion and the occurrence of an early
IgM response. In 3/7 people with a late IgM response this coin-
cided with expression of HIV antigen (EIA, Abbott Laboratories)
and the development of serious HIV related disease. HIV-Ag expres-
sion occurred in 5/50 people without a late IgM response and
serious disease developed in 2 of those.
MP7 Comparative Study of Human Immunidef iciency Virus
(HIV) Strains
VICTOR M.ZHDANOV, D.I.Ivanovsky Institute of Virology, Moscow,
U.S.S.R.
Human immunodeficiency virus (HIV) strains received from Fran-
ce and the U.S.A. and isolated in the U.S.S.R. (including indi-
genous and imported from Africa) were comparatively studied.
In experiments with monoclonal antibodies a sertain homogeni-
city of both standard and African strains was shown, and some
difference of indigenous strains isolated in the U.S.S.R. was
marked.
Restriction analysis showed a more marked variability of the
strains studied, although in experiments with molecular hybridi-
zation they appeared to be more homogenous. This points to a
high frequency of neutral mutations that do not affect amino-
acid composition but do affect recognition sites for restriction
endonucleases.
Plasmids were obtained that contain non-infectious genome of
HIV with removed LTRs and provirus was sequenced. Variations
were revealed within all genes, particularly in env region.
A hypothesis is proposed about the existence of a Northern
HIV variant with low virulence as compared with American and
African viruses. The virus causes predominantely asymptomatic
infection.
MP10 Pathologic Features of Cytomegalovirus Retinopathy Following
Treatment with the Antiviral Agent Ganciclovir
Jay S. Pepose*. C. Newman*, S. Koenig**, M.C. Bach***, T.C. Quinn**, R.F.
Ambinder*, et al., *The Johns Hopkins Hospital, Baltimore, MD, **National
Institutes of Health, Bethesda, MD, ***Maine Medical Center, Portland, ME.
We studied the eyes of 3 AIDS patients with cytomegalovirus (CMV) retinopathy
who expired while receiving ganciclovir therapy. Gross, microscopic and ultra-
structural studies of these cases revealed varying degrees of retinal scarring
and active cytomegalovirus lesions at the margins of the scars. CMV antigens
were localized in cells at all layers of retina at the border of the lesions
and in isolated cells in a perivascular location within histologically normal
appearing retina. These areas probably represent sites of recrudescence when
the drug is discontinued. In situ hybridization using a cloned cDNA probe of
human CMV corroborated the immunocytologic localization of virus. Ultrastruc-
tural studies revealed megalic syncytial cells containing mostly capsids
exclusively in the cell nucleus. In situ hybridization using an HIV riboprobe
did not detect HIV-infected retinal cells, whereas brain tissue from other
cases were positive using the same probe. The cytoplasmic electron-dense
membrane bound bodies that have characterized untreated cases of CMV retino-
pathy were absent in the treated cases. An attempt to isolate CMV in tissue
culture from the vitreous and retina of one of the cases yielded a negative
result. Our results indicate that ganciclovir does not effectively eliminate
CMV from the retina nor does it suppress expression of all viral genes.
Ganciclovir appears to function by limiting viral DNA synthesis and subsequent
packaging of viral DNA into infectious units, thereby accing as a virostatic
chemotherapeutic agent.
11
MONDAY, JUNE 1
MR11 Human immunodeficiency virus isolates differ in replication poten-
tial in vitro.
FRANCESCA CHIODI*. E.M. FENYb*, .1. ALBERT*, B. ASJO*. *Department of Virology,
Karolinska Institute, Stockholm, Sweden.
Human immunodeficiency virus (HIV) has been isolated from 33 HIV antibody
positive individuals with different clinical manifestations of infection. Peri-
pheral blood mononuclear cells (PBMC) from AIDS or pre-AIDS patients yielded
virus rapidly as detected by high reverse transcriptase CRT) activity in cul-
ture fluids. These viruses were able to establish a persistent infection in
several T4 antigen positive tumor cell lines (CEM, H9 and U937 clone 2) and
were designated rapid/high. PBMC cultures from individuals with mild or no
symptoms yielded virus more slowly and the RT activity was low. Cocult ivation
of PBMC yielding such slow/low viruses with the T4 positive tumor cell lines
showed no or only transient virus replication, as a rule. Cell free trans-
mission of viruses to PBMC from normal donors and to cell lines showed that
viruses classified as rapid/high are readily transmitted whereas viruses of
the slow/low type replicate poorly, if at all. In fact, slow/low viruses could
be divided into 4 groups on the basis of their transmissibility and growth
properties. Viruses in group 3 and 4 could efficiently replicate in the
Jurkat/ tatIT T cell line allowing radioimmunoprecipitation and restriction en-
zyme analysis.
MR14 Helix Twist Angle Analysis of Retroviral LTR Sequences
C.-S. TUNG and GERALD MYERS, Theoretical Biology and Biophysics
Group, Los Alamos National Laboratory, Los Alamos, NM, U.S.A.
Degeneracy in the coding regions of genomic sequences can be analyzed in
terms of "silent mutations" and conserved amino acid substitutions. In this
study, we are exploring an analytical approach to degeneracy in non-coding
DNA: the equivalent of a "silent mutation" is a base change that preserves the
helix twist angle of the double-stranded DNA. A structural homology is a
series of helix twist angles that are equivalent in two or more DNA sequences,
irrespective of whether they happen to be sequence homologues.
Genomic LTRs (long terminal repeats) found at the 5' and 3' termini of
retroviruses such as the HIV group, which utilize a trans-activating mode of
control of viral replication in contrast to other LTR-directed mechanisms,
offer an interesting class of sequences for this study. In particular, the
TAR region (trans-activating receptor or target) found downstream from the
mRNA start site has been the focus of our attention.
With a very stringent criterion of structural similarity, one helix twist
pattern can be identified in all human and simian viral TAR sequences, repre-
sented by the consensus sequence "ctccga." The pattern is found at the same
position for the most part; however, it occurs at a different position in
HTLV-I and visna virus, in the former as "ggccgc" and in the latter as
"ctccgg." With exception of visna virus, this pattern is found only in cer-
tain non-primate viral LTRs at yet a third position, which encourages us to
pursue this mode of comparative analysis.
MR12 HIV Entry into CD4+ T Cells Occurs Via pH- Independent Viral
Envelope Fusion to the Plasma Membrane
BARRY S. STEIN. S.D. GOWDA, J.D. LIFSON, R.C. PENHALLOW, K.G. BENSCH, E.G.
ENGLEMAN, Stanford University School of Medicine, Palo Alto, CA.
After binding to specific cell surface receptors, enveloped RNA viruses are
known to deliver their genetic information into target cells via at least two
distinct mechanisms: (i) by rapid internalization of virus into acidic
endosomal vesicles where envelope proteins undergo requisite low pH-dependent
conformational changes which facilitate direct virus envelope fusion with
endosomal membranes, or (ii) by direct fusion of virus envelope with the
plasma membrane of the cell in a pH-independent fashion. CD4 is the cell
surface receptor which confers HIV target cell tropism through interaction
with mature envelope (gpl20); however, the mechanism whereby this enveloped
RNA retrovirus enters susceptible cells is not known.
In our studies neutralization of acidic endosomal and lysosomal vesicles
(pH > 6.4) with various lysosomotropic agents including chloroquine, NH4CI ,
and monensin, did not prevent HIV entry. Viral entry was quantitated by Slot
Blot analysis of cytoplasmic HIV DNA isolated from CD4+ T cells exposed to
HIV for 4 hours in either the absence or presence of lysosomotropes. Speci-
ficity of the HIV DNA detected was confirmed by Southern blot which revealed
a 9.7 kb hybridizable fragment in each treatment group. EM studies of VB
cells acutely exposed to HIV at neutral pH revealed direct fusion of virus
envelope with the plasma membrane within minutes of mixing uninfected cells
with free virus at 4°C. No endocytosed virions were visualized upon
rewarming the virus exposed cells to 37°C. These results indicate that HIV
preferentially enters CD4+ T cells via pH-independent membrane fusion rather
than by a low pH-dependent endocytic route.
MP15 In vivo Transmission Studies with MnlV, a Primate Lentivirus Partially
' Related to HTLV-III
WILLIAM R. MORTON*, M.E. THOULESS*, E.A. CLARK*, H.D. OCHS**, R. BEN-
VENISTE , Regional Primate Research Center, University of Washington, Seattle,
WA, **Department of Pediatrics, University of Washington, ***NCI, Frederick,
MD.
A retrovirus has been isolated after co-cultivation of a lymph node from a pig-tailed
macaque (M. nemestrina) that died with lymphoma in 1982 at the University of Washing-
ton Primate Center. This isolate, designated MnlV (M. nemestrina immunodeficiency
virus) is partially related to HTLV-III, based on amino acid sequence homology and
immunological cross-reactivity of the major gag protein, p28. 10^ infectious MnlV
particles from an end-point diluted virus preparation grown on HuT 78 cells were inocu-
lated i.v. into two species of macaques (rhesus - M. mulatta and pig-tailed). All
macaques (six animals) became viremic and MnlV could be readily isolated from their
peripheral blood lymphocytes. Two of the six macaques have died with opportunistic
infections, anemia and depleted T4+ cells at 4 and 15 months after inoculation. All
macaques developed high titers of antibodies to MnlV, except for the animal that died
at four months.
In a second experiment, eleven young cynomolgus macaques (_M. fascicularis) have
been inoculated i.v. with MnlV isolated directly on human lymphocytes. Six of these
animals had previously received vaccinia virus containing the envelope protein of
HTLV-III and had antibody titers to gpl2U and gp41. These animals are being monitored
to examine whether the presence of HTLV-III antibodies protects against a subsequent
challenge by the related virus MnlV.
|y|p-f3 Characterization of Genetic Mutants of HIV that are Defective in
gag Gene Processing.
RAOUL E. BENVENISTE*. L.J. ERON««, K. NAGASHIMA* * * , M.A. GONDA***, *National
Cancer Institute, Frederick, MD, "Fairfax Hospital, Falls Church, VA,
***Program Resources, Inc., Frederick, MD.
An HTLV-III/LAV isolate obtained from an AIDS patient was shown to be
poorly infectious for human lymphocytes. SDS-PAGE analysis of proteins
associated with this virus, designated HIV(Fre—3), showed that it contained
large amounts of the gag viral protein precursor, Pr55. Electron microscopy
(EM) of infected HuT 78 cells revealed two populations of virus-producing
lymphocytes. One produced virus which matured and had a normal morphogenesis,
while the other produced only aberrant "immature" extracellular virus
particles. This lymphocyte culture was cloned on sheep choroid plexus cells
and 51 single cell clones were obtained. Some of the clones produce infec-
tious HIV (reverse transcriptase positive, mature gag proteins visualized on
SBS-PAGE) which by EM appear normal in all stages of maturation. Other
single-cell clones release non-inf ectious , structurally aberrant viruses
which contain an electron-lucent core surrounded by a semielectron-dense
incomplete ring of ribonucleoprotein , and thus resemble immature extra-
cellular virus particles. These clones lack detectable amounts of the mature
gag proteins and accumulate large amounts of the Pr55 gag precursor; some
also lack reverse transcriptase activity. Clones producing the non-infectious
particles cannot be superinfected by infectious HIV. Purified and lysed whole
virus preparations have been shown to lack an intact protease; the addition
of protease isolated from a "wild-type" virus results in the degradation of
Pr55 to intact mature gag proteins. These results suggest that the genetic
defect may be in the protease gene itself. These HIV mutants might provide a
useful model for the design of protease inhibitors.
MP16 ^ veri"fication testinq:A comparative study of the immunoreacti-
vity of a cloned envelope protein (qp 160) and commercially avail-
able viral lysate
M.V. O'SHAUGHNESSY*, M. COCHRAN**, G. SMITH**, -"Laboratory Centre for Disease
Control, Ottawa, Canada, **MicroGeneSys. , West Haven, Conn.
In most HIV antibody detection protocols, ELISA reactivity must be verified
by one of several methods including immunoblot, indirect-immunof lourescence
or radio-immune precipitation. In LCDC the immunoblot has been the standard
verification assay with more than 25,000 sera having been tested. Deficiencies
in the immunoblot which will be described include: the presence of contamina-
ting, co-migrating cellular products (e.g. a 24k polypeptide of cellular
origin), batch to batch variation in antiqen quality - including the propor-
tion of individual viral components and unusual patterns of antibody reacti-
vity against viral specific polypeptides.
The envelope gene of HIV (LAV) has been inserted into a Baculovirus and a
polypeptide of about 160k expressed in insect cells. The efficacy of this
bioengineered product as a diagnostic reagent has been evaluated usinq an
immunoblot format and a spot-blot variation of it. More than 500 sera have
been analyzed by both the standard immunoblot using a commercially prepared
viral lysate and the alternative procedures employing the cloned gene product.
Sera that react with only a p24 antigen in an immunoblot are considered HIV
antibody equivocal. 12 of 30 equivocal sera reacted with the gpl60 protein.
All 12 were confirmed as antibody positive by RIPA and 18 were antibody
negative. Similarly all of the 20 sera that reacted with only HIV qp41 also
recognized the qpl60 envelope protein. Our data indicate that both the
sensitivity and specificity of procedures employing the cloned gpl60 exceed
those of protocols which rely upon a commercially prepared viral lysate.
12
MONDAY, JUNE 1
MR17 Neutralizing antibodies and cellular Immune response In
goats Immunized with native envelope gpl20 or with
recombinant envelope proteins.
KAI J.E. KROHN*. W.G. ROBEY** . S. PUTNEY»*», P.J. FISHINGERw*
R.C.GALLO* AND A. RANKI* et al, ^Laboratory of Tumor Cell
Biology, NCI, Bethesda, MD, *Offlce of the Director, FCRF, NCI,
Frederick, MD, #*#Repligen Corporation, Cambridge, Mass.
Goats were immunized with native gpl20, purified from HTLV-IIIB
Infected cells or with recombinant peptides representing various
parts of the HIV ENV gene and produced in E. Col i or In an Insect
cells. Neutralizing antibodies were looked for by assessing the
ability of the sera to prevent cytolytic action of HIV on a
sensitive target cell, ATH-8. Cellular Immune response to HIV was
studied by assessing the proliferative responses of T cells
stimulated with whole heat killed HIV, purified gpl20 or with the
recombinant peptides. Native gpl20, two nongl ycosy l ated
recombinant peptides produced in E. Coll (PB1 and 5-90) and a
glycosylated envelope protein produced In insect cells all
elicited neutralizing antibodies. If the recombinant protein
contained sequences from gp41 , the neutralizing response was
group specific, otherwise only type specific antibodies were
seen. A group specific cellular immune response to three HIV
isolates were seen in animals immunized with glycosylated native
gpl20 or with the recombinant glycoprotein from insect cells. The
results suggest, that In spite of the great variability observed
in the external envelope of HIV, vaccines representing one
isolate may elicit a broad, group specific protective immune
response .
MP20 Membrane Fusion Activity and Entry of HI V- 1
MYRA 0. McCLURE*. M. MARSH*, A.G. OALGLEISH*, R.A. WEISS*,
*Chester Beatty Laboratories, Institute of Cancer Research, London.
Internal isation of enveloped viruses into cells proceeds by one of two
mechanisms. Some viruses (e.g. Sendai) fuse with target cell plasma membranes
in a pH-independent manner. For others, however, (e.g. influenza, VSV), the
fusion is pH-dependent. In these cases virions are internalised by receptor-
mediated endocytosis and fuse with endocytic vesicles (endosomes) to release
the nucleocapsid into the cytoplasm. The low pH triggers a conformational
change in the viral spike glycoprotein which renders them fusogenic.
We have ascertained whether HIV-1 follows either of these mechanisms of
entry. Weak bases (e.g. amantadine, NH4CI ) and carboxylic ionophores (e.g.
monensin), which have been shown to inhibit the entry of pH-dependent
viruses do not inhibit HIV-1 entry into CD4+ C8166 cells. Prolonged incubation
in NH4CI does, however, reversibly inhibit the production of infected virus,
both in C8166 cells and in chronically infected H9 cells. Furthermore, the
entry of VSV (HIV-1) pseudotypes is not inhibited by NH4CI , even though non-
pseudotype VSV is inhibited. These data suggest that HIV-1 induced membrane
fusion is not dependent on low pH but that weak bases affect the maturation
of virions. Immuno-electron microscopy for the CD4 antigen on C8166 cells
indicates, however, that receptor-mediated endocytosis may be a method of
internalisation of the virion-complex.
MP18 Preliminary Clinical Trial of Anti-Alpha IFN in Patients with AIDS: MP21 * Simple Method f
A Possible Approach for Immune Enhancement. Circulating Immun
JOSEPH A. BELLANTI*. SIMON V. SKURKOVICH**, STEPHEN M. PETERS*, SUMIT JOHL*, SUSAN R.HOLLAN ,G.FUST , B
NEZIH CEREB*, AARON J. HSU**. *Georgetown University School of Medicine, + Na 1 1 . I ns t . Haema t ol . Bl ood
Washington, D.C. and **ABC, Inc., Columbia, MD. Venerol ., Budapes t , HUNGARY
Based upon the hypothesis that acid-labile alpha IFN may down-regulate the In early and late (AIDS)
immune system (Skurkovich, S.V., Skurkovich, B. and Bellanti, J. A. , Clin . antibodies to antigens may
Immunol. Immunopath. , 1987, in press), a study was performed to evaluate the antibodies in blood. In th
safety and clinical efficacy of anti-alpha IFN in patients with AIDS. Two pa- tion can be expected in an
tients with CDC-defined AIDS who had recovered from P. carinii pneumonia, re- method for detecting HIV-a
ceived three daily intramuscular injections of sheep anti-alpha IFN immunoglob- Immune complex-enriched fr
ulin (1.5 to 9 x 106 I.U./day respectively) for a 6-day period during which tested by PEG precipitatio
time and subsequently thereafter (3 months and 3 weeks, respectively), clinical from complexed antibodies
and laboratory parameters were evaluated. Although no serious adverse or toxic activity of the F(ab' )2 fr
effects were observed following treatment, both experienced a mild maculopapu- original PEG precipitates
lar exanthem on the 9th to 10th day which disappeared within a week. In both HTLV-III kits as solid pha
patients on the 3rd day a mild transient lymphopenia was observed which disap- plates were detected eithe
peared by the 6th day. Following treatment both patients had a sense of well anti-human K-X-an t ibody or
being; patient #1 experienced an 8 lb weight gain within 14 days of treatment. fixation of HI V-an t i bod i es
Before treatment both patients had detectable serum levels of acid labile alpha PEG precipitate. Using bot
IFN (125 IU/ml). During the 6-day treatment period no IFN could be detected in activity was found in F(ab
the blood of either patient. However, 7 days after the cessation of treatment PEG precipitates in 9/10 S
serum IFN levels in patient #1 increased to 630 IU/ml which was predominantly pa t ients . Therefore , our me
gamma IFN. Although the results thus far are promising and suggest the H I V-an t i bod i OS hidden in i
approach is feasible with negligible side effects, the long term efficicacy of
anti-alpha IFN in AIDS will require further studies of dosage and frequency of
administration.
or Detecting HIV-Ant ibodies Hidden in
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MR19 Herpesviral Transactivation of the Human Immunodeficiency Virus
(HIV) Long Terminal Repeat Sequence.
HOWARD E. GENDELMAN*, JOHN LEONARD*, KAREN WECK* , ARNOLD B. RABSON* , DANIEL
CAPON**, MALCOLM A. MARTIN*, JEFFREY M. OSTROVE***. 'Laboratory of Molecular
Microbiology, and ***Laboratory of Clinical Investigation, NIAID, NIH, 9000
Rockville Pike, Bethesda, MD 20892; **Genotech, Inc., South San Francisco, CA.
During the course of infection with HIV many individuals became coinfected
with a variety of microorganisms. Since some of these pathogens may act as
cof actors capable of stimulating HIV expression and thus accelerate disease,
we examined one common coinfecting pathogen, herpesvirus type-I (HSV-1), for
its ability to increase HIV gene expression. When an HIV LTR clone linked to
the indicator gene chloramphenicol acetyl transferase (CAT) was transfected
into Vero or SW480 cells, then infected with HSV-1, a 25-fold stimulation of
CAT activity was observed. This effect was further increased by transfection
of HIV tat DNA into cells subsequently infected with HSV-1. In cotransf ection
experiments of HIV LTR-CAT or an infectious molecular clone of HIV and
recombinant plasmids containing three HSV-1 immediate early genes, segments
encoding ICP0 and ICP4 stimulated CAT expression or reverse transcriptase
activity while ICP27 had no effect. Analysis of HIV LTR deletion mutations
revealed that the target of the HSV-1 encoded products was distinct from
that responsive to the HIV tat gene. Primer extension experiments demon-
strated a transcription component to the HSV-1 transactivation.
MR22
and A.B
Regulation of HIV Long Terminal Repeat (LTR) Activity.
K. WECK*, K. CLOUSE****, H.E. GENDELMAN*, J. OSTROVE***, T. FOLKS**
RABSON*. *LMM, **LIR, & ***LCI; NIAID; NIH; Bethesda, MD 20892; and
DC.
Georgetown University, Washington,
The HIV LTR contains regulatory sequences that modulate viral gene expression.
In order to delineate the sequences responsive to the viral tat protein, a
series of mutations in the LTR tar region have been constructed employing
deletion mutations and synthetic oligonucleotides. When tested for their
ability to drive the expression of the chloramphenicol acetyl transferase (CAT)
gene in the presence of tat, it was observed that LTR sequences lying between
+37 and +62 were required for tat responsiveness. Additional mutations in
the tar region are currently being studied both by CAT assays and in recon-
structed viral genomes.
Expression of the HIV genome may also be regulated by cellular transcription-
al factors. We have been studying the activation of HIV expression in Ul
cells, a cloned macrophage cell line containing integrated proviral DNA and
expressing low levels of viral RNA. When Ul cells are treated with the super-
natant from lipopoly saccharide (LPS)- induced macrophages, viral RNA levels
increase approximately 40-fold. Thus, stimulated macrophages may produce
factors that transcriptionally activate quiescent HIV proviruses, presumably
by altering the cellular transcriptional milieu of latently infected cells.
The ability of purified monokines to augment HIV transcription in infected
cells is being studied and the location of LTR sequences required for this
activation is being analyzed employing HIV LTR segments mutated in the tar
region and in upstream regulatory elements.
13
MONDAY, JUNE 1
M R 23 structure/Function Studies of Cloned HTLV-III/LAV from Zairian and
French Individuals
JOSEPH YOURNO,* S. F. JOSEPHS/ *A. G. FISHER,* D. ZAGURY,** F. WONG-STAAL,* and
R. C. GALI/),* *Laboratory of Tumor Cell Biology, National Cancer Institute,
NIH, Bethesda, MD, **Universite Pierre et Marie Curie, Paris, France.
Different isolates of HTLV-III/HIV, the etiological agent of AIDS have
extensive genomic diversity in nucleotide sequence with greatest divergence
centered in the env regions and the most conserved regions in the gag and pol
genes. Mechanisms which generate such diversity may allow the virus to survive
host immune surveillance. Consistent with this, variants have been selected for
when the virus is grown in vitro in the presence of neutralizing antibodies.
To better understand the genetic divergence responsible for this phenomenon
and to prepare additional reagents which may be useful for vaccine development
it is necessary to study a large number of HTLV-III/HIV isolates. We have
isolated and cloned viruses from two individuals with AIDS, one from Zaire
(JY-1) and one from France (JY-2) . The clones were obtained by isolating 9 Kb
HTLV-III Sstl fragments stretching from the 5' leader to the 3r LTR from phage
lambda libraries. Comparison of the restriction enzyme maps of JY-1 and JY-2
and a prototype earlier American isolate, BH10, show that the 5' gag and pol
regions share 10 of 12 sites while the 3' portion is less well conserved with
7 of 11 sites in JY-1 and 7 of 11 for JY-2. JY-1 appears to be more closely
related to the American isolate than previously described Zairian isolates
(Benn et al., Science 2 30, 949). Substitution of the protein coding regions of
these viruses into the biologically active clone pHXB2-d yielded clones which
produced virus after transfection into Cos-1 cells. Nucleotide sequencing is in
progress.
MP26 Transactivation of Human Immunodeficiency Virus by Herpesviruses
C. BOHAN*, P. LUCIW**, p. PELLET*, A. SRINIVASAN*, *Centers for
Disease Control, Atlanta, GA. , **University of California, Davis, CA.
We examined the interaction of human immunodeficiency virus (HIV) and
herpes group viruses. For this purpose, a chimeric plasmid (pLTR-CAT) was
constructed in which the long terminal repeat (LTR) sequences derived from a
molecular clone of HIV were fused to a bacterial chloramphenicol
acetyltransferase gene (CAT). Transient expression assays in transfected
tissue culture cells were used to monitor the activity of the LTR. Basal
levels of CAT activity were measured in HeLa and human lung fibroblast (HLF)
cells transfected with pLTR-CAT. When HeLa or HLF cells transfected with pLTR
CAT were infected with herpesviruses, HIV-LTR directed expression of the CAT
gene was detected. Activation of HIV-LTR directed expression of CAT was
observed for herpes simplex viruses (HSV-1 and HSV-2), cytomegalovirus and
varicella zoster virus. Activation of CAT expression directed by the LTR was
observed by cotransfection of subgenomic fragments derived from HSV-1, HSV-2,
and CMV genomes. We have also constructed a series of recombinant plasmids
containing deletions and multiple point mutations in the HIV-LTR sequences
linked to the CAT gene. HeLa cells were transfected with such plasmids and
followed by superinfection with herpesviruses to identify the sequences
required for transactivation by herpesviruses. HIV-LTR directed expression
may be a useful model for studying the effects on HIV of various infectious
agents known to be present in individuals with AIDS or HIV infection.
MR24 Suppression of AIDS Virus Replication in vivo by D-Pem'cillamine.
+|P. Sarin*, Daisy Sun*, M. Civeira*, R. Schulof, Allan Goldstein ,
P. Chandra . Laboratory of Tumor Cell Biology, National Cance_r Institute,*
Bethesda, MD, George Washington, University School of Medicine , Washington,
D.C., University of Frankfurt , West Germany
D-penicillamine (DPA) has been shown to inhibit HIV (HTLV-III/LAV) repli-
cation in-vitro (Chandra and Sarin, Drug Res. 36: 1, 184, 1986). It was
therefore of interest to assess the in-vivo activity of DPA on virus repli-
cation in HTLV-III-infected patients with generalized lymphadenopathy (LAS)
or ARC. Patients were treated on a high-dose regimen (0. 5g escalating to 2g),
or a low-dose schedule (0.5g daily) for 2 weeks to 4 months. A suppression of
virus replication was observed in all cases, however the intensity of this
inhibition was dependent on the dose schedule and the duration of treatment.
In patients treated at low dose, the inhibitory response was in the range of
30-50%, which was reversed after two weeks of treatment termination. Three of
five patients treated at high dose showed a complete inhibition of viral repli-
cation, and this suppression of HTLV-III replication persisted up to 24 weeks
after the treatment was stopped.
MP97 SIV/SMM: Prevalence and Association with Disease in a Breeding
Colony of Mangabey Monkeys.
HAROLD M. MCCLURE*, D.C. ANDERSON*, W.M. SWTTZER**, E.A. STROBERT*, J.L. ORKIN*
AND P.N. FULTZ**, *Yerkes Primate Research Center, Emory University, Atlanta,
GA, **AIDS Program, Centers for Disease Control, Atlanta, GA.
A colony of mangabey monkeys at the Yerkes Center has a high incidence of in-
fection with SIV/SMM, a T-lymphotropic retrovirus that is morphologically iden-
tical and serologically related to HIV. This colony, established in 1969 with
wildborn mangabeys, currently consists primarily of lab-born animals. There
has been no difference in the incidence of disease in the mangabeys as compared
to other species at Yerkes. Twenty-six of 76 deaths (34%) were due to clinical
diseases , including enterocolitis, pneumonia, amyloidosis, septicemia and
meningitis. Candidiasis, lymphadenopathy and splenomegaly were rarely encoun-
tered. Two neonates were found to have a herpetic (CMV) glomerulitis. Two re-
cently encountered diseases in mangabeys, amebiasis and necrotizing gingivitis
(noma) , suggest that the virus infection may be associated with clinical
disease and death. Amebiasis occurred in an 11-year-old female; noma occurred
in a 5-month-old infant. Both animals were seropositive for SIV/SMM and virus
was isolated from blood and multiple tissues from both cases, including the
brain from the noma case. Although 88% of the adult mangabeys checked have
been virus positive, this is the first virus isolation from an infant. The
high infection rate in mature animals and occurrence of infection in an infant
suggests that transmission of SIV/SMM may be comparable to the transmission of
HIV (sexually or perinatally) . This colony of naturally infected mangabeys
may, therefore, serve as a model system for study of the epidemiology and
pathogenesis of an HIV-like retrovirus, and for identification of cofactors
that may be associated with the occurrence of AIDS (supported by NIH grant no.
RR-00165).
MR25 Nucleotide Sequence of an Active tat cDNA Clone of Simian T-Lympho-
tropic Virus Type III
SANDRA COLQMBINI,* S. ARYA,* L. JAG0DZINSKI ,** M. S. REITZ,* B. BEAVERS,* R.C.
GALLO,* and F. W0NG-STAAL,* *Laboratory of Tumor Cell Biology, National
Cancer Institute, NIH, Bethesda, MD, **Biotech Research Laboratory, Inc.,
3 Taft Court, Rockville, MD.
The human T-lymphotropic viruses shared, among other common properties, the
ability to regulate their own expression mediated by transacting viral regula-
tory proteins. The prototype AIDS virus, HTLV-I I I/HIV, has at least three pos-
itive transactivating genes ( tat- III , trs and sor) operating at various stages
of virus expression. Recently, a second subgroup of primate retroviruses
related to HTLV-III/HIV has been identified. The prototype of this subgroup is
the simian T-lymphotropic virus type III (STLV-IIIaq^) isolated by Kanki
et al., from African green monkeys. In order to understand the transregulatory
function of this new virus subgroup, we cloned and sequenced a functional
transactivating cDNA from STLV-III. The complete cDNA clone is 2049 nucleo-
tides in size. It comprises 4 exons and three open reading frames. These are
analogous in position and size to the tat, trs and 3'-orf genes of HTLV-III.
Alignment of the putative STLV-III tat gene with tat-3 revealed a highly con-
served core sequence which likely represents the functional domain. We assayed
the transactivating capacity of our cDNA clones by co-transfection with a
plasmid pSV2CAT containing the putative transactivation target sequences (TAR)
of the STLV-III LTR upstream of CAT. It showed marked transactivating function
and this function is maintained when we substituted pSV2 CAT with the corres-
ponding construct with HTLV-III LTR. We conclude that this new subgroup of
primate retroviruses are similar to the HTLV-III/HIV viruses in their genomic
organization and strategy for gene regulation.
MR28
Relationship between Core
Simian Immunodeficiency Viruses
0HTA*
FRG,
Polypeptides
as determined
-, H. SCHMITZ***
♦The Institute
,G.
of
Structural
Human and
Peptide Mapping
ELKE JURKIEwlCZ*, J. SCHNEIDER*, M. HAYAMI**, Y
HUNSMANN*, *German Primate Centre, Gottingen,
Medical Science, University of Tokyo, Japan, ***Bernhard-Nocht-Inst itut ,
Hamburg, FRG.
Simian immunodeficiency viruses (SIV/s) are serologically and
biochemically related to the human immunodeficiency virus type 1 (HIV-1)
the cause of AIDS. The SIVs isolated from macaques (SIVmac) and sooty
mangabey (SIVsm) induce an AIDS-like disease in rhesus monkeys. Recently,
two novel human retroviruses, HIV-2 and HTLV-IV, were found in West
Africa. They are antigemcally more related to SIV than to HIV-1. In order
to classify HIV. and SIV isolates, we have compared tryptic peptide maps of
the core polypeptides pl8 and p24 of HIV-2, three HIV-1 and five SIV
isolates. Peptide maps of all isolates are distinguishable. Differences
appear to be most prominent between the two groups of HIV-1 isolates and
SIVmac/SIVsm. HIV-2 is very similar to SIVmac and SIVsm. SIVs of African
green monkeys (SIVagms) are the most heterogeneous group. The core
polypeptides of one SIVagm isolate is more related to HIV-1. The two other
SIVagms also resemble more to HIV-1 with respect to their p24s, but their
pl8s are more similar to those of SIVmac /SIVsm/HIV-2 than to those of HIV-
1. Therefore, two SIVagm isolates could be gag gene recombinants between
human and simian viruses or their ancestors.
14
MONDAY, JUNE 1
MR29 Biochemical Features of the 3'orf Gene Product of HTLV-I I I/HIV
JONATHAN S. ALLAN. M.F. MCLANE, P.J. KANKI, M. ESSEX, Harvard
School of Public Health, Boston, MA.
We previously identified a 27kd protein (p27) from an HTLV-I lib
infected cell line which was itnmunoreactive with antibodies from infected
people and encoded by the 3'orf gene by amino acid sequence analysis. We
have extended our studies to learn more of the biochemical character-
istics of p27 in the hope of gaining some insights into the functional
aspects of the 3'orf gene. Initially, levels of expression of p27 were
evaluated among different HTLV-III/HIV isolates and those of STLV-III and
HTLV-IV using radioimmunoprecipitation (RIP) techniques. It was found
that multiple species of p27 exist in some cell lines which range in
molecular weight from 26kd to 30kd. Additionally, p27 is modified by
fatty acid myristylation as detected by 3[H"|myristate incorporation and a
similar species (p33) was found to exist in STLV-III and HTLV-IV infected
cells indicative of a conserved 3'orf gene product. P?7 was shown to be
cell -associated and cerulenin, an inhibitor of lipid metabolism, was
found to alter the migration of p27 by SDS-PAGE suggesting that this
species represents the nascent polypeptide.
Although greater than 20% amino acid variability in the 3'orf gene is
seen between some isolates, highly conserved regions exist and from a
search of gene bank sequences we observed limited amino acid homology
with EIB, an early adenovirus gene involved in tumorigenesis. These
homologous sequences were confined to the conserved regions between
HTLV-III/HIV isolates suggesting either structural or functional
constraints in the evolution of the 3'orf gene.
MD 90 In vitro produced factors promote the growth of Kaposi's sarcoma
mr.OC TTSTceTls
SHUJI NAKAMURA*. B. ENSOLI*, Z. SALAHUDDIN* and R. GALLO* . * National
Cancer Institute, Bethesda, MD.
Epidemic HTLV-III related KS is an aggressive disease of young people and
is a multifocal and histologically complex lesion consisting of spindle cells,
endothelial cells and fibroblasts. So far, its origin and pathogenesis remain
unknown. Here, growth of KS cells were compared to normal endothelial (NE)
and fibroblast like (NF) cells. Cell growth was assessed by cell number, 'h
thymidine uptake and mitotic index. Conditioned medium from HTLV-II-trans-
formed human T4+ cell lines (HTLV-II-CM) stimulated the growth of 6 of 6 KS
cells as well as NE cells, but was much more potent for the growth of the KS
cells. These KS cells, although slow growing, have been cultured with the
help of this factor(s) for over 9 months, and large quantities of cells have
been harvested for study.
Nine well known growth factors, including endothelial cell growth supple-
ment (ECGS) , basic fibroblast growth factor (FGF) and IL-1, were also tested
for their growth promoting effects. ECGS and FGF induced the growth of NE and
NF cells, but, they had little or no effect on the growth of KS cells. Con-
versely, IL-1 stimulated the growth of KS cells, although it plateaued early
as compared to HTLV-II-CM and had little or no effect on NE and NF cells. In
addition, molecular analysis revealed that the factor in HTLV-II-CM differed
from ECGS and FGF, but whether it dif feres from other known lymphokines, in-
cluding IL-1, is under investigation. In summary, we have developed an in
vitro system for the study of KS. Our results show that KS cells have a-
different growth factor dependency than NE and NF cells. This system should
provide further clues to our understanding of pathogenesis of KS.
MP30 Expression of Large Amounts of Native and Mutated Forms of the HIV
Envelope Proteins Using a SV40 Late Replacement Vector
DAVID REKOSH*. A. NYGREN***, E. LINDSTROM***, H. WTGZELL*** and M-L
HAMMARSKJOLD**, *Departments of Biochemistry and **Microbiology , SUNY at
Buffalo, N.Y. and ***Department of Immunology, Karolinska Institute, Stockholm,
Sweden.
An eukaryotic expression vector producing large amounts of the HIV envelope
proteins (gp 160/120) has been constructed by introducing the Sal I/Xho I
fragment from the BH10 isolate into a SV40 late replacement vector. The vector
is a shuttle vector that replicates to high copy numbers in both E. coli and
eukaryotic cells permissive for SV40 replication.
Transfection of the HIV recombinant into CV1 monkey cells gave high levels of
expression of gp 160 and gp 120 in approximately 30% of the transfected cells.
By several criteria the proteins were indistinguishable from those produced
during infection. The proteins were localized to both the cytoplasm and the
plasma membrane and some of the gp 120 was shed into the culture medium.
Approximately 0.5 ug of envelope protein could be extracted from 10 cells.
Thus this transient vector system provides an abundant source of native
envelope protein for purification and characterization.
In addition several recombinants designed to express mutated forms of the
envelope proteins have been created.
MP33 Comparative Structural Analysis of the Env Genes
lymphotropic Retroviruses (STLV-III and HTLV-III
Marvin S. Reitz, Jr. , C. Gurgo, G. Franchini, E. Collalti,
Staal , R. Gallo, Laboratory of Tumor Cell Biology, National
Health, Bethesda, MD 20892
Recently viruses have been identified in monkeys in Afric
are related to HTLV-III. They have been designated simian
viruses, type III (STLV-III), and appear to cause an AI0S-1
macaques. Viruses related to STLV-III have been identified
apparently immunocompromised humans from West Africa. In o
STLV-III and HTLV-III and to try to identify common structu
might explain their similar pathobiology, we determined the
tide sequence of the env gene of STLV-III. The overall nuc
homology to HTLV-III is 52%. The homology of the inferred
of the env protein to that of HTLV-III was 34%, substantial
to those of the lentiviruses visna (15%) and equine infecti
(14%). The small transmembrane env proteins were more clos
than were the external large envelope proteins (30%). Regi
between these env gene products tended to cluster within re
relatively strongly conserved among different HTLV-III isol
that these code for genetic determinants which are of funct
to parts of the viral life cycle, such as binding to the T4
In addition, there is a remarkable conservation of cysteine
of 23 cysteine residues in the HTLV-III env proteins are al
of STLV-III). This strongly suggests that they play a crit
lishing or maintaining the proper conformation of the viral
aspects of this work will be discussed.
of Group B T-
)
H.-G. Guo, F. Wong-
Institutes of
a which by serology
T-lymphotropic
ike disease in
in healthy and
rder to compare
ral features which
complete nucleo-
leotide sequence
amino acid sequence
ly greater than
ous anemia virus
ely related (40%)
ons of homology
gions which are
ates. This suggests
ional importance
receptor protein.
residues (2 out
so present in that
cal role in estab-
envelope. Other
MP31 Simple, Hapid, Quantal , Syncytium- Forming Micro-Assay for the
Detection of Neutralizing Antibody Against Infectious HTLV-I1 1/I.AV.
PKTBB L. NAIW. W.C. HATCH", N. DUNLOl" , W.G. ROBKY' , AND P.J. F1SCHINGBR* ,
•Office of the Director, Virus Control Unit, NCI-Frederick Cancer Research
Facility (FCRF), "Program Resources, Inc., NCI-FCRF, Frederick, MD 21701.
A need for a simple, rapid, quantal cell system for the sensitive detection
of neutralizing antibodies and evaluation of various antiviral agents against
HTLV-III/LAV is well recognized. Herein is described a syncytial -forming
assay that directly correlates with more complicated and cumbersome infectious
virus assays. A syncytial sensitive clone of CEM cells was identified and made
adherent to flat bottom 96-well microtit.er plates. These cells exhibit one-
hit kinetic syncytium formation at a multiplicity of infection of 0.005. These
syncytium develop by 5 days on a confluent cell monolayer background and
remain attached for easy quantitation. These syncytial foci are associated
with complete virion production and locally positive p24 immunofluorescence.
Five different HTLV-Ill/LAV isolates (Illb, LAV, MN, RFII, and Rut-Z, includ-
ing Illb reisolated from persistently infected chimpanzees, produce quantifi-
able syncytium, which varied slightly in their morphology of formation.
Various ant i HTLV- II1/LAV sera from various species (man, chimpanzee, goat,
equine, and rhesus) have been tested and found to contain titers comparable to
immunof luorescent methods. Infectious virus can be accurately and rapidly
titered in this assay and correlated to p24 and gpl20 when microtiter well
supernates are evaluated by competitive radioimmunoassay methods. This assay
has the advantage of allowing numerous, small volume samples of either anti-
viral or suspect antisera to be tested in a rapid and sensitive fashion.
Inherent with this system is a flexible method for studying various kinetics
of antibody/viral interactions, blocking, and various interference studies.
Research sponsored, in part, by NCI, DHHS, under Contract NOl-CO-23910, PRl.
MP34 HTLV-II in Patients with AIDS and Lymphoproli f erat ive Diseases:
isolation and characterization. S.z. SALAHUDDIN*, c. GUPGO*,
P.D. MARKHAM*, F. JENSEN**, R. FORD***, and R.C. GALLO*, *NIH, National Cancer
Institute, Bethesda, MD, **cytotech, San Diego, CA, ***Texas Medical Center,
TX.
HTLV-II was previously isolated from two patients with variants of hairy-
cell leukemia (1,21 and one hemophilic patient with AIDS (3). However,
recently serological (4) studies indicated that HTLV-II might be more widely
disseminated. During the process of screening patients for antibody to
HTLV-I/II and HTLV-III, several with diseases not previously associated with
HTLV-I infection were found seropositive for HTLV-I/II. A retrovirus was
isolated from peripheral blood or lymph node leukocytes of six of these
selected patients which, upon further characterization, proved to be HTLV-II.
Two patients with a history of intravenous drug abuse, diagnosed with dermato-
pathic lymphadenopathy, had concomitant infection by HTLV-II and HTLV-III.
HTLV-II was also isolated from one patient with prolymphocyte leukemia and
from three patients with hairy-cell leukemia. These and previous observations
demonstrate that in addition to its* association with, at least, some variants
of hairy-cell leukemia, HTLV-II is more widely disseminated and possibly
associated with other malignancies.
Science 218:571, 1982.
315:372, 1986.
1. Kalyanaraman, et al .
2. Rosenblatt, et al., N. Fngl. J. Med..
3. Kalyanaraman, et al., EMBO J. , 4:1455, 1985.
4. Robert-Gurof C, et al., J. Am. Med. Assoc, 255:3133, 1986.
15
MONDAY, JUNE 1
MP35 Analysis of Sera Exhibiting Atypical Reactions With HIV
KATHLEEN SHRIVER, J. KLANIEKI, R. HOUGHTON, R. MASINOVSKY, J.
McCLURE and A.J. WATSON, Genetic Systems Corporation, Seattle, WA, USA
During clinical trials of a screening assay for antibody to HIV (Genetic
Systems LAV EIA) , a small number of atypical sera (n=6) were identified which
were positive by EIA, negative by radioimmunoprecipitation (RIP) , and
positive only with single core antigens p25 or pl8 (with or without precursors
p55 and p40) by Western blot. A study was initiated to collect and charact-
erize a larger sample group in order to assess the significance of this
reactivity. In total, 91 atypical samples were analyzed. Twenty-five samples
reacted with p25, 42 with pl8, 19 with pl8 and p24, 4 with p25 and p34 and
one with pl8 and p34. In nine individuals where sequential samples were avail-
able, no significant changes in serum reactivity were observed over 6 mos. to
2 yrs., arguing that these samples do not represent seroconversions. Viral
cultures attempted from cells of nine individuals were negative when analyzed
by fluorescence, RT assays and antigen capture. Futhermore, no reactivity to
STLV-III, HTLV-I, or LAV-II viral antigens was found in 26 samples tested.
These results suggest that Western blot reactivity with core antigens alone,
in the absence of RIP reactivity, does not indicate prior exposure to HIV.
Atypical sera were further analyzed using a prototype second generation ELISA
which incorporated synthetic peptide antigens containing sequences from ENV,
(gp41), GAG (p25) and POL (p34) . Only 5.5% (5/91) of atypical sera reacted
in this assay, whereas a similar assay using _E. coli recombinant p25 and pl8
antigens detected 61% (16/26) of atypical sera. Immunoassays based on peptides
may therefore offer the opportunity to significantly reduce false positives
attributable to the reactivity of atypical sera.
MP.38 Cerebrospinal Fluid (CSF) Studies in Adult and Pediatric HIV
Infections
CECELIA HUTTO, G.B. SCOTT, E.S. PARKS, M. FISCHL, W.P. PARKS, Departments
of Pediatrics and Medicine, University of Miami School of Medicine, Miami,
FL
Studies of cerebrospinal fluid (CSF) in virus-positive adult and
pediatric patients were compared. The groups included 11 adults (20
specimens) enrolled in a trial evaluating 3'-Azido-3'-deoxythymidine (AZT)
and placebo and 14 children (19 specimens) with HIV infections in whom
lumbar punctures were done because of fever and possible sepsis. Sequential
isolation attempts from CSF were made from 2 children and 7 adults. All
patients were repeatedly virus-positive from peripheral blood leukocytes
and all had HIV-associated clinical disease. All children had delay in
growth and/or developmental milestones and 2 had progressive neurological
disease. HIV was recovered from the CSF of only 4/14 (29%)
children. Neither of the children with progressive neurological disease was
CSF virus-positive. CSF cell count and protein were normal in 3/4 children
with positive and 7/10 children with negative cultures. CSF cultures for
HIV were positive in 8/11 (73%) adults including 3 patients on multiple
occasions. Although the CSF cell count was abnormal more often in virus-
positive (100%) than virus-negative CSF (46%), cell counts even in virus
positive CSF were only slightly elevated (mean - 9 lymphocytes/ mm ). There
was no significant difference in the proportion of virus-positive and
virus-negative CSF with elevated protein, 62% (mean 57 mg/dl) and 50% (mean
52 mg/dl), respectively. Patients with virus-positive CSF culture only
became negative in patients receiving AZT (2/4). HIV is more readily
recovered from the CSF of HIV-infected adults than children even if
neurological abnormalities are present in the pediatric patients. The usual
parameters of inflammation, elevated cell counts and protein, apparently
are not predictive of the presence of virus.
MR36 Analysis of the Reactivity of Human Sera to a HIV env Region Capable of
Eliciting Neutralizing Antibodies in Animals Using Synthetic Peptides
M.-C. GANFIELD. DM. WASELEFSKY. W.R. KENEALY. D.L. REED.
T.J. MATTHEWS*. S.R. PETTEWAY. E.I. du Pont de Nemours, Medical Products
Department. Wilmington. DE. and *Duke University Medical School, Durham. NC.
Recent studies indicate that portions of the HIV env open reading frame encode
protein sequences which can elicit neutralizing antibodies in goats. We have
analyzed the reactivity of HIV positive human sera to these regions using overlapping
synthetic peptides. A rapid peptide synthesis method was used to make overlapping
peptides covering the entire gpl20 region. Peptides of 15 to 16 amino acids with 5
overlapping amino acids on each end were made. Seventeen peptides, covering a region
of IIIB previously shown to elicit neutralizing antibodies in animals (Pvull-Bglll).
and thirteen peptides covering the same region of an envelope variant strain RF.
which had sequences different than IIIB. were tested. Peptides were immobilized on
ELISA plates directly by glutaradehyde and analyzed using normal and HIV ELISA
positive sera. Three peptides from IIIB reacted strongly with 30-40% of the HIV
ELISA positives. Selected sera were fractionated on affinity columns made of
reactive peptides and the activity of eluted antibodies was assessed. In addition
peptide conjugates were injected into guinea pigs: and the ability of anti-peptide
antibodies to react with viral proteins and/or inhibit infectivity was tested. The
results of these experiments will be discussed.
MR39 Interaction between GP 120, the Major Env Protein of HIV,
and CD4: Binding Region in GP 120 and Role of Carbohydrates.
ANDERS NYGREN*, P.FL0DBY*; T. BERGMAN**, K. LUNDIN*, H. JORNVALL** ,
H. WIGZELL*. ,*Dept of Immunologi, Karolinska Institute, Stockholm, Sweden.
** Dept of Physiological Chemistry , Karolinska Institute, Stockholm, Sweden.
The interisolate variation of the env region of HIV is one of the major
problems for the production of an AIDS vaccine. In order to find a conserved
CD4-binding region in GP 120 we have performed enzymatic digestion of this
protein for subsequent testing in a simple binding assay developed in our
laboratory. Two fragments were found to bind to the CD4 receptor. Preliminary
analysis of these fragments indicates that the bindingsite in GP 120 is
located in the carboxy terminal region. Deglycosylated GP 120 (DG 120, MW 58-
60) has been shown to bind to the CD 4 receptor with much less
avidity than GP 120 in its native form. Further studies including kinetics of
the deglycosylation of GP 120 were carried out and revealed a significantly
different efficacy depending on the enzyme used. DG 120 was tested in our bin-
ding assay. Our conclusion is that carbohydrates stabilize the peptide con-
figuration necessary for CD 4 binding to occur.
MP.37 HIV Related Sequences in Insects from Central Africa
JEAN-CLAUDE CHERMANN*, J.L. BECKER*, U. HAZAN*, B. SPIRE*, F. BARRE-
SINOUSSI*, A. GEORGES** et al., * Institut Pasteur, Viral Oncology Unit, Paris,
France, ** Institut Pasteur, Bangui, Republique Centrafricaine.
We have studied the presence of HIV related sequences in more than 200 in-
sects from endemic area for AIDS in Central Africa. This analysis has been per-
formed using squash blot, dot Sot and southern blot techniques. Viral sequen-
ces have been found among insects from urban or suburban area, directly or in-
directly in contact with humans. Positive insects included mosquitoes, antlions
tse-tse flies, cockroaches, ticks and bed-bugs. Squash blot analysis indicated
that up to 30 % of mosquitoes from endemic area contained such viral sequences.
Studies on mosquitoes also suggested a transova'rian transmission of the viral
genes since positive results were observed both with males and females. Insects
with specialized feeding such as termites or crickets were constantly found
negative. Flies, bees, day-flies from Paris area were also negative. The spe-
cificity of the hybridization signals has been confirmed using several probes
as negative controls. Such controls included hybridization with pUC 18 , Kappa
globulin, HTLV1, type D SRV and M-MuLV probes. Hybridization with subgenomic
HIV1 probes also indicated that most of the viral genes are present in positive
insects. However the restriction patterns observed by southern blot analysis
is not similar to the one obtained with the prototype HIV1 strain. These re-
sults suggest that insects might be contaminated by infected human material
and thus could be carriers of HIV genes but not vectors as clearly evidenced
by previous epidemiological studies.
MP 4fJ Experimental assessment of bedbugs and mosquitoes as vectors of
Human Immunodeficiency Virus (HIV)
PETER G. JUPP and SUSAN F. LYONS, Department of Virology, University of the
Witwatersrand and National Institute for Virology, Johannesburg, South Africa.
In vitro experiments were conducted to assess whether the common bedbug
(Cimex lectularius) , the tropical bedbug (Cimex hemipterus) and the mosquito
(Aedes aegypti) could act as vectors of HIV. The insects engorged through a
membrane on a blood-virus mixture. At various intervals after feeding insects
were killed, stored at -70°C and subsequently tested in pools of 5 for reverse
transcriptase activity. This was done by inoculating each insect extract into
H9 lymphocyte cultures, passaging the cells for 3-6 weeks and then testing
culture supernatants for reverse transcriptase activity. HIV was thus shown
to survive in C. lectularius for up to 4 hours, in C. hemipterus up to 1 hour
but to remain undetectable in Ae. aegypti. Four attempts to transmit HIV by
interrupted feeding, using groups of 100 C. lectularius, from a blood-virus
mixture to uninfected blood failed. It is concluded that Ae. aegypti and
probably other mosquitoes are not vectors of HIV. The results also tend to
discount transmission by bedbugs. However, the survival of virus in bedbugs,
especially in C. lectularius, would permit the bugs to transmit HIV
mechanically between humans under natural conditions provided interrupted
feeding were to occur and the virus was sufficiently infectious. Whether the
former occurs is unknown but HIV is known to have a low infectivity.
16
MONDAY, JUNE 1
MR41
HIV Infection in Drug Addicts : an Epidemiological Study in Turin, North Italy.
IVANO DAL CCME», A. LUCCHINI**, S. COLOMBO*, G. GIULIANI*, E. NIGRA*, R. DIECTJDUE*
♦U.S.L. 1-23 TORINO Ass.San.Base-Servizio Tossicodipendenze, Area di Epidemiologia, Laboratorio di
Virologia, Torino, Italy, **Universita degli Studi-Istituto Malattie Infettive, Torino, Italy.
In 1985 we undertook a survey to estimate the prevalence of HIV infection and the risk factors as
sociated with seropositivity in drug addicts (DA) attending the N.H.S. Centers, Turin.
All 320 subjects enrolled were IV heroin abusers on different treatments. Mean age was 26.4 (S.D.
4.56), 78& males and 22% females. The prevalence of HIV antibody was 28%, slightly higher in f e -
males. The highest seroprevalence was in the 20-24 age group with a trend to decrease in older ages.
Seroprevalence increases with duration of addiction up to 9 years, beyond which it decreases.
In spite of free sale and large availability of syringes in Italy, needle sharing was referred by
81% of interviewed DA. The relative risk (RR) of this practice was 4.07 (C.L.95%: 1.46-12.25); 3.63
for occasional sharing (1.28- 11.06) and 6.10 for frequent sharing (1.82-20.81). Needle sharing in
prison was reported by more than 30% of DA with history of imprisonments.
Detailed sexual history demonstrated a correlation between number of partners/year (PA) and sero
positivity (RR 1.83 for 3-10 PA; RR 1.90 for 11-50 PA; RR 4.65 for 51 PA). Standardization for
sex and/or needle sharing confirmed this association. Having a steady partner, even if DA, appeared
to be protective. Homosexuality was infrequently reported and not associated with seropositivity.
At clinical examination, 3 or more enlarged lymphatic sites were found in 20.4% of DA (64.8% of
these were positive). RR of being positive in presence of lymphadenophathy was 10.34 (4.73-24.37) .
Since needle sharing and number of sex partners seem to be the most important risk factors in DA
and seroprevalence in Turin is still low compared to other italian cities, a timely and well planned
control program could limit the spread of HIV infection. A follow up, now in course, will determine
the impact of this policy. "Free needles" cannot be the mainstay in preventing HTV spread among DA.
MP44 Status of AIDS in the Americas
ST. JOHN, R.K. , 2ACARIAS, R., Pan American Health Organization,
Washington, D.C.
In 1983, the Pan American Health Organization initiated regionwide surveil-
lance for AIDS. Because AIDS was confined almost exclusively to the United
States, a very simple reporting system was installed based on the Centers for
Disease Control's case definition. Member Countries were requested to report
the total number of cases of AIDS and deaths due to AIDS every six months. The
objective was to follow the spread of AIDS within the Region.
This report summarizes the available data based on the PAH0 surveillance
system, as well as data from several special studies carried out in some of
the countries. The data are sufficient to define the overall picture of AIDS
in the Americas, although the exact magnitude of the AIDS problem is not known
precisely in each country.
The occurrence of opportunistic infections as markers for AIDS is variable
throughout the Region. With some exceptions, the specific frequencies of
certain infections are essentially the same as in the United States. Diar-
rhoeal illness is more common in Haiti and generalized Mycobacterium
tuberculosis infection is more common in Brazil and the Dominican Republic.
The homosexual/ IV drug user patient profile common in the United States
(Western AIDS) prevails in Latin America and the Caribbean, with a greater
proportion of homosexual and bisexual men and a much smaller proportion of
intravenous drug abusers. In the Americas, AIDS is predominantly a sexually
transmitted disease .
AIDS is a growing problem in the Americas, whose overall pattern, with the
exception of Haiti, appears to be following the pattern established in the
United States.
(Source: Health .Situation and Trend Assessment Program (PAHO).
MP 42 HIV ANTIBODY PREVALENCE IN BLACK MINERS BETWEEN 1970 - 1971*
SHER R*, ANTUNES E*, REID B**, FALCKE H**
xDept of Immunology, School of 'Pathology of the University of the Witwatersrand
and the South African Institute for Medical Research, Johannesburg, South Africa
x*Rand Mines South Africa.
Between 1970 - 197^ a pneumococcol vaccine trial was conducted in "black mine
workers in South Africa. Aliquots of serum collected during this trial were
stored at -20^C. In November 1986 these sera were tested for antibodies to HIV.
Participants in the trial came from Mocambique (1191)> Malawi (1080), South
Africa (171), Lesotho (55), Botswana (32), Angola (29) and Swaziland (16). As
initial screening with the Abbott HTLV-111 EIA gave many false positives, all
sera were tested with the Wellcozyme anti-HTLV-1 1 1 and positives were confirmed
with indirect fluorescence, Elavia-EIA and Western Blotting. Eleven sera were
found to be positive with the Wellcozyme test, six of which were positive with
indirect fluorescence. These sera were negative with Elavia and Western Blotting
Two sera, positive with Abbott EIA and indirect fluorescence but negative with
Wellcozyme and Elavia, gave moderate staining with Western Blotting to P17, 2U,
35, 55, 56 and GPl*1 and 120. One was from Malawi and the other Lesotho. This
study fails to provide convincing evidence of HTV infection in Malawi,
Mocambique and other Southern African countries between 1970 - 7^. In a
comparable group of mine workers surveyed in 1986 the prevalence of HTV
infection was found to be 3.71% in Malawians and 0.07^ in Mocambicans.
MR45
Prognostic value of HIV antigen capture assay in a
long-term prospective study of seropositive hemophiliacs.
JEAN-PIERRE ALLAIN*, Y.LAURIAN**, D.A.PAUL*, F. VERROUST** , M.LEUTHER*,
C.GAZENGEL**, et al., *Abbott Laboratories, N.Chicago, IL,
**AIDS-Hemophilia French Study Group.
Ninety-six hemophiliacs positive for HIV antibody entered a 28+6 month
prospective study. Every 4-6 months they were monitored for clinical and
biological parameters including 3 HIV markers: HIV antigen (HIV Ag), p24
and gp41 antibodies (Ab) . Eight subjects were HIV Ag positive at entry and
14 became positive during the study 7-47 months after seroconversion. HIV
Ag containing samples had low titer or undetectable p24 Ab but high titer
gp41 Ab. In the HIV Ag negative group, 66 subjects had high titer of both
p24 and gp41 Ab and 8 had low p24 Ab titer and high gp41 Ab titer over a
2-3 year period. Clinical comparison between the 22 HIV Ag positive and 56
HIV Ag negative subjects showed a significant increase in AIDS cases (2/0
P<0.05), immunodeficiency related infections (7/1 p<0.001), immune
thrombocytopenia (8/6 p<0.001) and severity of condition according to the
Walter Reed staging system (p<0.001). In this group of mostly asymptomatic
subjects at entry, neither T4+ lymphocytes nor T4/T8 ratio appear
predictive of clinical severity.
These results strongly suggest that the detection of HIV Ag associated
with low titer or undetectable p24 Ab is an indicator of HIV related
clinical complications and could be used to select patients for entry in
drug trials prior to the development of ARC or AIDS.
MR43 TRANSFUSION-ACQUIRED HUMAN IMMUNODEFICIENCY VIRUS (HIV)
INFECTION in NEONATES.
FRANK T. SAULSBURY*. R.F. WYK0FF", R.J. BOYLE*. "University of Virginia
Medical Center, Department of Pediatrics, Charlottesville, VA. ••South
Carolina Department of Health, Greenwood, SC.
Eleven neonates received blood from two HIV infected donors. All developed
laboratory and/or clinical evidence of HIV infection, usually in the first
year of life. Nine of 11 had serum antibody to HIV when tested between 9 and
16 months of age; two seronegative infants were severely hypogammaglobulinemia
when tested. Nine patients developed a variety of illnesses characterized by
hepatosplenomegaly, lymphadenopathy, chronic diarrhea, failure to thrive, and
thrombocytopenia. Infections, including pneumonia, mucocutaneous candidiasis,
and sepsis were a major source of morbidity and mortality. Two children have
remained continuously asymptomatic. In follow-up ranging from two to four
years, five patients have died, four others had HIV associated illnesses, but
recovered and are now healthy. All patients had immunologic abnormalities;
the most consistent finding was a decreased proportion of T-helper cells.
Three patients had panhypogammaglobulinemia. These infants had significantly
lower numbers of T-helper cells compared to patients with normal or increased
serum immunoglobulin concentrations (P=0.012). We conclude that exposure to
HIV via transfusion in the neonatal period results in an extremely high rate
of infection with substantial mortality and morbidity, but clinical recovery
occurs in some patients. Second, hypogammaglobulinemia may be more common in
infants with HIV infection than previously appreciated.
MP46 Antibodies to Human Immunodeficiency Virus in Clinical Patients
Presenting Mononucleosis-Like Syndrome.
JOSEPHINE MOSIflANN.A. KELLER, A. FLAVIAN0.M. JUNG. Institute Virion.
CH-88Q3 Puschl ikon/Zurich, Switzerland.
Serological tests were performed with sera of 401 patients clinically
presenting a mononucleosis-like syndrome. Antibodies to Human Immunodeficiency
Virus [HIV) were detected in 15 cases (3.7 percent). A close correlation of
positive results was obtained among enzyme immunoassay .Western blot (performed
in two different laboratories) . immunobinding assay, complement-fixation and
indirect immunofluorescence. The high degree of agreement among the results of
tests using different methodologies contributes to the significance of these
(unexpected) positive results.
HIV positive sera were also tested for other agents known to cause infections
or be reactivated in immunocompromized hosts. Thirteen out of 15 were sero-
positive for Cytomegalovirus, 7/15 for Toxoplasma gondii. 12/15 for Herpes
simplex virus, 15/15 for Epstein-Barr virus and 0/15 for human Polyoma virus.
No IgM antibodies were found to the above agents. except for one with Epstein-
Barr IgM,and one with border-line IgM to this virus. Syphilis serology was
uniformly negative.
These results should encourage the testing of sera for HIV antibody in
patients outside the so-called "risk groups". This is justified. even if the
test is not requested, since it is the only way to accumulate more epidemiolo-
gical data on the spread of this infection. Historically similar studies have
been performed on many other infectious diseases with excellent results.
should be no exception.
17
MONDAY, JUNE 1
MR47 Perinatal HIV infection: preliminary report of
prospective study on 71 infants.
JACQUELINE MOK+, Carlo Giaquinto*, Use Grosch-WBrner",
Anthony Ades**, Catherine Peckham**, +Departraent of Community
Child Health and City Hospital, Edinburgh, U.K., *Universita di
Clinica Pediatrica, Padova, Italy, "University of Berlin
Children's Hospital, West Germany, **Institute of Child Health,
London, U.K.
To define the natural history of perinatal HIV infection, three
European Centres collaborated in a prospective study to determine
the prevalence of infection in infants born to seropositive
mother, and to document the clinical and immunologic outcome.
Seventy-one children were identified at birth, and seen 3
monthly. Twenty-seven (38%) have been followed up for longer than
8 months. Forty-eight infants were delivered vaginally, 21 by
caesarean section. Breast feeding took place in 7 infants.
The clinical outcome in the infants could be grouped into the
following: I - Asymptomatic (n = 60)
II - Non specific signs (n = 4) which included unexplained
lyraphadenopathy , hepatosplenomegaly , neurodevelopmental
abnormalities .
III - HIV syndrome (n = 7). These infants presented with signs in
II as well as recurrent/unusual infections, opportunistic
infections, recurrent/protracted diarrhoea.
No correlation was seen between outcome and mode of delivery, or
breastfeeding. We propose a uniform classification for HIV disease
in infants and children, separate from the one currently used for
adult disease.
MR50 Ris'< of HIV SeroPositivity in Relation to History of STD's and Recr-
eational Drug Use in Sexual Contacts of Men with AIDS or ARC.
RANDALL A. COATES, L. CALZAVARA, S.E. READ, M.M. FANNING, F.A. SHEPHERD, M.M.
KLEIN, J.K. JOHNSON, C.L. SOSKOLNE, Faculty of Medicine, University of Toronto,
Toronto, Ont., Canada.
244 men who had had sexual contact with men with either AIDS or AIDS-related
complex (ARC) were recruited into a prospective study between July, 1984 and
July, 1985. At induction, data were collected on the sexual relationship bet-
ween the sexual contact and his primary case, as well as data relating to sex-
ual activity with other men, history of sexually transmitted diseases (STD's),
and use of a variety of recreational drugs. At recruitment, 141 of the sexual
contacts had antibodies to HIV while 103 were seronegative. All seronegatives
had last had sexual exposure to their primary cases at least three months prior
to antibody testing. After adjusting for number of sexual encounters with the
primary case and other men, the following variables were associated significan-
tly with HIV seropositivity in contacts: history of rectal gonorrhea (O.R.
(odds ratio)=2.8, p 0.001); history of syphilis (O.R. =2. 3, p=0.006); history
of hepatitis (O.R. =2. 9, p<0.0001); use of ethyl chloride (O.R. =2. 8, p=0.007);
use of 'uppers' (O.R. -2. 3, p=0.006); and use of MDA (O.R. =2. 4, p=0.004). Logis-
tic regression models which controlled for confounding by specific sexual act-
ivities with the primary case and other men revealed that history of hepatitis,
history of syphilis, and use of MDA remained significantly and independently
associated with HIV seropositivity.
MR48
AIDS in developing countries
RICARDO VERONESI, Faculty of Medicine, University of Sao Paulo, Brazil.
Brazil, with a population of 136 millions Inhabitants has. In 1986, the second
largest number of AIDS patients in the world. Around one thousand cases were
notified up to December 31,1986, sixty percent of such figures been notified
in Sao Paulo. Considering the evident underreporting of infectious diseases
and the fact that AIDS was not yet made compulsory for notification in this
country, very probably such numbers should be raised 50-100*. .
The perspectives for AIDS In Brazil, and as an extension in the 3 World, are
very pessimistic. Poor socioeconomic and cultural patterns of most of the po-
pulation, added to poor housing, promiscuity and high prevalence of malnouri-
shed people allow us to raise such dark predictions. Preliminary serological
H.I.v. antibodies surveys have shown 53* of homosexuals, 39% of transvetites ,
43* of haemophiliacs, 8* of renal haemodyalisis patients, 0.2-10* of blood do
nors, 2* of prostitutes and 100* of full-blown AIDS patients, to be positive .
Brazilian Indians living in the border to Venezuela did not show any evidence
of past infection with the H.I.V. Also, blood drawn from Brazilian Navy sailors
in 1974, resulted negative for H.I.V. antibodies. Around 200.000 serological
tests carried out in private blood banks in Sao Paulo city showed a 0.25* posi-
tlvity. In Rio 0.36* tests among 14.756 blood donors resulted positive for H.I.
V. antibodies. It was estimated that, in 1987, between 500.000 and one million
Brazilians will be infected by the H.I.V. Based on an observation of one case
of hepatic-splenic Schistosomiasis with AIDS we can speculate on the changing
patterns of the histopathological pictures of a few endemic diseases such as
Leishmaniasis, Chagas' disease. Malaria, Tuberculosis, Leprosy, Dengue, Yellow
fever and Paracoccidioidomycosis.
MR51 ^ne Epidemiology and Clinical Manifestations of AIDS in Israel.
YARDENA SIEGMAN-IGRA*, S. MAAYAN**, S.D. PITlik***, T. SCHWARTZ*,
C. C0STIN#, D. MICHAELI*, * Tel Aviv Medical Center, Tel Aviv, ** Hadassah
University Hospital, Jerusalem, *** Beilinson Medical Center, Petah Tikva,
t Ministry of Health, Jerusalem, Israel.
As of DeclJ.986, 23 cases of AIDS have been reported to the Israeli Ministry
of Health among persons residing in Israel. In contrast to the experience in
the United States and Europe, rates of AIDS were low and have progressed slowly
during the last four years (0.5 - 0.75 cases per million).
Risk factors for AIDS were identified in 22 patients: homosexuality in 12 ,
hemophilia in 8 and receipt of blood transfusions in 2. Eleven of the 12
homosexuals have, most likely, been infected abroad, and all hemophilia patients
had received imported commercial clotting factors. The two cases associated
with blood transfusions received blood donated in Israel.
The spectrum of clinical presentations and opportunistic pathogens was si-
milar to that reported in the Western World, except for one case of Mycobac-
terium Simiae systemic infection. Seroepidemiologic studies in 1984-86
suggest a low prevalence (<10%) of HIV antibody among homosexuals and IV drug
abusers .
Sexual relations abroad of persons at risk for AIDS and receipt of imported
clotting factors are the most important risk factors for AIDS in Israel.
Transmission of the virus among Israeli homosexuals seems to be infrequent
at the current level of exposure to the virus. The low prevalence of HIV
antibody in homosexuals and IVDA's suggest that Israel is a pre-epidemic area
for AIDS.
MR49 Risk of HIV1 Seropositivity in Relation to Specific Sexual Activities
of Sexual Contacts of Men with AIDS or ARC.
RANDALL A. COATES, L. CALZAVARA, S.E. READ, M.M. FANNING, F.A. SHEPHERD, M.M.
KLEIN, J.K. JOHNSON, C.L. SOSKOLNE, Faculty of Medicine, University of Toronto,
Toronto, Ont., Canada.
244 male sexual contacts of men with either AIDS or ARC were recruited into a
prospective study between July, 1984 and July 1985. At induction, data were col-
lected on the sexual relationship between the sexual contact and his primary
case, as well as data relating to sexual activity with other men. At recruitment
, 141 sexual contacts had antibodies to HIV while 103 were seronegative. All
seronegatives had last had sexual exposure to their primary cases at least three
months prior to antibody testing. After adjusting for the number of sexual en-
counters with primary cases and the number of other male partners, the following
sexual activities with the primary case were significantly associated with sero-
positivity in sexual contacts: receptive anal intercourse (O.R. (odds ratio)=3.4
, p<0.0001); insertive anal intercourse (O.R. =2. 3, p<0.01); receptive fisting
(O.R. =4. 3, p<0.01); receive a dildo in anus (O.R. =3. 9, p=0.002); mutual masturb-
ation solely (O.R. =0.45, p<0.05). Similar results arose when analysing data on
sexual activities with men other than the primary case. Also, seropositivity was
associated with sexual contact with men from U.S. centres (New York City O.R.=
2.4, p=0.003; Houston /Da 11 as O.R. =3. 7, p=0.002). Further, logistic regression
models which simultaneously adjusted for sexual activities with primaries and
other men, revealed that seropositivity was significantly associated with only
receptive and insertive anal intercourse with the primary cases and sexual con-
tact with men from Houston or Dallas. All seropositive contacts had either rec-
eptive or insertive anal intercourse with primaries or other men. Oral sexual
contact was never associated, significantly, with HIV seropositivity.
MR52 Assessing and Modelling Heterosexual Spread of the Human
Immunodeficiency Virus in the United States
VICTOR DE GRUTTOLA*, K. MAYER**, *Harvard Medical School, Boston, MA, **Brown
Univ. , Providence, RI.
Epidemiological investigation of the AIDS epidemic among heterosexuals has
been chiefly of two types: 1) studies of partners of individuals infected with
the Human Immunodeficiency Virus (HIV) and 2) population surveillance.
Although heterosexual partners of infected individuals (including those
without other risk factors) appear to be at high risk of infection, only a
small proportion of total number of cases of AIDS have been attributed to
heterosexual contact in the United States and Europe. To reconcile these
findings, we develop an epidemic model for heterosexual spread of HTV
infection and fit to surveillance data. Fitter parameter values are
restricted to a range that is consistent with findings from partner studies.
Because, at present, most HIV-infected heterosexuals and bisexuals have been
infected through other means (IV drug use or homosexual contact) , the model
considers two interacting populations: a small population of individuals
rapidly infected by high risk activity and a large population of individuals
at risk only from heterosexual contact. No precise predictions concerning
the future of the AIDS epidemic among heterosexuals is possible at this
time, but current epidemiological findings do not appear to preclude a major
heterosexual epidemic. Projections depend strongly on the delay between
infection ard infectivity. In addition to using the model far projection, it
can also be used to examine the assumptions required for interpretation of
results of case-control studies of HIV infection.
18
MONDAY, JUNE 1
MR53 HIV Antiqenemia: Association with Decreased Numbers of T4-cells and
Increased Risk for AMIS
FRANK DE WOLF*. J. GOUDSMIT*. D.A. PAUL**, J.M.A. LAMGE*, C. HOOYKAAS***,
R.A. COUTINHTj***, et al.
♦Academic Medical Centre, University of Amsterdam, **Abbott Laboratories,
North Chicago, 111., ***Dept. of Infectious Diseases, Municipal Health Ser-
vice, Amsterdam, The Netherlands
Sequential serum samples of 256 HIV antibody (HIV-Ab) seropositive and sero-
converted homosexual men, participating in a prospective study on the preva-
lence and incidence of HIV infection and risk factors for AIDS, were tested
for HIV antigen (HIV-Ag). Forty (20.2%) of 198 HIV-Ab seropositives were HIV
antigenemic throughout the study period of an average of 19.3 (± 0.5) months.
Among the remainina 158 HIV-Ab seropositive individuals and 58 HIV-Ab serocon-
verters 28 became HIV-Ag seropositive (attack-rate 14.3%). 114 (44.5%) of the
256 remained asymptomatic during the study period. Constitutional disease
developed in 39 (15.2%) and was seen more frenuentlv among HIV-Aa seropositive
than amona HIV-Ag seronegative individuals (p < 0.00001).
AIDS developed in 15 men; the AIDS attack-rate was 23.9% in the HIV-Ag sero-
positive and 1.3% in the HIV-Ag seronegative group (p < 0.00001; D = 23.292).
The mean number of T4+ cells declined during HIV-Ab seroconversion and stabi-
lized at a significant (p < 0.05) lower level in individuals seroconverting or
seropositive for HIV-Ag than in individuals without HIV-Ag after HIV-Ab sero-
conversion. This indicates that low and declining numbers of T4+ cells may
herald HIV-Ag seroconversion. The risk to develop AIDS and related disease
appears to be strongly associated with persistent HIV antiaenemia.
MR56
Heterosexual Transmission of HIV in Switzerland
ALINE JANETT, T. STUTZ
Federal Office of Public Health,
B. SOMAINI, H. VORKAUF, H. KAUFHANN, Swiss
Berne, Switzerland
Various sources are drawn on in Switzerland for the evaluation of the epide-
miological situation. In addition to the case of AIDS reported, we also recei-
ve information on the persons who attend the anonymous test units or of blood
donors whose HIV antibody tests show a positive result. Furthermore, all posi-
tive laboratory results are submitted in collective reports. The following re-
sults were obtained by end 1986.
Cases of AIDS: Of the 165 cases of AIDS in adults, 150 (=91 ») were men and
15 (=9 %) women. In the case of 6 of the Swiss men and 5 of the Swiss women,
heterosexual transmission of HIV is reported as the sole risk situation.
Blood donors: Of the 52 cases of HIV antibody positive blood donors analyzed
to date, 43 (=83 %) are male and 9 (=17 %) female. 5 (=12 %) of the men and 2
(=22 %) of the women reported heterosexual contacts as the sole risk situation.
Anonymous test : 335 of the men tested reported varied heterosexual contacts
as sole risk situation. 4 (=1.2 *) of these were HIV antibody positive. Of the
corresponding 178 women tested, 3 (=1.7 %) were HIV antibody positive.
Laboratory reports: Of the 4,268 HIV antibody positive reports, 3,111 (=73 »)
are accounted for by men and 1,157 (=27 %) by women.
Summary: Heterosexual transmission of HIV can already be well documented to-
day. The relevant measures to prevent increasing heterosexual transmission are
imperative.
MR 54 Natural History of HIV Infections in Haemophiliacs
ARONSTAM, A; WASSEF, M; ROY, A.
Treloar Haemophilia Centre, Holybourne, Alton, Hanpshire, U.K.
The natural history of HIV infection continues to unfold and ongoing data is
crucial. We have studied 48 HIV positive haemophiliacs. In 32 of these we
ware able to postulate the year of seroconversion through retrospective
sampling. These were 1980 (1) , 1981 (5) , 1982 (10) , 1983 (11) and 1984 (5) .
In the remaining 16 patients the year of seroconversion was no later than 1980
in 1, 1983 in 3, 1984 in 10 and 1985 in 2.
No case of AIDS has developed in our group. Seventeen (35%) have persistent
generalised lymphadenopathy (PGL) and 7 (15%) are thrombocytopenic. PGL was
first noted within the known year of seroconversion (year O) in one patient,
year 1 (1) , year 2 (1) , year 3 (3) , and year 4 (3) . The presence of PGL was
not significantly correlated with time since seroconversion nor with T helper
cell (T ) levels, although 5 of the 9 patients with lowest T. levels had PGL.
T. levels were measured in 36 patients and were subnormal in 10 (28%) .
Seroconversion year was known in 21 of these and a significant negative
correlation between time since seroconversion and T. levels was found
(r = .55 p = f.OOl) . The mean T. level in 9 patients who were known to have
seroconverted more than 4 years previously was .91 x 10 9/L, while the mean
level in 12 patients who had seroconverted less than 4 years previously was
1.8 x 10 9/L. The difference is highly significant (p = <.001) .
In spite of the absence of AIDS so far in our patients, we believe that the
progressive reduction in T. levels with time portends an ultimately high
incidence of serious AIDS, although the incubation period appears to be longer
than in other high risk groups.
MR57
HIV Antibodies in Seroconverters Followed by Weekly Intervals
EDGAR LAURITZEN*, B. KVINESDAL*, B.0. LINDHARDT**, A-G. POULSEN*,
*AIDS-T.aboratory , Rubella Department, Statens Seruminstitut , Copenhagen, "La-
boratory of Tumour Virology, The Fibiger Institute, Copenhagen, Denmark.
Sera from 26 patients were analysed for HlV-antibodies by five different me-
thods. The patients were initially seronegative and became positive. The ana-
lyses were an indirect ELISA with HIV-antigen from H-9 cells (A) , a commercial
indirect ELIFA, ELWIA, with antigen from CEM cells (B), a commercial competi-
tion ELISA, Wellcozyme (C) , a western blotting for HIV specific IgG (D), and
a western blotting for specific IgG, IgA, and IgM antibodies (E). The first
serum sample, which was positive by the screening test, (A), defined the day
of seroconversion.
Sera frcm 10 different patients were collected within 1-4 weeks before sero-
conversion, where 4 were positive by (B) and 3 by (D) 1-2 weeks before (A). A
singular reactivity on HIV-antigen p24 was observed for 6 patients by (D) and
for 7 patients by (E) 1-3 weeks before (A).
Sera from 9 patients were collected 5-10 weeks before seroconversion. In
this period 4 were positive by (B), 2 by (C), and 2 by (D) and (E), while they
<-rere borderline by (A). In the same period 3 sera were borderline by (A) and
p24 reactive in (D). Only four sera showed borderline reactivity before this
period.
Western blotting analyses were reactive earlier than the ELISA screening
test. Some patients were clearly seropositive 1-2 weeks before they were iden-
tified by the ELISA screening method. These patients would escape the HIV an-
tibody screening test.
MR55 Continuing Surveillance of HIV Associated Morbidity and Mortality
in a Well Defined Population
PETER JONES, MAUREEN A FEARNS, LINDA MCBRIDE, P HAMILTON, Newcastle
Haemophilia Centre, Royal Victoria Infirmary, Newcastle Upon Tyne,
United Kingdom.
In September 1985 we reported clinical and laboratory findings in 337
people in Northern England, including 143 multi-transfused haemophilic
patients (Jones P, et al, AIDS and haemophilia: morbidity and mortalityin a
well defined population, British Medical Journal 1985, 291, 695-9). Of 99
severely affected haemophiliacs 76 were anti-HIV seropositive; 3 of 36 female
sexual partners then tested were also seropositive. At the time of publication
3 of 4 patients with AIDS had died. 15 months later a further 9 patients have
developed AIDS; 4 are dead. One of these patients was the wife of a sero-
positive haemophiliac who developed Pneumocystis carinii pneumonia and dementia.
A further seropositive partner has given birth to a seropositive but clinically
well child. The third seropositive female remains clinically well. 51 other
female sexual partners have been tested and are seronegative; 41 had sero-
positive and 10 seronegative partners. Four of those presenting with AIDS had
no clinical markers suggesting impending illness other than seropositivity at
the initial survey; 2 presented with extra-cerebral lymphoma. A further
patient with abdominal lymphoma is presently receiving treatment.
Whilst the prognosis for anti-HIV seropositive haemophiliacs remains un-
certain these results suggest that AIDS may prove to be more common than
earlier predictions for this population first indicated. Heterosexual trans-
mission of HIV is less common than expected.
MP58 Absence of HIV infection in two sentinel cohorts of high-risk
black South Africans.
SUSAN F. LYONS. BARRY D. SCHOUB, ALAN N. SMITH, SYLVIA JOHNSON, GILLIAN M.
McGILLIVRAY, MRC AIDS Virus Research Unit, National Institute for Virology,
Private Bag X4, Sandringham 2131, South Africa.
As at the end of 1986 no cases of AIDS had been recognised in black South
African individuals; all 38 reported AIDS cases in South Africans have
occurred in white males belonging to the high-risk groups characteristically
seen in Western countries. To determine the possible introduction of HIV
infection from African countries to the north, two cohorts of promiscuous
African women, 56 black prostitutes "servicing" a large industrial complex
north-east of Johannesburg and 195 black females attending the major Johannes-
burg clinic for sexually-transmitted diseases (STDs) were investigated for the
presence of HIV infection. All sera were examined for HIV antibodies, both by
ELISA (ELAVIA - Pasteur Institute) and by indirect immunofluorescence (IF)
using HIV-infected H9 cells (obtained from Dr R Gallo).
None of the prostitutes and only one of the STD attendees were positive for
HIV antibodies (both by ELISA and IF); the latter individual was, however, a
migrant Malawian and not South African. Examination of these specimens for
other STDs revealed prevalences consistent with those seen for similar
populations elsewhere in Africa. In the prostitute cohort, 24 of 56 (43%) were
HBsAg or anti-HBs positive and 53 of 56 (95?) were positive for chlamydia
antibodies. Similarly, in the STD cohort, 81 of 195 (421) were positive for
HBsAg or anti-HBs, 27 of 108 (25X) were WR positive and 179 of 195 (92Z) were
positive for chlamydia antibodies.
There thus appears to be still no evidence of the spread and establishment
of endemic African AIDS in South Africa.
19
MONDAY, JUNE 1
IVIP59 T -Lymphocyte Subsets in HIV Infected Drug Abusers and Long-Term
AFsta iners
J.R. ROBERTSON'^, CAROL A. SK I DMORE* , M. STEEL**, D. BEATON**, --'-Edinburgh Drug
Addiction Study, Scotland, **Western General Hospital, Edinburgh, Scotland
A study group of HIV infected iVDA, unique in 2 ways. Firstly, we have
been able to pinpoint seroconversion dates, thereby excluding the possibility
of different subgroups with different lengths of seropos i t i v i ty . Secondly, the
group comprises some long-term abstainers who are antibody positive, thus it
has been possible to follow the clinical course of infection in both abstinent
and current IVDA. In infected IVDA the presumption is often that continued
use of drugs may increase the likelihood of progression to AIDS.
To determine the relationship of continued drug use to apparent disease
progression, as measured by T4/T3 cell ratio, 10 abstinent and 10 current drug
abusers had blood samples tested for T^/Tg ratio. Both groups had been sero-
positive for the same length of time.
Significant differences emerged in the ages of the two groups, the abstinent
group being older (p< .05, 18 df ) . This group also had a significantly
shorter length of heroin use (p< .005, 18 df ) . The T4/T3 cell counts were
not significantly different.
These results suggest that no advantage is shown in those stopping heroin
use, since in a comparable seropositive group abstinent from opiates
{including methadone) T^/Tg ratios continued to be unfavourable. The
provision of methadone for seropositive IVDA may be less appropriate than
reducing the risks to those who remain seronegative.
MR62
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MP60 Early Indications of Unidirectional Heterosexual Transmission of
AIDS in Botswana
WILLIAM D. QSEI, E. T. MAGANU, W. MANYENENG, R. K. VYAS, J. VAN DAM,
L. MAHLOANE et al., Ministry of Health, Gaborone, Botswana.
Botswana is situated south of the high prevalent regions of AIDS in Africa
but has identified only 7 cases in the past 2 years.
Transmission is presumed to be predominantly heterosexual.
23 sexual partners of these cases have been followed and tested. 211 in-
fectious diseases in-patients at 10 selected health facilities in the country
were also screened for HIV infection.
The majority of cases (85.7%) are females who also constituted 61.5% of the
positives among the health facility surveys. Approximately 62% of all known
HIV infected individuals are females.
3 females who had evidence of HIV infection. maintained one positive sexual
partner each and at least another who remained uninfected over the period.
In er.rly stages of AIDS in Botswana, it appears that males are more difficult
to be infected than females who are therefore at a higher risk in a hetero-
sexual relationship. This female preponderance is in excess of the sex dis-
tribution in the general population as well as the study population.
Differences in the anatomy and the physiology of the sexes and the varying
doses of the Human immune deficiency virus in semen and cervical secretions
have been given as some of the factors for this male to female transmission
in Botswana.
Definitive conclusions must await further follow-up.
MpCQ The Sydney AIDS Project: Factors Associated with Progession to
mr.ua . AIDS
BRETT TINDALL*, D. A. COOPER*#, J.BURCHAM*, B.DONOVAN**, T.BARNES**, R.PENNY*.
*NH&MRC Special Unit. in AIDS Epidemiology and Clinical Research, Sydney,
Australia. #St. Vincent's Hospital, Sydney, Australia. ** Private Practice.
In a prospective study of 996 homosexual men, 386 (38.8%) were HIV sero-
positive at enrolment. In 3 years, 32 of these seropositive men (8.3%) have
developed AIDS. Compared with seronegative subjects, seropositives were more
likely to have performed receptive or insertive anal or oral sex in the three
months prior to enrolment. Immunologically, seropositives had a significant
lower T4+ lymphocyte count and T4+:T8+ ratio and an increased T8+ lymphocyte
count, compared with seronegatives.
Seropositives who developed AIDS reported greater use of marijuana in the
previous 3 months than did seropositives who did not progress but the two
groups did not differ on other lifestyle variables. Splenomegaly and
hepatometaly were detected significantly more frequently as antecedent signs
in subjects who developed AIDS. The absolute T4+ lymphocyte count was the
most reliable antecedent indicator of development of AIDS. At enrolment (a
median of 8.5 months prior to diagnosis) subjects who developed AIDS had a
significantly lower T4+ lymphocyte count and T4+:T8+ ratio than did their
non-progressing counterparts.
Overall these findings support the role of the established risk factors for
the acquisition of HIV infection but have found no such co-factors for the
development of AIDS. This study emphasises the value of a low T4+ count as
the best measure of progression.
MP61 ^^ Infection in African Children with Sickle Cel] Anemia
BOSENGE N'GALY*, K. KAYEMBE**, J.M. MANN***, R.W. RYDER*,
H. MBESA**, H. FRANCIS* et al. , *Projet SIDA/Zaire, **University Hospital,
Kinshasa, *** CDC, Atlanta.
To assess the importance of transfusions and injections in the trans-
mission of HIV and to define the clinical spectrum of HIV infection in
children with sickle cell anemia (SCA), we studied 241 children with SCA
(aged 1-12 yrs; mean 6 years). We compared these patients ("124 boys, 117
girls) with 126 non-sickle cell (NSCA) children (64 girls, 62 boys) of the
same age. Thirteen SCA children were HIV(+) (5.4%) compared to 1 (0.8%) of
the NSCA group. Seropositivitv in the SCA group was associated with
increased lifetime numbers of transfusions [mean 5.8 in HIV(+) patients(P)
vs 3.4 in HIV(-)P] and the receipt of blood from paid donors (67% in HIV(+)P
vs 52% in HIV(-)P) but not with the number of injections during the last 5
years (mean 76.5 in HIV(+)P vs 78.7 in HIV(-)P. Among SCA children HIV(+),
patients were more likely than HIV(-) patients to present with failure to
thrive (62% vs 21%, p<.001), polyadenopathy (62% vs 37%, pc.05), weight loss
(38% vs 24%) or unexplained fever (23% vs 11%).
Transfusions in Africa appear to be a more important source of HIV
infection in patients with sickle cell disease than injections. The
pediatric spectrum of HIV infection in African sickle cell patients is
similar to the one described in African children without sickle cell disease.
MPfi4 Epidemiology of AIDS in Australia.
IVir.Ot BRUCE H. WHYTE*, A . J . DOBSON# , J. GOLD*, D.A.COOPER*. *NH&MRC
Special Unit in AIDS Epidemiology and Clinical Research, Sydney, Australia.
# University of Newcastle, NSW, Australia.
Since the first case of AIDS was diagnosed in Australia in late 1982 there
have been an additional 376 cases diagnosed including 14 women, of whom
200 have died. The majority, 88%, have been homosexual and bisexual men,
but 27 or 7% have been transfusion associated, 13 of them women. To the end
of 1986 there has been only one case resulting from intravenous drug usage,
although an additional twelve were homosexual/bisexual men who also used
intravenous drugs. Two cases have become infected as a result of heterosexual
intercourse.
The initial diagnosis of AIDS was an opportunistic infection in 74% of cases
and Kaposi's sarcoma in 18%. A further 3% were diagnosed with both
opportunistic infection and Kaposi's sarcoma. Non-Hodgkin's lymphoma was
the presenting disease in 5%.
A mathematical model based on a Poisson distribution was developed using
the numbers of cases among homosexual and bisexual men from 1982-1986 to
predict the future case load of AIDS. To those numbers, a constant figure
of ten cases annually was added to account for those cases belonging to
other groups. Using this model, we have predicted 500 new cases in 1988 and
1000 new cases in 1990. The cumulative total to the end of 1990 would be
3000 cases.
The epidemic of AIDS in Australia is following a similar pattern to that
found in other western countries, with greatly increased numbers predicted
in future years.
20
MONDAY, JUNE 1
MR65
Risk of AIDS after herpes zoster.
MR68
MADS MELBYE*, R.J. GROSSMAN**, J.J. GOEDERT***, R.J. BIGGAR***,
E. EYSTER****. *Institute of Cancer Research, Aarhus, Denmark,
** Private practice, New York, N.Y., *** National Cancer Institute
Bethesda, MD, **** Milton S. Hershey Medical Center, Pennsylvania.
All patients diagnosed with herpes zoster (N=112) between 1980
and mid-1986 in a closed internal medicine practice for homosexual
men in Central Manhattan were evaluated with respect to time of
eventual AIDS development or death. Using Kaplan-Meier survival
analysis, 22.8% (+/-5.3%) developed AIDS within 2 years after her-
pes zoster, and 45.5% (+/-11.1%) after 4 years. The longest obser-
vation period was 6 years, at which an estimated 72.8% of the men
had been diagnosed AIDS. Severity of the zoster (relative risk, RR
=4.6), the degree of pain (RR=3.4), and zoster of the cranial or
cervical dermatomes (RR=2.2) were all associated with a poor prog-
nosis. Other clinical conditions which additionally increased the
risk of AIDS included: oral thrush, oral hairy leukoplakia, amebi-
asis, and superficial (tinea) fungal infections. Oral thrush and
oral hairy leukoplakia manifestations were diagnosed an average of
1.2 and 1.1 years, respectively, after the diagnosis of herpes
zoster, making zoster an early indicator of an impaired immune sys-
tem. Among hemophiliacs, the period between the development of hu-
man immunodeficiency virus (HIV) antibodies and zoster ranged from
21 months to 88 months, with a median estimate of 56 months. Add-
ing the interval between HIV-seroconversion and zoster to the pos-
sible interval between zoster and AIDS, the risk of developing
AIDS after HIV-seroconversion must continue at least 10-15 years.
Classification of HIV Infection in the Third World
JEAN W. PAPE*, M-M. DESCHAMPS**, S. KELLIE*, R-I. VERDIER**,
W.D. JOHNSON*. Cornell Univ. Med. Coll. NY*, GHESKIO, Port-au-Prince, Haiti**.
405 patients were referred to our AIDS clinic in Port-au-Prince, Haiti from
July 1983 to June 1985 for diagnostic evaluations. HIV antibody (ijv3 p24, gp
120) was detected in 339 pts. (84%). Seropositive subjects were categorized
based on their initial clinical evaluation and recategorized 1 yr. later. The
signs and symptoms of patients in groups 2-5 were present for >1 month. Group 2
pts. had only prurigo. Group 4 had oral thrush alone (21) or with either tbc
(18), S. enteritis (5) or H. zoster (4). Group 6 met CDC criteria. During a 1 yr.
period 4/7 group 1 pts. developed thrush and 226/293 (77%) group 2-5 pts. died
or met AIDS criteria. The 66 HIV seronegative pts. initially evaluated had
other diagnoses (pul tbc, typhoid, malaria, giardiasis, etc). We conclude that
wgt. loss with either fever or diarrhea is the most common presentation of
AIDS and that prurigo is an early finding with a poor diagnosis. This classi-
fication defines the spectrum of HIV infection in Haiti.
Group Number of Patients (%)
Initial Evaluation
1 Asymptomatic
7
(2)
2 Prurigo
29
(9)
3 Adenopathy
7
(2)
4 Oral thrush
48
(14)
5 Weight loss and either
209
(62)
fever or diarrhea
6 AIDS
39
(11)
7 Dead
—
—
One Year Evaluation
(1)
3
7
1
36
27
211
54
(2)
(< 1)
(11)
(8)
(62)
(16)
MR 66 °=tf=}-irc«=pirBl fluid abnormalities in homaeexual/bisexual men with and
without neurcpsychiarric symptans.
justtn C. MCARTrlJR*, H. EARZADEGAN**, D.R. CDRNBLATH*, D.E. GRTEFTN*, R.T. JOHNSON*,
B.F. FOIK**, Tne Johns Hopkins University *SchoQl of Mediciiie arri ** School of
Hygiene and Public Health, Baltimore, MD, and the Multi-center AIDS Cohort Study
A longitudinal study of the neurcpsychiatric manifestations of human
iimunodeficiency virus (HIV) infection is underway within the MACS. 215
harosexual/bisexual men underwent reurcpsychiatric screening in Baltimore.
Cerebrospinal fluid (CSF) was obtained from 7 asymptomatic men who had become rECV-
seropositive during 30 months of observation (ASC) , and on 10 with najrr^sychiatric
symptoms, including 5 men seropositive > 30 months (SP) , 5 seroconverters (SC) .
CSF Findings
CSF pleocytosis (>5 WBC/cu itm)
Oligcclonal bands (>1)
Elevated IgG index (>0.8)
Positive HIV culture
Positive p24 antigen
CSF abnormalities are coanrxi in HIV-infected homosexual men, with or without
rieurqpsychiatric symptoms. The most cxnmai finding was the presence of oligcclonal
bards ard a lymphocytic pleocytosis. The most striking finding was the incidence of
abnormalities in asymptomatic seroconverters. Positive KB/ culture ard p24 antigen
were rarely detected, arri thus may be poor predictors for early brain involvement in
HIV infection. Serial observations in larger numbers of homosexual men will be
required to confirm this impression.
Symptcfliatic
Asymptomatic
Total
SP SC
ASC
(N=5) (N=6)
(N=7)
(N=17)
1 (20%) 3 (60%)
2 (29%)
6 (35%)
1 (20%) 3 (60%)
3 (43%)
7 (41%)
0 0
3 (43%)
3 (18%)
1 (20%) 0
1 (14%)
2 (12%)
0 1 (20%)
0
1 ( 6%)
MR 69 Kaposi's Sarcoma and AIDS in Haiti (1979-1986)
BERNARD LIAUTAUD*, J.W. PAPE**, M-M. DESCHAMPS* , R-I. VERDIER*, A.C.
LAROCHE*, F. THOMAS*, W.D. JOHNSON, JR.**, GHESKIO, Port-au-Prince, Haiti*,
Cornell University Medical College, N.Y. **.
We evaluated and treated 584 AIDS patients in Port-au-Prince, Haiti from June
1979 to December 1986. Kaposi's sarcoma (KS) was present in 53 patients (9%).
The percentage of AIDS patients with KS has decreased from 15% (1979-83) to 5%
(1985-86). KS lesions were the exclusive or predominant manifestation of AIDS
in 32/53 (60%) patients, while the other 21 (40%) patients presented with
opportunistic infections (01). KS lesions were disseminated in 60% of cases
with skin, lymph nodes, gastrointestinal tract and lungs as the common sites.
Male predominance was more marked for KS patients (92%) than for 01 patients
(72%). The annual percentage of female KS patients has been constant over time
while the percentage of female 01 patients increased from 14% to 28%. KS
patients were comparable to those with 01 in terms of age, socioeconomic
status, place of residence and risk factors. 15% of KS males and 20% of 01
males were bisexual, with other risk factors (blood transfusions, IV drug
abuse) noted in 18% and 11%, respectively. Pruritic skin lesions (prurigo)
were present in 23% of KS and 51% of 01 patients. HIV antibody was detected in
96% of KS patients tested and also in 83% of their heterosexual sex partners.
Kaposi's sarcoma in Haiti is clearly associated with HIV infection, is
decreasing in prevalence, and is not associated with any particular risk
factors.
MR67 * case °^ Acquired Immune Deficiency Syndrome without the Recognised
Risk Factors
PAUL GRINT*. M. RADEMAKER*. M.B. McEVO?* *St Bartholomews Hospital, London,
**PHLS Communicable Disease Surveillance Centre, Colindale, London.
Whilst the modes of transmission of HIV infection are now well established,
it is important to retain a clinical awareness of the possibility of this
infection in patients without apparent exposure to the recognized risk factors.
We report two cases of AIDS, apparently without the usual exposure factors,
in whom a temporal association was detected after detailed epidemiological
investigation.
The index case -a 45 yr old housewife, who developed Pneumocystis carinii
pneumonia following a severe herpes zoster infection, and was shown to be
anti-HIV positive. Three years prior to diagnosis she had been investigated
for "glandular fever" and subsequent generalised lymphadenopathy , but no
diagnosis was made. Detailed social history revealed no exposure to the
relevant risk factors. However, three months prior to the onset of the "gland-
ular fever", she had provided terminal home nursing care for a 33 yr old Afric-
an man, who died from an undiagnosed encephalitis. At this time she had un-
covered skin lesions on her hands. Review of post mortem pathology specimens
allowed a retrospective diagnosis of AIDS with cerebral toxoplasmosis to be
made for the African man.
The type of home nursing care given by index case, was quite different from
that normally provided by health care workers with the training and facilities
to prevent the spread of infection.
Prospective Study of AIDS in Hemophiliacs with Elevated Interferon
Alpha Levels
The NCI Multicenter Hemophilia-
MR70
M.E. EYSTER* , O.T. PREBLE**, J.J. Goedert*
Related AIDS Study Group, *The Pennsylvania State University College of
Medicine, Hershey, PA, **The Uniformed Services University of Health Sciences,
and ***The National Cancer Institute, Bethesda, MD.
We have previously shown that an acid labile form of alpha interferon (IFN)
was persistently elevated in the sera of 3 hemophiliacs prior to the onset of
AIDS. The prevalence and predictive value of serum IFN quantitated by a
semimicrobiological assay (NEJM 1983: 309, 583-586) was assessed in 469 HIV
seropositive and 346 seronegative hemophiliacs. Results at entry were as
follows :
IFN Of the 43 HIV pos. IFN pos. (*8 IU) hemophiliacs,
<8 IU -8 IU 7 had AIDS and 11 developed AIDS within 16 months
(42%). Four more (9%) had AIDS-related symptoms.
- 315 31 (9%) Twenty-one (49%) have remained well up to two
HIV years. Four additional patients converted from IFN
+ 426 43 (10%) neg. to pos. prior to the development of AIDS
during the study. In a subcohort of 84 hemo-
philiacs with HIV seroconversion dates, very high IFN levels (-20 IU) predicted
AIDS up to 1 year before diagnosis, even when controlled for duration of HIV
infection (p -.004). In conclusion, the prevalence of IFN in HIV seropositive
hemophiliacs was 10%. At least 42% (18/43) had AIDS (16%) or preAIDS (26%).
Persistently elevated IFN, especially high levels, usually heralded the onset
of AIDS in one year. The role of IFN in the pathogenesis of AIDS has not yet
been determined. However, its predictive value may be complementary to
quantitation of T cell subsets.
21
MONDAY, JUNE 1
MR71 Human Immunodeficiency Virus (HI V J Infection in Spouses of HIV Sero-
positive Active Duty Navy and Marine Corps Personnel
MARGAN J. CHANG, T.R. ZAJDOWICZ, Naval Hospital Portsmouth, Portsmouth, Va.
The United States Navy is conducting a Navy-wide HIV screening program of
aH active duty personnel. All personnel found to be HIV seropositive are
referred to one of four major evaluation centers. To date, 324 HIV positive
active duty personnel have been evaluated at Naval Hospital Portsmouth.
Thirty-three percent of these individuals are married. Evaluation of these
dependent spouses was offered to all HIV seropositive personnel. No spouse
in the immediate geographic area refused evaluation. Thirty-four spouses
have been evaluated. Ninety-four percent (32/34) were female; 6% (2/34) were
male. Mean age of evaluated spouses was 27 years with a range from 16-42 yrs.
Forty-four percent (15/34) were white, 41% (14/34) were black, 9% (3/34) were
Oriental, and 6% (2/34) were Hispanic. Risk factors for HIV infection in
spouses included being the steady sexual partner of an HIV positive spouse
(85%), being the recipient of multiple blood transfusions (9%), and being bi-
sexual (3%). Thirty-five percent (12/34) of all spouses evaluated were HIV
seropositive. Among spouses where the only risk factor was an HIV seroposi-
tive spouse, the seropositivity rate was 29% (8/28). Among 32 female spouses
evaluated, three (9%) had AIDS or ARC. Nineteen percent (6) of female
spouses were pregnant at the time of evaluation. One pregnant woman was HIV
seropositive. Two HIV seropositive children have been detected.
Dependent spouses of HIV seropositive active duty personnel are at signi-
ficant risk for acquisition of HIV infection. This population is young, fe-
male, and actively engaged in child bearing. Evaluation and counseling for
spouses and children are essential to any large-scale HIV infection
screening program.
MP74 Analysis of the AIDS epidemic in The Netherlands in comparison with
data from the San Francisco CDC study cohort
HANS A.M. VAN DRUTEN*, TH. DE BOO*, J.C. JAGER**, S.H. HEISTERKAMP** , R.A.
COUTINHO***, E.J. RUITENBERG**, et al. ,*University Nijmegen (MSA), The Nether-
lands, **National Institute of Public Health and Environmental Hygiene (RIVM) ,
Bilthoven, ***Municipal Health Service , Amsterdam
Using data from The Netherlands and the San Francisco CDC study cohort Mathe-
matical models were formulated to estimate a) the annual effective contact rate
i.e. the average number of sexual contacts per person per year that results in
transmission of HIV and b) the number of homosexual men already infected from
the cumulative number of persons with AIDS.
If there is a delay of 3 years, 20,000 homosexual are assumd to be at risk in
The Netherlands in the initial stage of the epidemic and the annual effective
contact rate is estimated to have a value between 1.0 and 1.2. The width of the
interval depends on the initial growth rate of the epidemic and the average du-
ration of the infectious period in persons infected with HIV. The results indi-
cate that the probability of transmission of HIV per sexual contact is low.
Given 200 homosexuals with full blown AIDS in The Netherlands, the number al-
ready infected adopts a value between 5,000 and 15,000.
The models were also used to predict the long term course of the epidemic.
The results indicate that in the absence of prevention HIV infection will be-
come endemic in high risk homosexual communities with a prevalence larger than
70%. Furthermore an efficacy of e.g. 50% in the reduction of the annual effec-
tive contact rate probably has a limited effect; one should aim at a 90% effi-
cacy (or more) .
The mathematical models and the simulation approach are helpful in predicting
the impact of intervention measures.
MP72 Serologic Evidence for Infection by HIV-2 in Guinea Bissau in 1980.
PATRICIA N. FULTZ*, W.M. SWITZER*, C.A. SCHABLE*, R.C. DESROSIERS** ,
D. SILVA**, and J.B. MCCORMICK***, *AIDS Program and ***Division of Viral Di-
seases, Center for Infectious Diseases, Centers for Disease Control, Atlanta,
GA, **New England Regional Primate Research Center, Harvard Medical School,
Southborough, MA.
Human immunodeficiency virus type 2 (HIV-2, originally called LAV-2) was re-
cently isolated from AIDS patients from the West African countries of Cape Verde
and Guinea Bissau. HIV-2 is more closely related to the simian immunodeficiency
viruses (SIV) than to HIV-1 both serologically and by nucleic acid hybridization.
To determine the past prevalence of HIV-2 in some areas of West Africa, we test-
ed 440 serum samples collected in Guinea Bissau in 1980. The samples originally
were collected to test for the prevalence of antibodies to Lassa virus in adults
living in rural areas. We first screened the serum for antibodies to an HIV-
like virus by ELISA using purified SIVmac as antigen. A large proportion (30%)
gave OD readings greater than 0.5, which was peculiar to human serum because a
large number of monkey serum (195 of 214) from Africa gave OD readings less than
0.2 in the same SIVmac ELISA. All of the human samples with OD readings greater
than 0.9 (28) were tested by immunoblot and immunofluorescence assays for anti-
bodies to SIV/SMM, HIV-2, and HIV-1. Five human serum samples were repeatedly
reactive by all assays to both HIV-2 and SIV/SMM. Antibodies to gag, env, and
pol gene products of HIV-2 and SIV/SMM were detected on immunoblots. Five of
440 human sera were positive for antibodies to HIV-1 using the Abbott HTLV-III
EIA kit, but none could be confirmed as true positives by immunofluorescence
and immunoblot assays. Thus, in 1980, 1.1% (5 of 440) of a random sample of
persons in Guinea Bissau had been exposed to a virus highly related to HIV-2
and SIV/SMM, but there was no evidence of infection by HIV-1.
MD7C; Exposure to the AIDS virus through articifial insemination in a
population of lesbians in California. CHERI PIES, MSW, MPH;
BRENDA ESKENA2I, Ph.D; AMANDA NEWSTETTER, MSW.; CHRISTY SHEPARD, R.N.
University of California, Berkeley, CA, U.S.A.
In 1985, Australian investigators reported that four women who were artifi-
cially inseminated tested positive for the AIDS antibody. All four women had
received semen from the same donor who was later found to be antibody positive.
None of the women had any other risk factors for AIDS. The purpose of the
present investigation is to examine in a more comprehensive study the trans-
mission of the AIDS virus through artificial insemination. We have chosen to
study transmission in lesbian women because lesbians do not, as a rule, engage
in heterosexual intercourse and therefore , we could eliminate the contribution
of specific sexual practices. In addition, lesbians often select gay men as
donors and the incidence of AIDS among the gay population of California is
very high.
In a pilot study of 48 lesbians in San Francisco, we found that all tested
negative for antibody to the AIDS virus. This study was expanded to include
lesbians across the state. Each woman who agrees to participate is tested for
antibody to the AIDS virus and completes a questionnaire designed to elicit
information about her donor insemination history (vaginal vs intrauterine
insemination, fresh vs frozen semen, antibody status of donor, health status
and sexual orientation of the donor, etc.) and her sexual, health, and repro-
ductive history. As of January 1987, 20 lesbians have participated. These
women reported obtaining semen from 14 homosexual , 10 heterosexual, and 3
bisexual donors (5 addtional donors were of unknown orientation). One homo-
sexual donor has a known positive antibody status and another died of AIDS a
year after donating semen. To date, all women have been seronegative. We
will report on an update of this study.
MP73 Absence of Association between HIV Seropositivity and Plasmodium
falciparum Malaria in Kinshasa, Zaire.
PHUC NGUYEN-DINH*, A. E. GREENBERG*, R. W. RYDER******, J. M. MANN**»***,
N. KAB0TE****, H. FRANCIS** »*****, et al., * Malaria Branch, Centers for
Disease Control, Atlanta, GA, ** Projet SIDA, Ministry of Health and Social
Affairs, Kinshasa, Zaire, *** AIDS Program, Centers for Disease Control,
Atlanta, GA, **** Mama Yemo Hospital, Kinshasa, Zaire, ***** Laboratory of
Immunoregulation, National Institutes of Health, Bethesda, MD.
Because Plasmodium falciparum malaria and HIV Infection coexist in several
areas of Africa, the relationship between these two entities was investigated
at the Mama Yemo Hospital (MYH) in Kinshasa, Zaire, between July and December
1986. Among 333 children evaluated at MYH, the HIV seropositivity rate in
children with £. falciparum malaria (1.2%) was not significantly different
from that in asymptomatic, healthy children (0.6%). Among 1046 children
presenting at MYH for various medical complaints, no significant difference
was detected between the HIV seropositivity rates in 540 children infected
with P. falciparum (2.8%) and in 506 uninfected children (4.9%). Among 1156
healthy adult MYH employees, a malaria slide posltivity rate of 6.2% and an
HIV seropositivity rate of 6.0% were found, with no association detected
between these two variables. In an ongoing study In pregnant women delivering
at MYH, the first 195 patients had a P_. falciparum infection rate of 19% and
an HIV seropositivity rate of 7.2%, with no association detectable. This
overall absence of association Indicates that P_. falciparum does not act as an
important opportunistic agent in individuals infected with HIV in Kinshasa.
MP76 Low ^sk °f Anti-HIV Seroconversion in Female Sexual Partners of
Haemophiliacs and their Children.
E.J. MILLER, R.R. MILLER, E. GOLDMAN, P.D. GRIFFITHS, P.B.A. KERNQFF
Departments of Haematology and Virology, Royal Free Hospital, London, UK.
The objectives of this study were to quantitate risks of HIV transmission
from haemophiliacs to their sexual partners and children; and to identify risk
factors for such transmission. A detailed questionnaire was used to assess
frequency and modes of sexual contact, contraceptive practice, and other risk
factors. The presence of anti-HIV, measured by a competitive ELISA assay, was
used as a marker of exposure to the virus. 100 contacts were studied. Contacts
of 45 seropositive patients (median period of seropositivity 3 yrs., range
3 mo - 6 yrs) comprised: 30 regular female sexual partners; 21 parents giving
clotting factor concentrates to their children; and 10 children aged less than
10 yrs of haemophilic fathers. Contacts of the 28 seronegative patients were
similarly distributed. Only one contact was found to be seropositive, giving
a 3.3?o prevalence rate in the sexual partners of seropositive patients. Risk
factor analysis showed nothing to distinguish this couple from other members
of the group except that both were abusers of i.v. heroin. Subsequently,
however, the man died from zoster pneumonia, the only patient in the study to
die from possible HIV related illness. At the time the study started, when
all the index patients but few of their sexual partners had been formally
counselled, only 23% of the 'seropositive' couples regularly used barrier
methods of contraception, compared with 1% in the seropositive group. Following
repeated counselling of both partners, the proportion using barrier methods
increased, but still remained a minority. All 5 children who must have been
conceived at a time when their fathers were seropositive remain well and
anti-HIV seronegative.
22
MONDAY, JUNE 1
MR77 Relationship between P. falciparum malaria and HIV seropositivity
at Ndola, Zambia.
OSCAR 0. SIMOOYA, R.M. MWENDAPOLE, S. SIZIYA and A.F. FLEMING, Tropical
Diseases Research Centre , Ndola , Zambia -
One hundred and seventy-two patients presented with symptoms suggestive
of malaria in January 1987, at the height of the transmission season.
Patients were screened for (i) anti-HIV using the Wellcozyme test,
(ii) malaria parasitaemia, and (iii) specific antibodies against P. falciparum
using immunofluorescence (IFA) test, significant titres being defined as 1:80
or greater. Two patients with P.malariae have been excluded from analysis.
Sixty-seven (39%) of the patients had P. falciparum and 28 (16%) were anti-
HIV positive. Of the 103 patients without malaria, 20 (19%) were anti-HIV
positive compared to only 8 (12%) of those with malaria (X2 = 1.15, p = 0.28).
Sixty-three (9*t%) of the patients with parasitaemia and 74 (72%) of those
without parasitaemia had significant IFA titre. No significant relationships
were found in the parasite positive or parasite negative groups between
antimalarial IFA and anti-HIV.
These data do not support the hypothesis that HIV infection increases the
risk of clinical P. falciparum malaria.
MP80 Seroepidemiologic evidence of HIV2 infection in Mali and other
West African countries and of its heterosexual transmission.
JEAN-MARC ALLAIRE+, S. CHAMARET+, S. FERRIS+, M. BARBIER++, A. GIND0+++,
L. M0NTAGNIER+, et al. ,+ Institut Pasteur, Unite d'Oncologie Virale, ++ Hop.
International de l'Universite de Paris, France, +++ Hop. Gabriel Toure, Bamako,
Mali.
HIV2 has been isolated recently from AIDS patients and healthy subjects from
West Africa. It differs from HIVI by antigenicity and molecular sequences.
Sera from 9 patients hospitalized in Bamako for "slim disease" were screened
for HIVI and HIV2 antibodies (Ab) by indirect immunofluorescence (IF) and
radioimmunoprecipitation assays (RIPA) . One patient, a zairian, was positive
for both HIVI and HIV2, and 3 for HIV2. One of the latter was hospitalized sub-
sequently in Paris presenting with major weight loss, chronic diarrhea, esopha-
geal candidiasis and infection with several opportunistic intestinal pathogens;
he died a few months later. A study of 43 family members revealed that his wife
was healthy but seropositive for HIV2, suggesting that HIV2 can be transmitted
heterosexually, A stepmother was also Ab-positive but all other family members
including his 3 children were Ab-negative.
This evidence of HIV2 infection in Mali prompted a wider study to determine
the prevalence of Ab to HIVI and HIV2 in 600 sera selected randomly from West
African students living in Paris. All sera were screened by IF ; equivocal
results were confirmed by RIPA. To date, screening of 1 00 sera obtained in 1984
revealed no Ab ; among 100 sera from 1986, one male was positive for HI^'I and
another for HIV2.
The complete results of these serologic studies will be presented.
MP78 Transmission of Human Immunodeficiency Virus from Hemophiliacs to
their Sexual Partners: Role of Parenteral Exposures
LYNN SMILEY*, G.C. WHITE II*, G. MACIK*, P. BECHERER*, K.J. WEINHOLD**, T.J.
MATTHEWS"", et al. *University of North Carolina, Chapel Hill and ** Duke
University Medical Center, Durham, N.C.
To evaluate the risk of transmission of human Immunodeficiency virus (HIV)
from hemophiliacs to their female sexual partners (SP), 31 infected hemo-
philiacs and their SP were studied. One man with 2 SP was counted as two
separate couples. HIV infection determined by Western blotting and/or virus
isolation was detected in 5 SP (15.621) of 32 HIV-infected hemophiliacs. Three
of the 32 hemophiliacs were intravenous drug abusers (IVDA). The 2 SP of 2
hemophiliac IVDA had HIV Infection (100%), whereas the third couple, which
included a nonlVDA sexual partner , showed no HIV transmission. Confidential ,
coded questionnaires were administered to 18 HIV-infected hemophiliacs and
their SP. Parameters examined included history of needlestick injuries while
the SP assisted in clotting factor treatments, receipt of any transfusions by
the SP, Intravenous drug abuse, condom usage, oral or anal sex, history of
vaginal infections, and monthly frequency of intercourse (since 1981). This
cohort excluded any IVDA. Of the 18 SP at risk, there was HIV transmission to
three ( 15%). Two of these couples reported no use of condoms. However, the
couple which did use condoms regularly reported 8 needlestick injuries. Seven
of the 15 uninfected sexual partners of HIV-infected hemophiliacs reported
no usage of condoms. There was one reported needlestick Injury In one SP In
this group. In addition to heterosexual transmission, these data indicate
that parenteral exposures are a potentially important risk factor among SP
of HIV-infected hemophiliacs. Also shown is the inconsistent use of barrier
contraceptives among couples at risk for heterosexual transmission of HIV.
MR81 Surveillance of Geographic Spread of HIV Infection
LYTT I. GARDNER, J.F. BRUNDAGE, R.N. MILLER,
D.S. BURKE, J.R. BUNIN
Walter Reed Army Institute of Research, Washington, D.C., 20307
The U.S. HIV epidemic began in a few circumscribed urban centers. We
examined the first year of data from screening civilian applicants to U.S.
military service to determine geographic spread of infection. A
"geographically weighted prevalence" (GWP) was calculated for each county (a
function of its first six months' crude county prevalence (CCP) and those of
contiguous counties) . We hypothesized that the GWP would predict subsequent
county prevalences better than prior CCP alone, if county prevalences are
influenced by their neighbors' prevalence. To test this hypothesis, we
examined a subset of 48 eastern U.S. counties. Data from these counties
revealed the following: For black applicants, the first six months' CCP vs.
second six months* CCP, correlation^. 10 (p=.50); GWP vs. second six months'
CCP, correlation^. 41 (p=.005). For white applicants, the first six months'
CCP vs. second six months' CCP, correlation^. 20 (p=.17); GWP vs. second six
months' CCP, correlation^. 34 (p=.02) . The hypothesis of geographic spread
from high prevalence areas into low prevalence areas is supported strongly for
the black applicant population, but less convincingly for the white applicant
population. Maps of the eastern U.S. displaying CCPs for the first, second
and third six month periods, and GWPs, reinforce statistical criteria on which
the conclusions are based.
MP79 HIVI and HI V2 infection in a french cohort of homosexual men, in
Paris, t . RuuZlOUx, D. BuCQufI, J>. MeTTETAL. J.F, DElASnEau, A.
MESSIAH and AIDES-MEDECINS. Laboratoire de Microbiologic, Hopital Necker,
Diagnostics Pasteur, Association AIDES-Paris, France.
A cohort has been composed in order to analyse several risks factors in
sexual practices among homosexual men in Paris (France). All subjects are
consultants of general practitioners and are asymptomatic. They will be follo-
wed up for a minimum of three years on clinical, immunological and virological
parameters. We present virological results on the first hundred included sub-
jects. The sera were tested by ELISA HIVI and HIV2 (Diagnostics PASTEUR) (DP).
All positive results were confirmed by Western Blot analysis HIVI and HI V2
(DP) : 34 % sera were strongly positive for HIVI, 1 % sera were positive for
HIV2 (confirmed by RIPA-HIV2 (Pr. MONTAGNIER) ) . This subject is malian and has
been living in France for ten years. An interesting point is the revelation of
only 6 ELISA HIV2 positive sera among the 34 HIVI positive sera {this raised
the question of peculiar cross reaction, or double infection or eventually
intermediary virus) .
Moreover, the detection of HIVI antigen has been performed by antigen-
capture (DP). Only two patients are strongly HIVI antigen positive (both of
them are AB HIVI positive). The specificity of these two positive results has
been confirmed by neutralising reactions. The two subjects are asymptomatic so
far and their follow-up will be informative. These two sera were also positive
with HIVI Ag test from ABBOTT Lab.
These preliminary results show a low prevalence of HIV2 infection compared
to HIVI but raise the question of the spreading of HIV2 among homosexual men
in Paris.
MDQO Transmission of HIV to portners of Seropositive Heterosexuals from
Africa.
H.TAELMAN, L.BONNEUX, P. CORNET, G.van der GROEN, P.PIOT. Institute of Tropi-
cal Medicine, Antwerp, Belgium; Medical Center, Ministry of Foreign Affairs,
Brussels, Belgium.
Heterosexual transmission of HIV among individuals originating from or having
resided for prolonged period of time in Africa was evaluated.
Thirty-eight spouses and/or regular portners of 35 HIV-seropositive hetero-
sexual males (18 Afr.,17 Eur.) and 10 spouses and/or regular partners of 10
HIV-seropositive heterosexual females (9 Afr.,1 Eur.) were tested for HIV-
ontibodies using ELISA and IF or Western-blot methods.
All the spouses and portners had their medical history including sex life
habits recorded and had a physical examination.
Overall seropositivity among the female partners was 73% (28/38) ond 40%
(4/10) omong the male partners.
HIV cultures carried out in 7 male and 6 female seronegative partners were
positive in 3 ond 2 respectively.
Overall HIV infection rate was thus 81% among the female partners and 60%
omong the male partners. Of the female partners, 3 had a history of promiscuous
heterosexual activity, 6 had < than 5 partners, and 29 were monogamous with no
other risk than heterosexual activity. Evidence for femole to mole tronsmission
was obtained by primoinfection in 2 cases, monogamy in 1 cose ond by positive
HIV culture in o seronegative male who had recent sexual contacts with o sero-
positive female.
Our data suggest that to be the spouse or the regular partner of on infected
heterosexual individual is a major risk factor for acquiring HIV infection.
HIV transmission rate in this study was significantly higher than rotes found
in the group of heterosexual hemophiliacs ond transfusion recipients.
23
MONDAY, JUNE 1
MDOO dIV Infection in Sexually Active Heterosexual Adults
Attending a New York City STD Clinic.
ALAN K. LIFSUN**, R.L. STONEBURNER* , M.A. CHIASSON*, D.S. HILDEBRANDT* ,
S. SCHULTZ*. H.W. JAFFE.** *New York City Department of Health, New York,
NY; **aIDS Program, Centers for Disease Control, Atlanta, Ceorgia
To evaluate heterosexual transmission of HIV among sexually active
persons, patients attending a sexually transmitted disease (STD) clinic in
New York City were enrolled in an ongoing case-control study that included
serologic testing for HIV antibody, hepatitis B, and syphilis and an
interview about sexual practices and known risk factors for HIV infection.
From December 1, iyd6, through January 21, 1987, 64 men and 25 women were
enrolled (72Z black, 13% Hispanic and 12% white; median age = 27 yrs;
current enrollment = 60-80 patients /month) . Antibody to HIV was present in 2
of 4 homosexual men, 5 of 11 bisexual men, and 6 of 9 heterosexual
intravenous drug abusers (IVDA). None of 65 heterosexual non-IVDA had HIV
antibody, including 10 persons (5 women and 5 men) who had sexual contact
with an IVDA. The remaining 55 heterosexual non-IVDA had a median of 15
different sexual partners since 1978; 41 (75%) had a history of at least 1
previous STD, 16 (29%) had engaged in rectal intercourse, 36 (65%) never or
rarely used condoms, and 15/38 (39%) men reported sexual contact with a
female prostitute. In the city with the largest number of heterosexual AIDS
patients in the United States , these preliminary results sugges t a low
prevalence of HIV infection among sexually active Heterosexual adults who
are not IVDA.
MP86 Natural History of Immune Function in HIV Infected Hemophiliacs.
JOHN L^_ SULLIVAN , D.B. BRETTLER, R.A. SCHORR, S.M. BAKER,
D.L. WILLITTS, P.H. LEVINE, University of Mass. Medical Ctr. and Worcester
Memorial Hospital, Worcester, Massachusetts, USA.
As part of a prospective study of immune function following human
immunodeficiency virus (HIV) infection in hemophiliacs, 93 hemophiliacs (9
seronegative, 11 seroconverters and 72 seropositive) have been followed over a
4 year period.
MEAN DATA FROM k YEAR OF STUDY SEROPOSITIVE AND SERONEGATIVE HEMOPHILIACS
Year 1 ,s Year 2 Year 3 Year k
N T helper" PWM'C'' T helper PWM T helper PWM T helper PWM
Normal Controls 30 928 100 995 100 972 100 1010 100
Seronegatives
Seroconverters
Seropo
itives
72
1228
95*.
740
45
11A1
849
727
1065
670
589
72
40
1062
415
519
38
=cells/ul; =%control counts per minute
Seroconversion in 11 of 93 occurred between year 1 and 2 of the study. HIV
infected individuals have shown a progressive decline in T helper cell numbers
and function as measured by pokeweed mitogen stimulation. Recent
seroconversion (within 2 years) following HIV infection is associated with
significant (p<.05) loss of T helper cells. One-third (33%) of our total
seropositive hemophiliac population has shown progressive decline of T helper
cells to 400/ul or less during a maximal exposure period of 4-7 years. These
data strongly support a high rate of progressive immunologic attrition in HIV
infected hemophiliacs.
MPfid Human Immunodeficiency Virus Infection in Patients with
Hepatitis B. Virus and Hepatitis Delta Virus Infections in
Los Angeles, 1977-1985.
KEVIN M. DE COCK, J.C. NILAND, H.P. LU, V. EDWARDS, C. SHRIVER, J.W. MOSLEY,
et. al. University of Southern California School of Medicine, Los Angeles,
CA.
Stored sera from 723 patients with acute and 228 with chronic hepatitis B
seen in Los Angeles between 1977 and 1985 were tested for antibody to human
immunodeficiency virus ( anti-HIV) . We first detected anti-HIV in homosexual
men in 1979 and in intravenous ( iv) drug users in 1981. For acute hepatitis
B, the seroprevalence of anti-HIV in homosexuals ranged from 14-33X, with no
significant change from 1980-1985; seroprevalence rates in heterosexuals,
including iv drug users , remained under 5%. Age stratified prevalence rates
were higher in homosexuals and iv drug users with chronic than with acute
hepatitis, and in homosexuals compared to non-homosexual subj ects . In
chronic hepatitis B, anti-HIV seroprevalence reached 50% in homosexual men
in 1983 and 30% in iv drug users in 1985. A significant association existed
between infection with HIV and hepatitis delta virus in homosexual men but
not in iv drug users. Anti-HIV seroconversion rates in homosexuals with
chronic hepatitis B were 22% in 1983 and 8% in 1985. Increased frequency of
HIV infection in chronic hepatitis B probably reflects more extensive
exposure . Our findings suggest that HIV transmission has reduced in recent
years in homosexual men, in whom delta hepatitis and HIV infection share
common risk factors.
NIP87 Serum HIV Antigen (HIV-Ag) as a Predictor of Progression to AIDS and
ARC in Homosexual Men
DENNIS OSMOND*, R. CHAISSON*, M. LEUTHER**, JP ALLAIN**, AR. MOSS*, *UCSF, San
Francisco, CA, and **Abbott Laboratories, USA
To test the presence of serum HIV-Ag as a predictor of subsequent disease,
we studied 30 initially healthy anti-HIV seropositive homosexual men undergoing
prospective study for two years. Ten subjects had less than 400/mm3 T-helper
cells at entry or at followup (Group 1). Ten subjects had greater than 600/mm3
T-helper cells at baseline and at followup (Group 2); and ten subjects had less
than 600/mm3 T-helper cells at baseline but had a net gain of 200 T-helper
cells at followup (Group 3). HIV-Ag was detected in sera using the Abbott sand-
wich enzyme immunoassay for HIV p24. HIV-Ag was present in 6 subjects, all in
Group 1. 6 of 6 HIV-Ag positive subjects developed ARC and 4 subsequently dev-
eloped AIDS. 1 subject (from Group 3) of 24 HIV-Ag negative subjects developed
ARC (p<0.0001). The remaining 23 subjects remained healthy for the entire
period of the study. 4 of the 6 with Ag positive specimens were positive at
baseline and followup (3 AIDS, 1 ARC); 1 at baseline only (AIDS); and 1 at
followup only (ARC). The 4 subjects developing AIDS were diagnosed from 26 to
32 months after the first HIV-Ag positive serum specimen. The presence of HIV
antigen in serum, as detected by this assay, is highly predictive of develop-
ment of ARC or AIDS, and may be detected up to 32 months prior to progression.
Supported by a grant from the Universitywide Task Force on AIDS.
MDOC HIV Screening in the High Risk Obstetric Population and Infant Sero-
logic Analysis
JOHN P. JOHNSON*, L. ALGER, P. NAIR, S. WATKINS, K. JETT, S. ALEXANDER;
University of Maryland School of Medicine, Dept. of Pediatrics and the Dept.
of Obstetrics, Baltimore, MD . and Biotech Research Laboratories, Rockville, MD .
Voluntary screening by a commercially available Enzyme Linked Immunoabsorbant
Assay (ELISA) for seropositivity to Human Immunodeficiency Virus (HIV) was
conducted in an inner city obstetric population over a six month period. Of
one hundred fifteen women who identified themselves to be at risk for HIV in-
fection and consented to testing, thirty-four, i.e., 29%, were confirmed sero-
positive. Most of the women (90%) had used intravenous drugs, the remainder
were sexual partners of IV drug users.
Ten children born to these women have been followed for six months or greater.
Of these, five children can be demonstrated to be endogenous seropositives:
Western Blot analysis revealed two children who developed IgM against gp41 or
p55 by 4 months of age and one child who developed new IgG bands against p55
and p66 at three months of age. Standard ELISA testing documented two child-
ren who lost and then reacquired seropositivity by nine months of age.
Three of the five children with serologic evidence of infection have clini-
cal disease: one has marked lymphadenopathy, one has AIDS Related Complex and
one has AIDS. The two children who developed IgM against HIV show no symptoms.
Neonatal serologic analysis of antibody to HIV has allowed identification of
those infants producing endogenous antibody, thereby permitting earlier
diagnosis and treatment of infected children. These results support earlier
evidence for approximately 50% perinatal transmission rate. The possibility
that early IgM synthesis against HIV may reduce the development of clinical
disease is suggested.
MR88 Association of Donor Characteristics with Transmission of HIV
Infection to Recipients
JOYCE C. NILAND*, THE TRANSFUSION SAFETY STUDY GROUP* **, *USC School of Medi-
cine, Los Angeles, CA, **other participating institutions.
By testing sera stored prior to the availability of routine anti-HIV screen-
ing, a national, multicenter study has identified 91 recipients transfused
with anti-HIV(+) components. Among these 81 (89%) are anti-HIV(+) and 10 (11%)
are anti-HIV(-). In 15 instances, 2 recipients in the study received blood
from the same donor. In 13 pairs, both recipients are anti-HIV(+). In 1 case,
one of the recipients became anti-HIV(+) and the other is anti-HIV(-); the
donor was a 19 yr. old male. In the last pair, both recipients are anti-
HIV(-); the donor was a 26 yr. old bisexual male.
In comparing characteristics of donors who transmitted infection (Group I) to
those who did not (Group II), similar sex and age distributions were seen.
Groups I and II also had similar mean enzyme immunoassay (EIA) absorbances
(0.99 vs 1.16, NS) and ranges. Group II had higher percentages with P150 (29%
vs. 5%, p=.10) and P120 (43% vs. 17%, p=. 12) on immunoblot (IB). All donors had
GP41 and P25 on radioimmunoprecipitation (RIP) and P24 on IB, and all but 3
donors in Group I had P41 on IB. A somewhat greater percent of Group I donors
came from a high AIDS risk area (53% vs 29%, NS). Among 25 Group I and 5 Group
II donors enrolled for further followup, 79% and 60% respectively are homosex-
ual or bisexual males. 93% of the Group I donors are free from clinical signs
of AIDS 1-2 yrs. post-donation, although 63% have T4/T8 ratios < 1. Thus, no
clear relationship between the characteristics of the donor and transmission of
HIV infection to the recipient can be seen. (Supported by Contract Nos. N01-
HB-4-7002 and N01-HB-4-7003 of the National Heart, Lung and Blood Institute.)
24
MONDAY, JUNE 1
MR89
GEORGE..
A. BARR
Hos pita
Ga. **•*
En«?l and
To e
couples
and HIV
seropos
partner
sero pos
se rone a;
Of t
were co
d 1 scord
the di s
ne ga 1 1 v
None
six mon
l nteres
e nga ge d
( 72X re
time pe
nonbeha
suscept
HI
Ev
£-__SEA
Y*. G
Is. Bo
Fe nwa y
Deaco
va lua t
we
serop
l ti vi t
s of A
l t l ve
at l ves
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ncorda
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corda n
e part
of th
th fol
t beca
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abilit
V Iran
i de nee
GE_LI I
LAMBA
s t on.
Commu
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e the
t udi ed
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v rate
RC wer
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use 27
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The se
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*, A.
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Ma
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artner
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s of A
. part
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of Transitu ss l o
AYERaaa, J GROOP
epartment of Hea
l sease Control .
Boston. Ma. A A A
on of HI V among
s of people with
healthy men. HI
IDS were 62% ( 16
ners of healthy
tners of healthy
ners:
n.
MAN****,
lth and
Atlanta.
A Ne w
homose xua 1
AIDS. ARC
V
/ 2b) .
7%) ,
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hat
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53(33
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ec t ed .
1 1 ve p
( ( 2
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s mi s s i
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%) were
each pa
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turned
This l
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ng this
addi tional
MR92 Relationships Between Decline in CD4 Lymphocytes and Other
Variables Among 1828 Seropositive Gay Men.
A Munoz, V Carey, BF Polk, A Saah, J Phair, L Kingsley, J Fahey, for the
Multicenter AIDS Cohort Study (MACS), NIH, Bethesda, MD. , USA
Longitudinal data were available at 4 visits six months apart. In order to
relate the decline in CD4 cells to changes in other variables over time and to
levels of variables available only at entry, we used an autoregressive model
in which one relates CD4 cell number to covariates, conditioning on previous
number of CD4 cells.
In the final multivariate model, the following variables were significant
predictors of subsequent number of CD4 cells after controlling for previous
number of CD4 cells: CD8 cells, platelets, serum IgA, hemoglobin and HIV anti-
body level. To measure the magnitude of the predictive power of these
significant variables, we compared the subsequent numbers of CD4 cells of two
individuals who differed by approximately one standard deviation in a given
covariate but were identical otherwise (including the prior number of CD4
cells). The percentage reductions of CD4 cells associated with differences in
a given covariate were as follows:
% fewer CD4 cells Difference in covariate
1.5 times the number of CD8 cells
decrement of 50,000 platelets
decrement of 1.0 gm% of hemoglobin
2.0 times the IgA level
decrement of 0.5 in 00 of HIV antibody
These data suggests that several covariates in addition to previous number of
CD4 cells have significant predictive power for estimating the decline in CD4
cells in HIV seropositive subjects.
7.8%
3. 73!
1.72
1.45!
1.43!
MP90 Prospective Immunologic Study of Intravenous Drug Abusers (IVDA)
Enrolled in a Methadone Program.
CHRISTINE A. FUSILLO, M.H. GRIECO, E.J. GINDI, D.K. BROWN, M.M. REDDY, E.B.
KLEIN/ St. Luke's/Roosevelt Hospital Center, New York, N.Y.
173 patients with IVDA had baseline evaluations from September, 1984 to
April, 1986 in a study designed to examine parameters associated with serum
antibody to HIV and predictive of conversion to ARC and AIDS.
53 patients or 31% had antibodies to HIV by ELISA with confirmation by
Western Blot, performed by C.W. Saxinger and S.H. Weiss at the NCI. The
following mean laboratory parameters were statistically different (p<£0.01)
between HIV-negative and -positive patients: (1) CDT./CDT„ ratio, 1.50 vs.
0.90, (2) Clq 30.2 vs. 56.5 ug/ml, (3) beta-2 M, 2595 vs. 3363 ug/1, (4)
absolute lymphocyte count 2578 vs. 1856/cmm, (5) % CDT , 34 vs. 27, (6)
absolute Tj 894 vs. 492/cmm, (7) % CDT- 25 vs. 33, (8) absolute T, 1436 vs.
1014/cmm, respectively. Total interferon titers (p<0.05) of negative vs.
positive mean values were 1:8.8 vs. 1:23.
None of the 53 HIV-positive patients had AIDS on initial evaluation but 16
(30%) had LAS. In the HIV-positive subjects, beta-2 M was increased above
2500 in 37, and the absolute T. count below 500 in 30. Interferon level was
elevated above 1:16 in 9. During the subsequent year, 5 patients developed
AIDS and a 6th developed severe recurrent bacterial pneumonias. All 6 of
these subjects were characterized by elevated beta-2 M (mean 4259) interferon
(mean 107) and low absolute T. counts (mean 203).
In this cohort of HIV positive subjects, 9.4% prospectively developed AIDS
within 1 year. All had elevated beta-2M and interferon levels and
absolute T. count averaging 203/cmm.
MR93 HIV-seroconversion in a Cohort of Homosexual Men in Stockholm be-
tween 1983 and 1986.
GORAN BRATT, A KARLSS0N, G v KR0GH, L M0BERG, G BI8ERFELD, E SANDSTROM. Venhal-
san, Sbdersjukhuset, Stockholm. Immunological Oept., National Bacteriological
Laboratory, Stockholm, Sweden.
Since Nov 1982, a clinic in Stockholm with gay staff has offered healthy gay
men venereological screening. A consecutive serie of 166 men who first attended
in Feb-May 1983 has been followed at yearly intervals. Examinations included
HIV-serology, T-lymphocyte subsets and serum-electrophoresis.
Results: In 1983 HIV-antibodies were found in 31/166 (18.78). In 1984 10
(8.08) of the 125 previously negative men who returned had seroconverted. A
further 4 (4.08) had seroconverted in 1985 when 101 previously negative men re-
turned, and of the 85 previously negative men who returned in 1986 5 (5.98) had
seroconverted. The T-lymphocyte subsets and IgG levels before (0) and at the
first (1), second (2) and third (3) year after seroconversion were as follows:
0 12 3
T4 (x10/l)
T8 (x109/l)
T4:T8
IgG (g/1)
0.97
0.81
0.38
0.42
1.3 +0.2
11.7 + 2.3
0.69
1.00
0.7
12.9
0.27
0.49
0.2
2.6
0.60 + 0.24
0.88 + 0.37
0.59 + 0.26
0.79 + 0.22
0.7
13.9
0.2
2.7
0.7
14.0
0.2
1.5
Conclusion: HIV-seroconversion is still seen in this prospectively followed
co-hort in spite of decreasing risk factors. The implications of this will be
discussed. Early after seroconversion there was a fall to a persistent low
level of T4 lymphocytes and a transitory increase in T8 lymphocytes. IgG in-
creased progressively during the follow up.
MR91 Female to male heterosexual transmission of HIV infection in Nairobi
D WILLIAM CAMERON**, FA PLUMMER**, JN SIM0NSEN**, JO NDINYA-ACHOLA*,
U D'COSTA*, P PI0T*** et al. *Univ Nairobi, Kenya Medical Research Center,
Nairobi City Commission, Nairobi, **Univ Manitoba, Winnipeg, *** Institute of
Tropical Medicine, Antwerp.
HIV is apparently transmitted with greater ease via heterosexual intercourse
in Africa than in other regions. Concomitant STD's particularly genital ulcer
disease (GUD) has been postulated as one co-factor which might facilitate sexu-
al transmission. In order to quantitate the risk of HIV acquisition by a man
after a single exposure to an infected woman and to determine if GUD increased
the risk of HIV transmission we are conducting a prospective study of men who
acquire an STTJ from a group of prostitutes with a known high prevalence of HIV
infection (>85 %, HIV+). All men presenting to our clinic with an STTJ who
reported one of these prostitutes as a source contact were enrolled in the
study. 277 men have been enrolled in the study of which 9 % were initially
HIV+. The major risk factor for HIV+ was a past history of GUD. Number of
lifetime sex partners, frequency of prostitute contact, number of injections,
blood transfusions and a past history of urethritis did not correlate with
HIV+. 130 seronegative men have been followed for a mean of over two months.
Seroconversion to HIV occurred in 6/54 men with chancroid, 3/69 men with ure-
thritis and 0/7 men with other diagnoses (p = NS). Overall HIV seroconversion
has occurred in 9/130 or 7 % of exosed men. The risk of HIV transmission from
an HIV-infected prostitute to a male sex partner is substantial and may be
facilitated by GUD.
UDQA Reactivity of Ghanaian Sera to Human Immunodeficiency Virus
(HIV) and Simian T-Lymphotroplc Virus III (STLV-III).
JULIUS A.A. MINGLE***, M. HAYAMI , M. OSEI-KWASI** , Y. ISHIKAWA***, A.R.
NEEQUAYE", V. NETTEY , et.al. "university of Ghana Medical School, Accra,
Noguchi Memorial Institute for Medical Research, Legem, Accra ,
Institute of Medical Science, University of Tokyo, St. Joseph Hospital,
Koforidua, Ghana.
Acquired immunodeficiency syndrome (AIDS) in Africa which was previously
confined to the East and Central African countries is now In West Africa.
The disease in Africa may take an epidemic character if measures are not
taken to check its spread. Prevalence rates and the risk groups therefore
need to be assessed and Identified. Detection of antibodies (Abs.) to HIV
and STLV-III antigens (Ags.) was carried out in human sera from blood
donors, prostitutes, sickle cell disease patients and others. The ELISA and
Immunofluorescence (IF) techniques were used for HIV Ags. and IF for STLV-III.
Out of a total of 997 samples (226 from prostitutes) examined for HIV and
737 for STLV-III. Abs. 93 including 57 prostitutes were positive for HIV
and 18 for STLV-III Abs. Some of the sera reacted better to STLV-III Ags.
Western blotting test also confirmed these differences.
Reports on Senegalese showed that some reacted to STLV-III Ags. Without
any disease. The Ghanaians reacting to STLV-III showed disease. The
Western blotting reaction suggests that some of the Ghanaians have been
exposed to a virus which may be closely related to STLV-III.
A new virus HTLV-IV has been reported from Senegal. Retrovirus infection
in Africa may therefore be more varied than in the Western Hemisphere.
Isolation and characterization of local strains of HIV and their inclusion
in tests as Ags. may be necessary to determine the incidence rates in some
of these African countries. Work is currently going on in this direction.
25
MONDAY, JUNE 1
MR95 Concomitant HTLV-I and HTLV-III Infections - A Serological Survey
in Washington, D. C. Area
KENNETH S CHANG*. LAI-CHE WANC-*, STEVE ALEXANDER**, T. LOG***, A. F. KUO***
PAULA STRICKLAND***, et al., *Laboratory of Cellular Oncology, National Cancer
Institute, "Biotech Research Laboratories, Inc., "'Commission of Public
Health, District of Columbia
A serological survey for the presence of antibody against HTLV-I and HTLV-
III (HIV) was conducted on serum samples collected in 1984 from four groups of
individuals: (A) VDRL (-) premarital individuals (n=113), (B) senile, chronic
disease patients in D. C. Village Hospital (n=155), (C) drug abusers (n=151),
and (D) male homosexuals (n=187) . ELISA positive sera were titrated and fur-
ther examined by immunofluorescence and Western blot tests. ELISA tests using
goat antihuman (IgA, IgG, IgM) serum were more sensitive than those using goat
antihuman IgG serum.
HTLV-I antibody positive rates for these groups were: (A) 5.3%, (B) 9.0%,
(C) 18.5%, and (D) 4.3%. HTLV-III antibody positive rates for these groups
were: (A) 0.9%, (B) 4.5%, (C) 10.6%, and (D) 4.8%. The majority of individuals
with positive tests were either reacting against HTLV-I or HTLV-III only.
However, some individuals who belonged to groups C and D showed antibodies
reacting against both viruses. These were confirmed by Western blot tests in
which pl9, p24, and env antigens of HTLV-I as well as pl7, p24, p41, and gpl60
antigens of HTLV-III were reactive with these sera. These preliminary results
suggest the possible occurrence of concomitant infection in these individuals
with both HTLV-I and HTLV-III, although other possibilities such as past se-
quential infections, and presence of cross reacting antibodies against viral
or cellular antigens can not be excluded.
MP98 Cutaneous and plasmatic Von Willebrand factor in AIDS : a marker
of endothelial stimulation ?
MICHEL JANIER*. B. FLAGEUL*, L. DROUET**, M.L. SCROBOHACI**,
A. PALANCIE*, F. COTTENOT*, * Department of Dermatology, ** Department
of Hemostasis, Hdpital Saint-Louis, Paris, France.
Patients infected by the human immune deficiency virus (HIV) (lymphadenopathy
syndrome (LAS), Kaposi's sarcoma (KS), opportunistic infection (01)) represent
a model in which endothelial stimulation is important.
We studied plasmatic values of Von Willebrand factor (VWF) as an indicator
of endothelial stimulation in 45 LAS, 23 AIDS KS and 9 AIDS 01 in comparison
with 19 normal controls and 12 classical KS. VWF was found to be elevated in
AIDS 01 (P < 10~7) and AIDS KS (P < 10~6) and at a lesser extent in classical KS
(P < 10~3) and LAS (P < 10~2). No correlation was found between plasmatic VWF
and a number of clinical and biological parameters : inflammation, immunological
status, age, tumoral Burden, renal and hepatic functions. This elevation seems
more to be linked to symptomatic or asymptomatic infections than to the KS
itself.
To ascertain the diffuse vascular proliferation in these situations, we studied
the number of vessels within the superficial dermis of clinically uninvolved skin
by an indirect immunoperoxidase method using an antibody directed against VWF
in 20 LAS 6 10 AIDS KS in comparison to 1 1 controls and 10 classical KS. An
increase in the number of vessels was found in LAS (p <0.01), AIDS KS (p<0.01)
and classical KS (p<0.05) suggesting that the endothelial stimulation is a diffuse
mechanism in these situations.
The absence of correlation between plasmatic VWF and cutaneous vascular
hyperplasia suggests that plasmatic VWF may be a good marker of endothelial
dammage but a poor marker of vascular proliferation.
MP96 Epidemiology of HIV Infection in Martinique, French Department in the
West Indies.
NICOLE HONPLAISIR* , C . NEISSON-VERNANT** , C .S0BESKY** , I . VALETTE* , F . DEMEULEMEES-
TER***, *Centre de Transfusion de Martinique, **Centre Hospitalier Regional de
Martinique, ***Inspection de la Sante , Fcrt de France, Martinique.
Since August 1985, 15207 blood donations from volonteer blood donors and 1399
high-risk people were tested using "ELAVIA" first generation assay. Positive
specimen were retested by Indirect Immunofluorescence on fixed cells and confir-
med with Western Blot (Pasteur) and Recombinant Env/Core protein assay (Abbott)
All confirmed seropositive people were clinically evaluated and assessed for
blood cell count, T Lymphocyte numbers and ratios, serum immunoglobulin and
Peta 2-iminunoglobulin levels, TPHA and Hepatitis B serologicals status and cu-
taneous multipuncture tests (Merieux).
Blood donors were compared to heathly controls. 0,2 % of blood donors and 6 %
of patients were positive whose 15 with AIDS. In blood donors, among 83 repro-
ductible Elavia test, 23 were Western Blot negative and 30 uninterpretable. Are
they seroconversion or due to other retrovirus ? Recombinant proteins assay
agree with Western Blot.
In 50 % of the donors, no usual risk factors have been founded, but hetero-
sexual transmision could been involved. 70 % of the subjects had histories of
S.T.D.
50 % of HIV positive, non-AIDS people are clinically asymptomatic, but have
biological abnormalities. The average of T Helper cells is significantly higher
for controls than for HIV positive.
The epidemiological caracteristics seems to be intermediary between those
existing in France and the United States on one hand and Haiti and Africa on
the other (heterosexual contamination and sex-ratio).
MP99 Activated T-cells and neopterin in HIV-infection.
"v DIETMAR FUCHS*,A. HAUSEN*,G. REIBNEGGER* ,E . R. WERNER*,
M.P. DIERICH**, H.WACHTER, institute for Medical Chemistry and
Biochemistry, **Institute for Hygiene, Ludwig Boltzmann Institute
for AIDS Research, University of A-6020 Innsbruck, Austria.
Neopterin is a low molecular weight metabolite which derives
from guanosintriphosphate . In vitro, it is produced from human
monocytes specifically upon stimulation with interferon gamma.
Extended studies confirm neopterin also in vivo to be a sensitive
marker for the cellular immune activation status. It is cha-
racteristic for T-cell activation, interferon gamma production
and monocyte activation. However, this does not implicate suc-
cessful effector mechanisms . -Activation of T-cells is the central
event regulating HIV-propagation and cell death in vitro. Our
data, based mainly on neopterin measurements, allow the following
conclusion in HIV-infection: 1) Activation of T-cells and
monocytes parallels progressive HIV-infection. 2) Neopterin ele-
vation reveals prognostic information. 3) There exists a si-
gnificant inverse correlation of neopterin levels and CD^t/CDSt
ratio in AIDS patients. 4) In a significant percentage of sero-
negative members of high AIDS incidence groups neopterin elevation
is preexisting. ' T-cell activation as predisposing factor for HIV-
infection and progressive disease is also deraonstratable in re-
cipients of blood transfusion, in pregnant women and in children.
Our data indicate: Activated T-cells are important for HIV-
propagation also in vivo. Neopterin measurement is of potent tool
in classifying and monitoring of patients infected with HIV.
MP97 Synthetic env- and gag- Peptides Are Recognized by HIV-specific
Antibodies
R.V. PETR0V, RAKHIM M. KHAITOV, L.A. F0NINA, A.L. LIOZNER, I.G. SID0R0VICH,
S.M. ANDREEV, Institute of Immunology, USSR Ministry of Public Health, Moscow,
USSR.
First generation of HIV-antibody diagnostic kits may be biohazardous and re-
quire verification due to strong immunochemical heterogeneity of the test sys-
tems. In order to solve these problems we synthesized peptide antigenic deter-
minants specific for the products of "env" and "gag" HIV gene expression and
produced monoclonal antibodies against some epitopes of HIV structural proteins
Env- and gag-specific structures were recognized among the produced spectrum of
peptides with the help of commercial sera which gave the extinctions comparable
with those obtained with the whole virus particles on polysterene.
Immunizing splenocyte cultures in vitro by whole immobilized virus or by the
synthetic peptides we obtained HIV-specific monoclonals.
We are studying the possibility of producing ELISA systems on the basis of
"peptide-monoclonal Ab" pairs to be used instead of the complicated systems of
the first generation which require immunoblntting with whole virus proteins.
MR100 Abnormal B-Cell Differentiation Response to Polyclonal B-Cell
Activators and Recombinant IL2 in AIDS and Pre-AIDS
JORN KEKOW*. PETER KERN**, and WOLFGANG L. GROSS*, *Department of Internal
Medicine, University of Kiel, Kiel, and **Bernhard-Nocht-Institut, Hamburg, FRG.
In AIDS, elevated serum Ig levels and autoimmune phenomena indicate B-cell
activation in vivo. Reports of HIV-infected/ activated B cells give evidence
for T-cell independent B-cell abnormalities. In order to characterize the
B-cell dysfunction and conditions for its modulation, functional studies were
done in 10 patients with frank AIDS and in 10 patients with persistent genera-
lized lymph node enlargement (PGL) and HIV-positive sera. The control con-
sisted of healthy heterosexual men. The in vitro experiments to assess the
differentiation response were done with mononuclear cells and highly purified
B cells. The Ig secretion into culture supernatants was measured by ELISA. In
7 day cultures the cells were stimulated with a T-cell independent polyclonal
B-cell activator (Klebsiella pneumoniae, KlebsM) and with rIL2. All patients
with AIDS failed to respond to these stimulants. rIL2 allone did not increase
the Ig levels in patients with PGL and in the normal control. However, co-
culture experiments using KlebsM and rIL2 showed a pronounced increase of Ig
levels in contrast to stimulation with KlebsM. This indicates an abnormal
B-cell differentiation response in AIDS, which is T-cell independent and inde-
pendent of exogeneous rIL2. However, in patients with Pre-AIDS.B-cell function
can be modulated. These results implicate that treatment of HIV-infected in-
dividuals by rIL2 affects not only the NK-cell/T-cell system but also the
B-cell system.
(Supported by the BGA/BMFT 'AIDS1)
26
MONDAY, JUNE 1
MR101 Abnormal Distribution of IgG Subclasses in AIDS and Pre-AIDS
JBRN KEKOW*. GUNTHER HOBUSCH*, PETER KERN**, and WOLFGANG L. GROSS*,
* Department of Internal Medicine, University of Kiel, and **Bernhard-Nocht-In-
stitut, Hamburg, FRG.
In AIDS, elevated serum Ig levels and autoimmunephenomena indicate B-cell
activation in vivo. This might be a result of infection/ activation by HIV. In
order to describe the characteristics of hypergammaglobulinaemia, especially of
the predominant IgG isotype, we studied the distribution of the IgG subclasses
in vivo and in vitro. The in vitro experiments consisted of 7 day lymphocyte
cultures stimulated with T-cell dependent (PWM) and T-cell independent (Kleb-
siella pneumoniae, KlebsM) polyclonal B-cell activators (PBAs). The IgG sub-
classes were measured by ELISA. The cultures were done with 8 patients with
frank AIDS, 8 patients with persistent generalized lymph node enlargement (PGL)
and a normal control. In all patients sera, we found the hypergammaglobulin-
aemia restricted mainly to IgG1. Only in patients with PGL, elevated spon-
taneous Ig levels in vitro were increased under stimulatory conditions, as
demonstrated by the measurement of all 4 subclasses in the culture superna-
tants. AIDS patients did not respond to the stimulants. According to the fin-
dings in sera of patients with PGL, the increase of total IgG after stimulation
resulted mainly from IgG1. These data indicate a B-cell activation in AIDS and
Pre-AIDS, that is restricted mainly to one IgG subclass, namely IgG1.
(Supported by the BGA/BMFT 'AIDS')
MR104 . .
Infection of Brain Cells with HTLV-III/LAV in vitro
WERNER MELLERT*. V. ERaE*, D. STAVROU**, S.GARTNER***, anTTTTOPOVIC*** .
*Gesel Ischaft fuer Strahlen- und Umweltforschung, D-8042 Neuherberg, **Clini-
cum Bogenhausen, D-8000 Muenchen, ***NIH, Bethesda, MD.
To understand the pathogenesis of the neurological disorders in AIDS pa-
tients it is important to determine the susceptibility of brain-derived cells
to HTLV-III/LAV. We examined cultured cells of glial origin as potential tar-
gets for HTLV-III/LAV infection. Normal and neoplastic cell lines positive
for glial fibrillary acidic protein (GFAP) and, with one exception, negative
for T4 antigen originating from fetal brain, astrocytoma or glioblastoma,
were used in these studies. Infection with HTLV-III/LAV was performed by co-
cultivation of these cell lines with a HTLV-I I IB-producer cell line (KE37/12-
IIIB) as well as by exposure of these cell cultures to cell-free culture
fluid harvested from this virus-producing cell line. Using an Immunoperoxida-
se method for the detection of HTLV-III/LAV antigens, virus-positive cells
could be detected both in the normal as well as in the neoplastic brain-de-
rived cells. The HTLV-I I I/LAV- infected cells exhibited a reduced growth rate
and an altered growth pattern compared to their noninfected counterparts.
These results indicate, that cells of glial origin can be infected with
HTLV-III/LAV and that virus can exert a cytopathic effect on these cells.
MP102 °ral Bacteria Stimulation of Production of HIV. DJORDJE AJDUKOVIC*
M. GORNITSKY." E.C.S. CHAN.'** S. GARZON."" H.
STRYKOWSKI."" D.D. PEKOVIC". * Inst i tut Armand-Frappier. "Dental
Department. Jewish General Hospital. "'Faculty of Dentistry. McGill University.
""Faculte de Medecine. Universite de Montreal. Montreal. Canada.
After blood, saliva was the second body fluid from which human immunodeficiency
virus [HIVJ was isolated. The origin of salivary HIV are infected lymphocytes from
the gingiva. These cells emigrate into the saliva at a rate of 10° per minute. This
emigration may increase up to 10-fold in oral diseases which are frequent in an im-
munocompromized host. Recent immunocytochemical studies show a higher incidence
of HIV in salivary lymphocytes (SL) than in peripheral blood lymphocytes IPBL] of
dental patients with AIDS. This suggests that the infected lymphocytes receive an
antigenic and/or mitogenic stimulation by the oral flora resulting in a higher expres-
sion of the virus. To test this hypothesis we have studied the stimulation of H!V in
CEM and AOl.3 permissive cell lines and PBL with cellular and cell-free fractions
of autologous and allogenic saliva and several cultured bacterial species considered
as periodontal pathogens. The stimulation was followed by immunofluorescence and
immunoelectron microscopy techniques and by reverse transcriptase assay. Oral
species known as inducers of lymphoblastic transformation show higher capacity for
stimulation of the production of HIV. Opposite results were obtained with bacterial
species suppressing lymphoblastic transformation. The use of saliva for detection
of HIV infection offers the following advantages: a] collection of the specimens does
not require a medical competence: b) quantity necessary for test can be easily col-
lected: c] high concentration of the virus allows easy detection of the infection.
It must be emphasized that successful attempts to isolate the virus by culturing.
which is associated with separation of salivary fractions, must also include elimination
of fraction which suppresses the lymphoblastic transformation.
MP 105 DYSREGULATED LYMPHOCYTE ACTIVATION IN AIDS.
MM Lederman, Z Toosi, and JT Carey, Department of Medicine, Case
Western Reserve University, University Hospitals and VA Medical Center,
Cleveland, OH.
Lymphocytes of patients with the acquired Immunodeficiency Syndrome (AIDS)
often display phenotypic markers of activation yet fail to transform in
response to mitogens and antigens. We examined the relationship among -*H
thymidine incorporation, interleukin-2 (IL-2) production, IL-2 receptor (IL-
2R) expression and cell cycle progression stimulated and unstimulated
lymphocytes of patients with AIDS (P) and controls (C). Peripheral blood
mononuclear cells (PBMC) of P incorporated less H thymidine in response to
phytohemaglutinin (PHA) and Tetanus toxoid (TT) than did PBMC of C.
(PHA: P-5335±1192cpm, C-51075±10120cpm p<0.01; TT: p-925±155cpm,
C«4970±1268cpm p<0.01). IL-2 production in response to TT as measured by
proliferation of a murine cytotoxic T lymphocyte line also was diminished in
P when compared to C (0±0 U/ml vs 7 . 5±3 . 9 U/ml , p<0.02). Freshly obtained
lymphocytes of P more frequently expressed IL-2R (12.2±3.8X vs. 2.5±0.4X
p<0.01)) as detected by anti-Tac reactivity yet failed to increase IL-2R
after stimulation with PHA or TT (A IL-2R PHA P-8.9±4.8X, C-30 . 0±10 .41,
p<0.05, AIL-2R TT P-0.110.3, C-3.1±0.4X, p<0.01). In two experiments, cell
cycle analysis using acridine orange and flow cytometry revealed increased
spontaneous progression through Gj by P lymphocytes and no difference in
PHA-induced Gj progression when compared to C. Thus lymphocytes of patients
with AIDS are apparently activated in vivo. Failure to proliferate in
response to mitogens or antigens may be attributable in part to a block in
transition past the Gj phase of the cell cycle.
MR103 Cross Reactive Recognition of Different Human T Lymphotropic
Retroviruses by HTLV-I and HTLV-III/ LAV Specific Cytotoxic T
Lymphocytes (CTL). ALAIN H. ROOK, S. KOENIG, H. MITSUYA, H.C.
LANE, and A.S. FAUCI, Department of Dermatology, Hospital of the
University of Pennsylvania, Philadelphia, PA., NIAID, and NCI, NIH,
Bethesda, MD.
The precise characteristics of the cellular response to viruses of the
human T lymphotropic retrovirus family, including HTLV-I and HTLV-III/LAV,
have not yet been well defined. Recent studies have demonstrated the fine
specificity of antibodies in the circulation of seropositive individuals which
in the presence of effector cells, selectively mediate antibody-dependent
cellular cytotoxicity in a non cross-reactive manner against either HTLV-I or
HTLV-III/LAV infected cells. Moreover, HLA-restricted HTLV-III/LAV
specific CTLs have been detected in the peripheral blood of some HTLV-III/
LAV seropositive individuals, and HTLV-I specific CTLs can be generated in
vitro using mononuclear cells from individuals with HTLV-I associated adult
T cell leukemia in remission. In this study, HTLV-III/LAV specific peri-
pheral blood CTL and a long term cultured HTLV-I specific CTL line were
used to examine whether these immune cells could lyse in a cross reactive
manner T cells infected either with HTLV-I or HTLV-III/LAV. Both the
HTLV-I and HTLV-III/LAV specific CTLs demonstrated the capacity to lyse,
in an HLA-restricted manner, T cells infected with either of the two
retroviruses. However, the CTLs failed to lyse HLA-matched target cells
infected with other viruses including cytomegalovirus or Epstein-Barr virus.
Thus, in contrast to the non-cross reactive specificities of serum antibodies,
retrovirus-specific CTLs appear to recognize retrovirus-associated common
antigenic determinants on different T lymphotropic retrovirus infected cells.
MPIflfi Prognostic Significance of Antllymphocyte Antibodies (ALA) in the
Progression of the Acquired Immune Deficiency Syndrome (AIDS),
BRENT DORSETT, WILLIAM CRONIN, HARRY L. IOACHIM, Department of Pathology,
Lenox Hill Hospital, New York, N.Y.
A large number of Individuals are presently known to have been infected with
the human immunodeficiency virus (HIV) but their risk of developing AIDS Is
yet uncertain. So far, the number of T-helper lymphocytes has been the only
marker used to assess status of Immune deficiency and prognosis. Previously, we
have demonstrated the presence of antllymphocyte antibodies In the sera of AIDS
patients. These antibodies react against lymphocytes expressing antigens recog-
nized by monoclonal antibodies OKT4 (CD4) and OKTu (CD2). In a comparative
study, we have found significant levels of ALA In 88Z of 200 AIDS patients and
in only 8Z of 50 non-AIDS patients and 2Z of 60 healthy males. To determine
whether the presence of ALA Indicates progression to AIDS, we Investigated
their levels in patients with AIDS-related complex (ARC) and in healthy homo-
sexuals. Of 45 ARC patients, who were all seropositive for HIV, 29 (64X) had
significant levels of ALA and of these 17 (59Z) progressed to AIDS during the
term of this study (18-30 months) .while 16 (36Z) had no elevated levels of ALA
and none progressed to AIDS. Comparison of the mean levels of ALA In progressor
versus non-progressor ARC patients shows a significant correlation (p*< 0.001)
between the increase of ALA and progression to AIDS. Of 87 healthy homosexual
males, 38 (44X) were seropositive for HIV and of these 42X had elevated ALA
while of 49 (66Z) seronegative for HIV only 6Z had Increased levels of ALA. Sub-
sequently,5 of 17 (30Z) patients chat were HIV+, ALA+ developed clinical dis-
ease (1 AIDS, 4 ARC) .while no patients that were HIV+, ALA- presented with clin-
ical symptoms. The present studies show a direct correlation between increased
levels of ALA and the progression of disease In HIV-infected Individuals.
27
MONDAY, JUNE 1
MR107 HIV RECOMBINANT ANTIGEN NEUTRALIZATION ASSAY:
TO ELISA AND WESTERN BLOT. N. Rolon, T. Hill
A. Sito, J. Geltosky and J. Britz. Ortho Diagnostic Systems Inc.
Raritan, NJ 08869
A SUPPLEMENTAL TEST
R. Kissinger,
Among blood donors, the reactivity rate for the detection of antibody to
Human Immunodeficiency Virus (HIV) is 0.1 to 1.5%. The Western Blot (WB)
test, currently used for confirmation of repeatably reactive ELISA results
identifies antibodies to specific HIV proteins. An alternative method to the
subjective and cumbersome WB utilizes recombinant gene products from the
envelope, core, and polymerase regions to neutralize ELISA reactive sera in
solution. A dilution of an ELISA reactive specimen is preincubated with a
mixture of the recombinant antigens and retested in the viral lysate ELISA.
A decrease in absorbance of 50% or greater relative to a non-neutralized
control verifies a specimen as positive. To date, over 200 WB confirmed
specimens with varied banding patterns have been effectively neutralized.
Of 24 ELISA reactive, WB negative, false positive samples tested, none showed
neutralization greater than 15%. Correlation between WB and neutralization
methods has been 100% consistent with patient diagnosis.
MR110 Immunoglobulin Isotype Abnormalities in Pediatric Human Immuno-
deficiency Virus (HIV) Infection. JOSEPH A. CHURCH, Childrens
Hospital of Los Angeles and USC School of Medicine, Los Angeles, CA, USA.
Hyperimmunoglobulinemia (Hyper Ig) is a common feature of HIV infection.
However, Ig isotype deficiencies have also been noted in sporadic case reports.
This study evaluated Ig isotype concentrations in 31 HIV-infected children,
22M, 9 F, ages 0.2 to 11 years (mean = 2.5 years) at diagnosis (Dx). AIDS was
diagnosed in 17, AIDS-related disorders in 10, and four patients (pts) were
asymptomatic. Risk factors included blood transfusions in 17 and parental
high-risk in 14. IgG, IgA and IgM were measured in all pts with a nephelo-
metric assay; IgG subclasses were measured in 19 pts with an immunoradiometric
technique (Specialty Laboratories, Los Angeles, CA). Results were compared to
age-adjusted normal values.
tlgG tlgA tlgM flqGl flgGl + IqG3
AIDS 12/17 11/17 5/17 3/9 1/9
ARC 9/10 6/10 2/10 1/7 4/7
Asymptomatic 2/4 1/4 0/4 2/3 0/3
IgG deficiency was seen in one AIDS pt at Dx and three terminally. IgG sub-
class deficiencies were seen in five at Dx: IgGl and IgG2 + IgG4 in two and
one AIDS pts, respectively; and IgG2 and IgG4 in two asymptomatic pts,
respectively. IgGl + IgG2 deficiency and IgG2 + IgG4 deficiency were seen in
two AIDS pts terminally.
In summary, the hyper Ig of HIV infection primarily involves total IgG and
IgA levels; IgGl and IgG3 are selectively increased in pts with hyper IgG;
IgG subclass deficiencies were found in seven pts including two asymptomatic
individuals.
MDiHC Neurological Involvement in AIDS: Roles of Cytomegalovirus and
Human Immunodeficiency Virus
MILAN FIALA*. D. CASAREALE*. L. A. CONE*, P. SHAPSHAK**, M.OSBORNE**, W.W.
TOURTELLOTTE**, *Eisenhower Medical Center, Rancho Mirage, CA; **Wadsworth
VAMC, and **UCLA School of Medicine, Los Angeles, CA.
In 28 patients with AIDS, neurological complications occurred in 13 (81%) of
16 patients with retinitis and in 1 (8%) of 12 patients without retinitis
(P<0.01 , chi square test). The onset of complications coincided with the
onset of cytomegalovirus (CMV) viremia or of retinitis. CMV was found in the
leukocytes of 15 (88%) of 17 patients and in the spinal fluid of 1 (17%) of
6 patients. CMV titer in the leukocytes ranged between 10-4 to 10"9 plaque-
forming units with higher values in acutely ill patients. AIDS patients had
CMV in mononuclear cells more often than non-AIDS patients. Genomic analysis
revealed that paired CMV strains isolated simultaneously from mononuclear and
polymorphonuclear leukocytes of two patients with AIDS differ in their
restriction fragment profiles with EcoRI, Bglll, and Clal enzymes.
Intra-blood-brain-barrier IgG synthesis was increased in 5 of 6 patients,
and the five had neurological complications. Elevated ratio of viral anti-
body titer in the spinal fluid to that in the blood was found with CMV (ratio
3.0 to 6.5) as well as with human immunodeficiency virus (HIV) (ratio 3.2 to
27.0). In patients treated with 9-(l,3 dihydroxy-2propoxymethyl) guanine ,
retinitis improved in 12 of 14, neurological symptoms in 2 of 4, and viremia
in 4 of 8 patients. As reported elsewhere, in vitro CMV enhances cell lysis
in a T4+ lymphoblastic line persistently infected with HIV. CMV thus appears
as a cof actor in AIDS with HIV. Anti-CMV treatment may be beneficial to
patients with acute neurological involvement.
Mpili Primary infection with Human Immunodeficiency Virus: Clinical and Laboratory
Features of 73 Cases.
ALASTAIR W MCLEOD, MT SCHECHTER, WJ BOYKO, KJP CRA1B.B WILLOUGHBY, B DOUGLAS,
et al. The Vancouver Lymphadcnopathy-AIDS Study, St. Paul's Hospital, University of British
Columbia, Vancouver, BC, Canada.
In an ongoing prospective study being conducted since November 1982, a total of approximately 600
homosexual men have been seen by their general practitioners and have undergone laboratory and HIV
antibody testing every 6 months. Of all 345 men who were HIV negative at enrolment, a total of 73
(21%) have seroconverted by the time of this analysis. Dates of seroconversion were estimated for
these individuals by taking the midpoint of the interval between the last negative and first positive
anti-HIV test result. Paired comparisons of results obtained a mean of 5.3 months before and after
seroconversion, revealed that an increase in mean IgG from 1138 to 1373 (p < .001), an increase in mean
IgA from 181 to 190 (p=.034), an increase in mean Clq binding from 8.8% to 16.4% (p<.001) and an
increase in mean CD8 count from 550 to 695 (p=.067), as well as a decrease in mean CD4/CD8 ratio from
1.67 to 1.34 (p=.023), and a decrease in mean WBC from 6468 to 5870 (p=.005), were associated with
seroconversion. The mean CD4 count did not fall significantly with seroconversion (895 to 873; p=.79).
Symptoms including fatigue, fever, night sweats, unintentional weight loss, diarrhea, arthralgias,
cough unrelated to smoking, dyspnea, oral thrush, herpes zoster, and skin rash, did not increase
significantly with seroconversion. In men who were free of generalized lymphadenopathy (GL) at
enrolment, 14 (61%) of 23 seroconvcrters developed GL around the time of seroconversion as compared to
only 11 (7%) of 151 persistently seronegative men during the same time period (p<.0001). These data
suggest that elevation of the CD8 count and a resultant fall in the CD4/CD8 ratio as well as elevations
of immune complex levels, IgG, and IgA, are early effects of HIV. It appears that CD4 cell depletion
does not occur early and thus may be a longer term effect of this infection. The rarity of symptoms
suggests that the majority of acute HIV infections may be asymptomatic or associated with only
relatively minor symptoms, with the exception of generalized lymphadenopathy which appears to
accompany a proportion of acute infections.
MP109 In tra-b! ood-brain barrier (B66) IgG synthes
clonal IgG bands <0B)) and abnormal serum b
"ii th AIDS, ARC and asymptomatic HTLV-1 II-posi t i ve compa
WALLACE W. TOURTELLOTTE*. P. SHAPSHAk*, M.A. OSBORNE*.
MITSUYASU*, M. GOTTLIEB*, et al . J *V.A. and UCLA Med.
CA; ** Mt. Sinai Med. Cntr., Miami Bet... FL.
Intra-8BB IgG synthesis was determined for HTLU-IIl-s
with AIDS, ARC. or asymptomatic and for normals by an e
and/or the presence of 06, (bands not present in or les
serum- by isoelectric -focusing (IEF). 887 (12/15) of pa
tia Complex (ADC; , 68Y. (3/5) of patients with known CMS
tions, and 687 (3/5> of neurol ogi cal 1 y asymptomatic pat
synthesis. 627 (8/13) of patients with ADC, 68V. (3/5) o
CMS opportunistic infections, and 807. (4/5) of neurolog
patients had ASB. Patients with ASB and/or CSF 06 had a
bands in each category. 887. (8/18) patients had an aver
corresponding to ASB but which were more intense in CSF
had CSF 0B (av. of 7 bands) and/or elevated rate and on
The data suggest that the majority of HTLU-III seroposi
stages of disease development and irrespective of neuro
elevated intra-BBB IgG synthesis rate, 0B, and a strikin
ASB compared to seronegative individuals. Elevated synt
of a specific HTLV-II1 CNS infection and may possibly b
impending neurologic disease in neurol ogi cal 1 y asymptom
probably due to polyclonal B-cell activation in the sys
These bands are also be seen in the CSF, with less or e
diffusion of IgG from the blood. It is necessary to per
matched serum with serum diluted to the same IgG concen
(rate and CSF ol i go-
ands (ASB) in patients
red to normals.
L. RESNICK**, R.
Cntrs. , Los Angel es,
erop
leva
s in
t ien
opp
en t
f pa
cal
n av
age
.77
ly 1
tiue
1 ogi
9 e
hesi
e a
at ic
term
qual
form
trat
osi 1 1 ue pat i en ts
ted rate formula
tense in matched
ts with AIDS Demen-
or tun i st i c i nf ec-
s had intra-BBB IgG
t i en ts wi th known
1 y asymp tomat i c
erage number of 7
of 637 of CSF OB
(4/55) of normals
patient had 1 ASB.
patients, at all
c disease, have an
evated number of
s may be i ndicat i ue
reflection of
patients. ASB are
immune system,
i n tens i ty , due to
IEF on CSF and
on as the CSF.
MR112 Effect of Phorbol Myri state Acetate on T-cell colony growth from
patients with AIDS, lymphadenopathy Syndrome (LAS) and seropositive
homosexuals. M. ALL0UCHE*, Y. LUNARDI-ISKANDAR*, C. VARELA-MILL0T*,
V. GE0RG0ULIAS*, W. ROZENBAUM**, CLAUDE JASMIN* et al., *INSERM U 268, Hop.
P. Brousse, BP 200, 94804 Villejuif, FRANCE;** See Mai. Tropicales, Hop.
Salpetriere, Paris, FRANCE.
We have shown previously that T-cell colony growth from peripheral blood
mononuclear cells (PBMC) of patients with AIDS, LAS and from asymptomatic
seropositive male homosexuals was impaired (1,2). In those experiments,
T colony formation was induced with PHA-LCM, a medium conditioned by
mitogen-stimulated normal PBMC. We thus investigated whether Phorbol Myristate
Acetate (PMA)could synergize with PHA-LCM to enhance and/or restore T cell
colony growth. In 8 out of 12 AIDS, and 4 out of 12 LAS patients, addition
of PMA decreased the plating efficiency whereas in 12 normal heterosexuals,
and in 5 out of 6 seropositive male homosexuals PMA maintained or increased
the number and size of colonies. The phenotype of colonies induced by
PMA+PHALCM was approximately the same in infected and non-infected subjects:
T3 and T4 were expressed on less than 20% cells, T8 ranged from 22 to 55%
and Til was always expressed on more than 75% cells. The Tac antigen
(IL2-receptor, IL2-R) was found on 38-97% cells in 2 AIDS and 4 LAS patients,
as compared to 14-80% Tac+ colony cells in normal heterosexuals. In contrast,
incubation of PBMC with 10 ng/ml PMA in liquid culture failed to induce
IL2-R expression in 4 out of 6 AIDS, 5 out of 11 LAS, and 2 out of 6
seropositive homosexual patients respectively, whereas in normal subjects
11-39% of PBMC became Tac positive. These results indicate that T cell colony
growth and T-cell activation are deeply impaired in AIDS and LAS patients.
1) Clin. Exp. Immunol., 1985, 60, 285-293; 2) Blood, 1986, 67_, 1063-1069.
28
MONDAY, JUNE 1
MP113 Ecto-5 'nucleotidase Activities in Mononuclear Cells, T- and B-lym-
phocytes from Patients with ARC/AIDS and from Clinical Healthy
Persons with HIV-antibodies.
Lisa Dalh Christensen, M. Svenson, V. Faber, Dept. of Infectious Diseases M,
Rigshospitalet, University Hospital, Copenhagen, Denmark.
Decreased activity of the cell-membrane enzyme ecto-5'nucleotidase (ecto-5'
NUC) has been found in mononuclear cells frwr. patients with infections or dif-
ferent types of immunodeficiencies. The aim of this study was to describe the
activity of ecto-5'NUC in patients with HIV antibodies and compare the level
to the mito- and antigene induced proliferation of mononuclear cells.
In the present study the activity of the enzyme have been investigated in mo-
nonuclear cells, T- and 8-lymphocytes from patients with ARC/AIDS and from cli-
nical healthy homosexual men with antibodies against HIV. Mononuclear cells
were prepared by density gradient centrifugation of frech venous blood and se-
perated in T- and B-lymphocytes by fluorescens activated cell sorting. Ecto-
5'NUC vas measured by a radioactive method.
Mononuclear cells from AIDS/ARC patients showed reduced activity of ecto-
5'NUC, the T-cell ecto-5'NUC was moderate reduced but all AIDS patients had B-
cell ecto-5'NUC below the normal range lower limit. In the group of patients
with antibodies against HIV but without clinical and amnestic signs of immuno-
deficiency the activity in the T-lymphocytes was within the normal range, but
some iof them showed decreased level 'in B-lymphocytes. Decreased B-cell ecto-
5'NUC was correlated to reduced proliferation after in vitro stimulation or
mononuclear cells with mito- and antigenes.
In conclusion: in patients with antibodies against HIV, decreased ecto-5'NUC
activity in B-lymphocytes is correlated to the immunodeficiency, whereas AIDS
patients with severe immunodeficiency ofteh had normal activity in T-cells.
MP11R The Biopsychosocial Research Center on AIDS: A Multidisciplinary Ap-
proach to the Investigation of the AIDS Disease.
CARL EISDORFER, J. SZAPOCZNIK, G. SCOTT, M. FLETCHER, N. KLIMAS, M. FORDYCE-
BAUM, et al. , University of Miami School of Medicine, Miami, FL.
Seven major studies are currently being conducted at the center. The objec-
tive of this research is to conduct a multidisciplinary, longitudinal study of
the AIDS disease which examines several HIV positive groups from a psychoneuro-
immunological perspective. The center is organized so that common strategies,
procedures and data are utilized by all studies. Similarly, a thematic empha-
sis is shared by all center components; factors are examined that influence the
transmission of disease, mediate the likelihood of increased pathology, and in-
fluence the course of infection.
The studies focus on: the psychosocial co-factors and cognitive AIDS-related
dementia in an HIV positive, homosexual population; the neurological aspects of
pediatric HIV infection; predisposing factors, course and rate of deterioration
following HIV exposure in a population of I.V. drug abusers; the effect of an
exercise intervention in a population of HIV- positive and negative gay men; an
intervention study which examines the prevalence and specific risk factors asso-
ciated with the presence of antibodies to the virus in both HIV positive and
negative I.V. drug abusers; the role of nutritional factors in the development
of AIDS in an HIV positive population; and, attitudes toward AIDS and health
core practices among a Haitian population. Variable assessment is extensive and
wide-ranging. Preliminary data will be presented from each study.
MR 114 "^e Frequency and Characterization of Qligcclonal Protein (OCP)
Bands in Individuals with HIV Antibodies
MIRKA DEUTSCH, M.A. Brown, C.F. Repetti, American Medical Laboratories,
ta.irtax, VA LEA
Sera from 20 adults with HIV antibodies were selected for determination of
the incidence and isotype of oligoclonal proteins (OCP) , and the relationship
of these bands to serum concentrations of IgG, IgA, IgM, C3 and C4. HIV
antibodies were assayed with ELISA and Western Blot. OCP were characterized
by immunofixation with H or L chain-specific antisera. Protein quantitation
was performed with rate nephelometry.
OCPs ware found in 13/20 (65*) of anti-HIV reactive sera. These CCPs ware:
G,K (3 samples); G,L (3 samples); G,K and G,L (6 samples); and K and L
without an identifiable H chain (1 sample). No IgA or IgM OCPs were evident.
The mean [IgG] for the CCP+ sera was significantly elevated (see Table) in
comparison to both the reference range and the mean [IgG] for the CCP- sera.
Mean serum levels of IgA and IgM were similar for both 0CP+ and OCP- samples.
There were, however, 9/20 individual sera with elevated IgA (332-929 mg/dl)
and 5/20 sera with elevated IgM (387-595 mg/dl). Nevertheless, the increased
levels of these isotypes were strictly polyclonal in character. The [C3] and
[C4) for most samples were within the reference ranges. No striking
differences in complement levels were associated with the presence of
oligoclonal bands or with elevated immunoglobulins.
mg/dl :
G
A
M
C3
C4
Ref Range
540-1380
70-312
56-352
83-177
15-45
OCP(+)
2896+ 495
289+ 55
266+ 45
110+ 11
27+ 5
OCP(-)
1632+ 236
427+ 91
21 7+ 55
112+ 8
31+ 4
p:0CP + to -
0.0344
0. 1856
0.5079
0.9179
0.6503
MP117 EBV and HIV Antibodies in Broncho-Alveolar Lavage (BAD and in Serum
of HIV Positive Children with or without Pulmonary Lymphoid Hyperpla
sia/Lymphoid Interstitial Pneumonitis(PHL/LIP)Complex . A Causal Association ?
L.BOCCON-CIBOD*, A.GRIMFELD", A.SARDET**, S. BARUCHEL"*, G.de THE****. Depart
ment of 'Pathology, "Pediatric Pneumology and "'Pediatrics, Hopital TROUSSEAU
Paris, ""CNRS Laboratory, Faculte Alexis Carrel, Lyon, France .
The PLH/LIP complex is a common finding in children with AIDS. The role of
EBV activation in determination of LIP has been recently suggested.
To assess the profile of EBV and HIV antibodies in HIV-positive children pre-
senting with pulmonary pathology, we investigated BAL in 27 consecutive pati-
ents. Out of those, for the last 13, we titered antibodies to HIV and EBV by im-
munofluorescence, both in serum and BAL. From the clinical view point, 5 had
PLH/LIP complex, 3 Pneumocystis carinii (PC), 2 other opportunistic infections
(01) and 3 had ARC. 4/5 of LIP cases had serum EBV profile suggesting viral ac-
tivation (IgG EA : high titers, IgA VCA : traces). 1/5 had normal EBV immunity.
In BAL, IgG VCA were detected in 3/5 LIP. In the 5 LIP cases, HIV antibody ti-
ters were significantly higher than in non-LIP patients (p<0,001). In the 8
non-LIP children, 6 (3 ARC , 2 01, 1 PC) had no EBV antibodies at all, 1 had a
profile of recent infection, 1 normal immunity. The CD4/CD8 ratio in BAL (mono-
clonal antibodies staining, immunoperoxydase technic) was very low in all HIV
positive children , regardless to pulmonary pathology : 0,20 +0,11 as compared
to 0,87 + 0,15 in normal children (p<0,001) but the absolute number of CD8
cells recovered by BAL was very significantly higher in LIP patients. In pulmo-
nary biopsies of LIP cases, we observed large predominance of CD8 lymphocytes
with very few B lymphocytes.
EBV activation may represent a critical cofactor enhancing both CD8 lymphoid
pulmonary infiltration and HIV replication in children with PLH/LIP complex.
MR115 ANTICARDIOLIPIN ANTIBODY, NEUROLOGIC COMPLICATIONS AND HIV INFECTION
RL Brev*. RW Houk* , TM Duginski*, PJ Patel**, Wilford Hall Medical
Center, San Antonio, TX* , Meharry University, Nashville, TN**
Serologic evidence of antibodies directed against cardiolipin (ACLA) , one of
many antiphospholipid antibodies, have been associated with thromboembolism,
recurrent abortion and a variety of neurologic disease. Lupus inhibitors,
also antiphospholipid antibodies, have been described in patients infected
with HIV and opportunistic infection. We measured ACLA IgG by an enzyme-linked
immunosorbant assay in 11 patients with HIV infection and either neurologic
abnormalities, thromboembolism or recurrent abortion. Normal values were
established in our laboratory. Raw data was transformed into a binding index
(.BIJ by the method of Loizou (.Clin exp Immunol U985) 62,738-745). A positive
value is defined as BI > 3 standard deviations above the mean (0.86 +/- 3i.58)
= 2.6 ). Only 2 patients had immune deficiency and none had opportunistic
infection. All but I patient had abnormal ACLA IgG values. The clinical
syndromes represented are as follows: thrombosis in 1, recurrent abortions in
1, headaches in 3, neuropsychiatry symptoms in 4, herpes zoster in 1, peri-
pheral neuropathy in 1. ACLA IgG value in this last patient was normal prior
to the development of his neuropathy, but became abnormal 4 months after his
symptoms began. These observations demonstrate that antiphospholipid anti-
bodies are not limited only to patients infected with HIV and opportunistic
organisms. A relationship between these antibodies and neurologic symptoms in
HIV infection is suggested.
MR118 Leu7 (HNK-1) Cells In AIDS And Related Syndromes.
C.AMIEL, T.MAY, M.C.BENE, G.FAURE, P.CANTON. Maladies
Infectieuses and Lab. Immunology. CHU de Nancy Vandoeuvre les
Nancy. FRANCE.
Leu7 (HNK-1) is a monoclonal antibody initially described as
specific of human natural killer cells. Previous reports have
related elevations of the lymphocyte subset defined by this
marker to viral infections. We investigated this specific
subset, in comparison with classical T-cell markers (CD3, CD4,
CD8 ) , in a population of 151 HIV-seropositive patients. AIDS was
diagnosed upon clinical examination in 26 of these patients. A
total number of 235 analyses was performed, using classical
indirect immunofluorescence techniques on peripheral lymphocytes
isolated by Ficoll gradient centrifugation. Percentages and
absolute numbers of each subset were plotted and compared.
Classical profiles were obtained for CD3 and CD4, significantly
lower in AIDS patients. The mean percentage and absolute number
of Leu7+ cells was increased in non-AIDS seropositive patients,
compared to normal controls (respectively 20.3% - 303
cells/mm3 and 10% - 255 cells/mm3). In AIDS patients, the
percentage of Leu7+ cells remained elevated, while their number
was significantly lowered. No significant correlation was obser-
ved between this subset and the CD8+ subset. In conclusion, our
data indicate the participation of a lymphocyte subset involved
in anti-viral mechanisms in the early stages of HIV infection.
29
MONDAY, JUNE 1
J-P. ALLAIN ****,
** Inst .Blomed.Sci . ,
Hel alnki ,Flnl and and
MR119 Characterization of the latent period and the
development of neutralizing antibodies In early sexually
transmitted HIV Infection.
ANNAMARI RANKI*, J. ANTONEN **, S. VALLE***.
K.J.E. KROHN*'**, *LTCB, NCI, Bethesda, MD,
Unl v.Tampere , Finland, *** private practice,
****Abbott Lab., North Chicago, IL.
We have prospectively followed Immunological and vlrologlcal
events In 15 Finnish men who contracted HIV Infection through sex
and seroconverted. A common finding was a latent period, lasting
for 4 to 18 months, when only viral antigen (sandwich EIA) or
anti-gag antibodies alone (Western blot and CIA-RA) were
seen .CI I nlcal I y , no symptoms except for an abrupt seborrheic
dermatitis in some were recorded. During this time, Tu cell
numbers were normal but a defect was seen In eel 1 mediated
immunity to soluble recall antigens In half of the cases, and In
no one neutralizing antibodies could be detected with the
sensitive ATH-8 cell mlcroassay. Using RNA In situ hybridization,
rare positive cells of monocyte-dendrl t 1c cell lineage were seen.
In the majority of the cases a full blown anti-viral antibody
response developed first after a verified DNA virus (EBV, HBV,
CMV) infection whereafter TH cells started to diminish. It Is
possible that these viruses enhance HIV replication by
transact i vat Ion . Neutralizing antibodies appeared first after the
full seroconversion, and the highest neutralizing titers were
reached along with the development of 1 ymphadenopathy . A fourfold
rise in the neutralizing antibody titer during the follow-up
period favoured a nonprogressive clinical course.
MR122 Cell-Mediated Cytotoxicity Against Human Immunodeficiency Virus-
Producing Cells
A.G. DALGLEISH, ANN SINCLAIR and M. MALKOVSKY, Retrovirus Research Group,
MRC Clinical Research Centre, Watford Road, Harrow, Middlesex HA1 3UJ,
England .
The cell-mediated Immune response to human immunodeficiency virus (HIV)
infection has not yet been studied sufficiently to clarify differences
between the host defence mechanisms of healthy persons and of
HIV-seropo8itive individuals. Here we report that peripheral blood
mononuclear leucocytes (PBL) from healthy persona and also to some extent
from HIV-seropositive patients (with or without an HIV-assoclated disease)
possess in vitro cellular cytotoxicity to HIV-producing cells in the
presence of antibodies against HIV-related antigens. This antibody-
dependent cell-mediated cytotoxicity of PBL is proportional to the
concentration of specific antibody, but the specific antibody alone is not
lytic for HIV-producing cells. Interestingly, lymphokine-activated killer
(LAK) cells also appear to display a potent cytotoxic action against
HIV-producing cells. Boosting these cell-mediated defence mechanisms could
be a useful therapeutic intervention in patients with the acquired
Immunodeficiency syndrome.
MR120 Human- Immunodeficency Virus Induced Hyperimmunoglobul inemia and
Its Associations with CD5 (Leu 1) Expression on B Cells.
D. J. MOODY, HARRY HOLLANDER, Y.J. WANG, D.P. STITES, UCSF School of Medicine,
San Francisco, CA 94143.
We hypothesized that elevated immunoglobulins in HIV-infected subjects
were related to the increased proportions of CD5+ (Leu 1+) B cells, human
equivalents to the Lytl+ B cells in mouse disease models. Analysis of circu-
lating levels of IgG, and IgA in healthy controls and HIV infected individuals
indicated that there was a significant (p<0.01) correlation (r=0.67 and 0.42,
respectively) with the proportions of CD5+ B cells in peripheral blood.
Individuals infected with HIV had significantly (p<0.001) greater proportions
of B cells expressing CD5 and total serum immunoglobulins than did healthy
controls. These changes were directly related to the severity of the disease
state of the HIV seropositive individuals (healthy homosexuals <AIDS related
complex <AIDS). The proportions of B cells expressing CD5 were significantly
(p<0 .001 ) and negatively correlated (r=-0.52) to the T helper/suppressor-
cytotoxic ratio. We observed a significant (p<0.0001) negative correlation
(r=-0.82) between the proportions of both the suppressor-inducer T cells
(CD4+/2H4+) and the B-cell differentiation factor secreting T cells (CD4+/
HB11-). Neither the elevated immunoglobulins nor the increased proportions
of CD5+ bearing B cells were significantly correlated to the proportions
of helper-inducer (CD4+/4B4+) or suppressor-inducer (CD4+/2H4+) T cells.
We conclude from these data that hyperimmunoglobulinemia is strongly associ-
ated with the increased proportions of CD5 expressing B cells and that these
elevations are probably caused by direct-HIV effects on B cells rather than
indirectly by the altered balance of immunoregulatory T-cell subsets.
MR123 T8-D44 POSITIVE LYMPHCCYTTC ALVEOLITIS IN HIV INFECTED PATIENTS
B. AUTRAN', M. DENIS*, M. RAPHAEL', J.M. GUILLON*, P. DEBRE* ,
C. MAYAUD* - ' Lab. d'Immunologie Cellulaire, H6pital PITIE SALPETRIERE,
Paris - * Service de Pneumologie , Hopital TENON, Paris, FRANCE.
A T lymphocyte alveolitis has been demonstrated in patients with the
Acquired Immunodeficiency Syndrom and Related Complex. We have further analy-
sed the Broncho-Alveolar Lavage (BAD fluid cells of patients seropositive
for HIV. 9 patients with (2) or without (7) lung abnormalities were selected
on 2 criteria : 1) a L.A. demonstrated in a 1st BAL fluid (mean lymphocytes :
55 %) , 2) the absence of any lung infection or tumour. A 2nd BAL confirmed
the L.A. in all patients. The alveolar lymphocytes and the peripheral blood
lymphocytes (PBL) were then simultaneously double-stained with the D44 mono-
clonal antibodies (moAb) specific for cytotoxic T8 lymphocytes (1), the anti-
T8, T4, T3 moAbs. The L.A. was composed of 74 % T8+ - D44 + lymphocytes. Both
the T4/T8 and the T8+ D44+/T8 ratios were significantly decreased compared
with the PBL values (p 0.005). Alveolar T8 cells were partially activated
since only 8 % expressed the IL2 receptor. An immunoenzymatic analysis of
the alveolar macrophages (A.M. ) could be performed in 4 of these patients
using the Leu 4 moAb and the CVK-A1 moAb specific for the pl8-HIV antigen
(2). Most of the A.M. were positive for both the T4 molecule and the pl8-HIV
antigen. These data suggest that in HIV infected patients, a L.A. could result
from a pulmonary recruitment of phenotypically cytotoxic T8 lymphocytes and
is associated with pl8-bearing alveolar macrophages.
REFERENCES :
(1) CALV0 C.F., B0UMSELL L., KOLB J. P. et al. J. Immunol. 1984. 132-2345.
(2) CHASSAGNE J., VERRELLE P., DIONET C. et al. J. Immunol. 1986. 136-1442.
MP121 The Sequential L°ss °f T Cell Functions Following HIV Infections.
ALAN WINKELSTEIN*, L.A. KINGSLEY, D.W. LYTER AND C.R. RINALDO JR.
University of Pittsburgh School of Medicine and the Pitt Mens Study, Pittsburgh
PA.
During the course of HIV infection, there appears to be a sequential loss of
T cell functions. To test this, the present studies examined four groups of
homosexual men: HIV antibody-negative (Ab-) (150); recent Ab seroconverters
(15); HIV Ab+ asymptomatic men (50) and those Ab+ men with chronic adenopathy
(68). The recent seroconverters were studied 2-19 months after their last
negative Ab test (mean 9 months) . Data are presented below.
%IL-2R
T cell
No with
T4 <400/mm
IL-
■2
Cells
Colonies
Synthesis
(U/ml)
Ab-
41.1
4421
8.8%
18.6
Ab converters
28.2*
4301
14.3
Ab+
25.0*
2608*
19.0
31.7
Adenopathy
25.2*
2412*
26.2*
16.2
*Signif icantly different from Ab- group
Thus, an early effect of infection is reduced ability of PHA stimulated cells
to express IL-2 receptors; this is seen in recent seroconverters. Shortly
thereafter, T colony growth is depressed; this can be seen in asymptomatic
homosexuals with normal numbers of T4 cells. T4 lymphopenia and decreased IL-2
production are later events. Colony responses correlate with the number of T4
cells and the expression of IL-2 receptors. These results suggest defective
ability to express IL-2 receptors and reduced T colony formation reflect immune
abnormalities associated with recent HIV infection.
MP124 Persistent Human Immunodeficiency Virus (HIV) Detection in
Seronegative Asymptomatic Carriers.
CM. FARBER+, S. SPRECHER-GOLDBERGER++ , CORINWE LIESNARD , K. HUYGHEN++ ,
J. C0GNIAUXt+, L. THIRY++ et al. + Hopital Erasme - Universite Libre de
Bruxelles. ++ Institut Pasteur du Brabant - Brussels - Belgium.
We describe 4 asymptomatic HIV infected patients in whom no anti-HIV
antibodies could be detected by any usual serological assays over a follow up
period of 16 to 23 months. All patients were at risk of HIV infection.
Evidence of HIV infection was demonstrated by culture of HIV from patients'
lymphocytes associated with reverse transcriptase assay. For each patient,
cultures were performed at least three times during the follow up period and
were consistently positive. Serological assays for HIV antibodies consisted
in enzyme-linked-immunosorbent assay, Western-Blot analysis, indirect immuno-
fluorescence, radioimmuno precipitation assay. For each patient, detection of
HIV antibodies was attempted on at least five occasions and remained negative.
During the follow up period, lymphocytes counts, mitogens responses and T4/T8
ratios remained normal, except in one patient. This patient seroconverted
after 23 months. This observation suggests that a HIV-carrier state without
any detectable HIV-antibodies and without clinical and biological significant
evolution can persist over extended periods of time, illustrating another
aspect of the natural history of HIV infection.
30
MONDAY, JUNE 1
MplOC Subclass and Isotope Specific Antibody Responses to HIV Infection
Analyzed by Western Blotting: Correlation with Clinical Status.
R. HICHAEL HENDRY,* K.R. JUDKINS,* A.E. WITTEK,* H.C. LANE,** AND G.V.
QUINNAN,* *Division of Virology, FDA, and **NIAID, NIH, Bethesda, HD, USA
To determine the fine specificity of antibody (Ab) responses to human
immunodeficiency virus (HIV) infection, we constructed an HIV Western Blot
(WB) using monoclonal Abs to each of the four immunoglobulin G (IgG)
subclasses and to IgG, M, and A isotypes. We analyzed 37 healthy HIV sero-
positives (HHS) and 41 AIDS patients. Total IgG WB patterns did not differ
between HHS and AIDS patients. However, a significantly greater proportion of
HHS individuals had both IgG 1 and IgG 2 Ab to pol (p66, p53, p31) and gag
(p55, p2A, pl5/17) antigens (Ags) when compared to AIDS patients. No signifi-
cant differences between the two groups were seen with IgG 1 or IgG 2 Abs to
env (gpl60/120, gp41) Ags. IgG 3 responses were almost entirely restricted to
gag Ags. However, there were no significant differences between the two groups
of patients in the frequency of IgG 3 anti-gag responses. IgG A responses were
relatively infrequent in both groups but were not restricted to any category
of HIV Ags, nor did the frequency of IgG 4 antibodies to any HIV Ags differ
between the two groups. IgM Ab responses in both groups were predominantly
against p24 and were significantly more frequent in HHS (47%) than AIDS
patients (22%) and IgM Abs to p64, p53, and pl5/17 antigens were also
significantly more frequent in HHS. Serum IgA Abs against most Ags were
observed in <10% of patients, but 25% of HHS had IgA Ab to p24 versus 5% of
AIDS patients. The detection of p24 antigen in serum or plasma by enzyme
immunoassay correlated with a decreased frequency of both IgG 1 and IgM Abs to
p24, but not to other HIV Ags. These differences in WB banding patterns
correlate with clinical status and may be useful in predicting outcomes of HIV
infection, and in delineating functional properties of anti-HIV Abs.
MDIOO Kinetics of Interleukin-2 Augmentation of Natural Killer Cell
Cytotoxicity in the Acquired Immunodeficiency Syndrome.
RAMSEY, K.M. , TRAN, C.B., E.V. PATTEN and J. A. REINARZ. The University of
Texas Medical Branch, Galveston, TX.
Natural killer cytotoxicity (NKC) of peripheral blood mononuclear (PBM)
cells is depressed among individuals with the acquired immunodeficiency
svndrome (AIDS). Tn vitro incubation of PBM with Tnterloukin-2 (IL-2) leads
to NKC augmentation, but not to the level of healthy controls. Therefore,
the kinetics of IL-2 augmentation of NK in AIDS were evaluated. PBM from
healthy adults and those with AIDS were incubated with interferons (lOOOU/ml)
alpha (rlFNaJ, beta (rIFNB ), rIL-2 (50U/ml) , or with medium for 1-12 hre
prior to a 4-hour Cr-release assay against K562 tumor targets. Mean lytic
units (LU/10 ) of NKC were as follows.
Controls (n - 14) AIDS (n - 16)
lhr 12 hr 1 hr 12 hr
10o~
PBM
rIFNB
rIFNa„
rIL-2
158*
178b
231b
413a
347a
454a
<5
<5U
<5
<5
<5
<5
8
55C
a - p <.05; b - p <.01 both from control PBM; c - p <.05 from AIDS PBM
Among both controls and AIDS PBM, the spontaneous NKC did not Increase with
Incubation time. Significant augmentation of NKC among controls wa6 observed
with IFNs and IL-2 after 1- and 12 hours (p<.05; p<.01), while NKC was aug-
mentated among PBM from AIDS only after > 12-hours of Incubation with IL-2.
These data suggest that the kinetics of augmentation of NKC in AIDS are
different from controls. Based upon these in vitro data, therapeutic
regimens using IL-2 in AIDS may require more prolonged exposure to augment
Immune responses.
MR126 Two T_ce11 Growth Factors Distinct from IL-2 Which
Provide a Proliferative Advantage to CD4 + T-Lyraphocytes .
JOSEPH E. GOOTENBERG and BRETT D. WALLACE, Georgetown University
School of Medicine, Washington, D.C.
Two factors from a human T-cell lymphoma cell line, designated
Leukemic T-cell Growth Factors I and II (L-TCGF I and II) will,
like IL-2, support the growth of activated, but not resting, T-
lymphocytes. These factors can be distinguished from human IL-2
and each other on the basis of molecular weight, isoelectric
point, temperature stability, resistance to inactivation by
proteolytic enzymes, and sensitivity to chemical reducing and
chaotropic agents. Anti-IL-2 antibodies do not react with either
L-TCGF, and concentrations of anti-IL-2 receptor antibody which
inhibit greater than 95% of IL-2 activity do not inhibit the L-
TCGFs.
IL-2 and the L-TCGFs appear to exert differential effects on T-
cell subsets. Unlike IL-2, the L-TCGFs will not support the
proliferation of a cloned mouse cytotoxic T-cell line, CTLL-2.
In addition, whereas IL-2-supported long term growth of PHA-
stimulated human T-lymphocytes yields populations enriched in
CD8+ cells, culture of similar cells in the presence of L-TCGF I
or II results in a predominance of CD4+ cells. These factors
represent new interleukins structurally and functionally distinct
from IL-2 which do not act through the IL-2 receptor. Their
biological significance and possible role in HIV-associated
immunodeficiency remain to be clarified.
MR129 Studies of "p24 Only" Immunoblot Reactivity to Human Immunodeficiency
Vi rus.
STEPHEN L. JOSEPHSON, N.S. SWACK, and W.J. HAUSLER, JR., Hygienic Laboratory,
The University of Iowa, Iowa City, IA.
As a reference laboratory providing comprehensive ELISA and immunoblot
testing of sera for the detection of antibody to Human Immunodeficiency Virus
(HIV), we have become increasingly interested in the interpretation of immuno-
blot results that demonstrate reactivity with p24 but not gp 41 viral protein.
In the present study, sera from 12 patients having p24 but not gp 41 or p55
reactivity to HIV antigen from Electro Nucleonics, Inc. (ENI) were retested
using HIV antigen from Oupont containing high (>100,000 Daltons) as well as
lower molecular weight viral proteins, ELISA (ENI) and indirect fluorescent
antibody (IFA) techniques. Five of 12 sera showed p24 and gp 110/120 Oupont
immunoblot reactivity and IFA reactivity. All but one of the 5 sera were also
ELISA reactive. Subsequent sera were obtained from 2 of the 5 patients,
including the patient with the ELISA negative serum, at 14 and 34 days after
the initial specimens. These later specimens both demonstrated p24, gp 41,
p55 and gp 110/120 reactivity on Oupont immunoblot as well as IFA and ELISA
reactivity. Sera from the remaining 7 patients studied demonstrated p24 but
not gp 110/120 Oupont immunoblot reactivity and were non-reactive by IFA.
Only 1 of the 7 sera was reactive by ELISA which was determined to be non-
specific. Subsequent sera obtained from 2 of the 7 patients after 25 and 28
days again demonstrated only p24 reactivity on Oupont immunoblot and were non-
reactive by IFA and ELISA. Sera from all 12 patients were absorbed with H9
cell lysate and were tested by immunoblot for reactivity to HTLV-I and HTLV-II
viral antigens. Absorbed sera retained HIV p24 reactivity. None of the sera
demonstrated p24 reactivity with HTLV-I or HTLV-II antigen.
MR127 Antibody Response to Human Immunodeficiency Virus in Homosexual
Men. Relation of Antibody Specificity, Titer, and Isotype to
Clinical Status, Severity of Immunodeficiency, and Disease Progression.
J.STEVEN MCDOUGAL, M.S. KENNEDY, J.K.A. NICHOLSON, T.J. SPIRA, H.W. JAFFE,
C.B. REIMER, et al. , Centers for Disease Control, Atlanta, GA.
We tested serum samples from 107 homosexual or bisexual men who are
seropositive for antibody to the human immunodeficiency virus (HIV) by Western
blot for antibody titer to specific virus proteins. The Isotype distribution
of HIV antibody was also determined using monoclonal antibodies specific for
IgM, IgA, and the IgG subclasses. Antibody titers to most viral proteins were
lower in sera from patients with the acquired Immunodeficiency syndrome (AIDS)
and In sera from men whose condition subsequently progressed to AIDS than in
sera from asymptomatic men and men with lymphadenopathy who have not
progressed to AIDS. The exception was antibody titer to the transmembrane
protein gp41, which was similar in all groups. We found no evidence of
Isotypic prominence or restriction of the antibody response. In multivariate
analysis, lower levels of T4+ T-helper cells were most highly associated
with (or predictive of) progression to AIDS. Antibody titers correlated with
T4+ T-cell levels, and therefore, declining titers are In part a function
(or consequence) of the severity of Immunodeficiency. However, lower antibody
titers to the envelope protein gpllO, the core protein p24, and the reverse
transcriptase enzyme p51/65 were also predictive of progression to AIDS
Independent of their association with T4+ T-cell levels. These data suggest
that differences in antibody levels are not simply a consequence of severe
immunodeficiency but may have a role in (or are a marker for) control of
infection.
MR130 HTLV-I Associated B Cell Transformation: A Model for
the Study of AIDS-Related 3 Cell Lymphoma.
CONSTANCE A. RAINER, VL NG , JW MARSH, J LIFSON, MS MCGRATK , UCSF
and San Francisco General Hospital, San Francisco, CA, USA.
The recent observation that sera from a high proportion of
AIDS-reiated B cell lymphoma patients react with both HTLV-I and
HIV proteins (Feigal, et al , this meeting) has led us to
investigate one of five immortalized numan 3 cell lines derived
by cocultivatlon of a lethally irradiated HTLV-I infected and
immortalized T cell line (CS-i) with normal human tonsillar
cells. We found that this B cell line, HKA-3 expresses and
secretes IgM, and produces HTLV-I envelope glycoprotein, gp6i .
Two dimensional gel electrophoresis further showed that secreted
HKA-3 IgM had anti-GP61 activity. A mouse monoclonal anti-
idiotype antibody developed against HKA-3 IgM bound to cell
surface forms of HKA-3 IgM and competed with HTLV-1 for ceil
binding. In vitro proliferation studies revealed that both
purified HTLV-I and anti-idiotypic antibodies specifically
increased HKA-3 cell proliferation, while control monoclonals and
purified HIV had no effect. These studies describe an
immortalized B cell line, HKA-3, transformed in association with
HTLV-I, which produces its own antigen, gp61 . Similar to normal
B-lymphocytes, KKA-3 cells proliferate, at least in part in
response to this antigen. Because KTLV-I may play a role In 3
cell transformation in vivo, this system may provide an
interesting new In vitro model for the further investigation of
AIDS-related B cell lymphomas.
31
MONDAY, JUNE 1
MP131 Isolation of HTLV-III/LAV Using Monocyte/Macrophages
as Targets for the Virus.
SUZANNE GARTNER, R.C. GALLO AND M. POPOVIC, Laboratory of Tumor Cell
Biology, NCI/NIH, Bethesda, MD.
HTLV-III/LAV isolates have been recovered from brain and lung tissues
of patients with AIDS. These tissues contained virus-positive cells which
exhibited characteristics of mononuclear phagocytes. These isolates had a
significantly higher ability to infect monocyte-macrophages (MM) than T
cells. (Gartner, et.al., Science, 233:215, 1986 and JAMA, 256:2365, 1986)
It is conceivable that this preferential tropism can account for the
considerable variability in the isolation of the virus from specimens of
HTLV-III/LAV-infected individuals utilizing conventional T cell culture
techniques. Using peripheral blood-derived MM and T cells as targets for
the virus, we attempted virus isolation from a number of specimens.
Several isolates were recovered from brain, peripheral blood adherent
cells, lung and skin using MM cells as targets. In most cases, we failed to
isolate virus from these specimens using T cells for cocultivation.
Isolates from peripheral blood T cells could be readily recovered by both
MM and T cell targets. In contrast, isolates from thymic tissue were
recovered by T cell but not by MM cell cocultivation. These results
further suggest that different variants of HTLV-III/LAV exhibit a
perferential tropism for MM or T cells. Furthermore, because the longevity
and magnitude of virus production in MM cells exceeds that of T cells, MM
cells are more efficient targets for virus rescue.
MR134 Anti-class II antibodies in AIDS patients and AIDS risk groups,
SILVIA de la BARRERA* LEONARDO FAINBOIM** GUILLERMO MUCHINIK*,GAS-
TON PICCHIO* SILVIA LUGO** MARIA M.E.BRACCO. *IIHEMA, Academia Nacional de Me-
dicina, ** CIMAE, Buenos Aires, Argentina.
The specificity of anti- lymphocyte antibodies against class I and class II
antigens was evaluated in AIDS patients and ; in i individuals at risk of AIDS (R-
AIDS: male homosexuals (Ho) and hemophiliacs (He)) with positive or negative
serology for HIV.
Anti-class II antibodies capable of inducing antibody-dependent-cell-media-
ted cytotoxicity (ADCC) against non-T cells and B lymphoblastoid cell lines
(P3HR-1K, Raji) were detected in AIDS patients and in R-AIDS with or without
HIV infection. This finding was confirmed by experiments in which class II
antigens in target cells were blocked with monoclonal anti-class II antibody
(DA6.231) and the cytotoxic reaction induced by patient's sera was abolished.
In contrast, ADCC was not impaired by preincubating the target cells with
monoclonal anti-class I antibody (W6/32) . Prevalence of antibodies to non-T
cells was confirmed by standard C-mediated microlymphocytotoxicity.
In addition to ADCC and C-mediated cytotoxicity, anti-class II and anti-class
I antibodies were assayed by their ability to interfere the binding of fluor-
escein labelled anti-class II (HLA-DR,Becton Dickinson) and anti-class I (W6/
32) antibodies to peripheral blood mononuclear leukocytes (PBMC) , non-T cells,
P3HR-1K and Raji. Anti-class II specificity was confirmed, and antibody titers
tended to be higher in Ho than in He, using non-T cells and Raji as targets.
High titers of anti-class II antibodies could contribute to impair antigen
recognition and aggravate the immune deficiency in this group of patients.
MP 13 2 Correction of Lymphocyte Dysfunctions _in vitro in ARC and AIDS
Patients as a Consequence of Isoprinosine Induced Changes in T
Cell Subsets and Antigen Presenting Monocytes (LeuM la ) .
PETER H. TSANG, Y. SEI, J. GEORGE BEKESI, Mount Sinai School of Medicine, New
York, New York 10029
Peripheral blood leukocytes from ARC and AIDS patients were analyzed follow-
ing PHA and PWM induced lymphocyte transformation with mAb(s) that identify
developemental (HLA-DR) and functional T-cells and monocytes. Significant
decreases in both suppressor regulating T subset (Leu 3 Leu8 ) and the reci-
procal inducer T subset (Leu3 Leu8 ) responsible for inducing differentiation
of B cells were observed. Simultaneously, the percentage of effector T and
the precursor T cells were increased, both of which were required for genera-
tion of suppression of cell mediated immunity. There was a selection of la
cells bearing Leu2 (Ts) markers and a concurrent reduction of antigen presenting
monocytes and activated T cells. Data suggest that the functional deficien-
cies in AIDS may be caused by defects in T cell activation as well as antigen
presentation by monocytes.
Isoprinosine stimulated B cell functions of ARC and AIDS patients, in a se-
lective fashion restoring both T cell dependent PWM induced transformation and
the spontaneous secretion of immunoglobulins by plasma cells while having no
effects on ^resting B-cells. Isoprinosine induced an increase in regulator T
(Leu3 Leu8 ) and inducer T (Leu3 Leu8 ) cells while potentiating la antigen
on T and monocytes during Glastogenesis . These events initiated a cascade of
cellular interactions leading to restoration of cell -media ted immune responses .
These interferences with the defective helper/suppressor regulatory pathways
may have important therapeutic implications.
MP135 Immunosuppressive Activity Associated with a Cell Line infected
with HTLV-III.
JAMES VI. SCHEFFEL, CHRISTI P. SCHEFFEL, and DENA TRAYLOR. Abbott Laboratories,
N. Chicago, IL 60064
Supernatants from an HTLV-III-infected H9 cell line were found to contain a
potent antiproliferative activity not found in supernatants of an uninfected
H-9 counterpart. The activity inhibited the proliferation of PBL activated in
vitro, as well as the growth of several cell lines, but was not directly cyto-
toxic. The activity was apparently not associated with intact HTLV virion in
that it was found only in the supernatant and not the pellet fraction of a
100,000 x g; 2.0 hr. ultracentrifuged preparation of culture supernatant. Un-
infected CEM cells would, upon being exposed to purified virus or pelleted
virus from infected cell line supernatant, produce antiproliferative activity
within one week postinfection. The activity was found to be protease sensi-
tive; labile to heat (65°C; 30 min), unrelated to alpha or gamma interferon,
and insensitive to indomethacin. Preliminary treatments of culture supernatant
with several different antisera to HTLV-III proteins have failed to neutralize
or immunoprecipitate the activity. Chromatography of concentrated supernatants
elucidated major peaks of activity with apparent molecular weights of >200 kd,
-65 kd and 9-17 kd. A substantial degree of purification was obtained after
affinity chromatography on hydoxyapatite, and active fractions eluted from this
medium were used to immunize rabbits and mice, which produced antisera
(IgG-fractions) capable of immunoprecipitating the antiproliferative activity.
MP133 Monocyte Function in a Male AIDS Patient and His Identical Twin
Phillip D. SMITH, L.M. WAHL, I. KATONA and S.M. WAHL. Cellular Immunology
Section, LMI, NIDR, NIH, Bethesda, Md.
To explore whether monocyte dysfunction may contribute to the impaired
lymphocyte proliferative responses in AIDS, we compared the accessory cell
function of monocytes from an AIDS patient with that of his healthy,
heterosexual, identical twin brother. Monocytes and T lymphocytes from the
twins were purified by counterflow centrifugal elutriation. The phytohemag-
glutinin (PHA) -induced proliferative response of the patient ' s lymphocytes in
the presence of his own monocytes was 13,000 cpra whereas that of his brother's
mononuclear cells was 102,500 cpm. However, replacement of the patient's
monocytes with those of his healthy brother resulted in a 3-fold increase in
PHA-stimulated lymphocyte DNA synthesis. In addition, the patient's monocytes
produced <30% the interleukin 1 (IL-1) activity of his twin brother's
monocytes. Therefore, we added purified exogenous IL-1 to cultures of the AIDS
patient's T cells plus his defective monocytes which resulted In a 3-fold
augmentation of DNA synthesis. Since the surface glycoprotein HLA-DR, a class
II histocompatibility antigen, is required for accessory function, we also
analyzed by fluorescence activated cell sorter the expression of HLA-DR on the
monocytes from the twin subjects. Although the percentage of HLA-DR monocytes
was reduced in the AIDS patient (55%) compared with that of his brother (83%),
the density of HLA-DR on the patient's monocytes was 2.5 times greater than
that expressed on the brother's monocytes.
Thus, monocyte accessory cell function in an AIDS patient was reduced
compared with that of his identical twin brother, and this reduction was due
in part to reduced IL-1 secretion and not to reduced expression of HLA-DR.
Accessory cell dysfunction may contribute to the immunosuppression in AIDS.
MR136 Malignant Prurigo of AIDS
BERNARD LIAUTAUD*, J.W. PAPE**, J. A. DEHOVITZ**, R.I. VERDIER*.
M-M, DESCHAMPS*. W.D. JOHNSON, JR.**, et al. , *GHESKI0, Port-au-Prince,
Haiti, **Cornell University Medical College, New York, N.Y.
During the period July 1983, to December 1984, we observed that 66/134
(49%) Haitian AIDS patients had intensely pruritic skin lesions (prurigo)
for which neither specific etiologic nor categorical diagnoses could be
established. Comparable lesions were not noted in 127 siblings and friends,
but were present in 6 HIV seropositive spouses of the AIDS patients.
Prurigo was an initial manifestation in 79% of these 66 patients and appeared
a mean of 8 months prior to the diagnosis of AIDS- Prurigo was characterized
by multiple erythematous round macules or papules which first appeared on the
extensor surface of the arms but subsequently involved the legs, trunk and
face* Histologically the lesions were characterized by varying degrees of
mixed (predominantly eosinophilic) perivascular inflammatory cell infiltrates
of the dermis. The lesions did not respond to any therapeutic regimens
employed and usually persisted throughout the AIDS illness. Demographic and
laboratory data did not distinguish AIDS patients with prurigo from those
without prurigo.
32
MONDAY, JUNE 1
MR137 CLINICAL AND IMMUNOLOGICAL FEATURES OF HETEROSEXUALS
INFECTED WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV).
RP BRETTLE, AJ France, ME Jones, CM Steel, GW Neil, PL Yap, City
Hospital, Blood Transfusion, Edinburgh.
An epidemic of HIV began in Edinburgh amongst heterosexual
intravenous drug misusers (IDM), one third of whom are female, in
August 1983 and reached 50% seropositivity by 1985. Edinburgh has
a large cohort of HIV infected heterosexuals Only 40% of
individuals infected via drug misuse are currently misusing.
We examined 115 HIV seropositive individuals, 5 homosexuals, 1
blood transfusion recipient, 3 heterosexual contacts of IDM and
106 IDM. Eighty two per cent of them have lymphadenopathy at two
or more non-inguinal sites, 76/101 have elevated IgG levels, 4
have had clinically significant thrombocytopaenia, 15 have a
leucopaenia <4.0x10(9)/l and 39 have a lymphopaenia <1 .4x1 0 ( 9) /l.
We performed lymphocyte subset estimation on 78 individuals and
22% have T4 cells <0.25x1 0(9)/l, 54% <0.5x10(9)/l and 83%
< 0.9x1 0 ( 9 )/l. There was no excess of current misusers or females
in any of the catergories. Significantly a total white cell count
missed 71% of patients with a lymphopaenia and a total lymphocyte
count missed 41% of those with a T4 count <0.9x1 0 (9)/l.
Within 4 years of infection there are significant clinical and
immunological abnormalities in a heterosexual population who
acquired infection via IDM despite the fact that only 40% are
currently participating in a high risk activity i.e. IDM. These
abnormalities are present despite the discontinuation of the high
risk activity for up to 3 years in some individuals. As yet we
are unable to say if progression is associated with continued IDM.
MR140 Neuropsychologic Evaluation of HIV Seropositive US Army Soldiers
D. HAEURCHAK, S. HARRISON, L. ANDRON, R. GRAPE, R. HANNON,
W. CLAYTON. Fitzsimons Army Medical Center, Aurora, CO USA
Thirty-three HIV seropositive asymptomatic soldiers identified on unit
screening were staged by Walter Reed classification and assessed for neuro-
logic disease. The 32 males and 1 female had a mean age of 28.1 and staged
7 as WR1, 23 HR2, and 3 WR3. Five patients, all WR2, had subtle neurologic
findings to include slowed rapid alternating movements, upper extremity
hyperref lexia, facial palsy and diminished short term memory and digit span.
Ten patients had CSF IgG index by nephelometry > .75, suggesting intrathecal
IgC synthesis. IgG index was not significantly different between abnormals
and normal exam patients ( . 98± .52 vs .621.20 p=.49). One patient each with
normal exam had abnormal EEG and MRI. Nine patients had 6-13 lymphocytes/
mm in CSF, 2 had CSF protein 50-70 mg/dl, none had CSF/serum albumin ratio
greater than .0065, and all had positive CSF HIV Western Blot when diluted
1:10. Mean WAIS-R PIQ scores were non-signif icantly higher in WR1 than WR2
(108.4+18.5 vs 97.7112.7 p=.56) and in normal exam versus abnormal exam
patients (101.7+14.4 vs 92.4±11.9 p=.43). Two patients had positive CSF FTA
and were treated for neurosyphilis. At six month follow-up all patients
remain on active duty with five of five showing mean WAIS-R PIQ improvement
of ±11.6+5.8 and none showing progressive neurologic disease.
MP138 GROWTH FAILURE IN CHILDREN WITH HEMOPHILIA AND HIV INFECTION.
Francine Kaufman* and Edward Gomperts, Univ. of So. Cal. Medical
School, Childrens Hosp. of L.A., L.A., CA, USA
It is not known whether infection with HIV virus in children with hemophilia
affects growth. As a consequence, the growth of 22 males with lymphadenopathy
syndrome secondary to HIV virus and hemophilia was evaluated. 66% were below
the 50th percentile for age but only 3 patients (pts) were found to have sig-
nificant growth failure of 3-4 yrs duration with the onset after HIV infection.
The pts were well except for lymphadenopathy; none had opportunistic infec-
tions. Height for weight was between the 25th and 50th percentiles. Results of
the endocrine evaluation which included the peak growth hormone (GH) response
to arginine-insulin and glucagon tolerance tests are listed.
Pt
Age
Bone
Height
Tanner
Growth
Rate
SmC
Peak GH
#
Yrs
Age
Age
Stage
Cm/Yr
U/Ml
Ng/Ml
1
15.3
14
14
2
4.7
1.2
21.7
2
14.7
11.5
11
1
3.2
0.53
20.2
3
8.5
6
5
1
3.0
0.4
14.1
(Normal (nl) growth rate >5 cm/yr; nl SmC 6-11 yrs, 0.50-2.06, 12-17 yrs, 0.78-
3.73; nl peak GH >10 ng/ml). All had normal thyroid function and Cortisol res-
ponse to insulin induced hypoglycemia. Pts 1 and 2 had mean 24 hour GH concen-
tration (GHC) determined by measuring GH every 30 minutes (normal > 3.0 ng/ml).
The GHC level was nl in pt 1 (4.95 ng/ml) and low in pt 2 (2.17 ng/ml).
CONCLUSION: Growth failure in pts with hemophilia and HIV infection is not rare
and does not appear to be due to classical growth hormone deficiency. In some
pts, this may be the consequence of the neurodysregulation of growth hormone
secretion and may be associated with hyposomatomedinemia . Further evaluation of
these pts needs to be performed to determine the incidence and etiology of
growth failure.
MP141 ^ne imPortance of Clinical and Laboratory Parameters in the
Management of AIDS Pneumonias
B. G. GAZZARD, M. ANDERSON, T. GARDNER, St. Stephen's Hospital, Fulham
Road, Chelsea, London, SW10 9TH.
A diagnostic bronchoscopy which was performed in 43 of 52 consecutive
patients with opportunistic pneumonias in the Acquired Immune Deficiency
Syndrome (AIDS) did not reveal a cause in 6. Thus there were 15
patients without a definitive diagnosis but all responded to high dose
Cortimoxazole and 9 developed other signs of AIDS within six months.
In 25 of the 52 patients Pneumocystis pneumonia (PCP) was confirmed as
the opportunist, but in only 3 was this by sputum induction. Cytomegalovirus
(CMV) was grown from bronchial lavage specimens in 15 patients but only
confirmed by transbronchial biopsy in 2. The lower the admission partial
pressure of oxygen (PA0_ ) the higher the diagnostic yield at bronchoscopy.
Seventy-five percent of our patients tolerated a full course of
Cotrimoxazole. The mortality in patients with mixed infections (20%)
was identical to that for PCP alone. Two of 5 patients in whom only
CMV infection was found, and 6 of 10 patients with both PCP and CMV
responded to Cotrimoxazole therapy alone.
The most potent indicator of prognosis was the admission PA0
(mean 9.6 KPA for survivors, and 6.7 KPA for non-survivors. P<0.01).
Simple observations of temperature and pulse were sensitive
indicators of survival. Repeated chest X-rays, blood gases and
bronchoscopy did not influence the management.
MR139 THE SPECTRUM OF PERIPHERAL NEUROMUSCULAR MANIFESTATIONS
WITH HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION.
JOSEPH R. BERGER, JOHN A. DIFINI, MARC A. SWERDLOFF, D. RAM AYYAR,
University of Miami School of Medicine, Department of Neurology, Miami, Florida.
Peripheral neuromuscular manifestations occurred in association with HIV infection in 29
patients (12 AIDS or ARC; 17 asymptomatic HIV seropositives). Seven patients presented
with a subacute polyradiculoneuropathy resembling Guillain-Barre syndrome (GBS) with
decreased nerve conduction velocities and increased CSF protein (5). All seven had full
functional recovery within one to six months. More than 50% of the patients with GBS
seen at our institution were HIV seropositives. Twelve patients presented with a slowly
progressive peripheral neuropathy manifested by increasing weakness (3), dysesthesia (4), or
both motor and sensory syptoms (5). Electrophysiological studies revealed the neuropathy
to be demyelinative in eight and axonal in four. CSF protein was typically increased (47-
138 mg/dl). Two patients developed brachial plexitis with weakness of the serratus
anterior, deltoid and the spinati and one had mononeuritis multiplex. Recurrent Bell's palsy
(3) and zoster sine eruption (3) were also noted. Two patients developed a generalized
myositis characterized by elevated muscle enzymes and abnormal electromyography.
Peripheral neuromuscular manifestations may occur early in the course of HIV infection,
long before the development of AIDS. These disorders are diverse in nature and often
disabling.
MP142 N°tnq?sychiatric Manifestations of Hunan Imnurrripf i dency Virus Infection:
Results of an Initial Screening Evaluation of HamRPxml/Rispxml Men.
JUSTIN C. MCARTH1R*. D. CSHCW**, O. SEINES*, C. ZHSKNMtU* , B. COHEN***, J. FHAIR***,
et al. "Johns Hopkins University, Baltimore, MD; **University of Michigan, Am Arbor,
MI, ***Narthwestern University, Chicago, EL, and the Multi-aenter AIDS Cohort Study.
A longitirlinal study of rieurcpsyohiatric lnariifestations of HTV is underway in
Baltimore and Chicago within the Multi-center AIDS Cohort Study. An initial screening
test battery (Phase 1) is followed, in participants scraening positive, by more
detailed neurr^sychiatric evaluation (Phase 2) , and MCE, EEE, CSF analysis, v*ere
appropriate. 363 hrrrRFxipil/bisexiial men were screened: 158 were HW-seronegative
(SN) , 157 had been seropositive (SP) > 30 months, and 48 had sercxnnverted (SC) during
30 months of observation. The frequency of positivity of Phase 1 screening instruments
is presented:
Phase LT Referral by
Phase I Instrument
Neurological Questionnaire
Psychiatric Sx Inventory
Cognitive Failures Quest.
Neurcpeyr*cdcgical Tests
Cptacon Vibration Test
Chicago (Total N = 148)
SP(N=€3) SNfN=48)SC(N=17)
Baltiiore (Total N = 215)
SP(N=74) SN(N=L10) SC(N=31)
12 (14%)
3 ( 6%) 2 (12%)
7 ( 8%)
1 ( 2%) 1 ( 6%)
6 ( 7%)
1 ( 2%) 2 (12%)
21 (25%)
7 (15%) 4 (24%)
6 ( 8%) 11 (10%)
14 (19%) 20 (1B%)
13 (18%) 15 (14%)
8 (11%) 9 ( 8%)
5(7%) 7(6%)
8 (26%)
7 (23%)
7 (23%)
2 ( 6%)
2 ( 6%)
This preliminary analysis indicates a relatively high rate of positive screening, in
all three groups, including seronegatives. Further ccrrelation with Phase 2 testing
will define the prevalence of nsurcpsycrdatric diarnuers and the predictive value of
the Phase 1 screen. Serial longiti rural testing of the two admits will cteLineate tne
incidence of neurcpsychiatric disorders.
33
MONDAY, JUNE 1
MR143 Neurological Recovery and Prolonged Survival in Progressive
Multifocal Leukoencephalopathy with HIV infection
JQSEPJ P.. BERGER*. LENNART HUCKE**. *Dept. of Neurology, University
of Miami School of Medicine, Miami, FL; **Dept. of Neurology, Harvard
Medical School, Boston, HA.
Pathologically confirmed progressive multifocal leukoencephalopathy
(PML) was the initial manifestation of HIV infection in two individuals,
a 39 year old homosexual man and 36 year old bisexual women. Both patients
experienced a dramatic, though incomplete, recovery of neurological function
and have survived in excess of 17 and 22 months, respectively, since the
onset of their neurological symptoms. Neurological improvement correlated
with improvement of abnormal immunological parameters in one patient,
whereas, the other patient displayed neurological recovery despite
deterioration in her immunological status and development of other
opportunistic infections. An uncharacteristically intense inflammatory
response for PML was observed in the brain biopsy specimens in regions where
the papovavirus was detected by electron microscopy; In 13 other HIV
seropositive patients with pathologically confirmed PML, progressive
neurological deterioration and death within 6 months were observed.
However, these two cases illustrate that PML associated with HIV infection
may demonstrate neurological recovery and prolonged survival.
MR146 Regression of Oral Hairy Leukoplakia with Acyclovir
LIONEL RESNICK*,J.HERBST*,D.V.ABLASHI**,S,Z,SALAH"DDIN**.B,FRANK*.
S.ATHERTON***,et al . ,*Mount Sinai Medical Center.Miami Beach ,FL, "National In-
stitutes of Health, Bethesda,MD,***University of Miami School of Medicine, Miami ,
FL.
The epithelial cells of the HIV-associated lesion, oral "hairy" leukoplakia
(OHL) .contain actively replicating Epstein-Barr virus (EBV). Orally administer-
ed acyclovir therapy resulted in clinical regression of OHL in 5 of 6 patients.
Regression of OHL was associated with an inability to detect EBV in the area
of previously recognized OHL.
A pilot study was conducted to evaluate acyclovir therapy (1.2gm/day for 20
days) in 13 HIV seropositive homosexual males with OHL involving the lateral
borders of the tongue. The presence of EBV in the lesion of OHL was documented
by electronmicroscopy (herpes-type particles) .immunofluorescence assay (IFA)
using 2 different monoclonal antibodies against EBV-VCA,in situ hybridization,
and by the presence of elevated levels of EBNA-infected cells after transforma-
tion of human fetal cord blood lymphocytes upon cocul tivation with OHL tissue.
Adjacent uninvolved tongue had no evidence of EBV antigens by IFA or in situ
hybridization. All patients had the presence of elevated levels of EB\NVCA and
EA antibodies in the serum. Clinical regression of OHL occurred 14 to 28 days
after initiation of therapy. After discontinuing treatment , OHL recurred in all
5 cases (range: 10-46 days). No regression of OHL was evident in the 7 un-
treated individuals after 6 months of follow-up. Regression of OHL was associ-
ated with an inability to detect EBV by IFA and jn situ hybridization in the
previously involved area of OHL. It appears that EBV infection and replication
is directly responsible for the clinical lesion of OHL. Acyclovir therapy in-
hibits the replication of EBV resulting in regression of the OHL lesion.
MP144 Polymyositis Associated with AIDS Retrovirus
MARINOS C. DALAKAS*. G.H. PEZESHKPOUR**, M. GRAVELL*, 3.L.
SEVER*, *NINCDS, NIH, Bethesda, MD., ** Armed Forces Institute of Pathology,
Washington, D.C.
Two homosexual men were initially seen with polymyositis as the only manifestation
of the acquired immunodeficiency syndrome (AIDS) retrovirus infection. They
presented with progressive proximal muscle weakness, elevated CPK and signs of
inflammatory myopthy in the muscle biopsy. They developed AIDS-related complex a
few weeks later and typical AIDS two to six months after onset of muscle weakness.
A third patient presented with dermatomyositis having the typical skin rash on the
face, around the eyes and on the chest, in addition to the other clinical and laboratory
signs of inflammatory myopathy. By use of anti-human T-cell lymphotropic virus type
HI antiserum and monoclonal antibodies to lymphocyte subsets in an
immunofluorescence technique, viral antigens were found in the OKTt-positive
lymphoid cells surrounding muscle fibers and invading the endomysia septa. We
conclude that an initial infection with the AIDS retrovirus can be associated with
polymyositis or dermatomyositis and this may be the first clinical manifestation of an
impending AIDS-related complex or AIDS.
MR147 "False-Positive" Antibodies to Human Immunodeficiency Virus (HIV)
Detected by an Enzyme-Linked Immunosorbent Assay (ELISA) in
Patients at Low Risk for Acquired Immune Deficiency Syndrome (AIDS)
FRANKLIN R. COCKERILL, III, M.D. , R.S. Edson, M.D. , R.C. Chase, B.S.,
J. A. Katzmann, Ph.D., H.F. Taswell, M.D., Mayo Clinic and Mayo Foundation,
Rochester, MN. .—.
ELISA testing for anti HIV antibodies using the Abbott ^kit was performed
on 290 sera from patient from 2 groups: (1.) at high risk for or having
symptoms of HIV infection and (2.) at low risk for HIV infection (231).
Group 2 included patients with non HIV related immune deficiencies,
dermatologic, neurologic, collagen vascular or hematologic disorders.
25 patients had high absorbancy ELISA results (>1.0 absorbance units).
All of these patients had positive Western blot (immunoblot) analyses and
were all in Group 1. 20 patients had moderate or low ELISA results (£1.0
absorbance units). 2 of these 20 patients had positive Western blots and
were in Group 1. The remaining 18 patients were in Group 2. 8 of these had
chronic liver disease, 4 had multiple myeloma and 6 had various disorders.
These 18 patients presumably had "false positive" reactions for HIV using
this ELISA test.
MR145 Progressive Neuropsychological Deficit in HIV Infection
IGOR GRANT*, J.H. ATKINSON*, C.J. KENNEDY, D.D. RICHMAN*,
S.A. SPECT0R, J. A. MCCUTCHAN, UCSD School of Medicine, La Jolla, CA, USA,
*San Diego Veterans Administration Medican Center, San Diego, CA, USA,
*UCSD School of Medicine, La Jolla, CA, USA.
To determine the characteristics and prevalence of cognitive deficit in HIV
infection, we performed neuropsychological (NP) assessments of 4 groups of
homosexual men. 1) AIDS (N=15) ; 2) ARC (N=13) ; 3) other HIV positive (N=16) ;
4) seronegative (N=ll) . All subjects were ambulatory and none presented with
clinical signs of AIDS dementia complex at time of testing.
Results. Neuropsychological abnormality was detected in 87% of AIDS, 54% of
ARC, 44% of other HIV seropositive, and 9% of seronegative men. Slowed infor-
mation processing was the most common finding, followed by impaired ab-
stracting ability and defects in learning and remembering.
Conclusion. It is possible that .cognitive impairment occurs early in HIV
infection and may be detected even in those who do not qualify for diagnosis
of AIDS or ARC.
MR148 Lymphoid Interstial Pneumonitis (LIP) in HIV-I or HIV-II infected pa-
tients.
L.J. COUDERC1, S. MATHER0N2, F. BRUN-VEZINET2, P. HERVE3, C. MICHON2,
J. P. CLAUVEL1. 1 : Hopital Saint-Louis 75010 Paris. 2 : Hopital Claude Bernard
75019 Paris. 3 : Hopital A. Beclere Clamart -FRANCE-
Eleven adult patients [9 male, 2 female ; haitian (7 cases), african (3 cases),
Caucasian (1 case) were] investigated for interstial pneumonitis. In 10/10 ca-
ses, lymphocyte count was increased (>140 x 10-fyml) in broncho-alveolar lavage
fluid and in 4/5 cases more than 80 % of the lymphocytes were Tg. No pathogens
were isolated. In 5 patients, open lung biopsy showed the histological picture
of LIP. Ten patients had persistent generalized lymphadenopathy (PGL), and the
Caucasian patient had AIDS. Blood T-cell count were decreased (<600/ml) in
all patients. HIV I-IgG antibodies were detected in 9/11 patients. The homose-
xual Caucasian man lived in Mauritania ; he showed IgG antibodies to HIV-II.
Ouring a mean fdllow-up time of 30 months (9-36), 3 patients had recurrent
bacterial infections ; their frequency decreased by use of I.V. gammaglobulin
in 2/2 cases. Four PGL patients developed opportunistic infections. The HIV-II
infected Caucasian patient died of a high-grade lymphoma with lung involvement.
Lung is a pulmonary manifestation of HIV-I or HIV-II infection. LIP seems to
be more frequent in black patients.
34
MONDAY, JUNE 1
MR149 Isolation of HIV from cerebrospinal fluid of patients
with AIDS related disorders.
DANIEL VITTECOO*. M. HARZICK*. F. FERCHAL*. Y. PEROL*. B. AUTRAN*. JC. CHER
MANN**. *St Louis Hospital , **Insti tut Pasteur, Paris, France .
We evaluated biological involvement of CSF by HIV in a prospecti
ve study by viral culture (reverse transcriptase activity) in the
CSF of 10 preAIDS patients (Walter Reed classification), 13 AIDS
without neurological symptoms, 10 preAIDS and 10 AIDS with neurolo
gical symptoms. HIV was isolated in the CSF in IB patients without
pleiocytosis (<15 cells/mm3) , and was correlated to viremia (13/15)
Presence of HIV Ln the CSF is related to the general status (10/23
AIDS), or to the neurological involvement whatever the symptoms
(9/20 AIDS and preAIDS) . Only 1 preAIDS (WR5) without neurological
symptoms was positive, all the other preAIDS patients were negative
(5 WR2.3 WR3, 1 WR4 ). Glycoprotein antibodies were found in the CSF
in all patients by Western blot analysis (gpllO, gpl60) . Intrathecal
synthesis of antibodies was evaluated by ELISA and did not have a
discriminating value. Presence of the virus in the CSF should be
investigated prior to any evaluation of an antiviral drug since a
failure could be due to a silent neurological involvement (6/23
without neurological symptoms).
A greater cohort of preAIDS patients is being evaluated and re
peated lumbar puncture data will be provided o establish a correla
tion with CT scans, general and neurological prognosis.
MR152 Salivary Gland Function in Early AIDS Patients
C.-K. YEH, K.A. BUSCH, D.K. WEIDLEIN, P.C. FOX and B.J. BAUM
CIPCB, NIDR, NIH, Bethesda, HD, USA
Saliva plays a primary role in modulating oral microbial colonization
patterns. Reports of xerostomia and oral candidiasis in AIOS patients suggest
the possibility of altered salivary gland status. The purpose of the present
study was to assess salivary gland performance in early diagnosed AIDS
patients. All patients were homosexual or bisexual males, HIV culture positive
± cutaneous Kaposi's sarcoma and/or lymphadenopathy. Patients were divided
into two groups; those being treated with AZT and others who had received no
treatment. Two control groups were used: healthy men and male patients with
complaints unrelated to salivary glands. Parotid and submandibular/sublingual
salivas were collected on ice and stored at -70° until analysis (volume, Na ,
K , CI", total protein, albumin, lysozyme). There were no marked differences
found between AIDS ± AZT patients and the non-AIDS control groups with respect
to electrolytes, total protein and salivary flow rates, for parotid and
submandibular/sublingual glands under both basal and stimulated conditions.
However, the frequency with which albumin was observed in saliva of both AIDS
groups was dramatically increased; being seen in 48/73 AIDS saliva samples but
in none of the 64 control samples. Albumin in gland saliva indicates the loss
of salivary epithelial integrity. Also both AIDS groups had 2-3 fold higher
levels (than controls) of lysozyme, an antimicrobial protein secreted by
salivary ductal cells. The data demonstrate (1) early-diagnosed, metabol ical ly
stable AIDS patients show evidence of specific salivary gland dysfunction and
(2) AZT therapy has no effects on salivary performance. These results suggest
that study of salivary antimicrobial factors will be important with respect to
the development of oral opportunistic infections.
MR150 Psychiatric Consultation to AIDS Patients, 1981-1986: A Consultation
Liaison Perspective
Henry W. Welsman, E. Harvey, M.D. Nienaltow, D. Eaton, St. Luke's-Roosevelt
Hospital Center, New York, N.Y., U.S.A.
The psychiatric morbidity associated with Human Immunosuppressive Virus(HIV)
infection reflects varied biopsychosocial etiologies and may require adapta-
tions in the provision of consultation services. The psychiatric care of AIDS
patients was evaluated by reviewing all service consultations to AIDS and ARC
patients between 1981 and 1986 at St. Luke's Hospital, a 776-bed teaching faci-
lity in New York. Specifically, these were evaluated in terms of reasons for
consult requests, time between admission and consultation, number of psychia-
trist's visits, psychiatric diagnosis, and treatment. The data were compared to
similar data for all general hospital patients consulted by psychiatry in the
same years.
In the 5 year study period, the number of consultations to HIV patients in-
creased 17-fold. The most common psychiatric diagnoses were adjustment disor-
ders (2k%) and organic brain syndromes (2k%) . Neuroleptic medication was used
frequently (28$). There were also variations in the treatment of patients in
different risk groups.
Compared with general hospital patients, reasons for requesting consultations
were similar (principally depression, suicidal ideation, and treatment refusal)
although HIV patients required 1/3 more visits than did general medical pa-
tients. Differences were also observed in the distribution of psychiatric diag-
noses and in the provision of suicide precautions.
The evaluation of psychiatric consultation data provides clinicians with a
way to gauge the effect of AIDS on psychiatric services. Furthermore, it offers
measures of the psychosocial morbidity and clinical needs associated with AIDS.
MR153 Natural history of HIV-1 infection in children .
CARLO GIAQUINT0*,A.DE ROSSI** .A.VAGLIA*** .G.CADEO****, A. AMADORI** .F.ZACCHELLO* ,
et al.,*Dpt. of Pediatrics ,**Institute of Oncology, University of Padova,***Dpt.
of Infectious Diseases, Vicenza,****Dpt. of Infectious Diseases, Brescia, Italy.
To investigate the natural history of perinatal HIV-1 infection we studied ba-
bies born to mothers belonging to high risk groups. Fifty eight infants and chil-
dren born to HIV-1 seropositive mothers have been studied over the last two years.
Blood samples were obtained at birth or in the first six weeks of life in 45 ca-
ses.All babies were evaluated serologically , virologically , and clinically every
two months; neuromotor assessment and evaluation of mental development were also
performed. Sera collected at birth or in the first six weeks of life from 45 uabies
were positive for IgG specific antibodies: however 30% of babies older than six
months became seronegative. Cultures from peripheral blood lymphocytes, tested for
reverse transcriptase activity .were negative in all seronegative children ;cultures
derived from 9 out of 25 seropositive children, older than six months, were positi-
ve in the reverse transcriptase assay.
Two infants had AIDS and 7 AIDS-related complexes. To date the other babies
younger than 18 months are clinically well and laboratory data are in normal ran
ge.In most of the older asymptomatic children T4/T8 ratios are < 1.0. Although so-
me babies received live oral polio vaccine and/or are shedding Cytomegalovirus
in the urine, none of them present clinical signs of infection due to these viru-
ses. Neurological development is normal in all asymptomatic infants while mental
evaluation is in progress.
MR151 Absence of Correlation Between Serological Results, Neutralizing An-
tibody Titers, and Progression of HIV-related Disease
HARRY HOLLANDER* J HIGGINS**, N PEDERSEN**, J YEE**, J CARLSON** *UCSF School
of Medicine, San Francisco, CA, USA **UC Davis School of Medicine, Davis, CA,
USA
We reviewed serologic and neutralization antibody data on 50 random HIV sero-
positive patients to determine whether any serological markers of clinical out-
come existed. At the time of initial specimen acquisition, 20 subjects were
asymptomatic or had HIV-related diseases but not AIDS. Eight had KS and 22 had
prior opportunistic infections with or without KS. The major serologic change
over time was the loss of the p24 antibody band. Eight of 11 subjects with
this pattern had had opportunistic infections. Patients with and without the
p24 band initially had similar rates of development of KS or new opportunistic
infections, and when loss of the band was seen, it usually occurred after the
onset of opportunistic infections. Serial ELISA titers were done on 31 sub-
jects. Eight of 31 had at least a four-fold fall in titer over the period of
observation. Only 2 of 8 had the fall in titer before the development of op-
portunistic infections. Five had a decline in titer after disease progression
and 1 was clinically stable despite the decline. Similar results were seen
with titer of immunofluorescent assays. Neutralization activity was measurable
in 30 of 31 subjects at titers of 1:4 to 1:128. Titers were stable over time
and there was no correlation between neutralization titer and initial diagnosis
or eventual progression of disease. Utilizing current serological techniques
and serial specimens, we find that changes in HIV antibody titer and immuno-
blot pattern are insufficiently sensitive and specific to predict course of
disease. Similarly, neutralizing antibody titer is not a good prognosticator
of disease progression.
MP154 Human immunodeficiency virus (HIV) -related polyradiculoneuropathy
(PRN) : lack of evidence for antiperipheral nerve antibodies (PNA).
SERGE PRZEDBORSKI*. C. LIESNARD », Ph. V00RDECKER •, H. TAELMAN •*, J.H.
GERARD *, S. SPRECHER •••, et al., ■ Hopital Erasme, Brussels, •• Institut
de Medecine Tropicale, Antwerpen, ••• Institut Pasteur du Brabant, Brussels,
Belgium.
Five patients (pts) who presented with flaccid paraparesis and high cere-
brospinal fluid (CSF) HIV antibody level were investigated in evolutive
phase. Four of these pts met the criteria of AIDS. Clinical picture consisted
of progressive distal and symmetrical weakness, with abolished reflexes. Mild
sensory impairment was present in 3 pts and absent in 2 pts. Nerve conduction
velocities were slowed in 3 pts. CSF protein was elevated (mean 364 mg/dl)
and white cells were 2 to 109/mm . Sural nerve biopsy performed in 3 pts
showed segmental demyelination with intact axons and no inflammatory cells
infiltration in 2 pts and was normal in 1 pt. Intrathecal synthesis of HIV
antibodies was found in 3 pts and CSF culture was positive for HIV in 1 pt.
All pts displayed polyclonal hypergammaglobulinemia. Except for HIV infec-
tion, other causes of PRN were excluded. The presence of circulating PNA
was investigated by incubating normal nerve with pts* serum and CSF then with
FITC-conjugated antibody to IgG, IgM and IgA. No binding was observed. The
presence of immunoglobulin deposits in sural nerve biopsy was investigated
in 3 pts by immunostaining with FITC-conjugated antibody to IgG and IgM.
No deposits were observed.
These data suggest that the pathogenesis of HIV-related PRN is not mediated
by PNA.
35
MONDAY, JUNE 1
MD-fCC Analysis of Bacteremias in Patients with AIDS.
,f"«"*W LEWIS SCHRAGER, RS KLEIN, K FREEMAN, M MOTYL, L RICCI, GH FRIEDLAND.
Montefiore Med. Ctr./N. Central Bx. Hosp./A. Einstein Coll. of Med., Bx,NY,USA
Bacterial infections may cause significant disease in patients (pts.) with
AIDS. To explore this issue, we studied bacteremias (Bs) occurring in a well-
defined AIDS population. Microbiology records at Montefiore Med. Ctr. (MMC)
and N. Central Bx Hospital (NCB) were reviewed for all significant Bs occurring
between 1/82 and 7/86. Bs were cross-referenced with a registry of pts. with
AIDS hospitalized during this time. Available records for these pts. were re-
viewed. Sixty-nine Bs occurred in 58 of 306 (19%) AIDS pts. for a rate of 22.5
Bs/100 AIDS pts. At MMC during this period 2,244 Bs occurred in 83,955 pts.
without AIDS for a rate of 2.7 Bs/100 pts. (p<0.05). The occurrence of B among
pts. with AIDS was not significantly associated with risk, group, age, gender or
race. However, B due to S. aureus was significantly more common in pts. with
intravenous drug use as their heirarchical risk behavior for AIDS (p<0.05).
Organisms most frequently causing B included S. aureus (21 episodes) S. pneu-
moniae (12), salmonella sp. (12), P. aeruginosa (7) and other gram negative
bacilli (13). Six episodes were polymicrobial. Twenty-six of 54 (48%) evaluable
Bs were community acquired, 22/54 (41%) were nosocomial (70% of S_. pneumoniae
were community acquired, 69% of S_. aureus nosocomial), and the remainder could
not be classified. Eighty percent of B occurred at or following the diagnosis
of AIDS (78% of community acquired, 96% of nosocomial). In 45% of patients with
B, the infection causing B was the reason for admission. Survival analyses re-
vealed no significant shortening of life expectancy among AIDS pts. with B.
We conclude that AIDS pts. are at significantly increased risk for B regard-
less of risk group or other demographic variables. Therefore, the increased
rate of Bs in AIDS pts. is likely the result of HIV infection. Although Bs are
frequent among AIDS pts. they do not appear to significantly influence survival
when appropriately diagnosed and treated.
MR158 Hypoxemia and neutrophilic alveolitis as prognostic factors of Pneu-
mocystis carinii pneumonia (PNC.C.P.) in HIV infected patients.
Pierre FOURET, F.PARQUIN, J.P.BEOQS, J.F.SICARD, C.M.MAYAUD, J.ROLAND et al.
Pathology and Chest Departments, Tenon Hospital, PARIS, 75020 - FRANCE.
This study concerns 46 HIV infected patients (pts) u/ith PNC.C.P. and without
identifiable associated infection. At the time of diagnosis of PNC.C.P., Pa02
and BAL data [total cells, number and percentage of lymphocytes (L) and neutro-
phils (PMN)]\i/ere evaluated. All pts u/ere treated u/ith Trimethoprime-Sulfametho-
xazole (TMP-SMZ) ; they were divided into 2 groups, according to the evolution
of their pulmonary disease (G I : 10 with fatal acute respiratory failure ;
G II : 36 with a favorable outcome).
The significant correlations between initial Pa02 and/or BAL data (cell count/mm^ ■
G I 107+77 ;G II 189+120) and evolution are indicated in the following table.
G
Nb pts
N
Pa02
mm Hg
PMN
PMN/L
Pa02<50
n pts/N
PMN>5/mm3
n pts/N
PMN/L>0.5
n pts/N
I
10
52 + 13
26 + 26
0.57 + 0.9
7/10
9/10
7/10
II
36
67 + 19
10 + 13
2.9 + 4.2
8/36
18/36
10/36
p<0.02
p<0.05
p<0.001
p<0.01
p<0.03
p<0.01
It is to be noticed that : DThere is a significant relation between Pa02 and PMN (%)
and 2)Post-mortem examination oflungfrom8 G I pts showed fibrosis in 7 cases.
Conclusion : Initial Pa02<50mm Hgand PMN/L (in BAL)>0.5u/ere present in 5/10 pts
of G I. Even though this association was also present in 4/36 pts of G II, it seems
a poor prognostic factor and, when present, probably indicates that other initial
treatment, e.g. a TMP-SMZ/steroid association, should be considered.
MP156 Pregnancy Outcomes and HIV Infection in Intravenous Drug Abusers
PA SELWYN, ANAT R FEINGOLD, EE SCHOENBAUM, K DAVENNY, V ROBERTSON,
J SHULMAN, et al., Montefiore Med. Ctr., A. Einstein Col. Med., Bronx, NY, USA.
Beginning 7/1/85 we studied the effect of HIV infection on outcome of known
pregnancies in intravenous drug abusers attending a NYC methadone program. Both
seropositive (SP) and seronegative (SN) women enrolled in a prospective study of
HIV infection were monitored for early pregnancy with monthly urine testing.
Additional women were tested for HIV serum antibody (Ab) after conception. Ob-
stetrical and infectious complications were monitored and serial HIV Ab and T-cell
studies performed. Among women not pregnant at the time of initial HIV Ab test-
ing, 12/71(17%)SPs vs.l9/145(13%)SNs became pregnant over 18 months of follow-up.
Among pregnant women informed of HIV Ab status <24 weeks gestation, 4/10(40%) SP
vs. 6/17(35%)SN elected to terminate. 33 pregnancy outcomes occurred in 26 SPs
without AIDS or oral thrush (mean age 30) , and 45 outcomes in 44 SNs (mean age 29) .
Number of Spontaneous „ , Elective, ^ Livebirths Livebirths
SPs
SNs
Outcomes Abortions Ectopics Terminations*
~37~
45
2(5%
~0~
2(5%)
14(43%)
11(24%)
weeks
3T9T5
7(16%)
weeks
13(397.) *p=NS
23(50%) F
Of 44 women carrying > 24 weeks (15SP,29SN), mean third trimester hemoglobin
levels (H.4 vs. 11.5) were not different. SP women had lower lymphocyte counts
(1769 vs. 2319) and T-cell ratios (0.88 vs. 1.65, p<.05). 5/15(33%) SPs were
hospitalized for infections; gastroenteritis (2) , pneumonia(2) , cellulitis ( 1), vs.
2/29(7%) SNs; gastroenteritis(l) , pyelonephritis(l) , (p<.07). The frequency of
other medical and obstetrical complications during pregancy or at delivery did
not differ between the two groups. There were no differences in self-report of
drug abuse during pregancy.
HIV Ab was not associated with a decreased occurrence of pregnancy in SPs, nor
with early or late adverse pregnancy outcomes . Data suggest that pregnant SP women
may be at increased risk of serious infectious complications. Frequency of elec-
tive termination was not significantly increased in SP women. These findings
have important implications regarding perinatal transmission of HIV infection.
MR159 Progressive Multifocal Leukoencephalopathy (PML) in AIDS Patients:
Diagnostic Considerations and Pathologic Findings.
S.A. HOUFF, D. KATZ, C. KUFTA, G. ELDER, D. VACANTE, E. MA30R, NINCDS,
NIH.Bethesda, MD.
PML, a subacute demyelinating disease due to JC virus (3CV), is seen frequently in
AIDS patients. We have previously reported the use of in situ hybridization with a
biotinylated JCV probe in the diagnosis of PML. Three AIDS patients with PML have
been studied with this technique on either brain biopsy or autopsy tissues. In one
patient, the diagnosis of PML was established within 4 hours of biopsy by m situ
hybridization performed on frozen sections using a modified technique developed by
one of us (EM)). Formalin-fixed biopsy tissue confirmed these findings. Areas of
demyelination associated with JCV infection of oligodendrocytes, and astrocytosis
were found throughout the biopsy. In another patient, areas of demyelination found in
biopsy tissue had none of the other pathological features of PML In situ hybridization
with the 3CV probe demonstrated infection of oligodendrocytes, which confirmed the
diagnosis of PML. Autopsy studies in two patients revealed extensive demyelination in
the white matter of the cerebral hemispheres. In one, JCV infected cells without
other pathologic changes were found scattered throughout the cerebral hemisphere and
PML lesions extended into the cerebral cortex. Our studies suggest that PML in AIDS
patients is often more extensive and histological changes may be more subtle than
when the disease occurs with other immunosuppressive illnesses. The use of in situ
hybridization is essential in rapidly establishing the diagnosis of PML in patients with
AIDS.
MP157 ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) ASSOCIATED RENAL
DISEASE: A LONGITUDINAL ANALYSIS. T.K.S. Rao. E.A. Friedman. SUNY
Health Science Center at Brooklyn, N.Y., USA.
Over a four year period between 1982 and 1986, among 800 patients with AIDS seen at
two urban institutions, 95 were evaluated for renal abnormalities consisting of varying de-
grees of azotemia, proteinuria and hematuria. We classified renal disorders in AIDS on the
basis of clinical presentation, hospital course, and renal histology (when available). There
were 23 patients with potentially reversible acute renal failure (ARF); 54 patients with
AIDS associated nephropathy (AAN); and 18 patients who developed AIDS while undergoing
maintenance hemodialysis (AIDS-MH) (Table).
YEAR
ARF
AAN
AIDS-MH
Cr<6
Cr>6
Cr<6 Cr>6
'82
0
0
0 2(2)
1(1)
'83
2
1(1)
2 9(7)
0
'84
1
8(4)
4 9(7)
4(4)
'85
1
1(0)
0 9(3)
6(6)
'86
2
7(1)
4 15(12)
7(7)
TOTAL
6
17(6)
10 44(31)
18(18)
Number ( ) represents pts dialyzed
Among the ARF group, 6 of 17 with serum Cr>6 mg/dl wno were dialyzed, 5 recovered
sufficient renal function and survived without further dialysis for a median 17 months. In
the AAN group, 44 of 54 patients developed irreversible uremia, and 31 were repeatedly
dialyzed. Median survival of dialyzed AAN patients was 1.4 months. In the AIDS-MH group,
all 18 patients were IV drug addicts, who developed AIDS within 7 months (median) of in-
itiating maintenance hemodialysis. Their median survival after diagnosis of AIDS was 1
month despite dialysis. From these data we conclude that renal failure both acute and
chronic in AIDS is increasing and survival continues to be very poor.
MP160 Tne Need for Tissue Diagnosis of Central Nervous System Lesions
with the Acquired Immunodeficiency Syndrome.
ELIAHU BISHBURG*. J. SLIM**, E.S. JOHNSON**^. KAPILA***, R.H.K. ENG****,
AN.J. State Department of Health, Trenton, St. Michael's Med. Ctr.,
***Univ. Hosp., Newark, VA Med. Ctr., East Orange, N.J.
Patients with acquired Immunodeficiency Syndrome (AIDS) who have central
nervous system (CNS) lesions and positive toxoplasma serology are often
presumed to have cerebral toxoplasmosis and are treated accordingly.
We examined records for 600 AIDS patients retrospectively and found 47
with CNS lesions on CT scan. Lesion types included multiple and single ring
enhancing as well as multiple and single hypodensit ies . Nineteen of these
patients had positive toxoplasma serology. Of the thirteen with brain
biopsies, 6 had toxoplasmosis, 2 had tuberculosis, 2 had encephalitis of
unknown cause, 1 had nocardia and salmonella, 1 had vacculitis and 2 showed
nonconclusive results. Biopsies of 3 of the patients with significant
toxoplasma serology showed no evidence of toxoplasmosis.
The majority of the cases (36) had been presumptively diagnosed as having
toxoplasmosis and treated with anti-toxoplasmosis regimen — pyrimethamine and
sulfadiazine (30) or pyrimethamine and trimethoprim-sulfamethoxazole (6).
That 8 of the 13 biopsies revealed diseases other than toxoplasmosis, some
of them treatable, suggests that other diseases may be common and that
biopsies of CNS lesions in AIDS patients are needed to make accurate
diagnoses to detect treatable diseases and to avoid unnecessary treatment.
36
MONDAY, JUNE 1
MR161 Sclerosing cholangitis in AIDS
PIERRE-MARIE GIRARD, C. MARCHE, C. LEPORT, C. MICHON,
D. ZOUBI, A.G. SAIMOT et al . , Hopital Claude Bernard, 75019
Paris, France.
Cholangitis was documented in 6 out of 101 AIDS patients (pts)
whose liver histology was available (surgical biopsy:l, needle
biopsy:53, autopsy:68). Right hypocondrial pain and prolonged
fever were present in 4 patients. Anicteric cholestasis occurred
in all patients and was major in 4 (alkaline phosphatases : 8 x
normal value). Diagnosis was made by endoscopic retrograde
cholangiography and laparotomy (1 pt ) , needle biopsy (2 pts)
and/or autopsy (4 pts). Sclerosing cholangitis associated with
pericholangitis predominated on proximal intrahepatic biliary
ducts. In 5 cases, numerous typical cytomegalovirus (CMV)
inclusions were present in both biliary epithelium and endothe-
lial cells. In one case, no intra-hepatic biliary duct
inclusions could be found at autopsy although CMV cholecystitis
was present. All patients had CMV viremia and disseminated CMV
infection ( yt 2 organs). These data show that cholangitis occurs
in 6% of AIDS patients and is one of the multiple factors
involved in the frequent cholestasis. Needle biopsy could
underestimate its prevalence because of the predominant proximal
biliary duct involvement. Cholangitis is mainly due to CMV but
can also occur without any opportunistic agent as already
reported in other immunocompromised status.
MR164
DIFFUSE CERVICAL CELLULITIS ASSOCIATED WITH HIV 1
INFECTION IN CENTRAL AFRICA.
E. VUILLECARD*, C.C. MATHIOT**, M.C. GEORGES-COURBOT**, A.J. GEORGES^,
Centre National Hospitaller Universitaire, Bangui, Central African Republic
(CAR), **Inscitut Pasteur, B.P.923, Bangui, CAR.
Within a seven month period ten cases of diffuse cervical cellulitis have
been observed in the stomatological department of Bangui general hospital.
All of them resulted from non-treated dental infection.
Clinical symptoms showed emphysematous gangrene and large facial necrosis.
Bacteriological examination of pus withdrawn by syringe under anaerobic
conditions allowed us to identify in one case Fusobacterium nucleatum and in
two cases Clostridium perf ringens, while no consistant interpretation was
possible in seven cases. Nine of ten patients were HIV 1 antibodies carriers
(ELAVIA and Western Blot) without any other symtom of confirmed AIDS.
We consider acute diffuse cervical cellulitis as a possible first symptom
of an A R C in HIV 1 positive patients, in Africa.
In this syndrom (ARC) , treatment consisting of large surgical debridement
associated with penicillin and metronidazole therapy, has always been
efficient.
MR162 Children's Hospital AIDS Program (CHAP): I Demographic and Clinical
Data 1984-1986
EDWARD CONNOR, S. MORRISON, M. BOLAND, L. EPSTEIN, V. JOSHI, J. OLESKE
Children's Hospital of New Jersey & UMD-New Jersey Medical School, Newark, NJ
Sixty three children with symptomatic HIV infection were enrolled in CHAP
from 1984-1986. 46% AIDS; 54% ARC. Male:female ratio 0.85:1. Ethnic origin
distribution: Black 52%; Hispanic 24%; White 21%; Haitian 3%. Risk factors:
mother IVDU 40%; mother sexual contact of IVDU 30%; both parents IVDU 10%;
neonatal transfusion 6%; maternal transfusion 5%; hemophilia 3%; Haitian 3%;
multiple risk 1.5%; unknown 1.5%. Excluding hemophiliacs, mean age at enroll-
ment was 1.88 yrs (0.2-7.75); 11/61 were enrolled at >4 yrs. 16/63 (25%) of
patients were first seen to be screened for HIV because of known risk: 8/16
were healthy; 8/16 had chronic symptoms; 35/63 were first seen for acute ill-
ness. Among these 63 children, signs and symptoms over 2 yrs included: rash
95%; lymphadenopathy 92%; hepatosplenomegaly 87%; fever 84%; respiratory
findings 79%; thrush 71%; encephalopathy 68%; FTT 56%; recurrent otitis media
49%; abdominal distention 48%; diarrhea 43%; clubbing 21%; gingivostomatis
19%; parotitis 11%; abdominal pain 11%; CHF 8%; epistaxis, joint pain,
conjunctivitis, GI bleeding, jaundice <5%.
There were 23 opportunistic infections (8 PCP, 8 Candida, 2 Toxoplasmosis,
3 disseminated CMV, 1 disseminated adenovirus, 1 MAI); 4/63 had neoplastic
disease (1 CNS lymphoma, 1 GI leiomyosarcoma, 2 pulmonary lymphoprol iferative
disease). 29 episodes of bacterial sepsis occurred; 20 streptococcal; 4
Salmonella spp. ; 3 H. influenzae; 2 S. aureus. LIP/DIP was documented in 23/63
(57%) of children. HIV is a chronic multisystem disease with protean mani-
festations. The practitioner must maintain a high index of suspicion for HIV
infection in children.
MD-1CC Asymptomatic Neurologic Infection in Persistent Generalized
Lymphadenopathy Syndrome Associated to HIV Infection.
B . CLOTET* . , J.H. BARRERA* ., G. ERCILLA**., M. GRIFOL*., J. TOR*.,
J . CANO* . , E. ARGELAGUES*** . 'infectious Diseases Unit, ***Blood Bank Unit,
Hospital de Badalona "Germans Trias i Pujol"; Blood Bank Unit Hospital
Clinic de Barcelona. Barcelona, Catalonia, Spain.
We searched by ELISA and Western blot techniques antibodies to HIV in serum
and CSF of 40 patients with PGL.A11 were intravenous drug addicts and none
presented neurologic manifestations -All CSF analyzed were free from red
blood cells. In 10 patients (25%) we found antibodies to HIV in serum and CSF
by both methods . Results are listed in the following table:
Patient No ELISA CSF WB CSF ELISA Serum WB Serum
pl8p24p33p41p55p68pll0
Pl8p24p33p41p55p68pll0
± + - + + + -
9 + ___ + ___ + + + _ + _ + _
10 + +±-±--- + + + - + -- +
Leakage of HIV-specific antibodies from the serum to the CSF can not be
excluded nevertheless immunoglobulins do not diffuse substantially into the
CSF in the absence of brain or meningeal inflammation, what leads us to
assume that these patients present asymptomatic CNS infect ion. Asymptomatic
neurologic infection may be an early event in HIV infect ion . Fol low-up may
confirm our findings.
MR163 DETECTION OF INFECTIOUS HUMAN IMMUNODEFICIENCY
VIRUS (HIV) IN SEROPOSITIVE INFANTS AND CHILDREN
PEGGY S. WEINTRUB, M.A. KOERPER , C. WALKER, D.W. WARA, J. A. LEVY,
M.J. COWAN
Departments of Pediatrics and Medicine, University of California,
San Francisco, CA 94143
While the majority of children infected with HIV develop
antibody, a significant number may have undetectable infectious
HIV in their peripheral mononuclear cells (PMC). We evaluated 26
seropositive children for the presence of infectious HIV in their
PMC and assessed in vitro immunologic parameters and clinical
status. Of the 13 seropositive, culture negative children, 6
acquired their infection from infected mothers, 2 from blood
transfusions, and 5 from factor VIII/IX transfusions. Normal T
and B cell immunity were found in 8 out of 13 and 11/13 were
clinically well. In contrast, of the 13 children who were
seropositive, culture positive (5 maternal transmission, 4 blood
transfusion, 4 factor transfusion), all (13/13) had abnormal T
cell and B cell immunity. Of the 13, 12 had AIDS or ARC and 2
have died. In 10 of the seropositive, culture negative children
followed prospectively there has been no significant disease
progression. In 4 seropositive, culture positive children
detectable virus was associated with clinical and/or laboratory
deterioration. Our results suggest that in seropositive children
the presence of detectable HIV in PMC correlates with severity of
laboratory and clinical evidence of disease and may be an
important prognostic factor.
MP166 Development of antigen and antibody titers against
various HIV-antigens in the course of HIV-inf ection
RUDIGER HEHLMANNJ, A. FISCHER*, A. MATUSCHKE*, G.G.
FROSNER", F.-D. GOEBEL*, V. ERFLE***. *Medizinische Poli-
klinik, Munchen, Max von Pettenkof er-Institut , Universitat
Munchen, ***Abt. Molekulare Zellpathologie, GSF Neuherberg,
Munchen
Prognostic significance has been attributed to the presence and
titer of HIV core and env antibodies. For this study, we analyzed
sera from HIV-infected persons with different manifestations of
the disease for the presence of HIV core antigen, and env anti-
gen. We used the Abbott antigen EIA and HTLV-III antibody con-
firmatory EIA to test for env and core and the Behring ELISA for
whole virus.
Healthy HIV-infected persons exhibit relatively high anti-core
antibodies. With the development of LAS and AIDS the median
antibody titers decrease as well as the overall percentage of
positive persons. A trend to a transient increase of anti core
titers has been observed in ARC patients. Most AIDS patients are
negative for core antibodies. The lack of core antibody is
usually associated with the presence of HIV antigen. In contrast,
there are no remarkable changes of the usually high env-antibody
titers during the process of disease development. These data in-
dicate that the combined use of different HIV tests in HIV-in-
fected persons during the course of disease development can be of
prognostic value.
37
MONDAY, JUNE 1
MP167 Dysmorphic Features in Children HIV Positive
J.FERMOSEL, M.D. GURBINDO, T.HERNANDEZ SAMPELAYO, R.PEREZ GARCIA
IPPP Hospital Provincial de Madrid. Spain.
The majority of children infected by HIV are born to HIV positive mothers.
Transmission of HIV may occur: early intrauterine; during materno-filial limpho-
cytary transfusion; during or after delivery.
Recently Marion et al. described an embryopathy probably caused by the first
mechanism of transmission. We have studied the morphological features of 22
children HIV seropositive, aged between 3 months and 3 years; 11 males and 11
females. All of them were born to intravenous drug abusing and/or prostitute wo-
men, HIV seropositive. The HIV antibodies were tested by both ELISA and IFI.
The dysmorphic features found were: Growth failure 40% (Height and weight less
than the third percentile for chronologic age); microcephaly 20% (HC less than
10th percentile); prominent forehead 45%; flattened nasal bridge 77%; long pal-
pebral fissure 86%; blue sclerae 81%; obliquity of the eyes 36%; triangular phil
trum 77%; marked and cleft prominence of the mental protuberance 59%; epicanthus
40%; low-set malformed ears 45%; markedly patulous lips 31%; simian creases 22%;
horizontal and deep flexion creases in palms 31%; clinodactyly 9%.
Not all children were equally affected with these dysmorphic features. The
most characteristic alterations affected to eyes and eyelids (86%). These percn-
tages are significative higher than those of children born to mother of risk-
group but HIV seronegative. Neither intraocular nor cardiac stigmata were found.
None mother was alcohol abuser. No other intrauterine infections were demonstra-
ted but one by CMV.
We confirmed, in our area, HIV associated embryopathy which also affected to
the hands and feet.
MR170 Arteriopathy in Children with AIDS
V. JOSHI, BRUCE PAWEL, E. CONNOR, J. OLESKE, S. MORRISON, J. MARIN-
GARCIA, ET AL
Children's Hospital of New Jersey, UMD New Jersey Medical School, Newark, NJ
Pathologic features with special reference to arteries of different organs
(heart, lungs, kidneys, spleen, intestine, brain etc) seen at autopsy in six
children with Acquired Immune Deficiency Syndrome (AIDS) are described. Small
and medium size arteries which were most commonly involved showed: a) intimal
fibrosis, fragmentation of elastic tissue, fibrosis and calcification of media
variable luminal narrowing and b) vasculitis/perivasculitis. In one case,
aneurysms of the right coronary artery with thrombosis and myocardial infrac-
tion were seen. Vasculitis/pervasculitis seen only in the brain may be
related to the agent associated with AIDS encephalopathy. The fibrocalcific
arterial lesions resemble Infantile Arterial Calcification of Infancy most
closely but because of differences in age incidence, clinicopathologic and
immunologic features and size and distribution of involved arteries, the
arterial lesions of pediatric AIDS appear to constitute a distinctive
arteriopathy. Infection(s) secondary to immunodeficiency resulting in
increased exposure to endogenous and exogenous elastases may be related to
pathogenesis. Role of HIV cannot be entirely ruled out. Luminal narrowing
from the arterial lesions may be related to atrophy, cell depletion, scarring
and necrosis/infarcts of different organs in children with AIDS. Pediatricians
should be alert to the possibility of arterial involvement in pediatric AIDS.
MR168 Clinical Patterns Emerging from Longitudinal Study of
Australian Haemophiliacs with HIV Antibodies.
R.J.GARSIA. P. A.GATENBY. A. BASTEN. P. F.KENNY. K. J.GALLAGHER M.I.DELFIN
Clinical Immunology Research Centre University of Sydney . NSW Australia
HIV-ELISA confirmed by Radioimmunoprecipitation or Western Blot showed
in 1984/85 a seropositive rate of 45% overall in a representative group of
161 Haemophiliacs from New South Wales. Retrospective analysis of the sera
of this population using ELISA and Western Blot has now established that
HIV antibodies were detectable as early as 1981.
Serial monitoring of the clinical status and T cell subsets of these patients
since 1984/5 and a subgroup of them since 1983 has revealed that almost
all the HIV Ab patients have followed one of the patterns ;
A: Decline in CD4 cells associated with a fall in CD4:CD8 ratio (14%)
B: Persistent low CD4 or CD4:CD8 ratio (25%)
C: Rising level of CD4 or CD4:CD8 ratio from a low baseline (8%)
D: Normal T cell subsets and ratio (39%)
E: Wide fluctuations in T cell subsets in the absence of a precipitant(14%)
Three patients (33%) with pattern "A" ,one with pattern "B" and one with
pattern "E" have developed symptomatic immunodeficiency with three
fatalities to date. Occasional episodes of autoimmune disease have occurred
in patients with patterns "B" and "C" but none of these individuals has
developed symptomatic immunodeficiency.
Whilst the very long term prognostic significance of these patterns
occurring in the five years after infection has yet to be determined this
data indicates that markedly abnormal T cell ratios may commonly persist in
HIV exposed Haemophiliacs without an adverse short term outcome.
MR171 WELSH AIDS CAMPAIGN
GEORGE, ALAN M* and GRIFFITHS, C**; Welsh Office*, Cardiff United Kingdom, and
Welsh AIDS-eampaign**, Cardiff.
This Campaign is an attempt on a country-wide basis to establish an
organisation to tackle AIDS as a community, behavioural, social and educational
problem rather than a medical one. The Campaign is funded by the Government
but is independent of it.
The aim is to provide up-to-date information for the public and professionals ;
to modify personal behaviour; to alleviate anxiety; to train volunteers,
health educators and professionals; to provide advice to individuals and
groups and to promote consistency in the message on AIDS presented by the
media and others working in the AIDS field.
It is thought to be the first project of its kind in a European country
and will thus be of interest to people in other countries including the
United States as considerable help was obtained from colleagues in New York
and New Jersey in establishing the Unit.
The demonstration will show in detail the programmes developed for use in
schools, with voluntary workers, health professionals and intravenous drug
abusers. The resources produced to meet the needs of these groups as a
result of the above programmes will be shown.
An evaluation programme is running concomitantly.
MP169 Spectrum of HIV Infection in Neonatal Recipients of Blood Products
THOMAS M. MUNDY*,J. WARD**, J. ALLEN**, S. PEPKOWITZ*,D. GOLDFINGER*,
L. LOEB***, et al . ,*Cedars-Sinai Medical Center, ***L.A. County Dept. Health,
Los Angeles, CA, **AIDS Program, Centers for Disease Control, Atlanta, GA.
Neonates who received blood products from multiple donors prior to blood
bank screening represent a population at risk for HIV infection and may have a
different presentation than infants at risk through vertical transmission.
We have tracked 56 neonates who received 60 blood products gleaned from 7
donors who were later found to have AIDS/ARC/sero-positivity; 4 neonates each
received products from 2 high risk donors. Two additional neonates received
multiple transfusions resulting in AIDS but no high risk donors were identi-
fied. Of the 60 products generated, only 1 donation occurred following the
institution of voluntary donor deferral in 1983.
Fourteen patients had died prior to study, including 11 who died during
their initial admission. HIV infection could have played a role in 6 of these
infants who lived 5 to 15 months after the implicated transfusion and who
subsequently died of infectious causes.
Forty-four infants were available for further study. 14/16 infants tested
are infected with HIV. 5/14 died of AIDS 1-4 years after transfusion. 8/14 are
living with AIDS/ARC at 4-6 years, including 4 in whom the diagnosis was not
considered until antibody screening was performed. One patient is seroposi-
tive but well at 7 years. Only 2/16 screened were sero-negative despite an
interval of up to 7 years between time of donation and confirmation of infec-
tion in the donors. Of the 28 patients remaining, 14 have been located and
study visits are pending and 14 have not been located to date.
Large numbers of neonates may have been infected with HIV prior to effec-
tive screening programs. A spectrum of disease due to HIV infection in pedi-
atric patients should be stressed as this diagnosis had not been considered in
5/14 of our infected children in spite of significant symptoms in 4 of them.
MR172 AIDS on Campus: Strategies for Response
ROSE WALTON, Department of Allied Health Resources, State University
of New York at Stony Brook, Stony Brook, NY
The social and political impact of AIDS creates a complex epidemic with far
reaching economic and psychosocial concerns for the health care and education
systems. The School of Allied Health Professions, SUNY at Stony Brook has
responded to the crisis through a community service project, and two major
educational projects. The community service project provided an information
and referral hotline as well as community educational and service activities.
That project is now a free-standing agency In the community. The SUNY AIDS
Education project is designed to reduce the fear and anxiety of AIDS in college
students. A comprehensive curriculum was developed and field tested during the
first year of the project and is being implemented on 50 of the 64 campuses
of the university and community college system. The implementation phase in-
cluded a training session for campus facilitators and an evaluation plan for
the program. These projects were funded by the New York State Department of
Health, AIDS Institute.
The School of Allied Health Professions has been awarded a training grant
from the National Institute of Mental Health to develop an AIDS resource center.
This project will include faculty development, student education, in-service
education, and provide consultative services and a quarterly newsletter.
A discussion of these projects, their impact on the School and University
in relationship to policy decisions will allow educators and health care
administrators to explore strategies for influencing institutional responses
to AIDS on the college campus and in health science centers in regard to stu-
dents and employees.
38
MONDAY, JUNE 1
MR173 ^he Application of Social Marketing Principles to AIDS Prevention
and Education Programs: Implications and Considerations drawn from
a Worldwide Survey
GEORGE MARSHALL WORTHINGTON*, L. de la Macorra**, V. Prieto**, *Worthington and
Associates Worldwide, New York City, NY, **Social Marketing International Asso-
ciation, Queretaro, Mexico.
Social marketing is the design, implementation, and control of programs seek-
ing to increase the acceptability of a social idea or cause in a target group.
It utilizes concepts of market segmentation, consumer research, concept de-
velopment, communication, facilitation, incentives, and exchange theory to max-
imize target group response. Synonymous terms might be "social cause market-
ing," "idea marketing," or "public issue marketing."
Social Marketing, as the application of basic marketing principles to gen-
erate a social benefit, has proven its effectiveness in a number of family
planning programs, particularly the retail sale of contraceptive products es-
pecially in the developing countries. Social Marketing International Associa-
tion, a professional membership association based in Mexico, decided to re-
search the feasibility of applying this experience together with basic market-
ing principles to prevention programs designed to reduce the transmission of
HIV, Six countries were chosen for case study presentation: the U.S., U.K.,
Brazil, the Philippines, Zaire and France. Case study presentations of all
country situations will be within the following seven point framework: 1) pro-
blem definition, 2) goal setting, 3) target market segmentation, A) consumer
analysis, 5) influence channels analysis, 6) marketing strategy and tactics,
and 7) implementation and evaluation.
Special emphasis will be accorded the utilization of the research findings
presented for the improvement or establishment of additional prevention educa-
tion programs both in countries reviewed and elsewhere utilizing marketing.
MR176
NICHOLAS
AIDS Educato
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te resources an
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tacles and how
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for more effect
rs Perceptions of Barriers to Effective
tion : Report on a National Survey.
LEE, Hunter College/CUNY,
conducted for the American Public Health
guidelines for effective AIDS education,
a convenience sample of 80 AIDS educators
tates. Twenty-five respondents participat-
emi -structured interviews, 25 were inter-
and 30 responded to a mailed question-
e educators working on AIDS for public and
s of their responses revealed common
onal and political barriers to effective
nal problems included integrating volunteer
ng service delivery and prevention, coord-
ate efforts, and developing effective
Educational problems included interpret-
ion for the public, communicating effec-
ulations, inadequate time for planning and
ing the impact of interventions. Larger
were difficulties in reaching minorities,
d public resistance to open discussion
their assessment of the consequences of
they addressed these consequences. Inves-
ese descriptions into specific behavioral
cle. The report concludes with recommen-
ive AIDS education.
MR174 Relationships Between Knowledge About AIDS Risk and Actual Risk Be-
havior in a Sample of Homosexual Men: Some Implications for Preven-
tion.
JEFFREY A. KELLY*, JANET S. ST. LAWRENCE**, TEDDY L. BRASFIELD*. & HAROLD V.
HOOD*, *University of Mississippi Medical Center, Jackson, MS, **University
of Mississippi, Oxford, MS and University of Mississippi Medical Center.
Ninety apparently-healthy homosexual men were administered an objective-
format, 33-item test of knowledge about sexual practices high-risk for HIV
transmission and a questionnaire eliciting information on sexual activities
over the preceding twelve months. All subjects lived in a city where AIDS
education brochures are distributed in gay bars.
Correlations were computed between Risk Knowledge Test scores (x = 25.6 of
33, range = 9 - 33) and frequency of actual high-risk conduct to examine re-
lationships between risk knowledge and risk behavior. Risk behavior in the
sample ranged from very low (0 partners, no occurrence of anal intercourse) to
very high (200 partners , 96 occurrences of unprotected receptive anal inter-
course) . Pearson product-moment correlations revealed that AIDS Knowledge
scores were not significantly related to number of different sexual partners
(r = -.02), frequency of unprotected insertive (r = +.10) or receptive (r ■
-.15) anal intercourse, oral intercourse with semen entry (r = -.06), meeting
partners at "sex clubs" (r = +.11), or other risk behaviors. Regression
analyses detected no relationships between AIDS risk knowledge and behavior.
Research in other health/behavior areas indicates that information provision
alone is often Insufficient to change longstanding, immediately-reinforced risk
behavior . In addition to informational campaigns , other community-based inter-
ventions may be needed to promote risk behavior change. Examples of such
approaches , and copies of study measures, will be presented.
MP177 Interactive Simulation as a Tool in the Decision-making Process to
Prevent HIV Incidence among Homosexual Men in The Netherlands.
MARCEL G.W. DIJKGRAAF*, G.J. P. VAN GRIENSVEN*, J.L.A. GEURTS**, *University of
Utrecht, The Netherlands, **University of Nijmegen, The Netherlands.
The current knowledge of the behavioral and physical system of forces which
cause the spread of HIV among homosexual men is incomplete and scattered over a
wide range of professional journals and reports . At the same time , the
discussion on what the effect of certain preventive measures on behavior of the
population at risk will be, Is in an early stage. The use of a computer stored
diffusion model on HIV among homosexual men can be a powerful , although
hypothetical, discussion- and decision-aid when considering the dynamic effects
of certain preventive measures . Formal models however, are mostly too
complicated for an effective and widespread use in this respect. The procedure
as proposed here, tries to solve this problem, by an Integration of computer
simulation with elements of gaming. The result Is a so called Interactive
simulation, in which persons-in-roles interact in a question-and-answer
relationship with a formal dynamic model programmed for a computer. The
instrument as designed consists of a) a formal computer stored model, In which
the existing knowledge on preventive measures and the behavioral and physical
side of HIV is defined clearly and b) a computer interaction procedure to
perform simulation experiments with preventive measures and c) a discussion
procedure for a group of persons with eachother and in Interaction with the
computer stored model , to explore and evaluate the short- and long term
consequences of preventive measures on the spread of HIV among homosexual men.
MR175 Clinical and Immunological Features of 100 HIV Antibody
Positive Individuals from an Alternate Test Site
JOHN HOWARD* * , F . SATTLER* , R . MAHON* , J . SPERLING* * , J . LEEDOM* , USC
School of Medicine, Los Angeles, CA, **Edelman Health Center. Los
Angeles, CA.
We evaluated 100 HIV antibody positive persons from the only
alternate test site in Los Angeles. Sixty-five were asymptomatic
(Group 1) and 35 complained of systemic symptoms (Group 2), such
as fever (31%), night sweats (61%), fatigue (66%) and weight loss
(6%) . Twenty-one ambulatory patients with AIDS manifested by a
prior episode of Pneumocystis car inii pneumonia within 90 days
(Group 3 ) served as controls . Irrespective of symptomatology.
Groups 1 and 2 demonstrated clinical and laboratory evidence of
immunodeficiency. Eighty had generalized lymphadenopathy, 16
onychomycosis, 6 oral thrush, and 2 biopsy-proven Kaposi ' s
sarcoma. Despite normal white cell counts, 40 (62%) of Group 1
already had T4 lymphocyte cell counts below 500 cells/mm3 and 31
(48%) had below 300 cells/mm3 (mean 468 cells/mm3). Thirty-one
(89%) of Group 2 had less than 500 T4 cells/mm3 and 16 (46%) had
less than 300 cells/mm3 (mean 324 cells/mm3). Group 3 had the
lowest T4 counts (mean 84 cells/mm3). Differences between mean T4
cell counts in the three groups were significant (P<0.001). In
addition, 75% of Group 1, 80% of Group 2, and 100% of Group 3
were anergic to seven intradermal antigens. We believe the high
frequency of clinical and laboratory evidence of immunodeficiency
in subjects evaluated at the Los Angeles alternate test site
justifies the allocation of funding for medical evaluation and
follow-up care for other test centers with similar findings.
MR178 flIDS Prevention, Information and Education for Health;
a model for a comprehensive strategy focused on the general public
as well as special target groups; practised in the Netherlands since 1983.
HANS MOERKERK*, Health Education Centre of the municipality of Amsterdam.
In 1983 the national government, public health authorities and organisations
affiliated with groups at risk for AIDS, joined hands and concluded that a com-
munication strategy had to be developed with the object to inform and educate
the population about possible HIV infection.
Inside the model for the strategy, two general objectives were determined:
(1) to help reduce the spread of infection, (2) to counteract prejudice and
misconceptions as well as unjustified anxiety and fear.
It was assumed that a 'step by step' approach had to be adopted: a short
term strategy {supplying knowledge = one way communication) and a long term
strategy (a process of systematized two way communication between sender and
recipient of the message in order to condition attitudes and values).
In practice it meant that first attention was given to groups at risk which
were approached by both health information and health education; through the
years the prevention activities were extended to larger groups inside the
general population and to the general public itself.
Large scale evaluation activities were incorporated in this communication
model, with promising results both on the level of knowledge and attitudes (cfv
Tielman 1987)(cfv Eyrond 1987); also press coverage in general was informative
and could be made part of this process of health promotion.
The dutch approach received positive attention from other european countries
and was a starting point for wider activities by The Council of Europe and the
European Common Market. The model included active participation of advertising
agents and marketing officers.
39
MONDAY, JUNE 1
MP17Q AIDS Information and Prevention Concept in Switzerland
BERTINO SOMAINI*, H. RYSER* , F. GUTZWILLER** , R. STAUB***,
H. RIEDENER***, *Swiss Federal Office of Public Health, Berne, Switzerland,
**Institute of Social and Preventive Medicine of the University of Lausanne,
Switzerland, ***AIDS Foundation Switzerland, Zurich, Switzerland
1. Initial position: All available epidemiological data show that, with res-
pect to frequency of cases of AIDS and HIV infection, Switzerland leads the
statistics for European countries. Thus, 26 cases of AIDS infection per 1
million inhabitants were recorded by September 1986.
2. Consequently, the federal health authorities have conducted various infor-
mative campaigns in conjunction with the Swiss AIDS Foundation since end
1985. For example, in March 1985 a brochure was distributed to all house-
holds. The results of this campaign were evaluated.
3. Since February 1987 the same instances have been running a national cam-
paign stressing the features:
a) use of the condom for all risk factor sexual contacts.
b) no sharing of syringes for i.v. use of drugs.
The results of this campaign will also be evaluated.
The close cooperation between the official body (Federal Ministry of Health)
and the private organization (Swiss AIDS Foundation) has been very fruitful
to date. The work is explained briefly and the objectives and elements of
the campaign and their evaluation presented.
MDiDO Prevalence of Antibody to Human Immunodeficiency Virus (HIV) and
Client Characteristics in the Wisconsin Alternate Site Testing and
P. DAVIS, Wisconsin Division
Counseling Program, 1985-86
EDWARD A.BELONGIA, J. VERGERONT, H. DOWLING, J.
of Health, Madison, WI USA
In June, 1985 a program providing free and anonymous HIV antibody testing
and counseling began at 30 sites other than blood or plasma centers in
Wisconsin. As of December, 1986, 2856 clients had been counseled and
completed a self administered questionnaire; 2789 HIV antibody tests were
performed, of which 245 (9.5%) were repeatedly reactive by enzyme immuno-
assay (EIA) and 197 (7.7%) positive by Western blot assay (WB) . Among gay/
bisexual men using IV drugs, 26 (31.7%) of 82 were WB positive compared to
126 (9.9%) of 1272 gay/bisexual men who did not use IV drugs (p<.001).
Analysis by race demonstrated 23 (40.3%) of 57 black gay males to be WB
positive compared to 129 (10.0%) of 1289 nonblack gay males (p<.001) ; none
of 31 black heterosexual IV drug users had detectable antibody to HIV.
Prevalence of HIV antibody was less than 5% in all groups other than gay/
bisexual males. Among gay/bisexual men, 84% reported changes in their life-
style or sexual practices due to concern about AIDS; 44.8% were not comfort-
able discussing their lifestyle or sexual practices with their health care
provider, but regional differences were noted. In Wisconsin, a state with a
relatively low incidence of AIDS, there are subgroups of individuals with a
high prevalence of HIV infection, the majority of whom reside in Milwaukee
or Dane counties. Intrastate regional analysis of HIV seroprevalence and
client characteristics is useful for the development of local educational
programs directed toward individuals at increased risk of acquiring HIV
infection.
MR180
AIDS Prevention among Homosexuals in Switzerland
ROGER STAUB*, H. RIEDENER*,
B. SOMAINI**, S. MOSER*, *AIDS Founda-
**Swiss Federal Office of Public Health,
tion Switzerland, Zurich, Switzerland,
Berne , Switzerland.
1. Initial situation: All available epidemiological data show that homosexual
and bisexual men still constitute the major group effected. Thus, 109 of 170
(=64 %) cases are accounted for by this group. Epidemiologists estimate that
some 15 % are infected today.
2. Objective : Prevention of new infection within this target group by educa-
tion. All are aware that anal sex constitutes a high infection risk. All are
aware that protection is possible in sexual contacts outside a monogamous re-
lationship of at least 6 years' duration by practising Safer Sex (= no unpro-
tected anal practises, no sperm in the mouth).
3. Procedure : The AIDS prevention campaign comprises three features:
- "The Hot Rubber": The Swiss AIDS Foundation operates the "Hot Rubber Company"
and markets the condom ("The Condom for the Gay Man") at all meeting points
(bars, saunas etc.) and by direct mail. A poster campaign with "poster of the
month" feature backs up the publicity.
- The Safer Sex Campaign: With brochures, posters, advertisements and articles
the Swiss AIDS Foundation draws attention to Safer Sex on the Swiss scene.
- Discussion groups: Local AIDS Help group in conjunction with homosexual
groups stage regional workshops on the subject of sexuality. The Swiss AIDS
Foundation operates the national hot line to safer sex.
4. Evaluation : A first cross-section inquiry will be conducted in January 1987,
Later, inquiries will be conducted every 6 months which snould provide quali-
tative results .
The concept will be illustrated briefly, with examples, and the first evalua-
tion presented.
MP183 Prevention Policy on AIDS among Drug Addicts in Amsterdam
ERNST C. BUNING, Municipal Health Service Amsterdam, Holland
By January 1st 1987 Aids had been diagnosed among 7 i.v. drug addicts in the
Netherlands. In Amsterdam 20-35% of the i.v. drug addicts has been infected
by HIV. To prevent or slow down further spread of the virus is therefore of
paramount importance .
Apart from drugfree treatment and resocialisation, the Amsterdam helping
system consists of (1) contacting addicts in the drugscene, police stations
and general hospitals, (2) harm reduction such as medical- and social primary
care, methadone prescription (e.g. "methadone by bus project"), needle and
syringe exchange and (3) health education.
This approach is essentially non-moralistic. About 70% of the addicts ia in
touch with this helping system.
Health education and needle and syringe exchange were intensified after Aids
became a focal issue. Emphasis is placed on safe-sex and safe-druguse .
Health education is carried out through leaflets, personal contact and condom
distribution to addicted prostitutes. Slot machines were also installed to
provide addicts with condoms.
Needle and syringe exchange is possible at 13 different locations throughout
the city. In 1986 350,000 needles and syringes were exchanged. No increase in
needle stick accidents has been reported among the general population.
Preliminary findings show that needle sharing has reduced. Counter effects
of the harm-reduction program could not be found: the number of i.v. drug
addicts has not increased, while the patient-load of drugfree treatment
programmes has doubled over the last 6 years.
MR181
WILLI
B. BRAN
bridge ,
tion , *
We se
of Bait
dangers
the int
imen tal
the f r
number
an anti
line,
and eff
ting th
The exp
of AIDS
changes
obta ini
that th
behavio
dis trib
entry i
street
l Evalua
i te In tr
S. MCAUL
tion
aveno
IFFE*
SON*
MA,
***H
n t e
imor
of
erve
and
quen
of e
body
The
ec t i
em t
er im
at
(e
ng a
is
r ch
utin
n to
corn
, K.
Gouc
ERO, Ba
x-addic
to te
AIDS .
ntion (
con tro
cy of h
xper ime
test o
results
ve in f
lis te
ental s
f ol lowu
g . , sha
n an t ib
as an
ange wo
g condo
trea tme
ers .
Will
her C
It imo
t out
ach i
Inter
85% o
1 nei
igh r
ntal
r sou
sho
indin
n to
ub j ec
p tha
ring
ody t
f f ect
uld r
ms an
t ea
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iams
olle
re ,
reac
ntra
view
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ghbo
isk
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ght
ed t
g IV
a me
ts (
n di
and
est)
ive
equi
d po
s ier
sing
rug Us
DOERI
ge , **
MD
h work
venous
s cond
1 lowup
rhoods
behavi
ec ts w
addi t i
hat th
DU ' S w
s sage
n=236)
d the
cleani
were
educa t
re mor
cket-s
and b
ddict Outreach workers to Edu-
ers about AIDS Prevention.
G** , P . BREER* , H. SILVERMAN*** ,
*Harvard Medical School, Cam-
Maryland Drug Abuse Administra-
ers to
drug u
ucted b
s compl
measur
or ; we
ho ente
onal in
e outre
ho were
and ace
had si
con trol
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not sig
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e concr
ize bot
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ed kn
also
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forma
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s ( n =
les,
nif ic
pproa
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ties
anti
mly as
(IVDU
and o
with
owledg
col le
rug tr
tion f
pproac
in t r e
amphle
can t ly
72) , b
use of
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ch , bu
nterv
of bl
body t
sign
S)
ne m
IVDU
e of
ted
eatm
rom
h wa
a tme
ts o
mor
ut b
con
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n tio
ach ,
es ti
ed a
bout
onth
S i
AID
data
ent ,
an A
s fe
nt a
n AI
e kn
ehav
doms
nc lu
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ns ,
mak
ng t
reas
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after
n exper-
S and
on the
obtained
IDS hot-
asible
nd get-
DS .
ow ledge
ioral
and
ded
reater
e.g.,
i ng
o the
MP184 Knowledge and Attitudes About AIDS Among College Freshmen in
Louisiana
WILLIAM L. ATKINSON1'2, V. KTSANES1, S. HASSIG1*2
■'-Tulane University School of Public Health and Tropical Medicine and
^Louisiana Department of Health and Human Resources, New Orleans, LA
In spring 1986, we mailed an AIDS knowledge and attitude questionnaire to
3231 randomly selected freshmen attending seven universities in Louisiana; 967
responded. Their mean age was 18.5 years; 65% were female. Most (93%) were
1985 high school (HS) graduates, 72% from schools in Louisiana and the remain-
der from schools in 38 other states. Only 28% responded that AIDS had been
discussed in one or more HS classes. The most frequently reported source of
information was television (60%) .
More than 90% were able to correctly identify major high risk groups for
AIDS (homosexual men, intravenous drug users), but 16% and 13% respectively
added household members of AIDS patients and blood donors as being at high
risk. Although more than 95% correctly identified major routes of transmission
(sexual, sharing needles), 14% believed mosquitoes and 6% believed donating
blood could transmit the disease. Respondent sex, type of HS, HS location, and
discussion of AIDS in a HS class did not significantly affect knowledge score.
Respondents reported that their knowledge of AIDS affected their behavior in
the following ways: choice of friends-17%, choice of sexual partners-59%,
number of sexual partners-59%, willingness to donate blood-18%.
Our findings indicate that college freshmen in Louisiana are well informed
about major risk groups, transmission and prevention of AIDS but that consid-
erable confusion exists concerning blood donation and casual transmission.
40
MONDAY, JUNE 1
MR185 Knowledge and Attitudes about AIDS in Rhode Islanders
8ARBARA A. DEBUONO, J.BRONDUM, H.D.SCOTT, L.GREEN, N.FARAONE, Rhode
Island Department of Health, Providence, Rhode Island.
A random digit dial telephone survey was conducted in December, 1986. Four-
hundred questionnaires were completed at a cost of $2,600. Fifty-six percent
of respondents were women; median age and educational level were 39 years and
12 years respectively.
Overall, general knowledge of AIDS transmission and risk groups was limited.
While 86% said AIDS could not be spread by casual contact, 24% thought that
sharing the same glass as a person with AIDS was a source of infection. Only
55% of respondents identified drug addicts as a risk group for AIDS and 20%
identified hemophiliacs. Forty percent felt that AIDS would not be a problem
in their community, and only 38% considered the blood supply safe.
Stratification of responses by age and educational level demonstrated that
AIDS knowledge varied directly with educational level and inversely with age.
For example, 75% of those with a college education identified drug addicts as
a risk group while only 42% of those with less than a high school education
did (X2 test for trend=26.9, p<.05);64% of those under 55 could identify drug
addicts as being at risk for AIDS but only 34% of those 55 and over could do
so (X2=27, p<.05). Those ages 18-24 were more likely than any other age
group to have changed their sexual behavior since learning of AIDS (X2 test
for trend=12.2 p<.05).
Such telephone surveys represent a cost-effective method of identifying
target groups for educational interventions and if applied periodically, can
serve to measure their success.
MP188 Behavioral Diagnosis for Effective Education of
HIV-Seropositive Patients.
EDWARD E. BARTLETT*. DAVID RABIN*, VIRGINIA TAGGART*, CYNTHIA
BANDEMER*, and JOSEPH BELLONTI**, 'Department of Community and Family
Medicine, "Department of Pediatrics, Georgetown University School of
Medicine, Washington, DC.
The US Surgeon General and National Academy of Sciences have
recently advocated that control of AIDS will require widespread public
education. Effective education, in turn, depends on a correct
behavioral diagnosis. This paper describes how a behavioral diagnosis
is accomplished as a basis for counseling HIV-positive patients. Such
counseling should address various co-factors implicated in the
progression of AIDS, and measures to stem the spread of the HIV virus.
Previous research reveals the following barriers to making
recommended behavior changes: low perceived efficacy of changing
sexual behaviors, lack of AIDS knowledge, difficulty in controlling
sexual impulses, high belief in biomedicine to Cure AIDS, and
non-supportive social norms. Additionally, anecdotal experience
indicates that several barriers exist to HIV-positive patients seeking
regular medical care: denial, social stigmatization, and fears about
confidentiality of information.
The paper concludes by describing how the behavioral diagnosis
technique can be applied to training health professionals to better
care for and educate HIV-positive patients.
MPIBfi HIV Antibodies in Needles and Syringes Used By Intravenous Drug
" Users.
ALEX D. WODAK*, K.DOLAN*, A.IMRIE#, J. GOLD**, B.M.WHYTE**, D. A.C0OPER*#.
•Alcohol and Drug Service, #Centre for Immunology, St. Vincent's Hospital;
** Albion Street Centre, Sydney Hospital, *#NH&MRC Special Unit in AIDS
Epidemiology and Clinical Research, Sydney, Australia.
The sharing of needles and syringes by intravenous drug users (IVDU) has been
recognised as a critical factor in the transmission of the human immuno-
deficiency virus (HIV).
A pilot sterile needle and syringe exchange programme was established in
an inner city neighbourhood in Sydney, Australia in an attempt to reduce
sharing of needles and syringes among IVDU. The contents of exchange syringes
were analysed for antibody to HIV by ELISA; the contents of reactive and
boarderline syringes were confirmed by Western blot. Of a sample of 300
needles and syringes exchanged, 1% were found to be antibody positive and
thus potentially infectious. Analysis of positive and negative control
syringes indicated that the proportion of potentially infectious needles
found in this study may have underestimated the proportion of infectious
injection equipment returned. These finding emphasise the importance of
removing used needles and syringes from circulation in addition to
supplying sterile equipment. This method of monitoring exchanged needles
and syringes is suggested as a means of evaluating measures designed to
reduce the transmission of HIV among IVDU. Rapid implementation of sterile
needle and syringe exchange programmes is imperative in Western countries
to stem the spread of HIV infection.
MR189 Prena
GILLE
tal diagnosis of congenital H.I.V. infection
S PIALOUX* F. Daffos**, F. Forestier**, M.A. Rey*
F. Brun-Vezinet
Bernard* , Centr
Paris , France**
In order to f
infected fetuse
two cases , f eta
blood was carri
puncture of the
only before a m
In these two
samples . HIV wa
detected by rev
not in fetuses
evident immnuno
were normal . No
tissues did not
This prelimin
congenital HIV
points must be
an uninfected f
relevant . The a
blood has been
Further studi
isolation of HI
eliminate HIV c
Laboratoire de Virologie, Hopital Claude-
e de diagnostic prenatal, Hopital ND Bon-Secours,
ind a
s and
1 bio
ed ou
umbi
edica
cases
s iso
erse
Immu
def ic
n spe
pres
ary s
is av
discu
etus
bsenc
avoid
es mu
V fro
ongen
way of di
those who
od samples
t at 24 an
lical cord
1 terminal
HIV anti
lated from
transcript
nological
iency : ly
cific IgM
ent lympho
tudy sugge
ailable us
ssed. The
through th
e of mater
ed.
st etablis
m fetal T
ital infec
stinguishing p
escape infect
with mother bl
d 27 weeks of
under ultraso
son of the pre
bodies were fo
stimulated T
ase activity o
investigations
mphocytes , T4/
titers were un
cytes depletio
st that prenat
ing this proce
theoritical ri
e fetal blood
nal blood cont
renat
ion
ood s
gesta
und g
gnanc
und i
lymph
nly i
did
T8 , r
eleva
n .
al di
dure
sk of
sampl
amina
ally
we co
ample
tion
uidan
y ■
n fet
ocyte
n one
not d
atio
ted a
between
mpared , in
Fetal
by direct
ce , and
al blood
and
mother but
emons trate
platelets
nd lymphoid
agnosis of
; even if many
contaminating
ing itself is
tion in fetal
h if no elevation of IgM and no
lymphocytes are sufficient to
tion .
MR187 A Survey of Knowledge and Attitudes Among Dentists Concerning AIDS
S. BRENT DOVE, JAMES A. COTTONE, University of Texas Dental School
at San Antonio, San Antonio, TX.
AIDS presents many problems for various health care professionals including
dentists. This is especially true with the renewed emphasis on infection con-
trol in the dental profession.
In order to assess knolwedge of the average practicing dentist concerning
AIDS, approximately 1,200 dentists were surveyed concerning AIDS etiology,
transmission, epidemiology, oral manifestations, methods of detection, treat-
ment, prevention, and sociological and behavioral attitudes. It was hypothe-
sized that dentists in larger cities with a higher incidence of reported AIDS
cases would have a better understanding of AIDS and ARC than dentists in cities
with fewer AIDS patients.
The results were analyzed using Pearson Product Moment Coefficient of Cor-
relation (Pearson's r) . The results indicated that although there is a corre-
lation between the number of AIDS patients in a city and a better understanding
of AIDS by dentists in that city, the increased knowledge did not generalize
to all areas surveyed. Other methods of educating dentists concerning AIDS, in-
fection control, and their role as health care professionals oonoeming pa-
tients with infectious diseases are needed.
MP.190 AIDS: A Public Health Challenge for States
RICHARD MERRITT, H. R0WE, C. RYAN, Intergovernmental Health Policy Project,
Washington, D.C.
The presentation summarizes the findings of a PHS funded document detail-
ing AIDS policy issues for state legislators and key health program officials.
Basic policy questions are discussed in twelve major areas including:
screening and testing, surveillance, confidentiality, potential discrimina-
tion, needs of special populations, education, other modes of intervention,
research, medical care, support services, financing and administration.
A range of state legislative, program and policy solutions from all fifty
states is described, highlighting specific case examples to illustrate how
states have developed sometimes different and sometimes parallel solutions to
similar AIDS related problems. Basic health policy concepts are also
discussed to help states frame their own AIDS programs and policies. Testing,
confidentiality and financing issues are emphasized -- the latter focusing on
AZT, its reimbursement, allocation, cost effectiveness and implications for
developing insurance mechanisms and systems of care for persons with HIV
infection. The study recommends that AIDS may be used as a vehicle for
developing paradigms for addressing fundamental health policy problems facing
the states. These include designing systems for chronic care, financing
catastrophic care and care for the uninsured.
41
MONDAY, JUNE 1
M P 191 Disinfection of IV Drug Paraphernalia Using Commonly Available
Materials: Hope for Controlling Spread of HIV Among IV Drug Users?
SUNITA JAIN», N. FLYNN*, E. KEDDIE", J. CARLSON", S. HARPER*, V. BAILEY", et
al." *Univ of Calif. Davis, ••Aquarian Effort, Sacramento, CA
HIV is spreading rapidly among U.S. IV drug users (IVDU) and will spread
widely from them to new populations through heterosexual and vertical trans-
mission (T). We have demonstrated that sharing of paraphernalia (P) continues
despite reasonable knowledge among IVDU of mode of T. Few IVDU regularly
practice disinfection of P between users.
We tested the ability of commonly available potential disinfecting agents
(DA) to inactivate HIV using a sensitive infectivity assay and questioned
IVDU regarding availability of these DA last time they shot up. HIV was not
infective after exposure to dilute household bleach or dish detergent, rub-
bing alcohol, vodka, or wine; beer and cola drink were ineffective. P with-
stood exposure to each DA at least 50 times without showing significant da-
mage. 70$ of IVDU related that one or more of these DA were easily available
last time they shot up (bleach 35$, rubbing alcohol 56$, wine 23$, liquid
dish detergent 49$). They expressed interest in learning simple techniques
for disinfection of P using these commonly available DA. We are developing
an instructional program for IVDU in drug treatment programs emphasizing a
simple, practical, 2-step disinfection technique in which P are rinsed in any
active DA and then in water before being passed to the next user.
In the absence of decriminalization of P and changes in P-sharing habits,
disinfection may offer the only hope for slowing the T of HIV among IVDU and,
subsequently, to their sexual contacts and offspring. We have identified
easily available DA and a simple disinfection technique which is effective in
vitro.
MDIQA Standardized Scales and Documentation of AIDS-HIV Knowledge and Prevention
for Health Care Professionals and the Public
HARVEY S. BARTNOF MP. UCSF School of Medicine and AVER I. AIDS Virus Education and Research
Institute, San Francisco, CA
The epidemic of AIDS and Human Immuodef Iclency Virus (HIV) Infections presents new problems
In educating health care professionals and the public. These problems Include: (1) rapid
accumulation of biomedical Information which may be relevant to clinical practice; (2) new
concepts In pathoblology specific to HIV Infections; (3) phobic blocks associated with groups
at higher risk which may preclude unbiased assimilation of Information on HIV; and (4) the
character of an expanding epidemic which Increasingly affects many aspects of society.
Due to these Issues, traditional means of education are Inadequate to deal with the necessary
dissemination of Information on HIV. In addition, a lack of standardization of AIDS Information
may enhance misconceptions, facilitate false Information, and markedly detract from optimal
clinical care of patient with AIDS or ARC. Misconceptions and false Information on AIDS
will only spread the epidemic even more. AVERI, AIDS Virus Education and Research Institute,
was founded In 1984 to deal with these Issues. AVERI provides educational programs about
AIDS for various sectors of the public and continuing education about AIDS and HIV for health
care professionals. Also, AVERI, In conjunction with Its Medical Advisory Board, has devised
three standardized scales to document assimilation of AIDS Information. No one (lay or physician)
should be providing counseling or educating others about AIDS without a passing score on
one of the scales. The first Is "BAPS," Basic AIDS Prevention Scale, for the lay public.
Second Is "AAPS," Advanced AIDS Prevention Scale, for health care professionals and health
care employees. For health care professionals treating AIDS and ARC patients, there Is "AAPTS, "
Advanced AIDS Prevention and Treatment Scale. In the opinion of the AVERI Medical Advisory
Board, B5t of all hospital personnel should achieve a passing score on "BAPS" and all hospital
and pre-hospltal health care professionals should be able to pass "AATS" If not "AAPTS."
Widespread use of these 3 test scales, along with quality AIDS-HIV education will decrease
the spread of the epidemic, decrease AIDS phobias, and optimize care of the AIDS patient.
MP192 Follow-up Counseling and Risk Behavior Assessment of HIV Antibody
Positive Military recruits
BETH A. DILLON, N.SPENCER, Colorado Department of Health, Denver, CO,
U.S.A.
Military Entrance Processing Stations (MEPS) began screening new recruits
in October 1985 by ELISA and Western Blot for HIV antibody (Ab). Positives
are not provided interpretation of results or counseling by MEPS. Colorado
Department of Health (CDH) regulations require reports of positives with
identifiers. Seventeen have been reported to CDH by MEPS (seropositivity
rate less than .13%). All reported positives were male (11 white, 3 black
and 3 hispanic) . The average age for positives (25) is older than negative
recruits where the majority are in the 17-19 age group.
By January 1987, CDH completed follow-up on 16 positives and confirmed or
provided counseling to 12 (75.0%), (2 were not located, 1 moved out-of-
state). Only 1 declined counseling. Of the 12, 11 were retested, with one
negative by both ELISA and Western Blot.
Risk behaviors were evaluated for the 11 counseled and retested
positives. Although prior to MEPS Ab testing, recruits sign an affidavit
denying homosexual/bisexual activity, during the CDH evaluation 10 of 11
positives reported homosexual or bisexual activity as a risk factor. One
claimed heterosexual contact with female prostitutes. Four of the
individuals reported 2 risk behaviors.
Transmission prevention counseling is essential for positives. Public
health follow-up ensures counseling, permits risk assessment and may
identify pools of heterosexual HIV infection.
MR195 Psychological Reactions of Individuals at Risk for AIDS
Participating in an Experimental Drug Trial
PAUL B. JACOBSEN*, S.W. PERRY**, R.B. ROBERTS**, *Memori a 1 Sloan-Kettering Can-
cer Center, New York, WY,**The New York Hospital, New York, NY.
Administration of anti-viral agents has been proposed as a means of preven-
ting the development of AIDS in asymptomatic individuals infected with HIV.
However, since these individuals typically feel physically well and, in addi-
tion, may be psychologically distressed because of their risk status, there is
concern about their willingness to adhere to an experimental drug trial. The
present study addressed this question by studying 26 homosexual/bisexual males
enrolled in a randomized double-blind trial of ribavirin. Subjects were with-
out manifestations of AIDS or ARC, but were HIV antibody and viral positive.
Standardized self-report measures of psychological distress (Brief Symptom
Inventory) and perceptions of treatment were administered during the first 2
weeks of the drug study and, again, 8 weeks later near the end of treatment.
Results indicated that mean levels of distress at the initial assessment were
2 to 3 standard deviations above norms for the general population but were
similar to norms for psychiatric outpatients and for other populations at risk
for AIDS. Analysis of variance showed that mean levels of distress remained
unchanged between the initial and follow-up assessments. In addition, T-test
comparisons demonstrated that the intensity of distress at both baseline and
follow-up was unrelated to patients' beliefs about whether they were receiving
active drug or placebo. None of the 26 patients refused to continue partici-
pation in the drug trial during the period of study. These findings suggest
that, while asymptomatic seropositive individuals may remain psychologically
distressed, they are likely to continue to adhere to placebo-controlled trials
of anti-HIV drugs.
MP193 Minnesota Counseling and Testing Sites: Analysis of Trends Over
* . Time. RICHARD N. DANILA*. J.M. SHULTZ*, H.T. 0STERH0LM*, K.L.
MACDONALD*, K. HENRY**, M. SIMPSON***. *Minnesota Department of Health,
**St. Paul-Ramsey Medical Center, ***Hennepin County Medical Center,
Minneapolis, MN, USA.
Counseling and testing sites (CTS's) opened in MN in July 1985 to provide
HIV antibody testing (with Western blot confirmation) to persons at high risk
for acquiring HIV infection. Data obtained during the first 12 months of
operation (4,906 client visits for 4,598 clients) were analyzed to assess
trends over time. The overall seroprevalence rate for all visits was 10.8%.
Among males, the highest seroprevalence rates were in homosexual men (422/
2440 [17 . 3%] ) . This rate did not change over time; however, the proportion
of clients who were homosexual men significantly decreased over time when
compared to the entire group (p<0.01). Thus, the overall monthly seropreva-
lence rates declined significantly (p<0.01). The number of repeat visits
increased significantly (p<0.01); however, this did not account for the ob-
served decline in seroprevalence, because rates of seropositivity were
similar for first-time and repeat visits (497/4,598 [10.8%] vs. 30/306
[9.8%]). During this time, a significant increase in the number of women
clients being tested was noted (p<0.01). Because the seroprevalence rate for
female clients was very low (5/638 [0.8%]), the increasing proportion of fe-
male clients may have also contributed to the overall decline in the observed
seroprevalence rate. Increases over time were noted in the number of hetero-
sexual clients with sexual exposure to a high-risk partner, the number of
clients reporting an HIV-antibody positive sex partner, and the number of
clients with an unspecified risk or no risk. These changing client demo-
graphics may have public health implications for designing outreach programs
aimed at counseling and testing persons at highest risk of exposure to HIV.
MP196 Physician Attitudes and Stigma Associated with an AIDS Diagnosis
■III. I3U JANET S. ST. LAWRENCE*, JEFFREY A. KELLY**, HAROLD V. HOOD**, STEVE
SMITH, JR.*, 4 DONNA J. COOK*, *University of Mississippi, Oxford, MS and
University of Mississippi Medical Center, Jackson, MS, **University of
Mississippi Medical Center
A randomly-selected sample of 163 physicians practicing in three cities (Co-
lumbus, OH, Memphis, TN, and Phoenix, AZ) were subjects in a study assessing
attitudes towards AIDS. These cities are the largest in states which rank near
the midpoint for AIDS prevalence. Each physician/subject read a 500-word vig-
nette describing a male patient; vignettes were identical except that the
patient's illness was identified as either AIDS or leukemia and the patient
was identified as either homosexual or heterosexual. Subjects completed ob-
jective measures assessing attitudes toward the patient after reading a ran-
domly-assigned vignette.
Multivariate ANOVAs showed that AIDS patients were considered more responsi-
ble for and deserving of their illness, dangerous, deserving quarantine, and
less deserving of sympathy (all £ < .05 to £ < .0001). Physicians reported
markedly less willingness to interact with an AIDS patient than an identically-
described leukemia patient in such contexts as conversation (p < .01), working
in the same office, living in the same apartment building, attending a party,
or continuing a past friendship (all £ <: .0001).
As HIV infection prevalence increases outside the nation's largest cities,
physicians in all practice specialities will see many more HIV patients.
Health-care providers may share some of the same attitude prejudices as the
general community. There is a need to develop better psychological/education
programs for health-care providers especially in areas where AIDS prevalence
will soon increase.
42
MONDAY, JUNE 1
MP197 An AIDS Training Program for Mental Health Professionals
ROSEMARY T. MOYNIHAN*. R. MCFARLANE*, G.H. CHRIST*, R. SAMET**,
D. BECKHAM*, S. RICHARDSON***, *Memorial Sloan-Kettering Cancer Center,
**Department of Mental Health, ***Gay Men's Health Crisis, New York, NY.
An AIDS mental health training program was developed in 1986 through a col-
laborative effort of New York City Department of Mental Health, the Memorial
Sloan-Kettering Cancer Center Department of Social Work and the Gay Men's
Health Crisis. To date, over one thousand professionals from voluntary and
municipal hospitals, community mental health centers, social service agencies
and chemical dependency units have participated.
An initial needs assessment revealed that generic information about the med-
ical and psychosocial aspects of AIDS was not sufficient. Substantive areas
identified for training included: fears of contagion; countertransference
issues relating to homophobia, aversion to treating drug addicts, feelings of
hopelessness and helplessness, and emotional overwhelm or bereavement; work
with the medically and terminally ill; coping with the enormity and intensity
of patient needs; maintaining updated medical information. Five additional
substantive areas were requested; drug addiction, minority culture issues,
neuropsychiatry issues, family and relationship therapies.
Pre-intervention evaluation revealed that participants had high levels of
knowledge of AIDS which were not significantly increased through participation
in the program. Positive change was observed at the end of the training in the
following areas: 73% reported more optimism in helping PWAs cope with their
illness; 75% reported greater empathy for PWAs; over 80% indicated they were
more confident of their AIDS knowledge; over 80% were more aware of the
psychological and medical needs, and over 60% indicated increased confidence
in their ability to deal with value and lifestyle differences with patients.
MP200 Psychiatric Illness in HIV-infected Men & Controls
J.H. ATKINSON. IGOR GRANT, C.J. KENNEDY, D.D. RICHMAN,
S.A.SPECTOR, J. A. MCCUTCHAN, San Diego VAMC & UCSD School of Hedicine, La
Jolla, CA. USA.
Psychiatric complications in hospitalized patients with acquired immune
deficiency syndrome (AIDS) and AIDS-related complex (ARC) are widely
reported, but little is known of the lifetime psychiatric history of
ambulatory men with AIDS, ARC, or of asymptomatic men infected with HIV
(human immunodeficiency virus). Lifetime prevalence and current psychi-
atric disorder in men infected with HIV, or at risk for infection were
examined using the Diagnostic Interview Schedule (DIS, Version III-A) ,
Profile of Mood States (POMS), and Symptom Checkliat-90 (SCL-90). We
examined four groups of homosexual men and a comparison group of hetero-
sexual men equated for age and socioeconomic status. The groups were (1)
AIDS (N=15); (2) ARC (N=13); (3) Other HIV seropositive (N=16); (4) HIV
seronegative (N=ll); and (5) seronegative heterosexual (N=22). Results;
Among all homosexual men (Groups 1-4) lifetime prevalence of any DIS
psychiatric disorder was 80.2%; major depression was 30. 4%; alcohol
abuse/dependence 32.1%; other substance abuse 39.3%; and anxiety disorder
(excluding phobias) 39.3%. There was no significant difference between
groups of homosexual men in prevalence of major syndromes. Over 30.3% of
men in Groups 1-4 experienced the onset of a DlS-disorder within the
previous six months. Group 5 subjects had markedly lower proportions of
major depression (10 X) and anxiety disorder (0%). Conclusion: Because
lifetime and recent prevalence of psychiatric disorder among ambulatory
men infected or at risk for infection with HIV is elevated, longitudinal
assessment and early psychiatric intervention may improve patient care.
MP.198 Control of Hypersexuality in HIV Carrier
CLETO PI GIOVANNI*, F. BERLIN**, *Metropolitan Psychiatric Group,
Washington, DC, * **The Johns Hopkins Hospital, Baltimore, MD.
A homosexual man with AIDS Related Complex sought psychiatric treatment be-
cause of anxiety associated with hypersexuality. He reported that he had un-
protected sex with as many as 40 anonymous partners weekly in bath houses; he
said he recognized the health hazard to himself and others posed by his behav-
ior but could not control his sexual drive. He gave written consent to weekly
intramuscular injections of medroxyprogesterone acetate, which rapidly and
profoundly lowered his testosterone level and reduced his sexual urges. He
also received supportive psychotherapy and antidepressant medication, with
marked mood improvement. Side-effects of the anti-androgen included mild hy-
pertension that required antihypertensive medication. This case report
suggests that a subset of HIV carriers who remain sexually promiscuous may
have an atypical paraphilia that is responsive to combined psychotherapeutic
and pharmacologic measures.
MR201 Behavior by Intravenous Drug Users that Can Transmit HIV. AS ABDUL-QUADER",
SR FRIEDMAN*, DC DES JARLAIS", M MARMOR*", R MASLANSKY"", S
BARTELME"*, et al., 'Narcotic and Drug Research Inc., "NYS Div of Substance
Abuse Svcs, *"NY University Med Center, ""Bellevue Hospital, NY, NY.
In New York, intravenous drug users (IVDU) are the main source of HIV transmission to other
IVDU and to heterosexual partner and in utero transmission AIDS cases. 1 95 Manhattan
methadone patients were interviewed in 1 986 about drug injection, sexual behaviors and
child-bearing plans. They had mean frequencies of 22 drug injections per month, of which 4.7
were in shooting galleries; they knowingly let others use their used syringes a mean of 6.6 times
per month. 125 male subjects each had mean total sexual frequency of 6 limes per month with a
mean of 1 .8 female partners. On average, each man had .6 igflyjar sex partners who were noj
IVDU. 61 female subjects each had mean total sexual frequency of 1 1 times per month with a
mean of 2.7 male partners. On average, each woman had .6 isgujar sex partners who were noj.
IVDU. 59/1 53 (39%) subjects intend to have further children. 49% of 1 65 subjects for whom
Abbott EUSA and Western blot HIV antibody test results were available were seropositive.
Subjects who had been in methadone treatment for more than 24 months had greatly and
significantly lower frequencies of drug-related transmission behavior than those in treatment for
lesser periods, although they did not differ significantly in sexual behaviors that can transmit
HIV. Drug injection frequencies were 53/month as compared to 5 (p<,0001); injection in
shooting galleries 12/mo. as compared to .84 (p<.007); and the frequency of knowingly letting
others use works they had already used was 1 7/mo. as compared to .76 (p<.0005). 39% of 28
women in treatment more than 24 months intended to bear future children, as compared to 69%
of 1 6 women in treatment two years or less (p<.06).
IVDU frequently behave in ways that can transmit HIV to other persons. Methadone treatment
appears to reduce such drug injection behaviors. Since methadone patients engage in considerable
potentially risky sexual behavior, AIDS education in such treatment programs should include
counseling about heterosexual and in utero transmission.
MR199 Support Groups for HIV Positive Women Including Those
With HIV Positive Infants.
BRIDGET WAGNER, GREENBERG R, HIGGINS B, NORRIS H, TAYLOR J, UCSF ,
San Francisco General Hospital , San Francisco, CA, USA
Epidemiological studies suggest that at present the
seroprevalence rate among sexually active heterosexual women in
the San Francisco Bay Area is between 0.5* and 5%. A need was
felt in 1985 to create support groups for HIV positive women.
Initially these efforts were unsuccessful. In September, 1986
the Women's AIDS Network tried again to establish support groups
for HIV positive women. As of January, 1987 one group for HIV
positive women has been established in San Francisco, and several
other groups are forming including one for seropositive
transexuals .
This poster is planned to share our experiences:
A. Establishing groups for HIV positive women: planning effective
outreach strategies and addressing the importance of
anonymity and confidentially.
B. Group structure ana client issues found to be effective.
C. Addressing different needs for different clients i.e., women
who have by vertical transmission Infected their children as
opposed to single women with multiple partners, or IV drug
users .
The psychosocial needs for HIV positive women are complex and
often different from homosexual men. Support groups can help
provide problem-solving, educational, and emotional support, and
at the very least "a safe place" to share experiences in order to
reduce feelings of isolation.
MpOflO Psychosomatic Distress and Depressive Symptoms Among
"r'U HTLV III/LAV Seropositive, Seronegative, and Untested
Homosexual Men
SUSAN D . COCHRAN, California State University, Morthridge, CA
Knowledge of HTLV III/LAV infection is sometimes advocated as a
means to encourage behavior change. However, such knowledge can
also have a negative impact on psychosocial functioning. The cur-
rent study examined levels of common somatic complaints and de-
pressive symptomatology in a sample of 150 gay men, none of whom
had been diagnosed by a physician with AIDS or ARC. The sample
was divided into three groups: those who reported positive HTLV
III/LAV blood testing results, those who had been found to be
negative, and those who had not had a blood test and did not know
their HTLV III/LAV infection status. Men indicated the presence
or absence of 15 common somatic complaints, 10 were consistent
with early ARC or AIDS symptoms and 5 contraindicated an ARC or
AIDS diagnosis. Men also completed the CES-Depression Scale.
Results indicated that the men who tested positive reported sig-
nificantly more somatic complaints, more AIDS-related complaints
and greater levels of depression than either men who tested nega-
tive or who had not been tested. They also showed a trend to
report more AIDS-unrelated somatic complaints. Men who tested
negative and those who had not been tested did not differ signifi-
cantly from each other on levels of somatic complaints or depres-
sion. Results suggest that knowledge of a positive HTLV III/LAV
result may have negative consequences for psychosocial functioning,
but a negative result does not lead to less distress than not
knowing.
43
MONDAY, JUNE 1
MR203
Transmis
DEBRA I
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of th
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terosexu
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ted the
ng non
erosexual Contacts Among Intravenous
Implications For the Heterosexual
Immunodeficiency Virus
BROWN, JR.**, B.J. PRIMM*. *Addiction
Corporation, Brooklyn, NY, **Harlem
he Columbia College of Physicians and
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MP206 Utilization of Nurse Practitioners in the SFGH
AIDS Clinic. BARBARA J, BRODIE, G. CARR,
San Francisco General Hospital AIDS Clinic,
San Francisco, California, USA.
The rapid expansion of the outpatient AIDS clinic at San
Francisco General Hospital required an increase in primary health
care providers. Nurse Practitioners were added to augment the
medical staff, and have an expanded role within the clinic.
During most clinic sessions both physicians and nurse
practitioners see patients. Nurse practitioners carry their own
caseload, guided by protocols and working in consultation with
clinic physicians. Two clinics are run solely by the nurse
practitioners. One is for studying and monitoring
investigational drug trials. The second is a unique AIDS
screening clinic, developed in response to a growing concern by
an increasing number of high risk individuals, who have no prior
diagnosis of ARC or AIDS. After formal clinic sessions, the
nurse practitioners remain available for medical backup, to
provide coverage for assessment and triage of emergencies and for
telephone consultation. This is a presentation of a descriptive
paper addressing the expanded nurse practitioner role within the
AIDS clinic, the advanced knowledge needed, and how guidelines
and protocols for nurse practitioner practice were developed to
meet the needs of the clinic.
MR204 Use of the "Needle Guard"
stick Injuries.
in the Prevention of Needle-
PAUL N. GOLDWATER*, A.D. NIXON**, R. LAW**, J . OFFICER*** , J.F.
CLELAND***; *The Adelaide Children's Hospital, North Adelaide,
South Australia, **Auckland Hospital, Auckland, *** The Medical
Laboratory, Auckland, New Zealand.
The "Needle Guard" system was evaluated during a 21 month period
during which 454,000 venepunctures were performed. It was shown
that "Needle Guard" users incurred a needlestick once in every
23,546 venepunctures, whereas, non-users of the "Needle Guard"
incurred an accident once in every 4,929 venepunctures (p<0.001).
This 79.9 percent reduction in needlestick accidents attributable
to the "Needle Guard" calls for a review of the non-recapping
guidelines issued by the Centers for Disease Control.
MR207 Oral manifestations of HIV infection: Suggested EEC classification
and prevalences in a Danish sample.
JENS J. PINDBORG, JUDITH RINDUM S MORTEN SCHIODT. Dental Department, Universi-
ty Hospital ("Rigshospitalet") , Department of Oral Pathology, Copenhagen, Den-
mark.
On 16-17 September 1986 the EEC convened a meeting in Copenhagen on oral
problems related the HIV infection. During the meeting a tentative classifica-
tion of 31 oral lesions in patients infected with HIV was agreed upon. The
classification divides the lesions into fungal, bacterial S viral infections,
neoplasms, and lesions of unknown etiology. Previously infections with Candida
albicans have been called oral candidiasis or oral thrush. However, there is
a need for dividing candidiasis into pseudomembranous, erythematous and hyper-
plastic types. In the past a number of the erythematous type of candidiasis
have been overlooked. The classification has been applied to 130 HIV infected
patients at the University Hospital of Copenhagen. Of these patients 38 had
AIDS, 16 ARC and 76 were just seropositive. Sixty-eight percent had one or
more oral lesions considered associated with the HIV infection. Candidiasis
was found in 41%, hairy leukoplakia in 37% and necrotizing gingivitis in 10%.
MR205 The AIDS Epidemic: A Projection of Its Impact on Hospitals,
1986-1991
JESSE GREEN, Ph.D., M. SINGER, MPH, N. WINTFELD, Ph.D., New York University
Medical Center, New York, NY
The AIDS epidemic in the United States will have a dramatic impact on the
health care delivery system, especially hospital facilities. By 1991, 12,831
hospital beds in the U.S. will be occupied by AIDS patients, more than by lung
cancer patients or automobile accident victims. In San Francisco, one of every
10 hospital beds and 19 cents of every dollar spent on inpatient and outpa-
tient therapy will go to treatment of AIDS. In New York, bed need for AIDS
will nearly triple from 645 beds in 1986 to 1,753 beds by 1991. In the rest of
the country outside these cities, the level of hospital utilization by 1991
(1.14S, of beds and 3.21 of treatment costs) will be close to what is being
experienced in New York City today. The impact of AIDS on hospital facilities
goes beyond these numbers. AIDS patients require added infection control pre-
cautions, nursing care, supplies, and complex case management services. Per-
haps the most difficult challenge is to face the task of treating young pa-
tients with a ravaging disease without the ability to offer a cure.
Dr. Green served as consultant to the Institute of Medicine, National Academy
of Science's Task Force on a National Strategy for AIDS. This paper was pre-
pared as background for the Institute's report, Confronting AIDS - Directions
for Public Policy. Health Care, and Research.
MP208 Multiple Funding Sources for Comprehensive AIDS Public Health
Services RICHARD CQNVISER, Ph.D. and S. YOUNG, New Jersey State
Department of Health (NJSDH), Trenton, NJ.
The population most seriously affected by AIDS in New Jersey consists of
IV drug addicts, their sexual partners and children. Because this
population has limited financial resources and political/community support,
and because federal funding for public health services is limited, the NJSDH
has had to take the lead in providing services. The Department's role has
been to provide seed money to develop and implement programs while
identifying other long-term funding sources to support ongoing service
delivery. A key element in the Department's strategy has been an increase
in drug abuse prevention and treatment.
The Department has sought to substitute a continuum of alternative care
services for lengthy stays in acute care facilities. Funding for the
alternative care has been sought from a variety of sources — state, federal,
private (Robert Wood Johnson) foundation, and Medicaid. Effective use of
the resulting mix of funds requires creative administration. Federal and
state funds support specific projects and personnel in unit projects; those
from the private foundation support in-hospital case management, post-
hospitalization services, and education. Supplemental funds from the state
support direct services not reimbursable elsewhere. The Medicaid waiver
supports home/community care for individuals as an alternative to
hospitalization. A matrix will correlate the funding mix with the continuum
of services planned by the state.
44
MONDAY, JUNE 1
MR209 Influence of disease and casemix severity on the hospital costs of
caring for AIDS patients, by Mary M. Fanning, T. Harmon, F.A.
Shepherd, H. Vellend, S. Minnick, Dept. of Medicine, University of Toronto and
Travenol Management Services, DeerfieTd, Illinois.
The estimated total cost of medical care for a patient with AIDS varies
considerably among several published studies and may reflect differences in
efficiency of care, disease severity of the hospital case mix as well as
accounting practices. Seventy-four percent of all AIDS admissions to Toronto
General Hospital between January 1983 and December 1985 were classified into
five diagnostic categories: simple Kaposi's sarcoma (S-KS), complex KS (C-KS),
simple Pneumocystis carinii pneumonia (S-PCP), complex PCP (C-PCP), and Central
Nervous System disorders (CNS). The average cost per admission was calculated
by methodology used by Travenol Management Services. Costs were lowest for
S-PCP (SCanadian 11,822) and S-KS ($12,020) and increased for the other
admission diagnoses: CNS ($15,716), C-KS ($18,045) and C-PCP ($26,395). Daily
hospitalization costs also varied among the groups: S-KS and C-KS - $560/d,
S-PCP $630/d, CNS $700/d and C-PCP $906/d and all were greater than the average
hospitalization costs for non-AIDS patients. Incremental costs of caring for
a patient with AIDS compared to a non-AIDS patient were at least 31% greater
and led to a net loss to the hospital. Admission diagnoses over the course of
illness varied considerably among patients categorized as KS or PCP at initial
diagnosis. Case mix changed over the observation period with increased severity
of disease and costs. A forecasting formula was derived and demonstrated the
influence of observed and projected changes in case mix severity on total yearly
hospital costs for AIDS patients. Strategies for cost containment will be
discussed.
MR212 T'1e Adequacy of Hospital Reimbursement for AIDS Patients
JOHN S. CLARK, D.B. McCallum, Institute for Health Policy
Analysis, Georgetown University Medical Center, Washington, DC.
Hospitals are having to balance the competing forces of cost
containment efforts by third party payors with increasing numbers
of AIDS patients who require particularly costly treatment. Reim-
bursement to hospitals for AIDS patient care has important finan-
cial consequences for hospitals and patients, and could affect
quality and access.
An analysis of 169 AIDS admissions between 1982 and 1986 at two
hospitals in Washington, DC explored the proportion of hospital
costs met by various payors and the efficacy of DRG reimbursement
for AIDS patient care.
Preliminary results suggest that commercial insurers (64 cases)
paid approximately 24% above estimated cost, while Blue Cross/Blue
Shield (40 cases) paid at about cost. The percentage of cost paid
by Medicaid (15 cases) differed substantially between admissions,
but surprisingly the vast majority fell between 5% below and twice
the estimated cost. Those who are without insurance (17 cases)
were able to pay only 5% of the cost of treatment, suggesting that
hospitals have a strong incentive not to admit these patients.
DRGs in which AIDS patients are commonly placed could result in
the under-compensation of hospitals (eg. DRG 398) or over-compen-
sation (eg. DRG 79). This suggests that if third party payors a-
dopt DRG based reimbursement strategies in the future, or if AIDS
patients become Medicare eligible, DRGs frequently used for AIDS
patients will need to be adjusted, or new DRGs specifically de-
signed for AIDS patients be created.
MR 210 AIDS/ARC Patients in Residential Drug Treatment Therapeutic
Communities: A Special Program
JOYCE JACKSON, G. RODRIGUEZ, R. BAXTER, S. NESHIN, N.J. State Dept. of
Health (NJSDH), East Orange, NJ
In New Jersey, where IV addicts comprise the majority of AIDS cases, many
patients continue to use drugs after diagnosis, have no stable living
arrangements, and are non-compliant with medical regimen. They continue to
transmit HIV by needle-sharing, sexual contact and perinatal ly. This paper
describes an effort by the NJSDH to address these issues by providing
funding for 30 beds in 5 residential drug treatment therapeutic ccmnunities
for AIDS/ARC patients.
Programs were contracted to provide 1) daily RN contact, 2) weekly
physician contact, 3) 5 hours MA level therapy weekly, 4) nutritional
support, 5) prescribed medications and supplies, and 6) transportation and
liaison with AIDS treatment facilities. Patients were referred by
hospitals and other agencies to NJSDH, where records were screened and
patients placed. To be eligible, patients must be ambulatory and capable
of self-care, alert and oriented, and willing to accept a structured
residential environment. By January 1, 1987, out of 60 referrals, 30
patients had been successfully placed. Problems have included cooperation
of referral sources, referral of nursing home level patients, patient
acceptance of environment, program willingness to modify concept and
practice to accommodate social, psychological, and pharmacological needs of
AIDS patients.
MR213 Foster Care Needs of Children with HIV Infection
MARY BOLAND, M. TASKER, P. EVANS, E. CONNOR, J. OLESKE
Children's Hospital of New Jersey & UMD-New Jersey Medical School, Newark, NJ
Children with perinatally acquired HIV infection are members of multiproblem
families. Of 50 families with 57 children, 17.50 (42%) of the families were
known to the family protective agency (New Jersey Division of Youth & Family
Services [UYFS] prior to the diagnosis of HIV infection. The families were
referred for neglect (3/17), abuse (2/17), and foster care placement (12/17).
In addition, 3/50 families were referred after diagnosis for neglect (1/3) and
placement support services (2/3). 21/57 children are in foster care because of
the following: death of a parent (4/21), illness of a parent (2/21), and ina-
bility or unwillingness of the parent to care for the child (15/21). Identi-
fying a foster home or facility willing to care for a child with AIDS is
difficult. Placement within the extended family occurred for 15/21 children
and 6/21 children were placed in DYFS approved foster homes. All placements
were maintained although extensive support to the foster family was required
once the child was diagnosed. Extended family members require education about
the disease as well as ongoing social and financial support if the placement
is to be successful. Human services agencies must be willing to care for these
children. Health care providers must be available to inform prospective foster
parents about the disease and assist foster parents deal with the health care
system.
MR211 Chronic Care for AIDS Patients: The Health And Hospitals
Corporation Model for Long Term Care
PAUL A. MOORE, H. RICHARDSON, NYC Health and Hospitals Corporation, N.Y.,
N.Y.
The NYC Health and Hospitals Corporation, as the largest provider of
hospital care to AIDS patients in the country, cares for the many patients
who remain hospitalized after medical clearance but for whom post acute care
placements are not available. About half of this population is homeless,
the remainder are certified for some form of long term care Skilled Nursing
Facility (SNF) or Health Related Facility (HRF) care.
HHC is currently providing long term care to a number of such patients in
"chronic care" beds at two of its facilities. Key elements of this service
modality are explored: referral and assessment, intensity of medical care,
relationship with acute care facilities and cost/revenue Issues.
MR214 Prevalence of Human Immunodeficiency Virus (HIV) Antibodies in
Prostitutes and their Clients in Addis Ababa, Ethiopia.
SEYOUM AYEHUNIE*. S. BRITTON**, TEBEBE YEMANE-BERHAN***. T.
FEHNIGER**. ^Department of Biology, Addis Ababa University, **Armauer
Hansen Research Institute, ***AU Africa Leprosy Rehabilitation and Training
Centre (ALERT) Hospital, Addis Ababa, Ethiopia.
To determine the prevalence of antibody reactivity against HIV infection we
studied 230 subjects, 60 prostitutes and 70 male clients who were seen at
three local clinics because of venereal disease complaints, and 100 control
subjects from the out-patient department of ALERT. Out of the 230 study
subjects 4 female prostitutes, 2 male clients and 1 from the control subjects
were found to be positive by the Organon ELISA test. However, when the
confirmatory test was done by Western Blot assay only the 4 prostitutes and
1 male client were seropositive showing reactivity to HIV polypeptide antigens
of P24, P34, gp41, P", P64, gp120 in molecular weight. These sera were
retested and confirmed positive by the State Bacteriological Laboratory in
Sweden. This limited seroepidemiological study has determined seropositive
individuals without clinical disease within the Addis Ababa geographical
region. The low number of seropositive individuals within the population
tested suggests a more recent establishment of HIV infection within this high
risk behaviour group than in equivalent studies of prostitutes and sexually
active individuals reported from other geographical regions of Africa.
45
MONDAY, JUNE 1
MR215 The Rlsin8 Demand for Hospital Beds by AIDS Patients and the
Fiscal Implications for Globally Budgeted Hospitals
STEVEN A.GROVER*. L. COUPAL*, N. GILMORE**. *Department of Medicine, Montreal
General Hospital, **Division of Clinical Immunology, Royal Victoria Hospital,
McGill University, Montreal, Quebec, Canada.
To evaluate the growing demand for hospital beds by AIDS patients, we ana-
lyzed the hospital utilization rates of AIDS patients followed at the Royal
Victoria Hospital (RVH) from 1981-1986. As of December 31 1986, 79 AIDS pat-
ients have been treated and 65 (82%) have been hospitalized resulting in 138
admissions (x = 2.1 adm./pts.). While the number of AIDS patients diagnosed
each year has increased 14.5 times, the annual admission and inpatient occu-
pancy rates have increased approximately 29 times. During the same period,
the total number of available medical beds has remained constant.
YEAR TOTAL 1981 1982 1983 1984 1985 1986 CHANGE=(1986-81)/81
New Cases 79
Admissions 138
Hospital Days 3512
Mean Stay 29.1
Our data indicate that the growth in demand for hospital beds by AIDS pat-
ients has exceeded the rise in the number of cases treated at the RVH. In
1986, 2.8% of all medical beds were occupied by AIDS patients. Should this
trend continue, AIDS patients will significantly increase the competition
for scarce hospital beds. This increased demand for hospital resources will
be further compounded if AIDS patients require more services in hospital than
the average non-AIDS patient. Fixed global hospital budgeting, as practiced
in Quebec, will not be able to respond to this change in case-mix and demand
for services unless precise costing of the services used by AIDS patients is
undertaken and health care planners respond appropriately.
2
3
4
14
25
31
14.5
2
4
5
21
45
61
29.5
61
124
242
274
962
1849
29.3
30.5
31.0
48.4
13.1
21.4
30.3
MP218 Observations on Clinical and Immunologic Parameters in AIDS/ARC
Patients Treated with IMREG®-1
A. ARTHUR GOTTLIEB, M.S. GOTTLIEB, C.H. KERN. Imreg, Inc. and Tulane Medical
School, New Orleans, LA and Cambridge, MA, USA.
Patients with AIDS or symptomatic ARC were enrolled in three studies of 16
patients each. Each group received IMREG®-! , an immunoregulator derived from
healthy human leukocytes, as follows: Group A: Once every four weeks, subcu-
taneously; Group B: Once every two weeks, subcutaneously ; Group C: Once every
two weeks, intradermally. The purpose of these studies was to determine if
IMREG®-1 could be safely administered in multiple doses, and to follow changes
in immune parameters and clinical indicia of these parameters in these patients
during treatment .
Delayed hypersensitivity to tetanus toxoid returned or increased in 47, 57
and 75% of patients, while the average number of T4+ cells increased or were
unchanged in 31, 44 and 81% of patients in groups A, B and C respectively. T4+
(helper) cells increased by 42%, 36% and 56% in the 5, 7 and 12 individuals of
each group that demonstrated increases in T4+ cell number.
During the treatment period there was no observed toxicity attributed to the
drug. No new opportunistic infections or deaths were observed, while patients
were on protocol. Hematologic parameters appeared to stabilize. Resistant
Candida infections responded to treatment. Some patients gained weight, while
in others there was no weight loss. We observed a decrease in serum uric acid
and immunoglobulin levels which may reflect decreased white blood cell de-
struction and modification of excessive non-specific B cell function. A Phase
III randomized placebo control clinical trial in symptomatic ARC and recent
onset Kaposi's Sarcoma patients is in progress and will enroll 150 patients.
Each patient will be followed for six months of treatment or until an endpoint
is reached.
lYinLlO Ampligen Therapy for HIV Related Immunodeficiency.
HORACE F. HENRIQUES*,G.L. SIMON**, D.R. STRAYER//,W.A. CARTER//, L. EINCK+,R.S.
SCHULOF**. Departments of Medicine** and Surgery* George Washington University,
Wash.,D.C. 20037 , Department of Neoplastic Diseases/*, Hahneman University Phila.,
PA. 19102, HEM Research, Inc. + Rockville.MD 20852,
Ampligen, a mismatched dsRNA which inhibits HIV replication in vitro, was given
to eleven HIV infected patients with ARC or AIDS to study the anti-viral and
immunomodulating effects of this drug. There was no drug toxicity or side
effects seen. Seven ARC patients received 200mg twice weekly for 12-16 weeks
and 5 were then placed on lOOmg twice weekly as a maintenance dose. Four AIDS
patients received 250mg twice weekly and this dose was maintained in 2 and
doubled in 1 based on clinical response measured at 8 weeks. All patients were
HIV culture positive and anergic by multiple skin tests at the start of the
study. All patients demonstrated reversal of skin test anergy within 8 weeks.
Lymphadenopathy resolved in 3/5 patients. In one patient both hepatospleno-
megally and parotid enlargement resolved with Ampligen. Chronic oral candidiasis
resolved in another patient. One patient developed PCP for the second time and
died after 7 weeks of therapy. No other AIDS related events were noted. In 9/11
patients there were changes in viral parameters: 1/9 became negative by lympho-
cyte co-culture, P24 antigen concentration decreased in 2/5. In 7/8 mRNA levels
and in 7/10 HIV polymerase concentrations decreased. T4 levels improved in 3 and
stabilized in 8 patients. After 6 weeks of maintenance therapy, patients remain
asymptomatic with intact DTH responses and no change in T4 levels or T4/T8
ratios. The clinical improvement noted in these patients paralleled the
apparent viral suppression. These promising results and the absence of drug
related toxicity, support the use of Ampligen in additional trials in HIV
infected patients.
MR219 Evaluation of Antitrypanosomal and other Antiparasitic Drugs in the
Therapy of Experimental Pneumocystis carinii Pneumonia (PCP)
PETER D. WALZER***, C.K. Kim***, J. Foy***, H. Hendrix***, M.J. Linke***, M.T.
Cushion***, VA Medica.l Center*, U. Cincinnati**, Cincinnati, OH.
New drugs are needed for the treatment of PCP in AIDS. We have compared
antiprotozoal agents with other antiparasitic drugs in the treatment of
experimental PCP. Rats were given corticosteroids for 8 weeks to induce PCP.
The drugs were administered during weeks 5-8, and therapeutic efficacy was
judged by examining lungs for PC using a semiquantitative histologic scoring
system in formalin fixed sections and counting organisms in lung homogenates.
Cationic antitrypanosomal agents were the most active compounds: diminazene,
imidocarb, amicarbalide, quinapyramine, and isometamidium had efficacy >_ that
of pentamidine, the standard drug; guanylhydrazone and ethidium bromide also
showed some activity. Efficacy and toxicity of these drugs were related to
dose and route and duration of administration. With successful treatment, PCP
score and counts fell from 4+ (heavy) and 109/lung to 0-1+ (neg-light) and
105-106/lung. The following drugs showed little or no activity against PCP:
quinine, quinidine, quinacrine, pentostam, chlorpromazine, spiramycin,
pentostam, and astiban.
The data suggest that drugs used in the treatment of a veterinary African
trypanosomiasis are highly active in the therapy of experimental PCP. Since
efficacy in the rat model has usually been predictive of success in humans,
these compounds represent a new therapeutic approach to PCP with important
potential clinical application.
MP217 Intravitreal Ganciclovir (BW B759U) in the Management of
Cytomegalovirus Retinitis
FRED M. USSERY, III, S. GIBSON, R. CONKLIN, D. PIOT, E. STOOL, et al.
Park Plaza Hospital Special Diseases Unit, Houston, Texas
Eight patients with unilateral or bilateral CMV retinitis associated
with the acquired immune deficiency syndrome were admitted to a protocol
designed to evaluate the efficacy of Ganciclovir (BW B759U) administered
by the intraocular route. All patients had been treated previously with
intravenous Ganciclovir ; however, thrombocytopenia and/or leukopenia had
necessitated the interruption of intravenous therapy.
In each case, two hundred micrograms of BW B759U dissolved in 0.1
ml Balanced Salt Solution were injected into mid-vitreous through the pars
plana under ophthalmoscopic visualization, with retrobulbar anesthesia.
Careful attention was directed to minimizing the likelihood of introducing
bacteria into the vitreous, to the maintenance of blood flow through the
retinal vasculature, and to rapid normalization of intraocular pressure
after the injection .
Suppression of the retinitis was observed in seven of the ten treated
eyes. Two eyes did not improve. One eye developed a retinal detachment
as a result of the procedure. Of ten treated eyes, eight required reinjection
within two to twenty days to maintain suppression of the retinitis. The
optimum schedule for reinjection is currently unknown.
The intravitreal route of administration of Ganciclovir is well-tolerated
by the eye and is associated with reasonable success in suppressing CMV
retinitis. It offers an alternative for maintaining vision in patients
unable to tolerate intravenous Ganciclovir.
MP 220 Effects of DHPG on Severe Cytomegalovirus Infection in AIDS
SA Danner., JKM Eeftinck Schattenkerk, OHE Visser, KW Slaterus
Depts of Medicine, Ophthalmology and Virology. Academic Hospital at the
University of Amsterdam. The Netherlands.
Cytomegalovirus (CMV) infection counts for much morbidity and mortality in
AIDS. DHPG, a new acyclic nucleoside analogue of guanine has good antiviral
effects against CMV in-vitro. We studied efficacy and safety of DHPG, 2.5 or
5.0 mg/kg body weight i.v. during 14 days, in clinical CMV infection in AIDS
patients, CDC classification system IV-C or IV-D. Diagnosis of CMV infec-
tion was made on the combination of virotogical, histological and clinical
grounds. A DHPG course was given 20 times in 18 patients for: retinitis (11
cases), pneumonia (5), colitis (3) and spinal cord infection (1): in 3 addi-
tional patients diagnosis of CMV pneumonia could not be confirmed virologi-
cally; these cases were included for safety analysis only. Virological re-
sults: CMV positive urine and throat cultures became negative in 13 out of
15 patients within 14 days of treatment, and again positive after cessation
in 5 out of 7 evaluable patients, mostly within 3 weeks. Clinical results:
the spinal cord infection didn't improve, colitis responded well in 2 out of
3, pneumonia in 2 out of 5 and retinitis in 7 out of 11 cases. Retinitis re-
lapsed within 4 weeks after cessation of therapy, so maintenance therapy, 2
times a week 5.0 mg/kg i.v. was instituted with good effect. In 3 patients
DHPG was given intravitreally , 0.4 mg per 14 days in order to avoid frequent
hospital visits. Results are promising and a pilot study is under way.
Thrombocytopenia was seen 3 times (requiring drug withdrawal in 1 case), mo-
derate leucopenia in most cases, reversible after drug cessation, tfe conclu-
de that DHPG is a relatively safe and effective drug in CMV infection in
AIDS patients, especially in colitis and retinitis. However, relapse prophy-
laxis is needed and platelet and white cells counts should be monitored.
46
MONDAY, JUNE 1
MR221
Mark A.
*UCSF Sc
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Randomized Prospective Trial of Ganciclovir Maintenance
Therapy for Cy tomega 1 ovri us (CMV) Retinitis
Jacobson*, HR Brodie*. J J 0 ' Donnel 1 * , CC Wofsy*, J Mills'
of Medicine and S.F. General Hospital, San Francisco,
hool
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MR224 Anti-CMV Treatment with DHPG Does not Affect HIV Antigen Levels in
AIDS Patients.
JOHANNES GAUB*. B.0. LINDHARDT***, A.-G. P0ULSEN*, C. PEDERSEN**, C.M.NIELSEN****,
V. FABER* et al . , Depts of Infectious Diseases, *Rigshospitalet and **Hvidovre
Hospital, **** State Serum Institute, ***The Fibiger Institute, Kabenhavn,
Dannark.
In a study of the anti-HIV effect of foscarnet in 15 patients with AIDS, HIV
antigen was found in 8 before treatment, and it disappeared temporarily during
and after treatment in 5 of these.
Four of the 5 patients had positive CMV culture prior to foscarnet treatment,
but negative cultures during and after therapy.
PROBLEM: Since foscarnet is effective against CMV as well as against retroviral
reverse transcriptase, its effect on HIV antigen could be secondary to its
effect on CMV, which may be a co-factor in AIDS development and progression.
DESIGN: We have studied HIV antigens in sera from 8 patients with AIDS and CMV
chorioretinitis, treated with DHPG (Syntex) for 14 days.
RESULTS: DHPG was effective against CMV clinically and virological ly.
Seven patients had HIV antigen in serum.
HIV antigens did not change during DHPG treatment.
CONCLUSION: The effect nf foscarnet on HIV antigen levels is probably indepen-
dent of its anti-CMV effect.
MP222 PHASE X TRIAL OF RECOMBINANT GRANULOCYTE-MACROPHAGE COLONY
STIMULATING FACTOR IN ACQUIRED IMMUNODEFICIENCY SYNDROME ASSOCIATED
LEUKOPENIA. J Groopman, R Mitsuyasu, M DeLeo*, R Donahue*, D Oette*, D Golde,
et al. New England Deaconess Hospital, Harvard Medical School, Boston, MA;
Genetics Institute, Cambridge, MA; Sandoz Pharmaceuticals, East Hanover, NJ;
and UCLA School of Medicine, Los Angeles, CA.
The granulocyte-macrophage colony stimulating factor (GM-CSF) is a glyco-
protein with a variety of in vitro activities including potentiation of myeloii
colony growth and stimulation of leukocyte function. Because of the frequent
decreased number and function of leukocytes in AIDS we performed a phase I
study evaluating safety and efficacy of GM-CSF. Recombinant GM-CSF (s.a. =
4.4 x lO^U/mg protein) was administered at doses of 1.3 x 103U/kg/d,
2.6 x 103U/kg/d, 5.2 x 103U/kg/d and 1.0 x 104U/kg/d to groups of 4 patients
at each dose. A single IV dose was followed by a 14 day continuous IV infusion
All patients were men with total peripheral WBC 3,500/ul. The drug was well
tolerated with mild symptoms of headache, myalgia, and nausea. Increased
liver function tests occurred in 3 patients. Recombinant GM-CSF was active in
vivo with elevations in mean peripheral WBC from baseline to day 15-17 of 1850
to 4575/ul (at 1.3 x 103U/kg/d) , 2675 to 8650/ul (at 2.6 x 103U/kg/d) , 1900 to
8743/ul (at 5.2 x 103U/kg/d) , and 2600 to 17,300/ul (at 1.0 x 104U/kg/d) . No
significant change in hemoglobin or platelet count was seen. The increase in
WBC was mainly due to neutrophils, bands, and eosinophils with a two four-fold
increase in total monocyte and lymphocyte counts. 2-10 days after discontinua-
tion of drug the WBC returned to near baseline. Recombinant GM-CSF is active
in leukopenic AIDS patients, well tolerated, and may have a clinical role as a
single agent or in combination with antiretroviral therapy.
MR225 Dose Response Study of Diethyldithiocarbamate (DTC or Imuthiol) in
Patients (PTS) with ARC and AIDS.
EVAN M. HERSH, E. PETERSEN, D.E. Y0CUM, R.S. GORMAN, J.M. DARRAGH, University
of Arizona Health Sciences Center, Tucson, AZ, USA.
In previous study, DTC at a dose of 200mg/M' was shown to significantly
improve symptoms and signs of ARC and AIDS and was shown to induce a trend
towards improved prognosis. In the current study pts. with ARC or AIDS were
randomly allocated (after stratification for ARC vs. AIDS, <_ vs. >2 symptoms,
<_ vs. >200 peripheral blood T lymphocytes per mm3) to receive or not receive
DTC for 16 weeks followed by a cross over to the other treatment arm on which
they were again treated or not for 16 weeks. Pts. received DTC 200mg/M2
intravenously (IV) weekly (QW)x4 wks, then 400mg/M2 (IV) QW x4 wks , then
800mg/M2 (iv) QW x4wks , then 800mg/M2 twice weekly x4wks. Doses of 200 and
400mg/M2 were non-toxic. Doses of 800mg/M2 either once or twice per week were
toxic, inducing chest pain and dyspnea, nausea and vomiting, fever and skin
rash. Thus far 19 pts. have been randomized, 11 to treatment and 8 to control.
Of these, 2 treated and 6 control have progressed. The treated patients
progressed after 4 and 15 weeks of treatment. The treated pts. had P. Carinii
pneumonia (PCP) while the 6 controls had Kaposi's sarcoma (2 pts.). PCP (2
pts.), M. avium intracellular (1 pt.) and severe progressive weight loss (31
lbs. over 3 months) with debililation (performance status, Zubrod, declined
from 1 to 4) (1 pt.). Evaluation of blood counts, blood chemistries, T cell
phenotypic markers, lymphocyte blastogenic responses to the mitogens PHA, PWM,
C0NA, and delayed hypersensitivity to recall antigens showed no major changes
except that 8/11 treated and 1/8 control pts. showed an increase in Til +
cells at 8 weeks. These results indicate that the maximally tolerated IV dose
is >400 and <800mq/M2. The apparent difference in prognosis suggests that
further controlled studies in larger numbers of pts. are warranted.
MR223 Efficacy of BWA515U in Treatment of EBV Infection in Hairy Leukoplakia
DEBORAH GREENSPAN*. 3.S. GREENSPAN*, Y. DE SOUZA*, S.K.
CHAPMAN", E. LENNETTE***, and V. PETERSEN*, 'University of California, San
Francisco, CA, "Burroughs Wellcome Co., NC, and **»Virolab Inc., Berkeley, CA.
We investigated the effects of BWA515U, a potent acyclovir prodrug, on the clinical
features and viral components of oral hairy leukoplakia (HI.), an AIDS-associated
lesion. We have previously shown the presence of EBV in fully replicating form in the
lesion of HL using cytochemistry, electron microscopy and DNA hybridization.
Fourteen patients with HL, none of whom had AIDS at the time of the study, were
assigned to drug or placebo groups on a randomized double blind basis. 250 mg of
BWA515U or placebo were taken orally t.i.d. for 14 days. Clinical photographs were
taken at 0, 7, 14 and 28 days. Biopsies were performed at day 0 from HL lesions and at
day 14 from lesions or from the site of lesions where they disappeared. 7/7 patients on
active drug showed significant or complete resolution of the lesion clinically, while 7/7
receiving placebo showed no change. Histological features of HL significantly
diminished in patients on active drug, while cytochemical and ultrastructural studies
showed elimination or dramatic reduction of EBV infection in the active drug group
only. This study shows that BWA515U was effective, on a short-term basis, in
eliminating the clinical, histological and virological features of oral hairy leukoplakia.
Supported by Burroughs Wellcome and the University of California Systemwide Task
Force on AIDS.
MR226
Treatment of AIDS Based on a Combination of Synergistic Drugs
OTTO J. PLESCIA*, D. Pontani**, C. Schaffner*, D. Sun***, P. Sarin***, and
S. I. Shahied**, *Waksman Institute of Microbiology, Rutgers-The State Univer-
sity of NJ, New Brunswick, NJ, "New Jersey State Department of Health,
Trenton, NJ, ***Laboratory of Tumor Cell Biology, NCI, Bethesda, MD.
Central to AIDS is the progressive loss of T4 helper cells by the cytopathic
action of HIV, dependent on replication of the virus in infected cells. Virus-
infected cells are a reservoir of virus that can spread to other normal T4
cells. Our strategy to control infectious HIV is based on three objectives:
(1) inactivate extracellular virus directly, (2) inhibit replication of HIV in
virus-infected cells, (3) increase the resistance of T4 cells to infection by
HIV.
AME, a relatively non-cytotoxic methyl ester derivative of Amphotericin B,
binds to sterols in membranes of cells and lipidenveloped viruses such as HIV.
In cultures of H9 test cells infected with HIV, AME (1 to lOuM) inhibits viral
replication, thus protecting H9 cells against HIV, and prevents the spread of
virus from virus-infected H9. AME also prevents the spread from virus-
infected lymphocytes of AIDS patients. Based on results of pretreating HIV,
virus- infected H9 cells, and normal H9 cells with AME, it meets all three of
our objectives. Clearly AME inactivates HIV, and in combination with
Foscarnet, an inhibitor of viral reverse transcriptase, it is more effective
because of synergism. Biological response modifiers are also candidates as
synergistic drugs. Our results provide a rational basis for using a combina-
tion of synergistic drugs for the treatment of AIDS.
47
MONDAY, JUNE 1
MR227 Treatment of ARC Patients with Sodium Diethyldithiocarbamate (DTC,
n
Imuthiol ). A Multicentric, Randomized, Double Blind, Placebo con-
trol led Trial
Members of the AIDS-IMUTHIOL FRENCH STUDY GROUP (Lyon, Paris, Strasbourg,
Tours), France.
This study was designed to evaluate the clinical efficacy, immunorestorative
potential and tolerance of Imuthiol in the treatment of ARC patients. Patients
were selected for presence of constitutionnal symptoms and T4 cell numbers
below 600/cu mm. They were randomized to be treated with either Imuthiol (10
mg/kg, once a week, oral route) or placebo capsules.
As of January 1987, 92 patients entered this study. After 4 months of treatment
improvement of the clinical status was observed in 42 % of evaluable Imuthiol
treated patients while 55 % were stable and 3 % worsened. In placebo group,
only 8 % improved while 86 % were considered as stable and 6 % worsened. Pro-
gression to AIDS occured in 5 out of 36 placebo treated patients, but none in
the Imuthiol group (N = 33). Weight loss or splenomegaly disappeared in all
Imuthiol treated patients who presented these symptoms on day 0.
After 4 months, 42 % of the Imuthiol treated patients had T4 cell numbers
over 600 cu mm. Recruitment of more than 350 additionnal T4 cells per cu mm
over the 4 month treatment was seen in 30 % of the Imuthiol treated group.
This trial will be completed before the meeting and results discussed.
MP230 Variation in the Humoral Immune Responses of Rhesus Monkeys
(Hacaca mulatta) Immunized with Formalin-Inactivated Type D
Retrovirus Vaccine and Correlation with the Clinical Disease Outcome
SUGANTO SUTJIPTO*, J.D. KLUGE*, M.B. GARDNER**, and P. A. MARX*, *California
Primate Research Center and "Department of Medical Pathology, University
of California, Davis, CA, USA.
As part of a vaccine trial, six healthy juvenile rhesus monkeys (Hacaca
mulatta) were immunized with a formalin-inactivated whole SAIDS type D
rhesus retrovirus serotype-1 (SRV-1) vaccine containing the adjuvant
threonyl muramyl-dipeptide. Following immunization, all six animals showed
antibody response against viral core and envelope proteins. The pattern of
antibody response in immunized animals was unchanged in response to chal-
lenge with a potentially lethal dose of SRV-1. All immunized animals were
protected from persistent viremia and remained clinically healthy. Two of
six non-immunized control rhesus which received adjuvant alone, developed
antibodies against core and envelope proteins following live virus chal-
lenge and exhibited only transient viremia. Four additional control rhesus
failed to develop detectable antibody post-challenge and succumbed to
simian immune deficiency syndrome (SAIDS).
Variations in antibody response of individual immunized animals were
observed even though all received identical viral proteins. These dif-
ferences may reflect the titer of antibody made by these animals to
specific viral proteins. This study demonstrated that early development of
specific virus-induced antibodies correlated with a favorable clinical
outcome.
MP.228 *n v,jvo Anti-Retroviral Properties of Recombinant Alpha
Interferon in AIDS with Kaposi's Sarcoma and Healthy HIV-
Seropositive Homosexual Hen
JOSEPH K0VACS*, H.C. LANE*, H. MASUR*, B. HERPIN*, J. FEINBERG**, A.S. FAUCI*.
♦National Institutes of Health, Bethesda, MD, **Schering-Plough, Kenilworth, NJ.
Alpha interferon is a leukocyte derived glycoprotein with anti-viral,
anti-proliferative and immunomodulatory effects. It has been shown to be
clinically effective in the treatment of AIDS-related Kaposi's sarcoma (KS)
in 20-40% of patients and to have in vitro activity against HIV. The present
study was designed to determine the in vivo anti-retroviral activity of
recombinant alpha interferon in 30 AIDS patients with KS in an open trial of
35 million units of interferon daily and in 60 asymptomatic HIV culture
positive homosexual men with more than 400 CD4+ lymphocytes/mm in a placebo
controlled trial. At this time 15 KS patients and 20 asymptomatic individuals
have entered the study. Of the 9 evaluable KS patients, 5 have had a
complete or partial anti-tumor response (mean CD4 count for responders = 445
vs. 101 for non-responders). Reductions in HIV-isolation were noted in 3/5
of the KS patients with an anti -tumor response and 0/4 of the
non-responders. Of the 10 evaluable asymptomatic HIV infected individuals
4/5 interferon treated and 1/5 placebo treated patients became culture
negative during study. Although the current sample size is too small to draw
firm conclusions, it appears that alpha interferon may have in vivo activity
against the AIDS virus.
MDOOI Experience in Treatment of Idiopathic Thrombocytopenic Purpura
(ITP) in HIV-positive Homosexuals by Perfusion of Plasma over
Staphylococcal Protein A-silica (Prosorba® Columns} .
HARRY W. SNYDER, JR. , J. BERTRAM*, F.R. JONES and the PROSORBA® CLINICAL
TRIAL GROUP. IMRE Corporation, Seattle, WA and USC Cancer Center, Los
Angeles, CA.
ITP is an autoimmune disease frequently found in association with HIV
infection in homosexual men. In ITP platelet-associated antibodies (PAA)
and/or circulating immune complexes (CIC) bind to platelets (Pit) and accel-
erate their destruction by the reticuloendothelial system. Recently a
clinical trial was conducted to evaluate removal of PAA and CIC from plasma
of ITP patients by perfusion through columns of protein A-silica. Twenty-
four patients were evaluated after receiving 4-8 treatments involving
absorption of 250 ml plasma. The patients presented with 50±6 x 103 Pit/mm3
and elevated PAA and CIC. During treatment Pit counts in 14 patients in-
creased 1.6-4.3 fold (mean: 2.5+0.3, P=0.04) . Coincident with this effect
were drops in PAA (32±9 ng IgG/106 Pit to 10+4 ng) and Clq-CIC (105±23 pg/ml
to 60±15 yg/ml, P=0.14) . Responses of 4 of these patients were transient
( <2 weeks duration) , while ther responses in 6 of the other 10 patients were
of greater than 6 months duration. Pit counts continued to rise in these
patients 1.3-4.5 fold (mean: 2.3+0.5) after termination of treatment. Pit
counts and PAA and CIC levels were not altered in nonresponder patients.
Serological parameters which were predictors of positive responses to treat-
ment were PAA >10 ng/106 Pit (P=0.04) and Clq-CIC > 60 pg/ml (P=0.04) . The
results suggest that extracorporeal removal of IgG antibody and CIC from
plasma modulates the autoantibody response and decreases Pit destruction.
MP229 Survival of the Human Immunodeficiency Virus Under Controlled
Drying Conditions on a Hard Surface.
SHERRY L. LOSKOSKI, L.S. MARTIN, W.W. BOND, Centers for Disease Control,
Atlanta, GA.
We determined the stahility of the human immunodeficiency virus (HIV) (LAV
prototype strain) after drying and storage under controlled temperature and
relative humidity (RH) using the ID-50 and antigen capture assays. HIV in
culture fluid (0.1 ml, ID-50=103) was placed on 1/2-in2 stainless steel
strips, and the strips were dried for 2 hr at 25.6°C and 28% RH in a
vertical laminar-flow safety cabinet. Strips were then stored at 25°C in a
desiccator jar over a saturated aqueous solution of potassium carbonate
(enclosed RH=42%). We removed triplicate strips from the jar at intervals of
1,3,5, and 7 days and assayed for viable virus. At each interval, 0.1 ml of
media was added to each strip for 10 minutes, and the eluent was assayed for
viable virus. A liquid control was performed In parallel. The virus titer
eluted from the strips was reduced approximately 1 log during iniital drying,
followed by a more gradual reduction over 7 days. The HIV titer held in the
liquid state also dropped markedly. These results indicate that, although
there is a 90% or greater reduction in titer after drying, HIV will survive
drying and storage for a period of time. Survival after drying may effect
future disinfectant chemical testing with this virus.
BflDOO? The Lookback Program in a High-Prevalence AIDS Region
STEVEN KLEINMAN AND K. SECORD , American Red Cross, Los
Angeles, CA.
The lookback program has been designed to locate, inform, and
test persons who received blood components prior to anti-HIV test-
ing from donors who were later found to be anti-HIV (+). Our pro-
gram provides anti-HIV testing, physician education, recipient
counseling and spouse testing if requested. We have identified 513
potentially infectious components donated from June 1983 to March
1985 and have thus far located 282 recipients of whom 163 (58%)
expired during hospitalization. The anti-HIV (+) rate in 53 living
recipients was 77% when tested 18-42 months post transfusion; this
rate did not vary over 3 seven month periods beginning in 6/83.
We have not yet observed a case in which recipients from 2 con-
secutive donations by the same donor have been anti-HIV(-) . Also,
in one case, a unit of rbc was split and given to 3 infants: 2
tested anti-HIV(-) but one tested anti-HIV(+). These findings of
a) a high infectivity rate of lookback donors, b) discordant anti-
HIV results in recipients of the same donation, and c) the diffi-
culty of obtaining anti-HIV results from recipients of consecutive
donations lead us to recommend notifying lookback recipients as
quickly as possible, rather than on a case by case basis. Coun-
seling sessions with 19 anti-HIV (+) recipients have been vital in
helping these persons to understand and cope with the information.
Anti-HIV testing of 12 spouses (6 male, 6 female) has been nega-
tive despite 1 to 3 years of continued sexual contact with the
anti-HIV (+) recipient. Anti-HIV testing and counseling services
will increase the public health benefits of lookback programs.
48
MONDAY, JUNE 1
MP233 Anti-HIV Testing of Blood Donations in the United Kingdom
HAROLD H. GUNSON and V.I. RAWLINSON, Regional Transfusion Centre,
Manchester, England.
Routine screening of blood donations for anti-HIV which commenced in the
U.K. in October 1985 has been performed principally using the Wellcome
competitive ELISA test. Donors are informed that the test will be carried out
and asked to sign their agreement. Those confirmed anti-HIV positive are
informed and counselled.
By the end of October 1986 approximately 2.8 million donations have been
tested and 61 (0.002%) were confirmed anti-HIV positive. Of the 59 anti-HIV
positive donors interviewed to date only 6 deny belonging to a recognised risk
group with respect to HIV infection, the majority comprising young homosexual
or bisexual men and intravenous drug abusers. Approximately 320,000 persons
donating blood for the first time have been anti-HIV tested and 15 (0.004%)
have been confirmed as positive. All those interviewed have admitted to being
in recognised risk categories. The majority of anti-HIV positive donors attend-
ing for blood donation did so because they did not consider that the self-
exclusion categories specified in the leaflet issued to all donors applied to
them since their homosexual activity or drug abuse had terminated several
years ago. A revised leaflet has now been issued to donors in an attempt to
resolve such misunderstandings.
Four confirmed anti-HIV positive donors had been tested previously. One was
found to give repeatedly equivocal results and the donation was not used. Of
the remaining three found anti-HIV negative one is known to have led to sero-
conversion following transfusion of products from the donation to two patients.
MR236 Tr
an
GEORGE FUST
Haemato
As a
transf u
samples
edly EL
control
IFA and
found t
sera, w
batches
matical
tivity
determi
sensiti
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MR234 Inhibition Enzyme Immunoassay for Determination of Anti-HIV
Specificity
NRAPENDRA NATH, C. WUNDERLICH, C. FANG, R.Y. D0DD, American Red Cross,
Jerome H. Holland Laboratory, Rockville, MD
Only a small proportion of donor blood found repeatable reactive in
currently available commercial enz-yme imrnuno assays (EIA) is specific for
anti-HIV when tested by Western blot (WB) assay. WB assay is subjective
and prone to technical variation and is therefore not suitable for
routine use as a confirmation test. We have developed an Inhibition EIA
that utilizes biotinylated human IgG anti-HIV and an antigen coated solid
phase from Abbott or Genetic System tests for anti-HIV. The Inhibition
EIA is based on competition-inhibition format and is designed to be used
in the field in conjunction with the commercial test in use for screening
of donors. Using Inhibition EIA we successfully identified as positive
53 of 55 WB positives and also found 64 of 65 WB negatives as
nonreactive. WB negative samples included 32 that were repeatably
reactive in Abbott EIA. We tested additional 166 specimens that were
repeatably reactive in Abbott EIA but demonstrating atypical or
"indeterminant" band patterns in WB. Only 1 was found reactive in
Inhibition EIA. This sample was later found to be WB reactive on retest.
Inhibition EIA is a simple, objective and reliable substitute for WB for
routine determinantion of anti-HIV specificity.
MP237 Evaluation of an Anti-HIV Screening Test Using HIV env Specific
Synthetic Oligopeptides
RICHARD S. SMITH*, M. HANSON**, D. BOSCH**, H.F. POLESKY**, *Johnson and
Johnson Biotechnology Center, San Diego, CA, **Memorial Blood Center of
Minneapolis, Minneapolis, MN. U.S.A.
A research ELISA test in which microtiter wells were coated with synthetic
peptides from the env region of the human immunodeficiency virus (HIV) was
evaluated for accuracy. Serum samples previously tested for anti-HIV with
licensed ELISA reagents and the Western Blot method were selected for testing
with the env peptide assay. The assay detected 25/26 (96%) samples that were
repeatedly reactive (RR) by ELISA and confirmed anti-HIV specific (p24 and
gp41 bands) by Western Blot. Two (2) patient samples that showed reactivity
to the gp41 band only were reactive on the env peptide assay. Of 35 samples
from healthy individuals that were RR by ELISA but reactive only with the p24
band on the env peptide assay 33 (94%) were non-reactive. The peptide assay
correctly identified as negative > 98% of 212 samples from blood donors who
were non-reactive for anti-HIV by ELISA and Western Blot. These preliminary
data indicate that the env specific peptide assay may provide a sensitive and
specific alternative to ELISA screening tests which use whole viral lysate.
MR235 Removal of human immunodeficiency virus (HIV)
by ultrafiltration
YOSHIAKI HAMAMOTO*, SHINJI HARADA* , NAOKI YAMAMOTO*, HIDEKI
IIJIMA**, SEI-ICHI MANABE**, HIIZU AIZAWA**, *Department of Vi-
rology and Parasitology, Yamaguchi University School of Medicine,
Yamaguchi, Japan, **Asahi Chemical Ind. Co. Ltd., Osaka, Japan
We intend to propose a new method to remove HIV perfectly from
a desired solution such as plasma. As a filter, the regenerated
cellulose membranes having various mean pore sizes were prepared
from the cupurammonium solution of cellulose through the micro-
phase ■ separat ion method. After the filtration of HIV preparation
with these membranes, we evaluated the infect ivity of HIV in both
filtrates and f iltrants through the assays for HIV- induced cyto-
pathic effect (CPE), immunofluorescence method for expression of
HIV-specific antigens and a plaque assay for quantitation of bio-
logically active virus using MT-4 cells. When the pore size of
the membrane determined by the water filtration rate method was
smaller than 30 nm, neither CPE nor fluorescnet cells were detect-
ed in MT-4 cells cultured with the filtrates five days after cul-
ture, whereas in the cells with filtrants, remarkable CPE was
observed and all cells were fluorescent three days after culture.
Moreover, under such filtration conditions, no plaque was formed
with the filtrates although the titer of HIV in the filtrants
showed 10° level of plaque-forming units per ml. In addition,
the novel porous polymeric membrane was found to scarcely absorb
protein molecules.
MR238 Prevalence of Antibodies against Various Epitopes of Envelope
(gp 120,gp41) and GAG Proteins of HIV in AIDS Patients.
TATJANA FRENKL*. E. HEIMER*, B. MCGHEE*, B. MALES*, M. USATEGUI*,
R. POTTATHIL*, et al.**, *Hoffmann-La Roche Inc., Nutley, N.J., U.S.A. and
**F. Hoffmann-La Roche & Co., Ltd., Basle, Switzerland.
Peptides corresponding to various conserved regions of envelope and gag
were cloned and expressed in £. coli . Fusion peptides that contain portions
of gag and envelope were also made. In addition, small peptides (10-30 amino
acids) corresponding to various regions of gp 120, gp 41 and tat were synthe-
sized by solid-phase peptide synthesis. Recombinant proteins and synthetic
peptides were tested for their immune reactivity against normal sera (600
samples) and HIV antibody positive sera (597 WB+ samples). We have identified
several highly antigenic epitopes of envelope ( amino acid sequences 58-68
and 487-511 of gp 120, 578-608 of gp 41), gag and tat that may be useful in
early identification of HIV infection. Peptides corresponding to these
antigenic epitopes were used as HIV antigen in an ELISA test for antibody.
One of these fusion proteins showed 100% sensitivity and lOOX specificity
when used as HIV antigen in a bead-EIA test for HIV antibody developed at
Roche. The data on a) purity of HIV peptides, b) antigenic epi tope-analysis
of gp 120 and gp 41 and c) development of a simple and accurate test for HIV
antibody will be presented.
49
MONDAY, JUNE 1
MP239 Effects of Drying on the Human Immunodeficiency Virus (HIV)
Diluted in Heparanized Bloody Serum or Media.
LINDA S. MARTIN, S.L. LOSKOSKI , Centers for Disease Control, Atlanta, GA.
We assessed survival of HIV after drying the virus in tubes and in covered
tissue culture plates. In both, drying required several hours. In the first,
tubes containing 0.1 ml of virus in media were dried under vacuum in a
desiccator and maintained dry until tested.
ID-50
Room temperature-Liquid Room temperature-Dried
to577
Day
0
1
3
5
6
4°C-Liquid
_ L0^'
104.8
107.0
103.9
1C-4-1
1CP
10-3.5 103.9
101.9 102.4
1C-2-1 i03.9
101.4 102.1
In another set of experiments, virus diluted in heparinized blood, serum
(both negative for HIV antibodies) or media (RPMI +10% FCS, +10% IL2) was
plated into 24 well plates, which were covered and allowed to dry overnight at
room temperature (RT) or 37°C. The dried matrix was then rehydrated and the
ID-50 titer determined. In 3 experiments, no virus was recovered after drying
at 37°C.
ID-50 before drying/after drying at RT
Matrix Exp.l Exp. 2 Exp. 3
Media 10J-°/10J-^ 10J-*/10J.u lC-O/Not Done
Serum 10*-8/103-4 103-8/<10l-° 103-0/<101-0
Blood 104-3/<102-0 105-°/<101-0 103-8/<102-0
These results suggest that survival of HIV following drying at room
temperature can vary.
MP?42 Long-Incubation HIV Infection in a Donor, Recipient and Children
LINDA A. CHAMBERS*, S. CHANOCK** , L. KUNCHES***, *American Red Cross
Blood Services-Northeast Region, Dedham, MA**The Children's Hospital, Boston,
MA***Massachusetts Department of Public Health, Boston, MA.
A case of transfusion-acquired HIV infection (TA-HIV) demonstrated a long
disease incubation period in the implicated donor, the transfusion recipient,
and her secondarily-infected children, suggesting that the involved HIV isolate
had reproducible, though unusual, infectious disease characteristics:
In 1978, a woman received 4 RBC units during her first pregnancy. Two years
later she had a second child with failure to thrive. By age 5, the child
developed adenopathy, tested positive for HIV antibody, and was diagnosed with
ARC. When the mother, husband and firstborn child were also found to be antibody
positive, the case was investigated as possible TA-HIV with secondary infection
of both children and the husband. Three of the donors were unlikely sources of
infection. The fourth - a 28 year old man - was found among the CDC-listed AIDS
cases using a confidential coded identifier. He had become ill in 1985 and died
9 months later with AIDS. The firstborn child has since developed ARC at age 8;
both parents remain asymptomatic.
The donor was infectious and asymptomatic for a minimum of 7 years. The
recipient has been silently infectious for 8 years and her first child
developed symptoms of congenital infection at age 8. This case represents an
early instance of TA-HIV and indicates the need to consider transfusions even
earlier than the 5 year incubation limit presently used by Red Cross to define
involved donations in reported TA-HIV.
MR240 Improved Immune Studies in HIV Antibody-Positive Hemophiliacs:
Association With Decreased Alloantigen Bombardment.
DOREEN B. BRETTLER*. A.D. FORSBERG*, P.H. LEVINE*, J.J. PETILLO**, K.
LAMON**, J.L. SULLIVAN*. *Worcester Memorial Hospital and University of
Massachusetts Medical School, Worcester, MA, U.S.A. and **Rorer Central Research,
Horsham, PA, U.S.A.
We have previously presented data to indicate that the immune defect in hemophilia
is multifactorial. Contributors include: HIV infection, other viral infections, and
exposure to a large array of alloantigens found in clotting factor concentrates. Factor
VIII:C purified utilizing a mouse monoclonal antibody to FVIILVWF was used exclusively
for 6 months to treat hemorrhages on a demand basis in 7 HIV antibody-positive patients
with severe hemophilia A. This therapeutic material has approximately 3,000 x the
specific activity of previously available products. Laboratory assessments included
ELISA assay to detect antibody to mouse protein and immunological data including
quantitative T cell subsets and skin testing on each patient on entrance to the study,
at 1 month, 3 months and at conclusion in order to ascertain whether immune function
in these patients would improve with the use of purer factor concentrate.
Six of seven patients did not develop significant levels of anti-mouse IgG antibody.
(One patient had a rheumatoid factor which interfered with the ELISA assay for
anti-mouse antibody and thus its presence could not be assessed.) There were no adverse
reactions to the material, and hemostatic efficacy was judged as excellent. There
were no significant changes in quantitative T cell subsets. Three out of six patients
lost their previous total skin test anergy and two other patients increased the number
of antigens to which they reacted. This concentrate proved to be safe and efficacious,
to have excellent half-life, and to be associated with apparent improvement in the
immune response.
MR243 CLINICAL STUDIES OF A SYNTHETIC PEPTIDE BASED HIV ANTIBODIES
TEST KIT
EDWARD P. KANG, D. WAYNE WALTERS, JAMES J.G. WANG AND CHANG YI WANG,
United Biomedical, Inc., Lake Success, NY 11042
We have developed an EIA kit for the detection of HIV antibodies using
synthetic peptides representing highly antigenic epitopes of the gp41
envelope and p24 core proteins of HIV as the solid-phase immunoadsorbent.
The total assay time is 45 minutes. An evaluation of this kit was
conducted in three geographically distinct blood centers and a hospital
laboratory with abundant patient populations known to be at risk for the
disease. Over 6200 samples have been evaluated from a random population
resulting in 0.65% initially reactive (IR); 54% of the IR samples were
repeat reactive (RR) giving rise to a RR rate of rate of 0.35%. Approx-
imately 10% of the IR were positive on the Western blot (WB) analysis. With
the assumption of 100% prevalance of antibodies to HIV in AIDS patients,
the sensitivity is estimated to be 100%. Thus the specificity, sensitivity
and the overall efficiency of the test kit is 99.71%, 100% and 99.72%
respectively. Seroconversion studies from twenty patients with over
200 specimens collected over a closely spaced period are compared with this
kit and other licensed kits and with WB analysis. Our kit demonstrates better
sensivity in detecting HIV antibodies in all patients. Five patients even
gave positive signals prior to that detected by WB analysis. RR samples,
tested by other licensed HIV test kits, have been studied in all three-blood
centers. All of the 580 WB positive samples are reactive with our test and
only three of the 125 WB negative samples are reactive. All these WB
negative specimens are RR by at least one other licensed test kits.
MD941 Risk of Human Immunodeficiency Virus (HIV) Infection for Recipients
of Blood From Donors Positive for HIV Antibody
JOHN W. WARD*, A GRINDON**, S. CRITCHLEY**, S. ZIEGLER** , C. SCHABLE*, S
HOLMBERG*, *AIDS Program, Center for Infectious Disease, Centers for Disease
Control, Atlanta, GA, **American Red Cross Blood Services, Atlanta, GA, USA
We evaluated recipients of previous blood donations from donors who were
later found positive for HIV antibody by enzyme immunoassay, but negative on
Western blot assay (EIA+/WB-) and from donors positive by both tests
(EIA+/WB+). Donors were evaluated by HIV culture and date of the EIA positive
donation. Of 109 donors of EIA+/WB- donations, 62 (57%) had 174 previous
donations split into 264 components. Of 180 recipients investigated, 94 (52%)
were dead; of the 86 who were alive, 69 (80%) were tested for HIV-antibody and
3 (4%) were positive. Two seropositive recipients had clotting disorders and
the other had previously received a large number of transfusions. Of 101
donors of EIA+/WB+ blood, 45 (45%) had given 94 previous donations split into
120 components. Of 83 recipients investigated, 44 (53%) were dead; of the 39
who were alive, 31 (79%) have been tested for HIV antibody, and 11 (35%) of
them were positive. Seropositive recipients and seronegative recipients were
similar for Che time interval between their transfusion and the donor being
found EIA+/WB+ (14.6 months vs. 15.2 months). Also, both groups of recipients
from these donors received about the same proportion of red cells (69% vs.
60%) and had no significant difference in likelihood of receipt of blood from
HIV-culture positive donors (4/7 vs. 6/7). Four of six heterosexual partners
of antibody-positive recipients were tested for HIV antibody; none were
positive. Previous recipients of blood from EIA+/WB+ donors are at significant
risk for HIV Infection. Serologic testing for HIV infection of other multiply
transfused persons may be indicated.
MR244 Screening Test Allowing Simultaneous Detection of HIV
Antibodies and HBsAg
LARRY MIMMS, B. BRAUN, K. MAYER, S. EARLE and L. VALDIVIA, Hepatltls/AIDS
R«D, Abbott Laboratories, Abbott Park, IL 60064
A combination HBsAg/anti-HIV enzyme Immunoassay (EIA) has been
developed allowing simultaneous detection of both HBsAg and antibodies
against HIV in sera and plasma. In this combination assay, polystyrene
beads coated with recombinant DNA derived (rDNA) HIV antigens (ENV and
CORE) and antibodies against HBsAG (anti-HBs) are Incubated with
specimen, washed, and then reacted with a solution containing rDNA HIV
antigens and anti-HBs conjugated to horseradish peroxidase (HRP0). This
assay requires no sample dilution because a specific antigen conjugate is
used rather than an anti-human antibody conjugate. Results Indicate that
this assay 1s up to 64 fold more sensitive than currently licensed
antl-HIV tests and is equivalent in sensitivity to Auszyme II. 68
AIDS/ARC sera, 250 anti-HIV positive sera, and 96 HBsAg positive sera
were all reactive 1n this assay. Less than 0.1% of the 4,000 random
blood donors tested were repeatably reactive 1n the combination assay.
Results from this assay do not allow discrimination or differentiation
between HBsAg and anti-HIV posltlvlty. Use of the combination assay may
eliminate the need to screen blood with two distinct Immunoassays.
50
MONDAY, JUNE 1
MP245 HIV AntibodY and Virus Detection in a Cohort of Haemophiliacs.
P. SIMMONDS , ROBERT J.G. CUTHBERT**, F.A. LAINSON*.
J.F. PEUTHERER*, CM. STEEL , C.A. LUDLAM**. *Dept . of Bacteriology,
Edinburgh University. Dept. of Haematology, Royal Infirmary of Edinburgh,
***MRC Clinical and Population Cytogenetics Unit, Western General Hospital,
Edinburgh.
The study group comprises 32 haemophiliacs who were exposed to factor VIII
contaminated with HIV in 1984. 18 patients in this group developed antibody
to HIV, the others have remained seronegative. Serum samples are available
from before exposure to the present day. In this work we compare
serological markers of viral infection, and relate this to the detection of
antigen in serum and the isolation of HIV from peripheral blood lymphocytes.
Serological tests for the detection of HIV antibody include Immunoblot t ing ,
indirect immunofluorescence, Abbott EIA for antibody to core and envelope
proteins, and Wellcozyme and Dupont EIAs. Antigen detection is by Abbott
EIA an Dupont RIA.
Antibody detection tests provide accurate determination of the time of
seroconversion. There was no significant difference in sensitivity between
the tests demonstrable in this study. However variation was observed
between individuals in the development of reactivity to the core bead in the
Abbot EIA. Futhermore, the pattern of bands in immunoblot t ing varied with
time following seroconversion. Antigen can be detected before
seroconversion in some of the HIV-infected haemophiliacs. A proportion of
these remain positive for antigen for a time following seroconversion.
Virus isolation studies have demonstrated the presence of virus in 2 of 15
seropositive individuals examined to date .
MP248 Antibody Reactivity To HIV Proteins As Measured By Commercial
Western Blot (WB) Assays
L. A. MOTLEY, R. C. FITZGERALD, B. S. PAREKH, K. C. PALLIS, D. GOLDSTEIN,
GEORGE B. LAMOTTE, Bio-Rad Laboratories, 1000 Alfred Nobel Drive, Hercules, CA.
The ability to distinguish reactivity of serum antibodies to individual HIV
proteins was studied by examining a series of patient sera samples, each assay-
ed with several different commercial Western Blot (WB) tests. Samples were
first assayed in serial dilutions by commercial ELISA tests. Results were con-
firmed by radioiramunoprecipitation assays (RIPA) . In most instances, the WB
assays showed reactivity to HIV antigens at titers significantly higher than
those found by commercial ELISA assays. However, detection of antibodies to
specific viral antigens varied considerably between the WB tests. This was
particularly true for detection of antibodies to the high molecular weight
viral glycoproteins, gpl60 and gpl20. Some commercial kits appeared deficient
in these antigens and were unable to detect antibodies to them. In contrast,
at least one WB assay was able to detect the viral glycoproteins at titers
beyond the end point for detection of p24, the major viral core protein. When
specimens testing negative or indeterminate for anti-HIV antibodies by ELISA
were tested by WB some kits occasionally showed non-viral reactive bands or
gave a non-specific dark background which confused interpretation. Moreover,
different band patterns were often found for the same serum dilutions with
different kits presumably as a result of having different relative viral anti-
gen concentrations on the strips. Our study demonstrates clear differences in
band patterns and sensitivity between kits especially in the high molecular
weight regions. Differences were noted in the correlation between RIPA and
some of the WB kits at the 160,000 and 120,000 MW glycoprotein bands.
MP 246 Tne Relati°nship of Antibody to HIV, Age, Sex and Treatment to
Lymphocyte Subsets in Congenital Clotting Disorder (CCD) Patients
MARY ANN FLETCHER* , THE TRANSFUSION SAFETY STUDY GROUP* **, *The University
of Miami School of Medicine, Miami, FLf ** other participating institutions.
The Transfusion Safety Study Group (TSS) is a multifaceted cooperative
investigation of factors modifying the occurence and expression of
transfusion- transmitted infections. Lymphocyte subset data on 608 patients
with CCD show lower T4/T8 ratios and numbers of T4+ cells and higher counts
of T8+ and T11+ cells in the 59% who were anti-HIV (+) (p=.01 to .0001).
These anti-HIV (+) patients had more T8+ cells expressing the class II
activation marker 12 (p=.0001), but fewer T11+ cells with the alternate
pathway T cell activation marker TA1 (p=.(*001). They also had an increase in
the suppressor inducer subset 2H4 (p=,0001). However, patients <10 years had
significantly elevated 2H4+/T4+, and lower 4B4+/T4+ subset (p=.0001), as well
as elevated lymphocyte counts (p=.0001) and T8 + , T4+ and T11+ cells (p=,05)
regardless of anti-HIV status, compared to older patients. Among anti-HIV (-)
patients, females had significantly higher %T4+, %T11+ cells and T4/T8 ratios
and lower % of T8 cells and I2+/T8+ cells (p=.05 to .0001). Within the group
of anti-HIV (+) patients, and also within the anti-HIV (-) group, %T8+, *T11+
and I2+/T8+ cells were higher and T4/T8 ratios lower in those patients
treated with concentrates rather than unpooled components (p=.05 to .00m).
In summary, significant differences in lymphocyte subsets were found when
comparing patients with regard to anti-HIV status, but age, sex and treatment
also affected these observations. Possibly, the T cell subset differences
detected affect the susceptiblity to and progression of HIV infection in CCD
patients. (Supported by Contract No. N01-HB-4-7003 of the National Heart,
Lung and Blood Institute.)
MP249 Clinical and Laboratory Follow-up of Asymptomatic Blood Donors with only Anti-Core
Antibodies_
A. BELL06UONO, F. MOZZI, L. VIANELL0, L. MASCARETTI, F. POLI, A. ZANELLA et al.
Centro Trasfusionale, Ospedale Policlinico, via F. Sforza, 35, 20122 Milano (Italy)
The clinical relevance of anti-HIV p15,p2it,p55 antibodies, single or associated, is still contro-
versial. We report the results of a clinical and laboratory follow-up of 59 subjects displaying
such an artibcdy pattern.
The subjects were asymptomatic blood donors, found to be positive at ELISA screening (OuPont,
USA) and confirmed by Western blot (WB) using in parallel reagents supplied by DuPont and by Diagno-
stics Pasteur (France) or Bio-Rad (USA). All sutjects but 5 denied risk factors for HIV infection.
CD'f /C 08 ratio by cytof luorometry (Spectrum III, Ortho Diagnostic Systems, USA), skin testing by
recall antigens (Merrieux, France) and screening for lymphocytotoxic antibodies were also performed.
Clinical evaluation, Western blot analysis and CDVCD8 ratio were repeated at 3-month-intervals for
5-21 months (median 9). Results ai e summarized in the table.
SUBJECTS
WB pattern
Inverted
CDVCD8
Positive lymphocyte
abs screening
Changes during follow-up
clinical WB pattern
anti-p15 alone 16 1/ 8 13/15 0/16 1/16^15^5,55)
anti-p24 alone 14 1/ 9 9/13 0/H l/lUp2<t,55)
anti-p'i5,2<t,55 29 3/17 11/15 1/29(AKC) 2/29jcomplete pattern
lf.-?t,*5, 55M
Sexual partners of 19 subjects were also examined and found to be seronegative except in 2 cases.
In conclusion, the above results suggest that the clinical relevarce cf anti-pl5-p2l,.p('5 <s
generally low at least in the follow-up period considered, but not nil. The unexpectedly high fre-
quency of anti-lymphocyte-antibodies in the examined subjects deserves further investigations.
MP247 lookback: The Greater New York Blood Program Experience
SUZANNE GAYNOR, J. PINDYCK, New York Blood Center, New York, N.Y.
Lookback, the policy of tracing recipients of previous transfusions from cur-
rently anti-HIV positive blood donors, was implemented in the New York region
in October, 1986 after lengthy deliberations. Due to the size of the region
served, (232 hospitals in N.Y.& N.J.) and the number of anti-HIV positive
donors (609 on October 1st) the complexity of the undertaking required careful
planning. The Blood Center established a Task Force representing hospitals,
physicians, attorneys and patients to advise on the optimal way for hospitals
and the blood center to proceed. Guidelines for hospitals and written informa-
tion to assist those notifying the patient were developed. With support from
community service agencies, a four hour training program for hospital personnel
was developed, covering AIDS epidemiology, screening, confidentiality and coun-
seling issues. The seven sessions held to date have been attended by 227 physi-
cians, nurses, social workers and laboratory personnel. These sessions will be
continued and expanded to meet hospital needs.
A microcomputer system generates product traces and forms to report outcome
of the hospital search. Information on 614 products dating back to January,
1983 has been distributed to 121 hospitals and this process will be ongoing.
To date, 158 responses from 1984-86 period have been received; 102 patients
(71%) are deceased. Of the 42 living patients, 22 were screened by the N.Y. B.C.
ELIZA, Western Blot and IFA are done on all samples. Eleven patients, or 50%
are Western Blot positive. Six patients were tested elsewhere; three (50%) are
Western Blot positive. Thus, this very preliminary data appears to validate the
decision to undertake the Lookback program.
MR250 Risk of HIV transmission by blood components during the two year period
prior to institution of routine anti-HIV screening. JOHN THOMAS% R.
BOWMAN,2,4'5 F.S. RHAME1'2'3, 1-School of Public Health, 2-Dept of Lab Med and
Path, 3-Dept of Medicine, 4-Blood Bank, U Minnesota Hosp, U Minnesota Minneapolis, 5-
American Red Cross St. Paul Regional Blood Center, St. Paul, MN.
To assess the HIV transmission risk due to transfusion of blood components prior to
3/85, we studied multiply transfused patients. Between 3/16/83 and 3/28/85, 1201
persons received 30 or more donor unit exposures (DE) at U MN Hosp. 541 persons were
excluded: hospital records indicated 521 had died without an anti-HIV serology, attend-
ing physicians denied permission to contact 9 patients, 11 hemophilia patients had re-
ceived coagulation factor concentrate. 660 patients (approximately 98,000 DE) were
further evaluated. 2 were known to be HIV infected: one was tested because of lymph-
adenopathy, one because of a look back study; neither had other HP/ risk activities. 36
patients (10,848 DE) had been anti-HIV tested (presumably because of their transfusion
history) of whom 12 (5,997 DE) were hemophilia patients who had not received coagula-
tion factor concentrate; all 36 were anti-HIV negative. Letters were sent to the re-
maining 622 evaluated patients requesting serum for anti-HP/ testing. 200 recipients
(21,686 DE) participated: 2 were anti-HIV positive. Both denied other HIV risk activi-
ties; stored serum taken from both just prior to the transfusions was anti-HP/ negative.
Donor evaluations are under way.
Of 236 multiply transfused persons (32,534 DE) tested because of their transfusion
history, 2 had become HIV infected. Persons receiving multiple donor exposures in the
period prior to anti-HP/ screening of donor blood may be at enough risk of HP/ infection
to warrant routine anti-HP/ screening.
51
TUESDAY, JUNE 2
Plenary Session II
Plenary Session III
Epidemiology and Prevention of AIDS and HIV Infection in the
United States
JAMES H. CURRAN, AIDS Program, Center for Infectious Diseases, Centers for
Disease Control, Atlanta, GA.
Between June, 1981 and January 26, 1987, 29,582 cases of AIDS were reported
to the Centers for Disease Control (CDC) from 50 States and territories and
the District of Columbia, Nearly 17,000 (57 percent) of these patients are
reported to have died. (70 percent were under 40 years of age, 93 percent were
men, and 73 percent were identified as homosexual or bisexual in orientation.)
Nearly 13,000 cases of AIDS were reported in 1986, a 58 percent increase over
1985 reports. The largest percent Increases were among heterosexual men and
women and in geographic areas other than New York, California, and Florida.
Among 6,000 cases reported in heterosexual men and 2,000 cases in women, 68
percent and 51 percent were directly associated with IV drug abuse. Over 22
percent of cases in women and 2 percent of cases among heterosexual men were
reported as contacts of persons with known HIV infection or in a group at
increased risk. Updated statistics and results of collaborative studies and
prevention efforts will be discussed.
T 2 1
■■*■•■ Vaccination against Retroviruses
WILLIAM F.H. JARRETT. Veterinary Pathology, University of Glasgow
Veterinary School, Bearsden, Glasgow, G61 1QH, Scotland.
The greatest degree of experience in vaccinating against retroviruses
is with Feline Leukaemia Virus (FeLV) .
Classical attentuation procedures cannot be used as the virus
promoters and enhancers of the long terminal repeats are potentially
oncogenic by insertional mutagenesis. Serious consideration has
therefore been given to subunit vaccines, cell membrane preparations
and recombinant virus constructs. The first effective vaccines to give
100% protection were cells killed by paraformaldehyde and adsorbed to
aluminium hydroxide. This stressed the importance of the presentation
of an antigen array; the effective epitope is on the surface spike
glycoprotein, gp70 and the effector arm is virus neutralising antibody.
The virus gp70 is highly expressed on the surface of infected cells.
Preparations of killed virus and adjuvanted free glycoprotein have been
unsuccessful as have preliminary attempts to immunise with env-gene
containing vaccinia recombinants. A highly successful vaccine has been
achieved using ISCOMS. Results, both laboratory and field, will be
presented. A similar prototype vaccine using HIV has been made and
used in monkeys and apes. It proved safe in a long term trial and
induced anti-HTV antibodies. Results will be shown and discussed.
T.1.2
T.2.2
Immunopathegenic Mechanisms and Immune Response in
HIV Infection.
Anthony S. Fauci, National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Bethesda, Maryland.
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
T 1 J Aids Epidemiology, Impact, Prevention and Control: The World
Health Organization Perspective.
Jonathan Mann, World Health Organization, Geneva, Switzerland.
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
T 9 3 CHEMOTHERAPY OF HIV INFECTIONS. Samuel Broder, M.O., National Cancer
" Institute, National Institutes of Health, Bldg. 10, Room 12N214,
Bethesda, MD 20892. We have found that with the ribose moiety of the molecule
in a 2' ,3'-dideoxyconf iguration, almost every purine or pyrimidine suppresses
HIV replication in vitro. However, dideoxythymidine had less activity in our
system than the others. Interestingly, the substitution of an azido group or
a cyano at the 3'-carbon in place of a hydrogen significantly restored the
anti-retroviral effect of the dideoxythymidine derivative. An analysis of
five adenosine congeners, which differed only in the sugar moiety, revealed
that reduction (an absence of the hydroxyl groups) at both the 2' and 3'
carbons of the ribose was necessary for an antiviral effect, and an additional
reduction at the 5 '-carbon (the site of phosphorylation after entry into the
target cells) nullified the antiviral activity. Recent studies suggest that
nucleosides which are in a 2' ,3'-dideoxy-configuration may have the capacity
to inhibit diverse retroviruses (both human and animal). The key determinant
of anti-retroviral effect seems to be the capacity of the target cell to
anabolically phosphorylate the nucleoside analogue; a lack of effective
anabolic phosphorylation will make a retrovirus appear to be drug resistant.
Clinical trials with AZT (the azido analogue of dideoxythmidine) have shown
good oral bioavailability and penetration across the blood/brain barrier in
patients with AIDS. Recent studies have shown that AZT can confer a significant
survival advantage to patients with AIDS compared to placebo. AZT can provide
significant clinical benefits to certain adults and children with AIDS-related
neurologic disease. Another dideoxy-analogue (dideoxycytidine) is now in phase
I testing and preliminary results suggest that it may have less bone-marrow
suppressive effects. The observations serve as a stimulus for further clinical
research and provide some measure of optimism in the search for successful
future strategies in treating AIDS.
52
TUESDAY, JUNE 2
Epidemiology — Serology
T 3 1 Detecting Antibody Against Human Immunodeficiency Virus (HIV)
During Early Infection using the Western Blot (WB),
Radioimmunoprecipitation Assay (RIPA), and Synthetic pENV9.
ALFRED J. SAAH*, H. FARZADEGAN*, T.H. LEE**, S.R. PETTEWAY***, C.R. RINALDO*,
J. P. PHAIR*, J.L. FAHEY*, *The Multicenter AIDS Cohort Study (MACS), Bethesda,
MD, "Harvard School of Public Health, Boston, MA, ***Central Research and
Development Department, E.I. du Pont de Nemours & Co, Inc., Wilmington, DE,
USA.
A current concept of the serological response to HIV infection in man is
that antibodies to HIV core antigens (p55, p24, pl5) are detectable earlier
than antibodies against envelope antigens (gpl60, gpl20, gp41) during initial
stages of antibody production following natural infection. As a related
matter, reactivity to synthetically produced envelope antigens during early
infection is relatively unstudied. Sera from 37 gay/bisexual men in the MACS
showed reactivity predominantly to core antigens in the WB that was
established as occurring early during seroconversion. Longitudinal specimens
from these men showed a WB band pattern that clearly confirmed infection with
HIV. 30 of the 37 early sera totally lacked antibody to gp41 in the WB; of
these, 27 (90%) were reactive for anti-gpl20/160 in the RIPA. When the same 30
sera were tested against pENV9 in an EL ISA format, 27 (90%) were also found to
be positive. One serum that was negative by RIPA was positive by pENV9 and
another that was negative by pENV9 was positive by RIPA. Both discordant sera
had solitary strongly reactive p24 bands in the WB.
We conclude that, given HIV infection, almost all sera that are reactive
only for anti-core in the WB also contain anti-envelope antibodies. Further,
the pENV9 assay seems to be equivalent to the RIPA for detecting early
antibodies to envelope proteins.
T3 4 Anti-gag Antibodies to HIV; Association with Neutralization and
Clinical Outcome in Cohorts of Homosexual Men
JONATHAN WEBER*, P. CLAPHAM*, R. WEISS*, D. PARKER**, R. CHEINSONG-
POPOV**, et al., *Chester Beatty Laboratories, Institute of Cancer Research,
London, **Wellcome Foundation Laboratories, Beckenham, Kent.
Sequential sera from 48 subjects infected with HIV-1 were examined pros-
pectively over a 36 month period for neutralizing antibody titre, and titre
of anti-gag antibody (p 24), and anti-env antibody (gp 41). Neutralization
was measured by the VSV pseudotype assay, and the g_ac[ and env titres were
assayed by ELISA on recombinant antigen, and by radioimmuno-precipitation. Data
were analysed in terms of clinical outcome of the cohort at 36 months. Subjects
who remained asymptomatic over 36 months had a significantly higher titre of
antibody against p 24, compared to subjects developing AIDS or ARC. There was
a trend towards increasing neutralizing titres over time in the asymptomatic
group, but this was non-significant. The titre of gp 41 was constant over time
in all subjects. There was no independent association between p 24 titre, and
neutralizing titre, which implies that the possible protective action of anti-
p 24 is not mediated through neutralization. However, three of six anti-p 18
monoclonal antibodies show weak neutralizing activity against HIV (ARV-2).
Further analysis of these cohorts for the relationship between p 18 and
neutralization will be present. As there is no evidence of a humoral response
to p 24, the role of p 24 as a target for cellular cytotoxicity will also be
presented.
T j o Reversion of HIV Serology from Positive to Negative in
' ' Gay/Bisexual Men Who Remain Healthy.
MICHAEL A. POLIS, B.F. POLK, J. P. PHAIR, C.R. RINALDO, P. NISHANIAN, A.J.
SAAH, et al., The Multicenter AIDS Cohort Study (MACS), NIH, Bethesda, MD, USA
Five of 4955 participants in the MACS have been identified as showing
reversion of their HIV ELISA test results from positive to negative, with
corresponding changes in the Western blot. Western blots were performed
simultaneously from serial frozen sera. Genetic relatedness of the
longitudinal sera was confirmed by evaluation of 7 serum proteins using the
same serum aliquots that were used for the immunoblotting.
Serum specimens were drawn at 6 month intervals over a period of 6 to 18
months after the initial positive test. Three participants had multiple bands
by Western blot that disappeared at the next sampling 6 months later (n=2) or
gradually over 12 months (n=l). The remaining two subjects did not become
completely negative by immunoblot but showed progressive fading of bands over
a 12 month period. Both of these men lost detectable antibody to p24 and gp41
but retained other bands, one for pl5 and p53, and the other for p55 and p64.
Whether these subjects have ever been infected with HIV remains to be
determined by culture. All sera were negative for p24 using an antigen
detection test. Clinical (lymphadenopathy, fever, diarrhea, weight loss,
fatigue, and thrush) and laboratory features (hematocrit and platelet, total
lymphocyte, T-helper and T-suppressor counts) were not significantly abnormal
and did not appear to parallel changes in the Western blot in the 5 subjects.
A case/control study is underway to help determine the cause of the
observed reversion and the significance of this phenomenon.
T 3 5 "^ antigenaemia precedes the developement of AIDS or ARC in pati-
ents with HIV infection.
COURT PEDERSEN*,C.M.NIELSEN,"-,B.r.VESTERGAARD~*,J.GERSTOFT-',K.KROGSGAARD,*,J.O.
NIELSEN*. ""'Department of Infectious Diseases, Hvidovre Hospital.^Statens Serum-
ins ti tut , Copenhagen , Denmark .
Sequential serum samples from 33 patients with HIV antibodies were tested for
the presence of HIV antigen using a newly developed double antibody biotin-avi-
din amplified sandwich ELISA (Statens Seruminstitut (Copenhagen) .
HIV antibodies were in all patients demonstrated before December 31st 1985,
and none of the patients had AIDS or the AIDS related complex (ARC) by that ti-
me.Serum samples were collected every fourth month. The median follow up time
was 38 months (range 24-65 months).
During the time of observation, HIV antigenaemia developed in 16 patients. Five
patients in whom HIV antigenaemia appeared developed AIDS, and 3 patients deve-
loped ARC. In contrast, only 1 patient without HIV antigenaemia developed AIDS.
HIV antigenaemia preceded the onset of AIDS by 7 to > 25 months, and the on-
set of ARC by 3 to > 24 months.
At the end of the follow up period (January 1987), 15/16 patients with HIV an-
tigenaemia had a decreased number of T-helper/inducer cells in periphereal
blood (< 0,5 x 10 /D.In contrast, only 7/17 patients without HIV antigenaemia
had a decreased number of T-helper/inducer cells.
In conclusion, the study indicates that the developement of AIDS or ARC in
most patients with HIV infection is preceded by HIV-antigenaemia .Thus, HIV an-
tigenaemia signifies active viral infection with resultant immunodeficiency,
and later the onset of AIDS or ARC. This may be of importance, when patients are
selected for treatment with antiviral agents.
T.3.3 Hi?h HTLV-I II/LAV Neutralizing Antibody Titers Correlate with Better
Clinical Outcome.
M. Robert-Guroff , J.J. Goedert, A. Jennings, W.A. Blattner, and R.C. Gal lo.
National Cancer Institute, Bethesda, MD, USA.
To investigate HTLV- 1 1 I/LAV neutralizing antibodies and protective immunity
we studied serum samples collected prospectively between 1982 and 1985 from 34
homosexual males. By ELISA, 26 subjects were sero-posi tive for HTLV- 1 1 I/LAV in
1982. Of these, 13 progressed to AIDS and 13 remained healthy. Eight subjects
seroconverted during the study. One developed AIDS, and 7 remained healthy.
Neutralization of cell-free virus infection of H9 cells by serially diluted
sera was assessed. Infection was monitored by immune fluorescence assay for
viral p24 expression, and titers, serum dilution"1 at which viral infection
was 60% of the control, were determined. Geometric mean titers (gmt) of
neutralizing antibody in the healthy serocon'verters increased from 13 in 1984 to
49 in 1985. The healthy seroprevalent individuals exhibited consistently high
gmt's: 121 in 1982, 99 in 1983, 125 in 1984, 281 in 1985. Progresses to AIOS
had significantly lower gmt's beginning 2 years prior to AIDS diagnosis. The
gmt's 3, 2, and 1 year before, and 1 year after AIDS diagnosis were 57, 36, 20
and 22, respectively. These results show that neutralizing antibody levels
rise slowly, but may remain at relatively high levels for several years in
association with a healthy clinical status. In contrast, consistently low
neutralizing antibody titers signal poor prognosis. The influence of higher
titers on long term survival should be further evaluated.
T.3.6
HIV ANTIGENEMIA AND AIDS
JOHN P. PHAIR, J. CH1IEL, C-B WALLEMARK, W. WU, J. HJPRIKAR, Northwestern University
Medical School and Howard Brown Memorial Clinic, Chicago, IL, U.S.A.
The frequency of human irmunodeficiency virus antigenania (HIVAg) was determined
using plasma obtained at semiannual intervals (1984-1986) from 121 homosexual or bisexual
men enrolled in a prospective study of the natural history of HIV infection. By design
the study contained 38 participants persistently negative for HIV antibody, 23 seroconver-
ters and 60 men seropositive at entry, including 27 who have developed AIDS. Plasma was
assayed for HIVAg using a solid phase immunoassay enploying beads coated with hman
anti-HIV (Abbott Laboratories, North Chicago, IL U.S.A.). Of the 83 seropositive men,
including the 23 who seroconverted, 34(42%) had HIVAg. The occurence of HIVAg was asso-
ciated with a decline in concentrations of antibody to p24 as determined by intensity of
precipitation bands seen on iimunoblots. 32(39%) developed HIVAg when relatively symptom-
free and within 2-22 months after entry, 22(26%) developed AIDS. 2(2.4%) subjects were
HIVAg positive after diagnosis of AIDS. Only 3 participants progressing to AIDS did not
demonstrate HIVAg. HIVAg was not detected before antibody developed in men with incident
infection. Mean interval between the first detection of HIVAg and diagnosis of AIDS was
315 days (range 56 to 688) in the 22 men with prior HIVAg (Gpl). rfcan CD4 number at the
first time of detection of HIVAg before the diagnosis of AIDS was 311 cells/mn3 1 164
(s.d.). Mean CD4 counts in the 10 men with HIVAg who did not develop AIDS (Gp 2) was 481
cells/mil3 * 202 (p=0.03 vs Gp 1), and in seropositive men without HIVAg (Gp 3) 710
cells/nm3 1 345 (p < 0.0001 vs Gp 1; p = 0.01 vs Gp 2). The rost carman clinical finding
in HIVAg positive men was generalized lymphadenopathy (56%), although 35% of participants
were asymptomatic and 26% had AIDS-related symptoms at the time HIVAg was detected. HIVAg
comnonly predates the onset of the opportunistic diseases which define AIDS and is asso-
ciated with severe CD4 depletion.
53
TUESDAY, JUNE 2
Virology — Antivirals
T A A Activity of 2 ' ,3 '-Dideoxynucleosides as Single Agents or in Combi-
nations against Pathogenic Human T-Lymphotropic Viruses In Vitro.
HIROAKI MITSUYA, S. MATSUSHITA, J.S. DRISCOLL, M. MATSUKURA, M.S. REITZ AND
S. BRODER ET AL. National Cancer Institute, Bethesda, MD 20892.
Purines and pyrimidines with the ribose moiety in a 2 ' ,3 ' -dideoxy-conf igu-
ration can significantly inhibit the ^n_ vitro replication of a wide range of
retroviruses without Inhibitions of the growth and functions of target cells.
Dideoxynucleoside analogues including erythro-3'-azido-2' ,3'-dideoxythymidine
(AZT) can completely block the infect ivity and cytopathic effect of HTLV-III
(also called LAV or HIV) against T-cells under conditions of the substantial
virus excess. Dideoxynucleoside analogues also block the Jji vitro infectivity
of HTLV-I, which can cause a wide spectrum of diseases including adult T-cell
leukemia, immunodeficiency state, and neurological abnormalities. A variety of
dideoxynucleoside derivatives have been tested for the activity against HTLV-
III. For example , the antiviral activity of 5-f luoro-2 ' ,3* -dideoxycytidine is
as potent as its parent analogue, dideoxycytidine (ddC) , while 5-bromo-, or 5-
methyl-ddC is inert against the virus. In cells protected by dideoxynucleoside
analogues the viral DNA synthesis and viral mRNA expression can not be detected.
Dideoxynucleoside-5' -triphosphates strongly inhibit HTLV-III reverse transcrip-
tase (RT) activity but much less mammalian DNA polymerase alpha activity. These
5 '-triphosphates serve as substrates for the HTLV-III RT to elongate a DNA
chain by one residue, after which the chain is terminated. In the case of ddC,
the relative intracellular concentrations achieved Jji vitro exceed those needed
for the DNA-chain termination. Combination of AZT and acyclovir shows a syner-
gistic antiviral effect in vitro. Combination of AZT and dideoxy adenosine or
ddC also shows a significant antiviral effect at low concentrations. These
studies may provide leads in current attempts to develop regimens for effective
chemotherapy against pathogenic human retroviruses.
T A 4 Phosphorothioate Analogs of Oligodeoxynucleotides: Novel Inhibitors
of Replication and Cytopathic Effects of HTLV-IIl/LAV(Human Immuno-
deficiency Virus) in vitro
MAKOTO MATSUKURA*, K. SHINOZUKA*, G. ZON**, H. MITSUYA*, J.S. COHEN* and
S. BRODER*, et al. , *National Cancer Institute and **Food and Drug Administra-
tion, Bethesda, MD 20892
Nuclease-resistant phosphorothioate analogs of several oligodeoxynucleotides
were tested Jjn vitro for antiviral activity against HTLV-III/LAV on human T-
cells. Two anti-sense sequences (14-mers) complementary to the HTLV-III/LAV
genome, a sense sequence, a random sequence, and homo-ollgomers of dA and dC of
two lengths (14 and 28-mers) exhibited a significant inhibitory effect on viral
replication and cytopathogeniclty under conditions of viral excess. The anti-
viral activity was strikingly linear with GC content; longer phosphorothioate
analogs were more effective than shorter ones. None of the homologous sequences
of unmodified normal oligomers, methylphosphonate analog, nor the 3-methylthy-
mine containing phosphorothioate analog (the latter would be chemically blocked
from binding to complementary sequences) showed any antiviral effects. The de
novo synthesis of viral DNA was completely Inhibited by 28-mer dC phosphoro-
thioate at >^ luM as assessed by Southern blot hybridization. However, even 25uM
of 28-mer dC phosphorothioate showed no significant inhibitory effect on the
expression of p24 gag protein in chronically infected cells. These results sug-
gest that the antiviral effect of phosphorothioate analogs of oligodeoxynucleo-
tides is brought about by binding to certain viral component(s), possibly viral
nucleotide sequences and thereby inhibiting de novo synthesis of viral DNA* We
have also observed that 14-mer dC phosphorothioate synergistlcally enhanced the
antiviral effect of 2', 3'-dideoxyadenosine. These data suggest that phosphoro-
thioate analogs of oligodeoxynucleotide could be a novel class of therapeutic
agent against acquired immunodeficiency syndrome (AIDS) and related diseases.
T 4 2 Inhibitory Effect of Various Reverse Transcriptase Inhibitors on
Tumor Induction by Moloney Murine Sarcoma Virus in vivo
MASANORI BABA*, R. PAUWELS*, J. BALZARINI*. E. DE CLERCQ* and D.G. JOHNS**
*Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000
Leuven, Belgium, **Developmental Therapeutics Program, National Cancer Insti-
tute, NIH, Bethesda, MD 20892, USA.
Tumor induction by Moloney murine sarcoma virus (MSV) in newborn NMRI mice
is a representative model for retrovirus infection in vivo. Daily treatment
with 3'-azido-2f ,3' -dideoxy thymidine (AzddThd) (125 mg/kg/day) protected more
than 80 % of the MSV-infected mice against tumor formation and more than 90 %
against death. Even treatment with 25 mg/kg/day of AZT significantly delayed
tumor formation, prolonged the life span, and protected 30 % of the infected
mice against death. In contrast, treatment with either 125 mg/kg/day of
21 ,3' -dideoxycytidine (ddCyd) or 625 mg/kg/day of 2* ^'-dideoxythymidinene
(ddeThd) only resulted in a slight delay of tumor formation and no increase
of survival rate. Mice treated with ddCyd at 625 mg/kg/day developed symptoms
of acute toxicity, such as anemia, resulting In death within 10 days after
the beginning of treatment. Combination treatment of ddCyd with deoxythymi-
dine prolonged the life span and protected several of the infected mice
against death. 2 ' ,3' -Dideoxy thymidine (ddThd) did not protect mice against
tumor formation and death, even at a dosage of 625 mg/kg/day. Other reverse
transcriptase inhibitors, i.e. suramin, Evans Blue and aurintricarboxylic
acid, were also ineffective in protecting the mice against tumor formation
and death at nontoxic doses.
T 4 5 Tumor Necrosis Factor-a and Interf eron-y Have Anti-HlV
Activity
GRACE H.W. WONG*, J. Krowka** , D.P. STITES**, and D.V. GOEDDEL* ,
♦Molecular Biology Department, Genentech, Inc., South San
Francisco, CA, **Department of Laboratory Medicine, University
of California, San Francisco, CA.
One consequence of the defective immune response in patients
with acquired immunodeficiency syndrome (AIDS) is an impaired
synthesis of cytokines. The cytokines tumor necrosis factor-a
(TNF-a) and interferon-y (IFN-y) act synergistically to protect
cells against HIV infection in vitro. In the presence of the
two cytokines, expression of the viral antigen p24 and HIV RNA
is dramatically reduced while levels of reverse transcriptase
activity and production of infectious HIV particles are strongly
inhibited. Combinations of TNF-a and IFN-y kill cells acutely
infected with HIV and inhibit the production of full length
genomic size of HIV mRNA in chronically infected H9 or HuT-78
cells. HIV infection does not induce the production of TNF-a
or TNF-3 mRNA, but HIV-infected cells are able to produce TNF
mRNA in response to mitogens.
T 4 3 Anti-HIV Properties of Castanospermine.
BRUCE D. WALKER*, MARK KOWALSKI*. WEI CHUN GOH*, LARRY ROHRSCHNEIDER
**, WILLIAM A. HASELTINE***, JOSEPH SODROSKI*. Dana-Farber Cancer Institute,
Dept. of Biochemical Pharmacology, Harvard Medical School, and ***Harvard
School of Public Health, Dept. of Cancer Biology, Boston, MA, **Fred Hutchin-
son Cancer Research, University of Washington, Seattle, WA.
Castanospermine (CAS, 1,6,7,8, tetrahydroxyoctahydroindolizlne) Is a plant
alkaloid that has been shown to be a potent inhibitor of glucosidase I, and
thereby prevents normal processing of glycoproteins. We tested whether this
compound might inhibit the function of the HIV envelope in infection and cyto-
pathicity. CAS dramatically inhibited syncytium formation in a transfected CD4+
cell line expressing the HIV env gene. CAS effects on HIV replication were also
examined using freshly HIV infected H9 cells treated with CAS. A dose-dependent
protective effect was observed, as assayed by cytopathic effect, reverse trans-
criptase activity, p24 radioimmunoassay, radioimmunoprecipitation, and virus
yield. The effect was greatest at doses which did not significantly alter cell
viability. CAS appears to exert its antiviral effects by alteration of the env
glycoprotein and not by alteration of the CD4 molecule. T4-gpl20 binding is not
altered by CAS, but processing from gp!60 to gpl20 is decreased by this com-
pound, suggesting that this is the mechanism of inhibition of syncytium forma-
tion. Antiviral effects of CAS appear to result from a decreased virion infec-
tivity due to inference with post-T4-binding steps in virus entry, as well as
a decrease in cell-to-cell virus transmission secondary to syncytium inhibition.
Experiments evaluating possible synergistic effects of CAS with other anti-HIV
agents are currently underway.
T.4.6
QUANTITATION OF THE HUMAN IMMUNODEFICIENCY VIRUS IN PATIENTS
TREATED WITH ANTIVIRAL AGENTS
SURAIYA RASHEED, RICHARD E. COOPER, AND SHU, SU
University of Southern California, School of Medicine, L.A. , CA.
Identification of HIV-infected cells and determination of virus titers
directly in individual's blood (i.e. prior to virus amplification) are
critical factors in the prognosis and possible therapeutic interventions of
patients at risk to develop AIDS. We have developed an extremely sensitive
in situ hybridization method using molecularly cloned HIV-probe to
quantitate the number of HIV infected cells prior to culturing in vitro. A
combination of this method with short-term culturing and antigen detection
assay, offers one of the most sensitive and specific systems to detect and
to quantitate levels of viral RNA, reverse transcriptase, proteins as well
as cytopathogeniclty of HIV in patients at risk to develop AIDS. These
techniques are particularly useful for comparison of the results before and
after the treatment of patients with the drug. Furthermore, antiviral
effects of various chemical compounds that are currently being used for
clinical trials in HIV-infected individuals can be quantitatively assessed
at the level of specific cell types that may be involved in the pathogenesis
of AIDS.
54
TUESDAY, JUNE 2
Clinical Management — Neurology
T 5 1 The Rr^ef Neuropsychological Examination for AIDS Dementia Complex:
Correlations with Functional Status Scales and Other Neuropsycho-
logical Tests
JOHN J. S1DTIS, HANNAH AMITAI, DONNA ORNITZ, RICHARD W. PRICE, Memorial
Sloan-Kettering Cancer Center, New York, NY.
The AIDS dementia complex (APC) is a progressive syndrome that is a
frequent complication of HIV infection. Although the natural history of ADC
has not been fully characterized, experience with moderate and severe ADC has
suggested that it shares features with the "subcortical" dementias. In order
to better characterize the natural history of ADC as well as systematically
assess the effects of antiviral therapies in multi-center studies, we have
developed a brief battery of neuropsychological tests that are sensitive to
some of the major features of ADC: motor slowing, poor concentration and
reduced spontaneity. The tests include verbal fluency, Trail Making A, Trail
Making R, digit-symbol substitution, finger tapping with dominant and non-
dominant hands, and a timed gait test. Our initial experience with these
tests indicates significant decrements in performance across patient groups
with increasing severity of HIV infection ranging from asymptomatic HIV
infection to AIDS. Moreover, in a series of 100 evaluations in over 60 AIDS
patients, these tests correlated significantly with a number of function
status scales including Karnofsky, Kurtzke and Blessed Scales, and, more
importantly, with AIDS-specific neurological history and examination scales
(correlations ranging from r = .4 to r = .8), and other neuropsychological
tests including additional WAIS subtests, memory and motor tests (correla-
tions ranging from r = .4 to r = .9). This brief battery constitutes a
functionally significant core of tests that is suitable for inclusion in
large population natural history and therapy studies.
T C A Cerebrospinal Fluid (CSF) Study in Forty-Four HIV-infected patients:
Clinical Correlation with Virus Isolation and Intrathecal Specific
Antibodies Synthesis.
Christine KATLAMA, M.A. REY, D. SALMON, P. NGOVAN , M. WOLFF, M.C. DAZZA
Hopital Claude-Bernard, Paris, France
CSF of 44 patients - 24 AIDS, 15 ARC, 5 asymptomatic - were studied for
presence of HIV in culture and antibodies by Elisa. None had neurologic oppor-
tunistic infections. Intrathecal HIV-IgG synthesis (ZAb) was assessed on a
ratio CSF-HIV x serum Alb : serum HIV x CSF alb 3.2. Presence of HIV was
demonstrated by detection of reverse transcriptase activity in supernatant of
cultures during 7 weeks. CSF characteristics and computerized tomography were
recorded. 25/44 patients (57%) had neurologic disorders possibly related to
HIV : encephalopathy (18), polyneuritis (3), meningitis (3) myelopathy (1),
and 19 were asymtomatic.
I
v e
ZAb 9
V 8
ZAb 9
V 9
ZAb 9
| V 9
| ZAb 9
TOTAL
-Number of patients |
-with possibly HIV
neurologic disorders!
13
8/13
5
5/5
22
12/22
0/4
25
Prevalence of HIV infection was high (91%) attested either by isolation of
virus (41%) or specific antibodies intrathecal synthesis (50%). But this was
not significantly associated with clinical evidence of HIV-nervous system
involvement since 28% (5/18) of the patients with positive CSF culture and 45%
(10/22) of those with intrathecal antibodies synthesis were neurologically
asymptomatic.
These results suggest that the clinical signification of the presence of HIV
in CSF remains unclear.
T C O Neurologic and Neuropsychologic Complications of
Lymphadenopathy Syndrome.
ROBERT S JANSSEN*. A SAYKIN**, J KAPLAN*, T SPIRA*, P PINSKY*. L
SCHONBERGER*. *Centers for Disease Control, Atlanta, GA, and **University
of Pennsylvania School of Medicine, Philadelphia, PA, USA.
To determine whether there is an association between neurologic and
neuropsychologic abnormalities and human immunodeficiency virus (HIV)
infection in lymphadenopathy syndrome (LAS), we studied 39 seropositive
patients with unexplained lymphadenopathy for >3 months (mean duration of
LAS=A.l years) and 38 homosexual/bisexual men (controls) who were
seronegative for HIV. Participants were evaluated with a neurologic symptom
questionnaire, neurologic examination, a 5-hour battery of neuropsychologic
tests, immunologic tests, and magnetic resonance imaging. Fifteen patients
(38%) with LAS had histories of symptoms of peripheral neuropathy and 9
(23%) had a history of herpes zoster radiculitis. Overall, 21/39 (54%)
patients and 3/38 (8%) controls had a history of symptoms or signs of
neurologic abnormality (odds ratio=13.6; p<0.001). By neuropsychologic
assessment, 9/18 (50%) patients and 2/26 (8%) controls were abnormal (odds
ratio=l 2.0; p<0.002) . Of those abnormal on the neuropsychologic assessment,
the majority scored in the mildly impaired range. Magnetic resonance imaging
was abnormal in one patient and one control. Neither neurologic nor
neuropsychologic abnormalities correlated with absolute T-helper lymphocyte
count or T-helper/T-suppressor lymphocyte ratio. These results indicate an
association of neurologic and neuropsychologic abnormalities with LAS. They
suggest that mild neurologic abnormalities in LAS are common and that HIV
may be the cause.
T.5.5 Tne Clinical Spectrum and Time Course of HIV-associated "Aseptic"
Meningitis
HARRY HOLLANDER, S STRINGARI, UCSF Schools of Medicine and Nursing, San Fran-
cisco, CA, USA
To better define the entity of HIV-associated meningitis, we reviewed the
results of 80 consecutive diagnostic lumbar punctures in homosexual men with
HIV infection to identify those with CSF pleocytosis. Twenty individuals had
>6 cells per mnr. Six of these had a secondary opportunistic infection docu-
mented. Fourteen others had no secondary pathogen or neoplasm identified by
CSF cultures or cerebral imaging studies. All 14 were either known to be HIV
seropositive at the time of study or had prior manifestations of HIV disease,
including 3 subjects with KS. None of the 14 had prior major opportunistic in-
fections. Two patterns of disease were observed. Six men (group 1) had acute
onset of a self-limited illness characterized by headaches and fever, with me-
ningeal findings in 3. One of 6 had a focal neurological deficit. Eight (group
2) had a more indolent course. Seven had chronic headaches, no fever and no me-
ningeal or neurological findings. One presented with cognitive dysfunction and
ataxia but no headache. Mean values of CSF leukocytes and protein were higher
in group 1 patients. Pleocytosis lasted for several months in 2 patients in
group 2 who were restudied. CSF HIV culture was positive in 3 of 4 cases stud-
ied. We conclude that HIV-associated meningitis occurs commonly and relatively
early in the course of HIV infection compared to HIV encephalopathy. Headache
rather than cognitive dysfunction is the most common clinical manifestation.
The course can range from an acute meningitis to more low grade chronic sympto-
matology. CSF inflammation usually differentiates this condition from other
HIV-associated neurological complication. HIV-associated meningitis does not
recessarily predict the development of other HIV-related neurological syndromes..
T.5.3 Cerebrospinal Fluid (CSF) Findings in HIV-infected
Persons Without Clinically Evident Neurologic Disease
ANN C.COLLIER. R.W. Coombs, B.Nikora, L.Corey, H.H.Handsf ield,
University of WA, Seattle, WA. USA.
To evaluate the frequency of subclinical CNS infection with
HIV, we performed cerebrospinal fluid (CSF) examinations and CSF
cultures for HIV on 24 homosexual men with AIDS (post PCP without
other active infections, mean age 36) and 10 subjects with
persistent generalized lymphadenopathy (PGL, mean age 37). None
of the 34 subjects had clinical symptoms or signs of CNS
dysfunction. All AIDS patients had Karnofsky scores >70 and all
PGLs had scores >80. Mean T4 counts were 100/mm and 560/mm3 in
the 2 groups; all AIDS and 3 PGLs had T4 counts <400/mm. All
were HIV-seropositive. HIV was isolated from peripheral blood
lymphocytes in all 34 patients. HIV was isolated from unfiltered
CSF in 42% of AIDS and 50% of PGL subjects. CSF pleocytosis (>5
WBC/mm3) was noted in only 3 of the HIV+ CSFs; 6 had CSF protein
>40mg/dl. All CSFs had normal glucose values; none had
detectable cryptococcal antigen or other viral pathogens. There
were no differences in any CSF, clinical, or immunologic
parameters in CSF HIV-positive and negative subjects. HIV can be
isolated in CSF from half of AIDS and PGL patients without
constitutional complaints or overt neurologic symptoms or signs.
The frequency of CSF HIV infection appears unrelated to the
clinical stage of disease. The clinical significance of CSF HIV
is unknown at present and requires further study.
TEC Polyneuropathies in Subjects Infected with HIV
'■0-U JEAN-ALBERT GASTAUT' . J.L. GASTAUT"; J.F. PELISSIER"" ,
J.B. TAPK0*, M. FINAUD, Y. CARCASSONNE*, et al . , 'Institut Paoli-Calmettes,
Marseille, FRANCE, •• Hopital Sainte-Marguerite, Marseille, FRANCE,
*** Hopital de la Timone, Marseille, FRANCE.
The neurotrophic effects of HIV are well documented. It can be directly or
indirectly responsible for a wide variety of peripheral disorders and symp-
toms. In order to detect clinical and infraclinical polyneuropathy we under-
took a prospective study on the peripheral nervous system of HIV seropositive
subjects (38 men and 2 women) with a mean age of 31 years (range 20 - 24).
This population included 22 homosexuals, 13 drug addicts, 1 addicted homo-
sexual and 4 bisexuals. Five were symptomless carriers, 13 had ARC and 22
had AIDS. All 40 patients underwent clinical neurological and electrophy-
sical (E.M.G., motor conduction and sensitivity, F waves) examinations and
sural nerve biopsy was performed on 23/40 (57,5 %).
Peripheral neurologic anomalies, mainly quadridistal paresthesia, were
noted in 18/40 patients (45 %). In 27/40 patients (67,5 %) clinical examina-
tion revealed evidence of sensory neuropathy : especially distal hypoesthesia
to touch and vibration and, less often, hypoesthesia to pin pricking and loss
of Achilles jerk. Electrophysiologic data was more or less corroborative of
exclusively or predominantly sensory polyneuropathy 33/40 patients (82,5 %) :
midly lowered sensory motor conduction or greatly lowered action potentials
and less often spontaneous denervation or prolongation of F wave latency. The
results of 14/23 nerve biopsies are available. In 10/14 findings showed neuro-
pathology involving axons (8 cases), myeline sheath (1), and circulatory im-
pairment (1). Sensory polyneuropathy is frequent in subjects infected by HIV
and especially in AIDS patients. It is usually well-tolerated with mild and
even no symptoms and slowly degenerative.
55
TUESDAY, JUNE 2
Prevention/Public Health — Reaching the
General Public
T 5 1 Market Research for Australia's National AIDS Education Program
ALEX FROUDFOOT, E. HAZELL, N. MITCHELL, Department of Health,
Canberra, Australia.
The Program's objectives are: (a) to provide factual information to the
total population and (b) to motivate individuals to adopt behaviors to
reduce viral transmission.
To identify areas of need, preparatory market research was undertaken.
This included: (a) a 30-rainute interview/questionnaire covering 750 men and
750 women aged 16 to 60 from the general population; (b) 30-minute
questionnaires administered to 200 children aged 12-15 years; and (c)
surveys of gay men and IV drug users involving detailed interviews and
questionnaires .
Preliminary results for adults showed public awareness that casual
transmission is not likely (761), that condoms can reduce the risk of
transmission (931), and that vaccines are not available (941). However only
19Z were correct on 7 of 8 knowledge items, condom usage appears to be low
and 40X still consider the blood supply unsafe. Only 49X are aware of
heterosexual transmission and 36X of needle sharing as transmission routes.
Seventy-two per cent disagree that sex should be limited to marriage. The
public approved general population (91X), childhood (811) and risk group
(80X) educational programs. Barriers to education include lack of perceived
immediacy of threat (50X) and the belief that one's own knowledge about AIDS
is adequate.
J g A THE EFFECT OF A GOVERNMENT AIDS MEDIA CAMPAIGN ON A GENERAL
POPULATION : ANTIBODY TEST REQUESTS AND REASONS.
HELEDD NICHOLAS, PAULINE LEONARD, LESLEY GLOVER, DORIS PARR AND DAVID MILLER,
Academic Department and Department of Genito Urinary Medicine, Middlesex
Hospital/Medical School, London.
The impact of a Government television, newspaper and billboard AIDS
advertising campaign was assessed by comparing the numbers of requests for
antibody testing in the three months before and after the campaign began.
Numbers were compared in five groups : homosexual and heterosexual men, bisexual
men, heterosexual women and bisexual women. Reasons given for requesting the
test were also compared.
In the three months after the campaign, the numbers overall increased by
239%. Across groups, the numbers were as follows:
Hem. Men Het. Men Bi. Men Het. Women Bi. Women N
Pre: 58.7% 20.2% 8.4% 12.4% 0.3% 431
Post: 27.8% 37.4% 7.7% 26.8% 0.3% 1032
While the actual number of homosexual men and bisexual women requesting the test
remained constant, the numbers of heterosexual men and women wanting the test
increased four and five-fold respectively. The number of bisexual men doubled.
In lower-risk groups, requests for testing concerned anxiety over casual sexual
contacts at heme and abroad. No-one from these groups was found HIV antibody
positive, and 8% (n=16) were found seropositive from homosexual and bisexual
male attenders. The Government campaign appears to have raised considerable
anxieties in the lowest-risk groups while having little impact in groups with
known higher seroprevalence
T.6.2
Evaluation of Health Education in Britain.
T.6.5
Evaluation of School-Based AIDS Education Curricula in San Francisco
LORRAINE SHERR. JOHN GREEN Dept. of Psychology, St Mary's Hospital London UK
In the United Kingdom today the Government has embarked upon Health
Education and have utilised National Press, Television advertisements and
Household leaflet drops. This study presents data on the evaluations of these
steps.
Higher and lower risk subjects, comprising consecutive attenders at STD
clinics, General Practice clinics and university students were monitored
before and after each campaign. It was shown that maximum impact occurs
at the first time a medium was used (41.9% overall noticing advertisements at
first down to 2*t.1%). Quality of content was initially low and improved as
attention decreased. Prior to the press campaigns knowledge was limited and
errors and anxiety were high. The press campaign increased levels of infor-
mation (t=2.13 df 516 p=.03 (first campaign) t=%97 df=^17 p=,001 (second).
Closer analysis showed that this was accounted for by filling in gaps and not
adjusting misconceptions. The campaigns had no effect on changing sexual
behaviour.
Television advertisements had minimal information and used fear arousal
to draw attention to leaflets. Exposure was high (95% of subjects monitored
had seen the advertisement). General and health education value were low.
Subjects found the household leaflet useful. Subjects still state the
medical profession as their desired primary source for information.
RALPH J DICLEMENTE*, CA PIES**, EJ STOLLER**, J HASKIN***, C£ OLIVA**,
GV PJjmERFCKD*'**, *University of California, San Francisco, **San Francisco
Department of Public Health, and ***San Francisco Unified School District,
San Francisco, CA
To design and develop effective AIDS prevention curricula for middle school
and high school students in San Francisco, we conducted a baseline survey,
teacher trainings, and evaluation of a pilot demonstration program. The base-
line survey showed insufficient knowledge of HIV prevention and misconceptions
about casual contagion. We subsequently developed AIDS curricula and piloted
them in 3 middle schools and 3 high schools. Non-intervention control classes
were surveyed at each of the middle and high schools. All 640 students com-
pleted a pretest. The intervention group received 3 periods of AIDS instruct-
ion. A post-test, identical to the pretest, was administered to both groups.
Pretests showed that both had comparable knowledge. Post-tests indicated that
students in the intervention group had a significantly higher mean score for
AIDS knowledge (p<0.0001) than the control group. Specifically, 88% of the
students in the intervention group were aware that condoms are one way of pre-
venting AIDS compared to 71% in the control group (p<0.0001), and 90% in the
intervention group agreed that is is unsafe to have sex with someone whose
health history is unknown compared to 81% of the control group (p<0.0001).
We conclude that specially designed AIDS curricula can significantly increase
adolescents' short-term knowledge which may result in changes to lower-risk
sexual behavior.
T.6.3 Uhat tne public Wants to Know: The National AIDS Hotline
MICHAEL J. ROSENBERG1'2. R. K0HMESCHER3, M. B0NH0MME2, R. LAZAROUICZ1,
^American Social Health Association, Palo Alto, CA,2Family Health
International, Research Triangle Park, NC, ^Centers for Disease Control'
Atlanta , GA.
In mid-December 1986, operation of the national hotline for AIDS
information was transferred from the Centers for Disease Control to the
American Social Health Association. The hotline provides a taped message
which refers callers to an operator for further information. The new
service was expanded from 5 days /week , 9 hours/day to 7 days /week, 24
hours /day coverage . In the first month of operation, the number of calls
steadily increased, with taped messages going from 600/day to 1,700/day at
its peak, and operator calls from 100/day to 700/day. Twenty-six percent
of the operator-answered calls were received on weekends or holidays; 30%
were received between the hours of 6 pm and 8 am.
Baaed on a sample of every fifth operator call, most were to request
information (89%), with highest demand for information on means of
transmission (33%) , general information (27%) , or testing (15%) . The
average call lasted 6.8 minutes. Most calls were made because the caller
was curious (51%), though a high proportion requested information because
they had either symptoms of AIDS, had been tested positive, or had a test
pending (23.7%). Most callers were male (52%); 12% of men and 1% of women
callers identified themselves as gay. Information was requested by 16% of
callers, with twice as many requests coming from women as from men, and
the highest proportion of mailings was to the northeast (30%).
T.6.6 AIDS and Adolescents: Knowledge, Beliefs, Attitudes and Behaviors
Lee Strunin, R. Hingson, Boston University School of Public Health,
Boston, MA.
Adolescents are a group at high risk for exposure to AIDS. A random sample
survey of 860 16-19 year olds in Massachusetts indicates that many adolescents
are still misinformed or confused about AIDS and AIDS transmission. Fifty-five
per cent of the adolescent respondents said they are sexually active but only
15 per cent of them reported changing their sexual behavior because of concern
about contracting AIDS, and only 20 per cent of those who changed their
behavior used effective methods. Eight per cent of both sexually active and
inactive adolescents did not know that AIDS Is transmitted by heterosexual
sexual intercourse. Thirteen per cent had used psychoactive drugs other than
alcohol and marijuana with one per cent injecting drugs. Of those psychoactive
drug users 8 per cent did not know that AIDS can be transmitted by injecting
drugs. There is no significant difference in knowledge between the sexually
active and non-active adolescents concerning sexual behavior and AIDS
transmission, or between the drug users and non-users concerning drug use and
AIDS transmission. Because their knowledge of the mode of AIDS transmission is
limited many adolescents, including those in the highest risk subgroups of
sexually active or psychoactive drug users, do not know what sexual and drug
precautions are needed to prevent transmission of the virus. School systems
and health care providers should systematically educate this population about
AIDS to counter the current misinformation and confusion.
56
TUESDAY, JUNE 2
Epidemiology — Surveillance: Incidence,
Prevalence and Trends
T 7 1 Temporal Trends of Prevalence and Incidence of HIV Infection Among
Civilian Applicants for US Military Service: Analysis of 18 Months
of Serological Screening Data.
JOHN F. BRUNDAGE*, D.S. BURKE*, L.I. GARDNER , J. HERBOLD *, J. VOSKOVITCH tt,
R.R. REDFIELD , Walter Reed Army Institute of Research, Washington, D.C.
Office ^jj the Assistant Secretary of Defense (Health Affairs) , Washington,
D.C, United States Military Entrance Processing Command, North Chicago,
Illinois.
Each month since October 1985, approximately 50,000 civilian applicants for
U.S. military service have been screened for antibody to HIV. Of the 641,917
applicants screened during the program's first 12 months 86% were male, 74%
were white (not hispanic) , and 57% were younger than 21 years. Applicants
represented all 50 states, the District of Columbia, and several U.S.
territories. Overall (1.5/1000), sex-specific (male: 1.6/1000, female:
0.6/1000), and age-specific prevalences did not significantly vary between the
first six-months of screening and the second. A "temporal trend term" (first
six month period vs. second six-month period) did not predict antibody status
in a multivariate model that controlled for birth year, race/ethnicity, sex,
population density, and regional AIDS incidence. When data from high antibody
prevalence sub-groups were analyzed separately, there were suggestions of an
independent effect of a "temporal trend term." For example, among black male
applicants, the adjusted odds ratio (second six months vs. first six months)
was 1.07 (95% CI: 0.97-1.18). Estimates of prevalences, incidences, and
temporal trends, overall and in demographically and geographically defined
sub-groups, from 18 months of screening data will be presented.
T.7.4
Incidence of HIV Infection in Homosexual Men in a High Risk Area:
Implications for Vaccine Trial Oesign. Cladd E. Stevens, Patricia
E. Taylor, Edith A. Zang, Santiago Rodriguez de Cordoba and Pablo Rubinstein,
The New York Blood Center, New York, New York, U.S.A.
Early in 1984 the Laboratories of Epidemiology and Immunogenetics of The
New York Blood Center enrolled a cohort of 850 homosexually active men in a
prospective study of the acquired immune deficiency syndrome. Of the 773 men
tested for anti-HIV by ELISA (Dupont) and Western Blot (Biotech) at entry,
57.75! were seronegative and therefore were considered susceptible to HIV.
In the three years since the study began, the participants returned for
follow-up every 4 months. As risk factors related to HIV infection became
known, the men were periodically advised regarding unsafe sexual practices.
As a consequence, sexual activity changed dramatically, especially in numbers
of partners and frequency of receptive rectal intercourse. However, in these
past 3 years 37 men have seroconverted, a life-table attack rate of 10.055.
The 4-month incidence decreased from 2.25?! in the first 4 months to 0.68% by
the fourth interval at 1-1/2 years. Since then, however, the incidence has
remained stable at about 1% in each 4-month interval. Seroconversion highly
correlated, but not exclusively, with the practice of receptive rectal inter-
course and nearly 35% of seronegative men continued this practice despite
advice to the contrary. These data suggest that, despite educational efforts
regarding safer sex, some homosexual men persistently engage in high risk sex.
Such men may be candidates for vaccine efficacy trials if vaccines become
available for testing. Additionally, the appearance of multiple antibodies to
HIV proteins and T-lymphocyte alterations at the time of seroconversion sug-
gest end-points which may distinguish between vaccine and virus-induced anti-
body and end-points for evaluation of vaccine efficacy.
T 7 2 Analysis of Demographic and Epidemiologic Data Concerning HIV Antibody
Positive Recruits and Active Duty Air Force Members.
RICHARD E. WINN, 5. A. 7.AJAC, H.E. APPLEMAN, G.P. MELCHER, R.N. 30SWELL, M.E. EVANS. Wi 1 Eord
Hal! USAF Medical Center, Lackland AFB, TX.
Since the beginning of testing for HIV antibody by the U.S. Air Force, over 268 active duty
members (ADH) and 38 recruits IREC) have'been identified as being positive using both an Elisa
and Western Blot techniques. The majority of both groups are asymptomatic; AIDS has been
diagnosed in H.9% of ADH. The overall incidence of seropositivity has remained relatively
constant at approximately 0.1* (one per thousand) for REC and ADM. REC and ADH have all been
interviewed for demographic variables and examined by the infectious disease service. The
average age for REC was 21.8 and for ADM 26.9. The percentage of males was 97% REC/96% ADH.
A racial difference was observed between REC and ADH with proportionately more black than
white REC positive for HIV. Referral locations were diverse and reflected US Air Force
assignments in general. Only 19% REC/11.5% ADM admitted to homosexual or bisexual activity.
The mean number of heterosexual partners of REC/ADH was 13 .8/68.4 with a range from 1 to >
1000 lifetime partners. Homosexual partners were more frequent: mean > 200. Harriage was
infreguent, as predicted, in REC. Twenty nine percent of ADH were married. Age at first
intercourse was similar in both groups. Among heterosexual REC and ADM, despite lower sexual
promiscuity than occurs in homosexual populations, sexually transmitted diseases were
frequently reported. REC/ADM gonorrhea occurred in 30/37%, syphilis in 11/11.5%, herpes
simplex 3/6%. NGU and condyloma acuminata were reported more frequently in ADM, 17.3% and
13.5% respectively. Exposures to prostitutes ranged globally from Europe to Southeast Asia
and was highly reported in ADM, 37%. Although heterosexual preference in sexual activity and
exposure to prostitutes suggests a higher transmission rate by heterosexual sex in the Air
Force, disproportionate prevalence of anal condyloma in ADM not admitting to association with
high risk groups suggests non-truthful reporting of sexual preference by some ADM and REC.
T.7.5 Tne Surveillance of Clinical Viral Hepatitis Type B and Primary,
Secondary and Early Latent Syphilis in Homosexual and Bisexual
Men in MN: Implications for Human Immunodeficiency Virus (HIV) Transmission
MICHAEL T. 0STERH0LM, K.L. MACDONALD, S.J. SCHLETTY, M.D. NIELSEN, R.N.
DANILA, Minnesota Dept. of Health, Minneapolis, MN, USA.
Since 1982, a marked decline in the incidence of rectal gonorrhea and
syphilis has been noted among homosexual men nationwide. To determine the
implications of declining rates of selected bacterial sexually transmitted
diseases (BSTD's) on HIV transmission among homosexual and bisexual men,
we compared statewide surveillance data for these groups obtained between
January 1982 and July 1986 for incident cases of primary, secondary and
early latent syphilis and acute clinical viral hepatitis type B (with
hepatitis B serving as a marker for the sexual transmission of HIV). A
mean of 79 cases (range, 61 to 90) of syphilis occurred during each six-month
interval before July 1984. Despite similar surveillance efforts, marked
decrease in incident cases was noted between July 1984 and June 1986, with
a mean of 16 cases (range, 11 to 21) reported for each six-month interval.
However, no change was noted in the number of acute clinical hepatitis B
cases reported through active laboratory-based surveillance. The number
of clinical hepatitis B cases reported by six-month interval ranged from
12 (July-December 1983) to 19 (January-June 1986); intravenous drug abuse
could be documented as a risk factor for only 8% of cases. Results of this
study indicate that among homosexual and bisexual men declining rates of
syphilis and other BSTD's among homosexual and bisexual men may not reflect
a concurrent reduction in the transmission of selected viral STD's, such
as viral hepatitis type B. We believe these results may have significant
implications when interpreting the impact of risk reduction programs on
HIV transmission nationally.
J.7.3 AIDS in Heterosexual Contacts: a Small but Increasing Group of Cases
MARY CHAMBERLAND, C. WHITE, A. LIFSON, T.J. DONDERO, AIDS Program,
Centers for Disease Control, Atlanta, GA.
Patients with AIDS who have no identified risk other than heterosexual
contact represent 4% of all AIDS patients reported in Che United States. As of
January 16, 1987, this group includes 521 patients who had heterosexual
contact with a person with AIDS or at risk for AIDS (HC) and 589 persons who
were born In foreign countries where heterosexual transmission plays a major
role. The racial/ethnic distribution of the 521 HC patients is similar to that
associated with IV drug abuse: 48% black, 26% Hispanic, 25% white, and 1%
Asian. Males account for only 18% of HC cases versus 78% of non-HC patients
who are heterosexual in orientation. The proportion of male HC patients has
not increased significantly since 1983. The geographic distribution of HC
patients differs significantly by sex: 67% of females are reported from New
York, New Jersey, and Florida, compared with 43% of males (p<0.0001). The
"at-risk" sexual partners of the HC patients Include IV drug abusers (64%),
bisexual males (female HC patients only) (14%), individuals from countries
where heterosexual transmission plays a major role (4%), transfusion
recipients (1%), and hemophiliacs (1%). Risk status of the contact partner is
under investigation for the remaining 16%. During 1986, tne total number of
reported HC patients increased by 135% from 218 to 513, while reported cases
among homosexual/bisexual men and IV drug abusers increased by 82% and 81%
respectively. This reflects a 10 month doubling time for HC cases compared
with a doubling in 14 months for homosexual/bisexual men and IV drug abusers.
HC patients have increased from 1.0% of all AIDS cases in 1983 to 2.3% In 1986
(p<0.0001). Although the overall proportion of HC cases remains small, it will
increase. Additional studies are needed to characterize and track this group.
T 7 fi Community Surveillance for HIV Infection in Zaire
' Robert W. RYDER*, W. BERTRAND**, R.L.COLEBUNDERS*. B. KAPITA*.
H. FRANCIS*, M. LUBAKI*, *Projet SIDA, Kinshasa, Zaire, **School of Public
Health, Kinshasa.
To assist Zairian physicians in diagnosing HIV infection, a no-cost screening
program was established at Mama Yemo Hospital, Kinshasa. Despite logistic
difficulties in transport, sera from 8871 patients were referred during 1986,
of which 54% was HIV(+) by repeat ELISA. Among children 70% of cases occurred
between the age of 0-3. Three times as many children aged less than 1 year were
HIV(+) compared to children aged 1-3 years old. Seventy percent of all cases
occurred in patients aged 15-40 years. Striking differences in the female:
male sex ratio were observed: less than 15 years old F:M ratio=l:l; 15-30
years F:M ratio=6:l; greater than 30 years F:M ratio=.64:l.
The diagnostic accuracy(number of tests positive/total tests submitted) of
physicians working in the Tuberculosis Sanitorium or in adult diarrheal
disease wards were the highest; 85% and 74%, respectively. These data docu-
ment in Zairian physicians a considerable awareness of and ability to clini-
cally diagnose HIV infection.
The overall female:male infection ratio in our study(l.l:l) is similar to
the figure widely used in describing the epidemiology of HIV infection in
Africa. However, we found that cases of infection clustered in two risk
groups, young women(age 13 to 25) and middle to older aged men. These
differences in age-specific, sex-specific HIV infection rates should be
considered before any HIV prevention activities involving behaviorial modifi-
cation in Africa are initiated.
57
TUESDAY, JUNE 2
Clinical Trials — AZT and Ribavirin
jaDoratones ,
in vivo,
T.8.1 Decline in Serum HIV p24 Antigen (Ag) in Patients
Treated with AZT.
RICHARD E CHAISSON, J-P ALLAIN, M LEUTHER, W PARKS, S LEHRMAN, P
VOLBERDING, "JCSF School of Medicine, Abbott
Burroughs-Wellcome Co., USA.
To assess the anti-retroviral effect of AZT
measured serum HIV-Ag in 157 AIDS or ARC patients enrolled in a
multicenter placebo-controlled trial. Patients received AZT 250
mg or placebo every 4 hrs, with dose reduction for toxicity. HIV
p24 Ag was detected using a polyclonal IgG sandwich enzyme
immunoassay. Sera were obtained at entry and at 4 week
intervals. 36 of 79 (46*) AZT patients and 40 of 78 (51*) of
placebo patients had Ag detected during the trial. 28 patients
in each group had a baseline and later specimen for comparison.
Baseline HIV-Ag levels were 297 pg/ml for AZT patients and 234
pg/ml for placebo patients (p=NS).
Significant decreases in HIV-Ag in AZT patients were seen at 4
weeks (AZT group mean = 70 pg/ml, placebo mean = 223; p=0.0002),
8 weeks (AZT mean = 56 pg/ml, placebo mean =283, p< 0.0001) and
12 weeks (AZT mean = 53 pg/ml, placebo mean 84 pg/ml; p=0.0052).
Differences persisted through 20 weeks, though sample sizes were
small. No HIV-Ag positive subject in either group had anti-p24
antibodies, and decline in HIV-Ag in AZT patients was not
associated with reappearance of anti-p24. We conclude that HIV-
Ag levels are an important marker of anti-retroviral activity in
a substantial proportion of AIDS and ARC patients.
T 8 4 THE TQXICITY 0F 3'-AZID0-3'-DE0XYTHYMIDINE (AZIDOTHYMI-
DINE) IN THE TREATMENT OF PATIENTS WITH AIDS AND AIDS-
RELATED COMPLEX: A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL.
AZT COLLABORATIVE WORKING GROUP
A double-blind, placebo-controlled trial of oral azidothymi-
dine (AZT) was conducted in 282 patients with AIDS or AIDS-
related complex (ARC). Although significant clinical benefit was
documented serious adverse reactions, particularly bone marrow
suppression, were also observed. Nausea, myalgia, insomnia and
more severe headaches were reported more frequently by AZT
recipients. Macrocytosis developed within weeks in most
subjects. Anemia, with reductions of >25'/. in baseline hemo-
globin levels, occurred in 38'/. of AZT recipients and 13*/. of
placebo recipients (p <0.05). Hemoglobin levels below 7.5 g/dl
developed in 24% of AZT recipients and V/. of placebo recipients
(p <.001). 21'/. of AZT recipients and only V/. of placebo recip-
ients required multiple transfusions (p <.001>. Neutropenia of
less than 500 cells/mm occurred in 16'/. of AZT recipients
compared to 2'/. of placebo recipients (p <.001). Patients who
entered the study with low T*» lymphocyte counts, low serum
vitamin B12 levels, low hemoglobin, or low neutrophil counts
were more likely to experience hematologic toxicity.
Acetominophen co-administration was also associated with a
higher frequency of hematologic toxicity. Although a subset of
patients has tolerated AZT for an extended period with few
problems, the drug should be administered with caution because
of its recognized toxicities and the limited experience acquired
with the drug to date.
T.8.2 Therapy of AIDS Patients with Early Kaposi's Sarcoma with
3 ' -Azi do-3 ' Deoxythymi d i ne
ROBERT WALKER, H.C. LANE, H. MASUR, J. KOVACS, S. CARLETON, A.S. FAUCI,
et al. , National Institutes of Health, Bethesda, MD.
3'-Azido-3'-deoxythymidine (AZT) is a nucleoside analogue which has been
shown capable of inhibiting the replication of HIV in vitro and prolonging
life in AIDS patients 120 days following an initial~b~out of Pneumocystis
carinii pneumonia. The present study was designed to determine the effects
of AZT on a group of patients at an earlier stage of HIV infection, namely
AIDS patients with Kaposi's sarcoma only and with more than 200 T4
lymphocytes/mm . A 40 patient study was designed with patients randomized to
1 of 4 groups. Group 1 patients received placebo, group 2 patients received
250 mg AZT po q4h, group 3 patients received 0.05 mg/kg AZT iv q4h, and group 4
patients received 2.5 mg/kg AZT iv q4h. Patients were treated for 12 weeks. As
of this writing, 36 patients have entered the study and 22 have completed 12
weeks. Analysis of the available data has revealed that there was a
reduction in Kaposi's sarcoma in 0/6 patients on placebo and 4/16 patients on
drug. Viral cultures have become negative in 1/6 patients on placebo and
6/15 patients on drug. No significant changes have been seen in immunologic
parameters including total lymphocyte and subset counts, lymphocyte blast
transformation to mitogens or antigens or natural cytotoxicity. Thus, based
upon reduction in KS lesions and decline in viral shedding, AZT may be of
value for the treatment of early AIDS patients with Kaposi's sarcoma.
T 8 5 Ribavirin delays progression of the lymphadenopthy syndrome (LAS)
to the acquired immune deficiency syndrome (AIDS).
P.W.A. MANSELL*. P.N.R. HESELTINE**, R.B. ROBERTS***, G.M. DICKINSON****, J.M.
LEEDOM** et al., *University of Texas, Houston, TX, **University of Southern
California, Los Angeles, CA, ***Cornell University, NY, ****0niversity of
Miami, FL, U.S.A.
Ribavirin, a synthetic guanosine nucleoside analogue has In vitro activity
against the human Immunodeficiency virus (HIV). Ribavirin's role in preventing
progression of LAS to AIDS was evaluated in a randomized, double-blind,
placebo-controlled, multicenter trial. One hundred and sixty-three homosexual
men with LAS were treated with oral ribavirin or placebo for 24 weeks,
followed by no treatment for four weeks. All were HIV culture positive, had
lymphadenopathy for six months or more, hematocrits > 35% and fewer than 500
(+ S.D. of the method) T4+ cells. Those with chronic symptoms of HIV infection
(diarrhea, fever, thrush, weight loss) were excluded. Fifty-two received 800
mg of ribavirin daily and none developed AIDS; 6/55 (11%) given 600 mg/day of
ribavirin and 10/56 (18%) taking placebo developed AIDS (p-0.007). Difference
in outcome correlated with ribavirin plasma levels. This therapeutic effect
was not explained by differences In T4+ cells or hematocrit at initiation of
therapy. Qualitative HIV cultures remained positive and measured Immunologic
function did not increase in the treated groups. Three of 107 (2.81) receiving
ribavirin discontinued treatment because of insomnia or nausea/vomiting.
Ribavirin was associated with a mild compensated anemia; no one required a
blood transfusion. There was one death, AIDS-related, In the placebo group.
Prolonged ribavirin therapy is well tolerated and delays the progression to
AIDS of immunologically compromised men with LAS. Ribavirin deserves further
study as a therapeutic agent for HIV infection.
T.8 3 Clinical Evaluation of the Central Nervous System in
HIV Infected Patients on Azidothymidine (AZT) .
C.J. KENNEDY , R.S. TESCHKE, J. HESSELINK, J. BERGER, M. FISCHEL,
D. RICHMAN, et al. University of California, San Diego, CA.
During a double-blind, placebo-controlled trial of AZT, 32 AIDS
and ARC patients in San Diego were intensively investigated to
detect any effect of AZT on the central nervous system. In
addition to the standard protocol, study participants had: peri-
pheral blood and CSF culture to detect HIV; magnetic resonance
imaging (MRI) of the brain; a detailed clinical neurological
examination; and a comprehensive neuropsychiatric assessment.
There was no effect of AZT on the frequency of positive HIV
culture in blood or CSF, nor on the patterns of MRI abnormality.
The clinical neurological examinations showed a beneficial effect
of AZT; 0/13 patients improved in the placebo group, and 5/16 in
the treated group. However, the overall effect did not meet
criteria for statistical significance (P = 0.12, Mantel-Haenzel
Test) . Neuropsychiatric testing detected no difference between
the groups. These studies have been extended in two ways. First,
CSF specimens are under analysis to determine HIV antigen load,
using an antigen capture assay. Second, the clinical neuro-
logical examination data is being pooled with comparable data in
a further 30 patients from another AZT study center (Miami) to
evaluate better the significance of the differences described
here. Our working hypotheses are: (1) that AZT leads to an
improvement in neurological functioning, and (2) that physical
neurological examination is the most sensitive available tech-
nique to detect this effect.
T O C Serum HIV Core Antigen in Symptomatic ARC Patients Taking Oral Riba-
virin or Placebo.
ANDREW VERNON? R.S.Schulof**for the RIBAVIRIN ARC STUDY GROUP. *Johns Hopkins
University, Baltimore MD.**George Washington University, Washington DC,
We measured HIV p24 core antigen (AG) in serial sera of symptomatic ARC pat-
ients as part of a multicenter, placebo-controlled, randomized trial of oral
Ribavirin. Fifty-six men with ARC were randomized to placebo or one of two
oral ribavirin regimens . AG was measured by sandwich enzyme immunoassay in
samples taken at weeks 0 and 12. Counts of T4 lymphocytes and culture for HTV
were performed at both times. Mean AG levels (+/- S.E.) were:
Week N Placebo 600 mg qd 800 mg qd
0 56 275 +/- 81 325 +/- 118 174 +/-51
12 49 203 +/" 60 382 +/- 114 324 +/- 85
Our data fail to show a statistically significant difference in mean AG levels
of ribavirin-treated ARC patients and placebo controls (p=0.28 by ANOVA; p=0,19
by t test comparing drug and placebo) . There was no significant difference in
change in mean T4 cell counts when comparing patients on drug with those on
placebo (p=0.35, t test). Culture positivity was similar in drug and placebo
groups at week 0 (29/37 drug; 14/19 placebo) but was different at week 12
(23/33 drug; 15/16 placebo; p=0.08 FET) . Five patients developed AIDS by
Week 12. Seventeen of 49 men tested on two occasions had no AG at either time.
These data are qualified by small numbers and by 7 drop-outs. We will present
data on 150-200 patients, measured at 5 points over 24 weeks, with quantitative
aspects of culture. In sum, we found no effect of oral ribavirin on serum AG
levels; our data suggest that an effect on virus culture positivity may be
present.
58
TUESDAY, JUNE 2
Immunology — HTV-Specific Cytotoxicity
T 9 1 HIV env~ and gag- Specific Cytotoxic T Lymphocytes (CTL's) in
Seropositive Subjects
BRUCE P. WALKER*. S. CHAKRABARTI** , B. MOSS**, T. J. PARADIS*, M. S.
HIRSCH*. R. T. SCHOOLEY*. * Massachusetts General Hospital and Harvard
Medical School, Boston, MA 02114. **Laboratory of Viral Diseases, NIAID,
NIH, Bethesda, MD 20892.
Using recombinant vaccinia viruses to express HIV genes, we have detected
circulating HIV-specific CTL's in homosexual males seropositive for the
AIDS agent. EBV immortalized B cell lines established from 8 seropositive
subjects and 5 seronegative controls were infected with recombinant
vaccinia viruses expressing the HIV env (VAC/env) or gag (VAC/gag) gene, or
a control vaccinia vector expressing the bacterial lac Z gene (VAC/lac) ,
and used as targets in a chromium release assay. Freshly isolated
autologous peripheral blood mononuclear cells were used as effector
cells. HIV env- and gag- specific cytotoxic responses were detected in
seropositive subjects, but not seronegative controls. At an effector:
target ratio of 100:1, mean specific lysis of the different
vaccinia- Infected target cells In seropositive subjects was a) VAC/env 37.5
+ 6.2% (p<.005 vs VAC/lac) b) VAC/gag 17.2% ± 3.8% (p<.05 vs VAC/lac) c)
VAC/lac 11.2 + 3.3%. For seronegative subjects, these values were a)
VAC/env 8.6 + 1.2% b) VAC/gag 7.8 ± 1.1% c) VAC/lac 7.7 ± 1.1%. The env -
specific cytotoxic response was inhibited by 67-100% by addition of a
CD3-specific monoclonal antibody, indicating that the effector cells are T
lymphocytes. This demonstration of HIV-specific cytotoxicity in
seropositive individuals should prove useful in further investigating the
immunopathogenesis of AIDS and in evaluating vaccine strategies.
T 9 4 Gpl20-Specific Cell-Mediated Cytotoxicity in Patients Exposed to HIV
KENT J. WEINHOLD*, H. KIM LYERLY*. T.J. MATTHEWS*, M.R. CAIRHS**,
D.T. DURACK**, AND D.P. BOLOGNESI*, *Department of Surgery and **Medicine,
Duke University Medical Center, Durham, NC
As part of an ongoing investigation of cellular anti-HIV reactivities, we
examined the ability of peripheral blood mononuclear cells (PBMC) obtained from
patients at various stages of disease to directly lyse cells bearing only gpl20
determinants. Autologous CD4 cells were coated with purified HTLV-III gpl20
and used as targets In 4-hour Cr release assays for cell-mediated cytotoxicity
(CMC). Gpl20-specific CMC was apparent in HIV seropositive individuals at all
stages of disease. Levels of CMC were highest in asymptomatic patients while
ARC and AIDS patients exhibited only sporadic and low CMC. The activity was
not MHC-restricted and was mediated by a CD3~, CD4~, CD8~, CD16 population
of effector cells. Although not strictly Interleukin 2 (IL-2)-dependent ,
CMC was greatly augmented by exogenous IL-2. Cold target competition studies
revealed that anti-gp!20 effector cells also recognized K562 targets. Taken
together, these results suggest that a sub-population of 'NIC-like' effector
cells, not present in seronegative individuals, mediates the destruction of
gpl20 coated targets. The antigen receptor on these cells recognizes 'group'
determinants, since CD4 targets coated with purified gpl20 from the widely
divergent HTLV-IIL- isolate were lysed to the same degree as cells coated
with HTLV-III gplZO.
These results not only document the presence of virus-specific cellular
cytolytic elements present in HIV seropositive Individuals but also highlight
gpl20 as a target antigen for immune cytolysis. Additionally, the ability of
gpl20 adsorbed CD4 cells to serve as targets for CMC suggests a possible
mechanism of Immunopathogenesis in which lympholysis might occur in the
absence of infectious virus .spread.
T Q O Detection of HLA Restricted Human Immunodeficiency Virus (HIV)
Envelope Antigen-Specific Cytotoxic Lymphocytes (CTL) .
DAVID H. SHEPP.* D. MANN,***, S. CHAKRABARTI,** B. MOSS,**, F. DAGUILLARD,****
AND G.V. QUINNAN,* *Division of Virology, FDA, **NIAID, NIH, ***NCI, NIH,
Bethesda, MD and ****D.C. Comm. Public Health, Washington, DC, USA
Because cell-associated virus may be important in transmission and
pathogenesis of HIV infection, vaccine-induced protective immunity may require
induction of CTL killing of infected cells. To measure HIV envelope-specific
CTL, peripheral blood mononuclear cells from asymptomatic HIV seropositive
individuals were stimulated in vitro for 5 days with autologous, irradiated,
HIV infected T-lymphoblasts. Human skin fibroblast target cells matched to the
donor at one or more HLA-A or B loci, or mismatched, were infected with
recombinant vaccinia containing the whole envelope gene of the HTLV-IIIB
strain of HIV. The same target cells infected with recombinant vaccinia
lacking this insert served as controls. Targets were labelled with 51Cr and
at 19 hours after infection were incubated with effector cells at an
effector: target ratio of 25-30:1 for A hrs. ^*Cr release was then measured
and the percent lysis calculated. HIV envelope-specific lysis was determined
by subtracting the results with the control from those with the envelope
recombinant. Six of 8 donors tested showed significant (p<0.05) HIV
envelope-specific lysis (mean % lysis 9.4 +/- 2.2). Cells from HIV
seronegative donors did not show significant lysis. Among donors showing
positive responses, 8 of 12 matched but only 2 of 9 mismatched targets were
lysed (p=0.05). Memory cells capable of developing HLA-restricted, HIV
envelope-specific cytotoxic activity are present in the peripheral blood of
some asymptomatic, HIV infected individuals. HIV envelope antigens can serve
as targets for these responses and measurement of CTL may be an important part
of evaluation of the immunogenic ity of candidate vaccines.
T 9 5 Cytotoxic T Cells, that Recognize Human Immunodeficiency Virus
(HIV) Envelope Glycoproteins, Isolated from Chimpanzees Immunized
with a Recombinant Vaccinia Virus Expressing HIV Glycoproteins
JOYCE M. ZARLING*, PATRICIA A. M0RAN*, JAN McCLURE+, PENNATHUR SRIDHAR*, JORG
V. EICHBERG**, and SHIU-L0K HU*; *0ncogen, Seattle, VA; **Southvest Foundation
for Biomedical Research, San Antonio, TX; +Genetic Systems Corp., Seattle, VA.
Little is known concerning T cell mediated immunity to HIV. Hovever, ve
previously reported that a recombinant vaccinia virus, v-env5, expressing HIV
envelope (env) glycoproteins gP41 and gpllO induces T helper cells in
macaques, that recognize HIV by proliferating and by producing interleukln-2.
It was not determined, hovever, whether immunization with such a recombinant
virus can also prime HIV specific cytotoxic T cells (CTL). In this study,
immunization of chimpanzees, the closest relative of man, with v-env5 (but not
with a recombinant vaccinia virus that expresses a herpes simplex virus
glycoprotein) resulted in the generation of T helper cells that proliferate
following stimulation with HIV or with purified env glycoproteins. In
addition, cytotoxic T cell clones were also isolated from v-env5 immunized
chimpanzees following stimulation of lymphocytes with env glycoproteins.
These CTL clones lyse autologous target cells infected with v-env5 but not
with parental vaccinia virus. Our results thus indicate that immunization of
chimpanzees with a recombinant vaccinia virus expressing HIV envelope
glycoproteins results in the generation of HIV specific T helper cells and CTL
and also that HIV envelope glycoproteins serve as target antigens for
cytotoxic T cells of primates. HIV specific T helper cells and CTL, such as
those we have demonstrated, may play a role in limiting dissemination of HIV
or preventing the development of AIDS.
T.9.3 Cytotoxic T Cells Directed Against Target Cells
Expressing HIV-1 Proteins
SCOTT K0ENI6, P. EARL, 0. POWELL, H.C. LANE, B. MOSS, A.S. FAUCI, et al.,
TJTRT NIAID, Bethesda, MD.
We previously detected HIV-specific cytotoxic T cells (CTL) in peripheral
blood mononuclear cells (PBMC) of healthy HIV seropositive individuals as well
as 2 AIDS patients who had received bone marrow (BM) transplants from their
HIV seronegative identical twins. HIV-specific CTL activity was not found in
PBMC of HIV seronegative individuals or in non-transplanted AIDS patients
(2nd Intl Conf AIDS). In order to determine which viral proteins are important
in the detection of HIV-specific CTL responses, recombinant vaccinia viruses
expressing different products of the HIV genome were utilized. PHA-stimulated
PBMC or EBV-transformed B cells were infected with recombinant vaccinia
viruses expressing either gpl20 and 41 (env), gpl20 alone (env), or gp55 (gag)
and used as targets in a 4 hour Cr-release cytotoxicity assay. Cells infec-
ted with a vaccinia vector that contained a bacterial lac gene were used as a
control. PBMC obtained from healthy HIV seropositive individuals or a cohort
of 12 AIDS patients participating in a study of AZT used in combination with
BM transplantation, served as effector cells. Most CTL activity was detected
against the env region (15-48% specific lysis at an effector:target ratio of
100:1) although lysis of target cells expressing gp55 was also seen. HIV was
sporadically isolated from PBMC of most of the individuals with CTL activity.
Given the fact that in vitro priming was unnecessary to elicit CTL responses,
these data suggest that HIV specific CTL are stimulated in vivo and may be
effective in suppressing viral replication. These studies have potentially
important implications in the delineation of the nature of a protective immune
response in HIV infection and in devising strategies for vaccine development.
T Q fi HIV Antibodies in Human Sera Induce Cell-mediated Lysis of HIV-
infected Cells.
EMMANUEL A. OJO-AMAIZE, P.G. Nishanian, D. Keith, Jr., J.L. Fahey and J.V.
Giorgi . UCLA School of Medicine, Los Angeles, California, U.S.A.
The capacity of human immunodeficiency virus (HIV) antibody-positive sera to
recruit non-immune lymphocytes to lyse HIV-infected T cell lines was investi-
gated. Sera from twenty-seven asymptomatic homosexual men with normal CD4/CD8
cell ratios were shown by ELISA to have antibodies to the whole HIV. At
dilutions between 10~2 and 10 , twenty-two of these sera caused lysis of HIV-
infected target cells (MOLT-4f and CEM-CCRF) above the level of spontaneous
lysis caused by either peripheral blood lymphocytes (PBL) alone, or lysis of
HIV-antibody-coated uninfected target cells in the presence of added PBL. HIV-
antibody negative sera did not cause lysis. Fractionation of the HIV-antibody
positive sera on protein-A affinity columns showed that the ADCC- inducing
molecule resided in the Ig-fraction. Thus, identification of the extra
cytotoxic activity in the IgG fraction is indicative of antibody -dependent
cellular cytotoxicity (ADCC) . Varying capacity to cause ADCC was observed
among the different HIV-antibody positive sera. Using radioimmunoprecipitation-
SDS-PAGE analysis with [35S] -methionine-labeled HIV-infected cells, it was
shown that antibody to the HIV envelope protein, gp120 was present in reactive,
but not in ADCC inactive, sera. There was no correlation, however, with
presence or absence of antibodies to p24, p55 or gp41 antigens.
These results suggest that HIV envelope proteins play an important role in
HIV-specific responses.
59
TUESDAY, JUNE 2
Psychosocial — Psychosocial Research: At Risk
Populations
T. 10 . 1 ^e P1™^ prevention of AIDS: An urgent research agenda.
Stephen Hullev. Susan Allen, Mindy Fullilove, Thomas Coates. University of
California, San Francisco, CA, 94143.
AIDS is a fatal and incurable disease that has already had an unprecedented impact on the
health and social structure of our society, and the adverse effects of the epidemic will intensify
as those who are already infected develop clinical disease. These facts lend urgency to the need
to develop more effective approaches to preventing the further spread of infection.
AIDS is a behaviorally transmitted disease, and culture-specific behavioral interventions are
the only known approach to primary prevention. In order to develop a more effective public
health response there is a need to greatly enhance our pursuit of the following research agenda:
1. Population based epidemiologic studies to inform us on the distributions of HTV infection,
and on the distributions of high risk behaviors and their antecedents, in various segments of the
population, and,
2. Health education intervention studies to reveal the most cost-effective approaches to
reducing high risk behaviors, and to tailoring preventive strategies to those segments of the
population (such as the black and hispanic minorities) that are at disproportionely high risk.
This research agenda is staggering in size, since these issues should be addressed in many
cultural and language settings throughout the world, not just in the United States. There is a
need for more fiscal resources to support these efforts, and for more health scientists to become
involved in their pursuit.
T 10 4 Preventing Human Immunodeficiency Virus Contagion Among
Intravenous Drug Users: The Impact of Street-Based Education on
Risk-Behavior
John K. Watters, Ph.D. Haight-Ashbury Free Medical Clinics
An evaluation of a street-based, AIDS prevention and health education
project directed at out-of-treatraent intravenous drug users (IVDUs) was
conducted in San Francisco. Two waves of IVDUs were interviewed and data
obtained on drug use and medical history, sexual practices, needle-hygiene,
beliefs and knowledge about AIDS transmission, and HIV serology performed.
Each wave contained respondents who were sampled from non-clinical
populations of IVDUs not connected with treatment programs and clinical
populations of IVDUs enrolled in 21-day drug-detoxification programs. The
first wave (n-438) was conducted during Winter/Spring, 1986 and the second
wave (n-500) was conducted during Winter/Spring 1987. The intervention —
which placed "community health outreach workers" in San Francisco
neighborhoods with large numbers of IVDUs — was implemented at the
approximate mid-point between observations.
Preliminary findings suggest significant change between waves in adoption
of the recommended needle-hygiene procedures. Additional findings include
reported reductions in needle-sharing, increased use of condoms, and
increased AIDS knowledge. HIV infectivity was significantly higher among
the non-clinical group (16%) than the clinical group (71) in the 1986 wave.
Preliminary results suggest an approximate doubling of HIV infectivity
between the 1986 and 1987 waves.
T 10.2 Persistence and Change in Sexual Behavior and Perceptions of Risk
for AIDS among Homosexual Men.
KAROLYNN SIEGEL, J.Y. CHEN, F. MESAGNO, G. CHRIST Memorial Sloan-Ketterlng
Cancer Center, New York, NY, USA
A longitudinal study of modifications in sexual behavior among asymptomatic
homosexual men Cn=1 61) in New York City was conducted. Participants were
interviewed at two time points (T1 and T2) six months apart. Based on respon-
dents' reports of their behavior during a recent "typical" month, the riski-
ness of their sexual behavior was scored from 0 to 4. Scores were based on
available epidemiological evidence concerning sexual behaviors associated with
HIV associated conditions. Respondents were also asked to rate their own be-
havior on a scale from 1 to 10 based on how risky they thought their current
practices were in terms of contributing to their chances of getting AIDS.
When change between T1 and T2 was examined, a number of patterns emerged.
For almost half (47$) of the respondents there was no change In their risk
rating. About one-third (36%) received a lower risk rating at T2, and the re-
maining men (17%) received a high risk rating. A full 41% of the men studied
were practicing risky sex at both assessment points, while only 29? were en-
gaging only in safe sex at the two time points. The remaining 30? had shifted
categories (20? risky at T1, safe at T2; 10? safe at T1, risky at T2).
When respondents' subjective ratings of the riskiness of their behavior were
compared with the objective scores, it was determined that as many as four out
of every five men engaging in risky sexual behavior may be underestimating the
danger inherent in their behavior.
The implications of these findings for future public health efforts will be
discussed.
T 10 5 Determinants of Current Psychiatric Disorder in AIDS
Spectrum Patients.
SUSAN TROSS*, D.A. HIRSCH, B. RABKIN, C. BERRY, J.C.B. HOLLAND,
Memorial Sloan-Kettering Cancer Center, New York, NY.
Current psychiatric status was examined at diagnosis in gay
men with AIDS (A=90) and ARC (ARC=40), and compared with that of
healthy gay men (H=149) in New York City. Standard psychiatric
interviews, using structured interview schedules, were conducted
to obtain D.S.M.-III diagnoses by reliable interviewers (Kappa =
/\».70). 42% of the entire sample had any current disorder--
chiefly adjustment disorder (81% of disorders). Rates were
higher for the A (52%) and ARC (63%) groups than for the H group
(31%). The A, and especially, ARC groups also exceeded the H
group ofl self-reported psychological distress ot) the Brief Symptom
Inventory (p=.001). Hierarchical multiple regression analysis was
performed to identify the determinants of psychiatric disorder.
The resulting equation accounted for 20% of the variance. A
series of significant predictors (p/.Ol) were associated with the
following increments in explained variance: history of past major
affective or anxiety disorder (3%); diagnosis of AIDS or ARC
(5%); number of AIDS spectrum physical symptoms (4%); and extent
of self-reported psychological distress (J%). Reactive psychiatric
disorders are a common and highly treatable complication of AIDS
and ARC-- which may be readily detectable from the patient's
own report.
T 10 3 KN0WLEDGE 0F H.I.V. CONTAMINATION MODALITIES AND ITS CONSEQUENSE
ON SEROPOSITIVE PATIENTS BEHAVIOUR.
A.PESCE, M. NEGRE, J. P. CASSUTO. Ligue Regionale Francaise de Lutte
contre le S.I. D.A. - 8, rue Hotel des Postes - NICE - 06000 - FRANCE
We made investigation on behaviour of 150 patients infor-
med of their H.I.V. seropositivity , Living on French Riviera, which is the
second French place for A.I.D.S. rate. Characteristics of this population
are the following : drug addicts : 100 (67 %), homo and bisexuals : 32 (21%)
exclusive heterosexuals : 10 (6,5 %) , transfused : 8 (5,5 %) ; median age
(17-79) : addicts : 25, homo and bisexuals : 29, transfused : 41. For each
group specific contamination risk was known on an average of 16 months for
addicts, 35 months for transfused patients. Drug addicts stopped syringe
exchange in 51 % of cases, drug (heroin) in 36 % and use condoms : 33 %.
Among 73 % of homosexuals who carry on sexual practices, 37 % use condoms,
almost of heterosexuals who carry on sexual activity use protective mean
(4/5). In this study, transfused population is not significant because of
lack of seropositivity knowledge and lack of sexual activity in all patients
related to severity of initial disease.
Although these results appear disappointing, they do
signify a real change in practice of risk patients, which justify repe-
titive and specific public information conciousness being heterogenous
according to the groups .
T 10 6 Two-Year Longitudinal Study of Behavioral Risk Reduction in a
Cohort of Homosexual Men
JILL G. JOSEPH*, S. Montgomery*, R.C. Kessler*, D.G. Ostrow*, CA. Emmons*,
J. P. Phair**, *University of Michigan, Ann Arbor, MI, USA, **Northwestern
University, Chicago, IL, USA
A cohort of approximately 650 homosexual Chicago men provided behavioral and
psychosocial data from mid-1984 to mid-1986. A four level objective risk
index was constructed and validated using HIV serological data. This index
summarizes number and type (e.g. monogomous; anonymous) of sexual partners,
frequency of receptive anal intercourse, and use of condoms. Although 35? of
the cohort was categorized as at high risk originally, by Wave 4 this was true
of only 6.0%. Similarly, while 6.1? were originally completely avoiding risk
behaviors, two years later 13.4% were doing so. Components of the health
belief model at Wave 1 were used as predictors in a series of multiple
logistic regressions which examined subsequent risk reduction. Indices were
constructed to quantify knowledge of AIDS, perceived risk, perceived efficacy
of behavioral change, social network characteristics, peer norms, difficulties
with sexual impulse control, and beliefs in technological solutions to the
AIDS crisis. Of these, knowledge (p<.01-.05), peer norms (p<.01-.02), and
difficulties with sexual impulse control (p<.01-.02) were consistently
predictive of behavioral risk reduction. This provides evidence for the role
of cognitive, social and psychological factors in behavioral risk reduction.
60
TUESDAY, JUNE 2
Roundtable Discussions
T.11
Access Issues Associated with AIDS:
Discrimination, Services, Care
Panel Moderator: Jeffrey Levi
National Gay and Lesbian Task Force
Washington , D.C.
Tom Stoddard, Lambda Legal Defense and Education Fund, New York, New York
Ben Schatz, National Gay Rights Advocates , San Francisco, California
Tim Westmoreland, Council House Subcommittee on Health and the Environment,
Washington, D.C.
Adam Carr, Victorian AIDS Council, Richmond, Australia
Katy Taylor, New York City Human Rights Commission, New York, New York
T.14
Legal, Ethical and Public Policy Issues:
International Perspective
Panel Moderator: Richard Riseberg
Public Health Service, HHS
Washington, D.C.
Ronald Robertson, Department of Health and Human Services, Washington, D.C.
LeRoy Walters, Joseph and Rose Kennedy Institute of Ethics, Washington, D.C.
Bernard Dickens, University of Toronto, Toronto, Canada
Harvey V. Fineberg, Harvard University, Boston, Massachusetts
Sev Fluss, World Health Organization, Geneva, Switzerland
Michael D. Kirby, Court of Appeals, New South Wales, Australia
Eric Matthews, University of Aberdeen Kings College, Aberdeen, Scotland
Helen Roscam-Abbing , University of Limberg, Maastricht, The Netherlands
Brenda Almond, The University of Hull, Hull, England
T.12
T.15
Use of AZT in HIV Infections
Panel Organized By: John La Montagne
National Institute of Allergy and Infectious Diseases
Bethesda, Maryland
Douglas Richman, Veterans Administration Medical Center, San Diego,
Cal if ornia
Paul Volberding, University of California, San Francisco, San Francisco,
California
Margaret Fischl, University of Miami, Miami, Florida
Sandra Lehrman, Burroughs Wellcome Company, Research Triangle Park,
North Carolina
Psychological Distress and Maintenance of
Behavior Change in HIV Illness
Panel Organized By: Peter Bridge
ADAMHA
Bethesda , Maryland
Panel Moderator: Ellen Stover
National Institute of Mental Health
Rockville, Maryland
John Newmeyer, CEO Youth Projects, Inc., San Francisco, California
Peter M. Davies, South Bank Polytechnic, London, England
Jeff Moulton, Langley Port Psychiatric Institute, San Francisco, Californi
David Ostrow, University of Michigan, Ann Arbor, Michigan
Thomas Coates, University of California - San Francisco, San Francisco,
California
T.13
Encouraging Physician Counseling for AIDS Prevention
Panel Organized By: Neil R. Schram
LA City/County AIDS Task Force
Los Angeles, California
David McEwan, Honolulu Medical Group, Honolulu, Hawaii
Brian Willoughby, Vancouver, Canada
Mark Behar, Milwaukee, Wisconsin
Alan Novick, Yale University, New Haven, Connecticut
Biology of HTV
T.16.1
The AIDS Virus Genomes: Structure and Function.
Flossie Wong-Staal, National Cancer Institute, National Institutes of
Health, Bethesda, Maryland .
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
61
TUESDAY, JUNE 2
T.16 2 Molecular Basis for Approaches for Diagnostic, Therapeutic, and
Prophylactic Measures for Control of AIDS.
WILLIAM A. HASELTINE**, JOSEPH SODROSKI*. CRAIG ROSEN*, ERNEST TERWILLIGER* ,
ANDREW DAYTON*, ROBERTO PATARCA* . *Dana-Farber Cancer Institute, Dept. of Bio-
chemical Pharmacology, Harvard Medical School, and **Harvard School of Public
Health, Dept. of Cancer Biology, Boston, MA.
The studies of the replication cycle, genetic regulatory pathways and mecha-
nisms of cellular cytopathicity of the AIDS virus will be presented in the con-
text of their potential for the development of improved techniques for the con-
trol of the disease.
Specifically, studies of the cis and trans elements of the viral genome will
be presented. In this study, the structure/function of envelope glycoprotein
will also be discussed as it pertains to early steps of infection, cytopathic
effect and immunoprophylactics. The potential for other viral genes as targets
for anti-viral drugs, including the protease reverse transcripatase and endo-
nuclease integrace genes will also be discussed.
T.16. 5 EXPERIMENTAL IMMUNE ACTIVATION AGAINST AIDS VIRUS IN HUMANS
D. Zagury, Z. Lurhuma, K. Mbayo, J.J. Salaun, R. Leonard, J. Bernard,
M. Fouchard, B. Reveil, B. Goussard, J. Vane.
Universite Pierre & Marie Curie (Paris) - Institut J. Godinot (Reins) - Faculte de Medecine
de Kinshasa et INRB (Kinshasa).
The diversity of subtypes of human iitraunodef iclency virus (HIV) represents a major
difficulty in the immune defense mechanisms against AIDS because a humoral response induced
by one HIV strain may generate neutralizing Abs only against that strain and not against
other HIV strains. That prompted us to investigate whether a cell mediated immune response
(CHI) would overcome the subtype diversity limitations. Previous studies showed that
infected T cells proceed, before release of virions, through an immunogenic stage, where
the cell may a) trigger a CHI and b) represent a target for a specific cytotoxic T Cell
(CTL). These data rationalize our operative strategy, to trigger a CMI against HIV
infection by either non infectious fixed autologous cells expressing HIV antigens at the
cell surface (for seropositive immune deficient organisms) or a vaccinia recombinant (Vr)
expressing Gp.160 env protein from HTLV.III-B (for seronegative organisms). After
preliminary experiments on monkeys showed the innocuity of both treatments, we treated by
their fixed cells infected in vitro, 2 volunteers ARC patients, followed 3 months after, by
8 others. No clinical complication whatsoever occurred up to now and immunological
parameters improved significantly. Ve also immunized with Vr a seronegative individual
(D.Z., one of us) no clinical manifestation nor immunological defect occurred during the
immunization. Ve then immunized 10 individuals high risk seronegative immunologically
normal individuals, all volunteers. D.Z. and these individuals presented a normal vaccine
course without any complication. In our presentation we will report the results of
clinical and biological follow up and the degree of the immune response against different
strains of HTLV.III. Finally we will discuss the scientific, ethical and economic
conditions required for clinical trials of vaccines against HIV. All these researches have
the full support of the Zairian Executive Council and its Ethics Committee.
Poster Session
I .10.0 Genetic Variability of the AIDS Viruses.
Simon Wain-Hobson, Institut Pasteur, Paris, France.
TR1
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
Correlation between Metabolism and Antiretroviral Effect of AzddThd
(AZJ) and ddCyd in Murine and Human Cell Systems in vitro and in vivo.
JAN BAI^ARINI , R. PAUWELS , M. BABA , E. DE CLERCQ , S. BRODER and D.G
JOHNS . Ttega Iwtitute for Medical Research, University of Leuven, B-3000
Leuven, Belgium; Clinical Oncology Program and ■"""Developmental Therapeutics
Program, National Cancer Institute, NIH, Bethesda, MD 20892, U.S.A.
2' ,3'-Dideoxycytidine (ddCyd) is superior to 3'-azido-2' , 3 T -dideoxy thymi-
dine (AzddThd) in suppressing the in vitro infectlvity of human immunodeficien-
cy virus (HIV) in human ATH8 cells. In contrast, AzddThd inhibits the in vitro
transformation of C3H mouse (MO) cells by Moloney murine sarcoma virus (Mo-MSV)
at an inhibitory dose (ID..) of 0.06 uM, that is at a concentration at least
400-fold lower than the ID1. of ddCyd. Daily AzddThd treatment (125 mg/kg/day)
of NMRI mice infected at 3 days after birth with Mo-MSV almost completely pre-
vented MSV-induced tumor formation and resulted in a complete survival of the
mice. At 25 mg/kg/day, significant delay in tumor formation and considerable
prolongation of the life span of the mice was observed. In contrast, ddCyd
treatment at 125 or 25 mg/kg/day only resulted in a slight delay of tumor for-
mation, without any effect on the survival rate of the mice. Since AzddThd-5'-
triphosphate (AzddTTP) and ddCyd-5' -triphosphate (ddCTP) are assumed to be the
active antiretroviral metabolites in the cell, we compared the levels of these
metabolites in human and murine cells. Under similar experimental conditions,
lower ddCTP but higher AzddTTP levels were observed in murine L1210 cells than
human ATH8 cells. Thus, the antiretroviral effect of AzddThd and ddCyd corre-
lated well with their corresponding intracellular 5 '-triphosphate levels. The-
se findings strongly suggest that the Intracellular levels of the 5 '-triphos-
phate metabolites of 2' ,3'-dideoxynucleosides determine their efficacy for in-
hibition of retroviral infections and that the potency of these agents are
greatly influenced by cell type dependent metabolism.
T 16 4 The Iromuxiobiology of the External Envelope Viral Glycoprotein
' THOMAS J. MATTHEWS*, SCOTT D. PUTNEY**, JAMES R. RUSCHE**, ROBERT
C. GALL0***, DANI P. B0L0GNESI*, *Duke University Medical Center, Durham, NC,
**Repligen Corporation, Boston, MA, ***National Institutes of Health, Bethesda,
MD
The interaction of gpl20 with the CD4 surface lymphocyte marker is critical
for the processes of virus infection and virus mediated cell/cell fusion. We
have examined the relationship between the segments of gpl20 responsible for
each of these activities as well as those serving as target epitopes for virus
neutralization. These results will be discussed in terms of vaccine and
interventive strategies for the disease.
TR2
A Model of Human Immunodeficiency Virus (HIV-1)
ALBERT F.BYK0VSKY, Institute of Epidemiology and Microbiology, Moscow, U.S.S.R.
fte'have carried out a comparative study of various strains of HIV-1, such as:
LAV (obtained from Prof .L.Montagnier, Institute Pasteur, Paris, France), HTLV-111
(from Dr.R.Gallo, Bethesda, USA), ARV (from Dr. J. Levy, San-Francisco, USA), the
latter two were received from Prof .V.M.Zhdanov. The molecular organization of sub-
virion components of HIV-1 was examined using the high-resolution electron micro-
scope. We studied as components as the core, ribonucleoprotein, the reverse trans-
criptase, gp 120, gp 41, p 24, p 18 and p 13. The diameters of the virions with
single core were about 140-160 nm, but the diameters of the virions with two cores
were about 200-250 nm.
The cores were rod- or conic-shaped and usually were located excentrically. Rod-
shaped cores had the size of 130-150x40-50 nm, conic cores had the height of 100-
130 nm and the diameters of 60-70 nm in the upper sait and 10-15 nm in the base
one. The core shell contained spherical structures with the 3ize of 6-7 nm x 3-4
nm. The nucleoids, consisting from ribonucleoprotein threeds (2 nm in diameter),
were packaged in special way into loops (diameter of 5-6 nm).
The intermediate layer of virions contained globular structures (2-3 nm). Sphe-
rical structures on the surface of virions (10-11 nm) contained central channel
(2 nm).
"Minimal forms" of HIV-1 (dismeter 50-70 nm) were also found. The visualization
of components of HIV-1 let us construct a stereo model of the virus.
62
TUESDAY, JUNE 2
TDO Monoclonal Antibodies to Peptides of
Neutralise Variant Isolates of HIV
A.G. DALGLEISH, R.C. KENNEDY*, P.C. CLAPHAM**, T.
and M. MALKOVSKY, Retrovirus Research Group, MRC
Watford Road, Harrow, Middlesex HA1 3UJ, England;
and Immunology, Southwest Foundation for Blomedic
TX 78284, USA; **Chester Beatty Laboratories, Ins
Fulham Road, London SW3 6JB, England.
We have previously shown that rabbit antibodies
envelope peptides neutralise virus infectivity in
J. ^. 3065-3071, 1986; Kennedy et al., Science 23
now show that monoclonal antibodies against 3 dif
neutralise different isolates of HIV as determine
reverse transcriptase and long term infectivity a
Important implications for the development of ant
the gpAl Molecule
C. CHANH*, G.R. DREESMAN*
Clinical Research Centre,
Department of Virology
al Research, San Antonio,
tltute of Cancer Research,
raised against HIV
vitro (Chanh et al., EMBO
1, 1556-1559, 1986). We
ferent gp41 peptides all
d by syncytia, pseudotype,
ssays. This data has
i-HIV vaccine.
TR6 Evidence for lentiviral etiology in an epizootic of lymphoma
and immunodeficiency in stump-tailed macaques (Hacaca arctoides)
LINDA J. LOWBNSTINB*. N.W. LERCHE*, H. JENNINGS**, J. YEE**, a. UYEDA**, M.
GARDNER**, et al., 'California Primate Research Center, **Schools of
Veterinary Medicine and Medicine, University of California, Davis, CA, USA.
Infections of nonhuman primates with simian T-lymphotropic lentiviruses
(STLV-IIIs) serologically related to HIV and KtV-2 provide important models
for human AIDS. Reports in the literature suggest that these viruses are
endemic in some populations of African monkeys, e.g. African green monkeys
(Cercopithecus aethiops) and sooty mangabeys (Cercocebus atys), but do not
cause disease. Natural infections in captive macaques are rare but inocula-
tion of macaques with isolates from macaques or African monkeys causes an
AIDS-like disease. Retrospective studies of a naturally occurring epizootic
of immunosuppression and lymphoma in stump-tailed macaques (StH) that oc-
curred between 1976 and 1978 at the California Primate Research Center have
revealed that sera from many StM reacted strongly with HTLV-III (HIV); LAV-2
(HIV-2); STLV-lll (macaque and sooty mangabey). None of the sera reacted
with the simian immunosuppressive type-D retroviruses which are the common
cause of epizootic simian AIDS (SAIDS) in macaques in the U.S. Inoculation
of a juvenile rhesus (M^ mulatta) with a lymph node homogenate from a StM
that died in 1977 of lymphoma produced lymphadenopathy and decreased T4/T8
ratio. The animal developed antibodies cross reactive with human and simian
lymphotropic lentiviruses. Virus recovered from this rhesus had Mg++ depend-
ent reverse transcriptase and the ultrastructure of a lentivirus. This
documents the first naturally occurring propagating epizootic of lentivirus
associated SAIDS in captive macaques and provides an additional isolate for
comparison with known human and simian lentiviruses.
TR4 IH vitr0 Infection of Primate Lymphocytes by HIV-1 and Expression
of CD4 Epitopes
MYRA 0. HcCLURE*. Q. SATTENTAU**, P. BEVERLEY**, J. HEARN***,
A.J. ZUCKERMAN****, R.A. WEISS, *Chester Beatty Laboratories, "Department of
Human Tumour Immunology, University College London, ***Institute of Zoology,
****Department of Medical Microbiology, London School of Hygiene and Tropical
Medicine, London.
Peripheral blood monoclonuclear cells (PMB) from a number of primate specie?
were infected in vitro with HIV-1.
PBM were phenotyped for expression of epitopes of the CD4 antigen with a
panel of CD4 monoclonal antibodies (Mabs) by indirect immunofluorescent
staining and FACS analysis. The greater the divergence of the primate species
from man, the fewer epitopes were conserved, and only one epitope was consis-
tently represented in all species tested. This could be detected by the C04
Mabs leu 3a, MT310, F101-65 and 94bl, all of which strongly inhibit the virus
CD4 interaction in human cell lines. Infection of the primate PBM with super-
natants of HIV-1 was tested after stimulation with PHA and IL-2. Samples of
infected PBM or supernatants from these cultures induced a cytopathic effect
in the C8166 CD4+ indicator human cell line. Preliminary data also show
induction of RT activity in infected PBM and the presence of pl8 by immuno-
fluorescence. These data may indicate primate species which could be suscept-
ible to infection. J_n vivo tests are in progress. They may also indicate which
part of C04 is essential for virus binding.
TP7 Absence of HTLV-IV in Central Africa
PHYLLIS KANKI*. J. ALLAN*, F. BARIN**, M. ESSEX*, *Harvard School
of Public Health, Boston, MA, "University of Tours, Tours, FRANCE.
HTLV-IV was first described in Senegal and has been shown to be prevalent in
most countries of West Africa where reports of AIDS cases are still infre-
quent. In contrast, AIDS and HTLV-III/HIV are observed at high and increasing
rates in discrete regions of Central Africa. This study was conducted to
assess the prevalence of HTLV-IV in 7 countries of Central Africa and to
determine any association with AIDS or a related disorder. Serum samples from
healthy controls, tumor patients, ARC, tuberculosis, STD patients, and AIDS
were kindly provided to us as a collaborative study with T. Quinn, n. Clumeck,
F. Mawovondi , I. Lausen, D. Zagury, L. Thiry, J. Craighead, C. Saxinger, and
L. Falk; Zaire, Cameroon, Zambia, Kenya, Tanzania, Burundi, and Uganda were
represented in the sample population.
All 1,430 serum samples were analyzed by radioimmunoprecipi tation and
SDS/PAGE and immunoblot for antibodies to HTLV-IV. The cross-reactivity
between HTLV-IV and HTLV-III/HIV antigens has been well documented and appears
to be the strongest in gag and pol encoded antigens. Therefore, a positive
HTLV-IV response was distinguished by a specific response to the env antigens
of HTLV-IV, the gpl60/120 and gp32 (transmembrane). NONE of the l74"30 samples
analyzed demonstrated antibodies to the env-related antigens of HTLV-IV; in
HTLV-III/HIV antibody positive samples, cross-reaction to the gag and pol
antigens of HTLV-IV was frequently observed.
HTLV-IV was not detected in 7 Central African countries surveyed, whereas
HTLV-III/HIV in association with AIDS and related disorders was quite common.
Further study on these two viruses of apparently differing pathogenicity will
be important to our general understanding of various members of the HTLV
family and how they have evolved.
TR5 Characterization of a Monoclonal Antibody Specific for the HIV-1
Precursor Glycoprotein.
B. KRUST'. A. G. LAURENT1 , A. LE GUERN2 , 0. JEANNEQUIN2 , L. M0NTAGNIER1
and A. G. HOVANESSIAN1 . 'Unite d'Oncologie Virale, 2Hybridolab, Institut
Pasteur, 25, rue du Dr. Roux, 75724 Paris Cedex 15, France.
HIV-1 infected M0LT4-T4 cells provide an efficient system for the production
of cellular precursor gpl60 of HIV envelope glycoproteins, gpl20 and gp41.
The precursor gpl60 was purified on an immuno-affinity column containing
antibodies from sera of HIV-1-seropositive patients. The precursor gpl60 was
then isolated by preparative polyacrylamide gel electrophoresis. Two out of
4 BALB/C mice immunized with these purified preparations of gpl60, developed
specific circulating antibodies after 5 injections at 2 weeks interval. A
hybridoma cell line was subsequently isolated producing monoclonal antibody
(IgGl, <) specific for gpl60. This monoclonal antibody can immunoprecipitate
specifically gpl60 present in HIV-1-infected cells. In an immuno-blotting
assay, it identifies mainly gpl60 and manifests a slight affinity for the
mature glycoprotein, gpl20. The monoclonal antibody is probably directed
against an epitope in the polypeptide residue of gpl60 since it can recognize
a 90,000 Mr deglycosylated polypeptide, product of gpl60 digestion by Endo H.
It does not cross-react with any protein of HIV-2 by immunoblot or immuno-
precipitation assays. By virtue of its specificity, the monoclonal antibody
might provide a powerful probe to detect opl60 in cells and tissues which
might express partially the HIV-1 genes.
JP8 HIV Infection of B Lymphoblastoid Cell Lines
JAMES E. MONROE*, G. LENOIR**, C. MULDER*, *UMMS, Worcester, MA,
USA, International Agency for Research on Cancer, Lyon, FRANCE
We examined the susceptibility of B Lymphoblastoid cell lines to HIV infec-
tion. A series of EBV genome-negative and EBV-converted Burkitt Lymphoma cell
lines, and other EBV-infected cell lines, exhibiting both permissive and non-
permissive EBV infection, were studied. Initial studies showed that only 1 of
4 EBV-negative Burkitt Lymphoma cell lines and 10 of 20 EBV-positive cell
lines could be infected with HIV-IIIB. HIV infection was monitored using re-
verse transcriptase and cytoplasmic RNA dot-blot assays.
Further studies using two different strains of HIV (IIIB, RF) and a LAV 2
strain (N°I-532) followed. The C-8166 syncytia assay was also used to moni-
tor infection. Twenty-two of 24 cell lines could be infected with at least
one of the three virus strains. In certain cell lines, virus production was
very low and detectable only by the syncytia assay. Each cell line which
could be infected with HIV was found to express T4 surface antigens.
It is clear from this study that prior EBV infection has no major effect on
HIV susceptibility. Southern blot analysis of DNA extracted from long-term,
HIV-nonproduc ing cell lines detected integrated HIV genomes. This study in-
dicates that T^-positive B lymphoblastoid cells may serve as a reservoir
for latent HIV infection, even in the absence of EBV infection.
63
TUESDAY, JUNE 2
TDQ Detection of HIV-Specific Sequences Using in Vitro
Nucleic Acid Amplification and Oligonucleotide-Based
Affinity Chromatography
THOMAS R. GINGERAS*, D.D. RICHMAN**, G.R. DAVIS*, AND D.Y. KWOH* ,
*The Salk Institute Biotechnology/Industrial Associates, Inc., La
Jolla, CA, USA, **University of California, San Diego School of
Medicine, La Jolla, CA, USA.
The polymerase chain reaction (PCR) protocol, first described
by Siaki et al. [Science (1985) 230:1350-1354] , permits a 10''-
fold increase in the copy number of a 350 bp region from the env
gene of the HIV RNA genome. The products of this in vitro ampli-
fication can be labeled by incorporation of 32P-dCTP during the
last cycle of amplification. Although the labeled nucleotides can
be incorporated into both HIV-specific and human-host cell-speci-
fic sequences, the labeled HIV-specific fragment can be detected
by a rapid and simple hybridization procedure using support-bound,
HIV-specific oligonucleotides. This protocol has been applied to
the detection of HIV present in cultured cell lines (CEM) and in
clinical samples derived from a longitudinal study of a cohort of
240 homosexual men at various degrees of risk for AIDS. Results
from the application of this detection protocol to these samples
will be discussed.
TR12 Western Blot Assay Patterns of Early Antibody Response to the Human
Immunodeficiency Virus. Patricia E. Taylor, Cladd E. Stevens and
Pablo Rubinstein, The New York Blood Center, New York, N.Y., U.S.A.
Stored serial serum samples from 103 homosexual men who participated in
hepatitis B vaccine efficacy trials begun 1n late 1978 and who showed serocon-
version during the subsequent 8 year period for antibody to the human Immuno-
deficiency virus (ant1-HIV) were tested by the enzyme-linked Immunosorbent
assay, ELISA, (Dupont Inc.). Sera obtained at and three to six months prior
to anti-HIV positivity by ELISA were also examined by Western Blot (WB) pro-
cedure (Biotech Laboratories, Inc.). The WB patterns for 59 of these men
showed anti-HIV reactivity for p24, p41 and other HIV proteins at the same
time as ELISA reactivity was first observed. The remainder showed diverse
patterns of early ant1-HIV reactivity, the most common being ant1-p24 reacti-
vity with or without anti-p55. In 12 men anti-p24 was the first antibody to
HIV to appear by WB. In five of these the ELISA result was negative when
anti-p24 appeared and, in another, ELISA gave a positive reaction in a serum
sample taken two months before the ant1-p24 positive sample. The remaining
seven were both ELISA and WB positive. The appearance of ant1-p55 preceded
anti-p24 and other antibodies in six instances. Ant1-p4l was not found before
the appearance of anti-p24 or ant1-p55 or before antibody was detected by
ELISA.
No relationship was found between the pattern of early ant1-HIV response
as observed by WB and the T helper to T suppressor cell ratio obtained in
early 1984 when studies of cell-mediated immunity were initiated.
TP1fl Immunoaffinity Purification of the Major Envelope Glycoprotein from
■i.iu HTLV-III-Infected H9 Cell Culture Media.
STEPHEN W. PYLE*. W.G. ROBEY**, J.W. BESS, JR.*, P.J. FISCHINGER**, R.V.
GILDEN*, L.O. ARTHUR*, *Program Resources, Inc., NCI-Frederick Cancer Research
Facility (FCRF), Frederick, MD 21701, **0ffice of the Director, Virus Control
Unit, NCI-FCRF, Frederick, MD 21701, USA.
Purified external envelope glycoprotein, gpl20, of the human immuno-
deficiency virus (HIV), the name proposed for the retrovirus causually assoc-
iated with acquired immune deficiency syndrome (AIDS), has been shown to
induce the formation of neutralizing antibodies when inoculated into
laboratory animals and is, therefore, being evaluated as a prototype vaccine.
The gpl20 is not tightly associated with the virus and is shed into the
culture fluids used to propagate HTLV-IIIb-infected H9 cells. We have utilized
an immunoaffinity resin, prepared by coupling IgG from AIDS patient sera to
Sepharose 4B, to purify gpl20 from this culture fluid. In a typical run, virus
is removed from the culture fluid by continuous-flow ultra-centrifugation, and
144 liters of the fluid is chromatographed over the immunoaffinity resin.
After washing, bound HTLV-IIIb envelope glycoprotein was eluted with low pH
buffer. Following extensive dialysis against distilled water, the gpl20 was
further purified by polyacrylamide gel electrophoresis, HPLC or differential
precipitation. This purified gpl20 induced both precipitating and neutralizing
antibodies in laboratory animals and will provide a valuable reagent in AIDS
vaccine research and HIV envelope studies.
Research sponsored, at least in part, by the National Cancer Institute,
DHHS, under Contract Number N01-CO-23910 with Program Resources, Inc.
Tp-10 Demonstration of Antigenic Variation in HIV Envelope Proteins by
Competitive Radioimmunoassays.
J.W. BESS, JR.*, S.W. PYLE*, AND L.O. ARTHUR*, *Program Resources, Inc., NCI-
Frederick Cancer Research Facility, Frederick, MD 21701, USA.
Competition radioimmunoassays have proven extremely useful not only in
quantitation of biologicals but for establishing immunological relationships
as well. We have purified the outer envelope glycoprotein (gpl20) of HTLV-IIIB
and used it in establishing competition radioimmunoassays. A broadly specific
immunoassay was obtained when HTLV-IIIB gpl20 was used as the radiolabeled
probe in a competition assay with serum from an AIDS patient. All HIV variants
tested in this assay competed completely with equal efficiency providing an
assay for quantitating gpl20 in viruses and other biological samples. Use of
antisera generated against purified HTLV-IIIB to precipitate '2S-I HTLV-IIIB
gpl20 provided an immunoassay which differentiated HIV variants. HTLV-IIIB
competed completely in the assay while the variant HTLV-IIIRF gave only
partial competition. Use of these radioimmunoassays, along with an HTLV-IIIRF
gpl20 currently being developed, will provide rapid sensitive assays for
establishing HIV envelope relatedness. This information, coupled with data
from envelope nucleotide sequencing data and cross-neutralization results,
will be potentially invaluable in assessing HIV isolates to be used in vaccine
strategies.
Research sponsored, at least in part, by the National Cancer Institute,
DHHS, under Contract Number NO1-CO-23910 with Program Resources, Inc.
TR11
Expression in _E. coli of open reading frame gene segments of Human
B-lymphotropic virus (HBLV)
MING-CHIU FUNG*, S.C. FUNG*, S.F. JOSEPHS**, M.L. BERMAN***, F. WONG-STAAL**,
N. CHANG*, *Baylor College of Medicine, Houston, TX, **National Cancer
Institute, National Institutes of Health, Bethesda, MD, ***Bionetics, Inc.,
Kensington, MD.
Human B-lymphotropic virus (HBLV), a new member of the herpesvirus family,
has been recently detected in several patients with lymphoproliferative
disease including the chronic mononucleosis fatigue syndrome. Several
subgenomic fragments of HBLV have been molecularly cloned into bacterial
plasmids and partially characterized. A combined cloning/expression protocol
was used to identify a gene encoding a viral protein that is immunoreactive
with sera from patients infected with HBLV. Random fragments were generated
from the HBLV subgenomic DNA derived from pZVH14 by DNase Bal 31 digestion
or sonication were inserted into an expression vector pMLBllll and the HBLV
DNA sequences were expressed as proteins fused to /3-galactosidase. Several
different open reading frames were mapped along the subgenomic DNA fragment.
Sera from patients infected with HBLV were used to screen for HBLV
immunoreactive fusion proteins. Two expression plasmids were isolated and
their specif ic fusion proteins were identified with patient sera in the
Western blot analysis. The HBLV DNA sequences represented in these two clones
were mapped within a single open reading frame on the HBLV genome. Using
affinity chromatography and SDS-PAGE, the HBLV-^-galactosidase fusion protein
was purified and monoclonal antibodies were raised against them in mice.
TP1d Topographical Analysis of HIV p24 using Monoclonal Antibodies
Ini KEVIN J. REAGAN, A. L. PIEPER, M. A. WALSH and R. L. TYSON, E. I.
Du Pont de Nemours and Co., Inc., Medical Products Department, Wilmington, DE
19898.
We have prepared panels of monoclonal antibodies reactive with the major
internal core protein (p24) of Human Immunodeficiency Virus (HIV). Balb/c mice
were immunized with partially purified virus or isolated viral proteins and
immune splenocytes fused with variant 653 or P3x63 Ag8 mouse myeloma cells.
Reactive hybridomas were initially screened on Du Pont HTLV-III ELISA plates.
A further characterization of antibody specificity was accomplished by
Western Blot reactivity with electrophoretically separated virus, surface and
cytoplasmic immunofluorescence on virus-infected H9 cells and reactivity with
recombinant core proteins.
Over 20 monoclonal antibodies specific for the p24 core protein were
isolated and used to construct a functional epitope map. We identified four
reactivity patterns representing three distinct antigenic sites on this
protein.
64
TUESDAY, JUNE 2
TP15 Complete Nucleotide Sequence of the Simian T-Lymphotropic Virus
Type III and Genetic Analysis of a New Subgroup of AIDS-Related
Human T-Lymphotropic Viruses
GENOVEFFA FRANCHINI, et al. , Laboratory of Tumor Cell Biology, National Cancer
Institute, NIH, Bethesda, MD.
A new primate retrovirus, simian T-lymphotropic virus type III (STLV-III),
recently has been isolated from healthy African green monkeys and is apparently
non-pathogenic in its natural host. However, spontaneous infection and inocu-
lation of STLV-III into Macaque monkeys induce a disease like human AIDS.
Independent isolates of human retroviruses related to STLV-III have been
obtained from healthy individuals (HTLV-IV) and patients with AIDS (LAV-2 and
SBL-6669) from West Africa. We molecularly cloned the STLV-III genome and
generated probes from the gag and envelope genes and determined genetic
relatedness by Southern analysis of these simian and human retroviruses. Our
results indicate that all these retroviruses are genetically closely related to
each other. HTLV-IV and STLV-III genomes differed only in 2 of 15 restriction
enzyme sites while LAV-2 and SBL-6669 exhibited greater polymorphism as
compared to HTLV-IV and SXLV-III. Computer analysis of the nucleotide sequence
obtained from the cloned STLV-III genome in comparison to that of HTLV-III
showed a high degree of homology, suggesting common ancestry of these two
viruses. Comparison within specific viral genes has allowed characterization
of biologically important regions within the env gene and functional domains of
some of the genes encoding regulatory proteins for the AIDS and AIDS related
viruses.
TP18 Synthetic peptide analogs of HIV proteins are recognised by
naturally acquired antibodies.
D.STAPLETON1, S.CUMMINGS D.MCPHEE2, B. KEMP1, R.DOHERTY2.
1: Department of Medicine, Repatriation General Hospital, Heidelberg, VIC.
2: Department of Virology, Fairfield Hospital, Fairfield, VIC. AUSTRALIA.
Predicted amino acid sequences of HIV proteins were scanned for potential
antigenic epitopes using the Welling Antigenicity program (FEBS lett. 188,
215-9, 1985) . Conserved, hydrophilic sequences identified were synthesized
as 13-21mer peptides using automated Merrifield solid phase techniques.
Peptides synthesized included gpl20(2-13), gpl20(55-65) , gp41 (582-596) ,
gp41(579-600), gp41(659-670), gp41 (766-778) , ptat(60-72), and ptat(46-58).
Peptides were studied by ELISA for recognition by human antibodies. All
peptides could be recognised, with sera from 98% of viraemic patients
recognising gp41 (579-600) , and 73% of identical sera the truncated form
(582-596). These results concur with those of Wang et al (PNAS, 83,6159-
6163, 1986). Ptat(60-72) was recognised by 52% of sera from viraemic
patients.
Serum from one viraemic patient with antibodies against core proteins
only on immunoblot assay did not recognise any of the peptides. Individual
profiles of recognition of peptides did not vary over time, but differed
substantially between individuals .
These findings demonstrate the significance of natural variability of
HIV isolates, and offer a means of further defining conserved, immunogenic
epitopes for serodiagnosis or vaccine development.
TR16 Phorbol 12-Myristate 13-Acetate Enhances HIV Promoted Gene
Expression and Acts Upon a 12 Base Pair Functional Enhancer Element.
JOSH D. KAUFMAN. G.S. BUSHAR, C.P. GIRI , AND M.A. NORCROSS , Division of
Virology, FDA, Bethesda, MD, USA
Phorbol 12-myristate 13-acetate (PHA) is a potent inducer of T-cell immune
functions and has recently been demonstrated to increase viral replication in
cell lines infected with Human Immunodeficiency Virus (HIV) . In order to
define sequences required for viral induction by PMA, cell lines were
transiently transfected with viral long terminal repeat (LTR) sequences
directing chloramphenicol acetyl transferase (CAT) gene expression. 10 ng/ml
PMA added to transfected cell cultures 24 hr before harvest reproducibly
increased both CAT mRNA and enzyme expression 2 to 5 fold. Induction of CAT
expression occurred in T-cell lines, monocyte lines, and cultured peripheral
blood lymphocytes.
Sequences necessary for basal and PMA induced levels of CAT expression were
determined by transfecting cells with deletion mutants constructed from the
original LTR-CAT expression plasmid. Removal of U3 DNA 118 base pairs (bp)
upstream of the mRNA start site improved basal and induced levels of CAT
expression up to 5 and 50 fold, respectively. Deletion of DNA 68 bp upstream
of the mRNA start site eliminated the basal expression level and prevented PMA
induction. Basal and induced levels of CAT expression were restored by
introducing a synthetic oligonucleotide containing a 12 bp LTR sequence. The
enhancer-like sequence could be inserted at a site distal to the CAT gene open
reading frame and functioned in a position and orientation independent manner.
In summary, the data defines a transcriptionally active and PMA inducible
regulatory/enhancer element critical to the control of HIV gene expression.
TP1Q Chronic Infection of Non-human Primate Gibbon Ape (Hylobates lac)
by Raman Immunodeficiency virus (HIV), HTLV-IIIB. P.D. MAFKRAM*,
W. JARRETT**, E. GARD*, M.G. SARNGADHARAN*, and R.C. GALLO***. *Department Of
Cell Biology, Bionetics Research, Inc., Rockville, MD; "Department of Veter-
inary Pathology, University of Glasgow, Scotland; ***Laboratory of Tumor Cell
Biology, National Cancer Institute, Bethesda, MD.
Many attempts have been made to identify animal model systems suitable for
the study of pathogenesis resulting from infection by HIV and its prevention oi
treatment. To date, the persistent infection and immune response following
inoculation with virus or tissues from AIDS patients had been documented in
only one animal, i.e., chimpanzee (Pan troglodytes) (1,2). We describe here
the extension of these observations to an additional non-human primate, the
gibbon ape (Hylobates lar). The infection, recognized by isolation of infec-
tious virus from peripheral blood mononuclear cells and appearance of specific
antibodies, was detected within two weeks following i.v. inoculation with
concentrated HTLV-IIIB, and has persisted for several months. During this
period of time, other than possible lymph node involvement, no noteworthy
pathological symptoms were detected. In parallel experiments, animals from
three other primate species, i.e.. Rhesus monkey (Macaca mulatta) , African
green monkey (Cercopithecus aethiops) , and common marmoset (Calithrix jacchus
jacchus ) , gave no evidence of infection and only sporadic or transient immune
response was observed.
1. Alter, H.J., Eichberg, J.W. , Masur, H. , et^ al.. , Lancet ii:549, 1984.
2. Francis, D.P., Peorino, P.M., Broderson, J.R., et al., Lancet ii:1276,
1984.
TP17 Inhibition of HIV by Species of Recombinant Interferon Alpha
VICKI MASISON*, M BRUNDA**, P GAGE**, J GR00PMAN*. *Division of
Hematology/Oncplogy , New England Deaconess Hospital, Harvard Medical School,
Boston, MA; **Hoffman La Roche, Nutley, NJ
It has previously been reported that recombinant interferon alpha-A has a
dose-related suppressive effect on HIV replication in peripheral blood
mononuclear cells in vitro. Based on this initial work, we investigated the
effects of 6 species of recombinant human interferon alpha on HIV (HTLV-III B
strain) infection of the T lymphocyte cell line H9 and the raonocytoid cell
line U-937. Both cell lines were mycoplasma free and maintained an RPMI 1640
with 20% fetal calf serum. Cultures were treated with either a single dose or
multiple doses of recombinant interferons alpha A, A/D, C, K, I, or D at
concentrations of 16, 256, and 1024 U/ral. Viral infection of target cells was
quantitated by indirect immunofluorescence .and reverse transcriptase (RT)
activity in H9 on days 7 and 11 and in U937 on days 14 and 18. A dose
response for HIV inhibition was seen with all species of alpha interferon.
Single doses of interferons A, A/D, K, and I at 1024 U/ml completely
Inhibited HIV replication In both H9 and U937. Interferons alpha C and D were
less inhibitory by 1-2 logs of RT activity. Approximately 50% inhibition of
HIV infection was seen at 256 U/ml. Multiple doses of all six alpha
interferon species were effective in U937 cells with total suppression seen
with all species at 1024 U/ml. Cell viability was not Impaired with
interferon therapy; indeed, the survival of both H9 and U937 cells was
improved by 10-25% in the presence of 256-1024 U/ml of interferon. These
studies demonstrate that the interferon alpha family has antiretroviral
activity in vitro in lymphoid and monocytoid cell systems and may be
clinically useful in the therapy of AIDS.
TP20 A Possible Role for Epitopes other than CD4 in the Receptor Complex
for (HIV). D.V. ABLASHI*, P.D. MARKHAM**, S.Z. SALABUDDIN*,
F. VERONESE**, AND R.C. GALLO*, 'National Cancer Institute, Bethesda, MD.,
**Bionetics Research, Inc., Rockville, MD.
It was demonstrated that the receptor for HTLV-III on T-helper lymphocytes
includes the CD4 protein complex. However, we have demonstrated that EBV
genome positive B-lymphocytes can be infected by HTLV-III regardless of the
presence of CD4 detectable by immunofluorescence of immunoprecipitation pro-
cedures. To further investigate these observations, monoclonal antibodies
directed against multiple CD4 epitopes were used to compete with HTLV-III
infection of two highly susceptible lymphoblastoid cell lines. This treatment
failed to completely block HTLV-III infection of either CD4- or CD4+ B cell
lines at concentrations that completely blocked the infection of CD4+ T-cells
including fresh leukocytes from human peripheral blood and established T cell
lines. B-cell specific monoclonal antibody (OKB-7) blocked EBV infection of
B-cell lines but did not block infection by HTLV-III, suggesting that HTLV-III
does not use the EBV receptor. These observations further suggest that CD4
proteins are not required for the infection of all susceptible target cells.
However, the presence of these epitopes may constitute a high affinity recep-
tor for HTLV-III. Concerning susceptable B-cells, EBV may code for or induce
the synthesis of molecules that fulfill the receptor function.
65
TUESDAY, JUNE 2
xpo-l Immunological and Chemical Analysis of HTLV-III pl5
F. diMARZO VERONESE1, R. RAHMAN1, T. COPELAND2, S. OROSZLAN2,
R.C. GALLO3, M.G. SARNGADHARAN1 , 1Bionetics Research, Inc., Rockville , MD;
2Lab. of Molecular virology and carcinogenesis, NCI-FCRF, Frederick, MD, 3Lab.
of Tumor Cell Biology, NCI, Bethesda, MD.
The first open reading frame of HTLV-IIIB genome has been identified as the
gag gene. The proteins encoded by this gene are pl7 as the amino terminal
protein, p24 as the middle peptide and pl5 as the carboxy terminal end. A
monoclonal antibody recognizing pl5, designated M35/2F8 has been developed and
used to further characterize this protein. pl5 was purified from an extract
of H9 cells producing HTLV-IIIb by an immunoaf f inity procedure employing
immobilized purified M35/2F8 IgG. In addition to pl5, M35/2F8 purified the
precursor of gag proteins p53, a smaller intermediate p39, and at a lesser
concentration a very small peptide of approximately 6 kD. In contrast, M35/
2F8 purified only p6 when viral extract was applied to the immunoaf f inity
column. H9 cells producing HTLV-IIIB were then labeled with [ 35S]-cysteine
and [3H]-leucine, immunoprecipitated with M35/2F8 and analyzed by SDS-PAGE.
No immunoprecipitation of p6 has been observed when cells or virus were
labeled with ( 35S)-cysteine. However p6 was distinctly immunoprecipitated
when [3H]-leucine labeled cells were analyzed. These results demonstrated:
that gag pl5 is indeed processed into two smaller products p7 and p6 as anti-
cipated, that M35/2F8 recognizes an epitope Oil tlie cysteine- free""p"eptlder"pS"
and that p6 arises from a maturation cleavage of pl5. To confirm its viral
origin, [3H] -leucine labeled p6 was subjected to radiolabel sequencing.
Leucine was unambiguously assigned at position 1 and 13 of the 40 cycles
examined. The amino acid sequence determined is a perfect match with a pre-
dicted sequence at the carboxy terminus of the gag gene starting with Leu448.
TR24
Human Immunodeficiency Virus (HIV): Fine Structure and Immunolo-
calization of Virus Strucutral Proteins and HLA-Determinants.
HANS R. GELDERBLOM, M. OZEL, H. REUPKE, E.H.S. HAUSMANN, G. PAUL1*
M.A. KOCH, Robert-Koch-lnstitut des Bundesgesundheitsamtes und *lnstitut fUr
Virologie der Freien Universitat Berlin, Nordufer 20, D-iooo Berlin 65
Thin section electron microscopy (EM), serial sectioning and tilting experi-
ments were applied to elucidate the fine structure of HTLV-III B and LAV-2.
On the envelope 70 - 80 knobs are observed having a diameter of 15, and a
height of 9 nm. Knobs are arranged according to surface replica EM, in a
T = 7I symmetry and are shed concomitant to the morphological maturation
of HIV. Adjacent to the inner leaflet of the viral membrane an electron-
dense matrix protein is seen which enlarges parallel to the long axis of the
elongated prismatic viral core.
The antigenic architecture of the virion was investigated by pre-embedding
immunoferritin EM and immunogold labeling of ultrathin cryosections. The
core shell shows tubular symmetry and p24 antigenicity, while pi7 determinants
are associated with the matrix protein: both were not detectable on the outside
of the virion. The major envelope gpi20 forms the knobs and gp4i represents
the transmembrane protein. HLA-antigens were shown to be incorporated in the
envelope corresponding to the antigenic make-up of the virus-producing cell.
Combining morphologicalahd immunological observations a structural model
of HIV is proposed.
TR22 Interaction of Human Immunodeficiency Virus with Neural Cells Isolated from the
Human Fetus Nervous System
BRIAN WIGDAHL*. Rhonda A. Guyton*, Luzi A. Pfenninger*, and Prem S. Sarin**, *The
Pennsylvania State University College of Medicine, Hershey, PA, USA,** Laboratory of
Tumor Cell Biology, National Cancer Institute, Bethesda, MD, USA.
Human immunodeficiency virus (HIV), the primary etiological agent of acquired
immunodeficiency syndrome (AIDS), has been implicated in the causation AfDS-associated
neurological dysfunction and may be responsible for an increasing number of neonatal
immunologic and neurologic disorders. However, as yet there is no model system available to
investigate the interaction of HIV with the developing human nervous system in vitro. To
examine the intracellular events associated with HTV infection of the human fetus nervous
system we infected cells obtained by enzymatic dissociation of aborted human fetus dorsal root
ganglia and their attached spinal roots and nerves. The expression of the HIV gag gene
protein products (pi 7 and p24) was detected in a subpopulation of cells with a non-neuronal
morphology, reaching a maximum within 3 days. Although 70% of the non-neuronal neural
cells were pl7- and p24-positive 3 days after infection, a majority of the cell population
survived acute HIV infection, with the expression of pI7 and p24 decreasing below the limit of
detection by 12 days postinfection. Additional studies have demonstrated that the number of
HIV-pl7/24 nonneuronal neural cells detected 3 days postinfection decreased in direct
correlation with increasing time of in vitro maintenance of the human fetus neural cells prior to
HTV infection. These results suggest that in vitro maintenance of the neural cells after isolation
from human fetus DRG and adjacent spinal root and peripheral nerves may result in plasma
membrane alterations that interfere with HTV attachment and/or penetration or an intracellular
physiological change that impairs at least the expression of the gag gene protein products pl7
and p24 after infection or possibly a combination of both. This system may prove useful for
examining the neuropathogenesis of HTV infection of the developing human nervous system .
TP25 ^n Assay for HIV-p24 Antigen With Chemiluminescence
Detection Using Antibodies Against Synthetic Oligo-
peptide Fragments of the Major Core Protein
HARTMUT R0K0S*. A.GADOW*, R.KUNZE**, B.SCHWARTLANDER** ,
B.FRENZEL***, W.RONSPECK*** , 'Research Laboratory, Henning Berlin,
Berlin, Germany, **Robert Koch-Institut , Berlin, ***Biochrom,
Berlin.
Antibodies against 2 separate epitopes of p24, the major core
protein of the human immunodeficiency virus were obtained in sheep
on immunisation with short synthetic oligopeptides. After purifi-
cation by affinity chromatography, one antibody is coupled to
polysterene beads as solid phase, the other to a diacyl hydrazide
as chemiluminescence label. This Lumitest sandwich-type immuno-
assay requires a one-step incubation at room temperature over-
night. The assay protocol includes pretreatement with sodium dode-
cyl sulfate for denaturation, thus minimizing risks in handling
infectious material and reducing interference from human anti-
bodies against p24, present in many sera, often leading to false
results in other antigen assays.
In 9 out of 24 follow-ups of male homosexuals taking part in a
prospective study, p24 antigen was detected up to 6 months prior
to seroconversion. In serial samples of 1 additional patient who
showed after seroconversion persistently very low antibody titers,
p24 antigen was found always.
The assay can be used to determine LAV-2 in cell culture super-
natants, too, as these antibodies are highly cross-reactive with
the p24 protein of this variant.
TP23 Glycosylat Ion Inhibitors Block the Expression and Function of HIV
Glycoproteins and Their Receptor(s)
HERBERT A. BLOJJGH* ■ R. PAUWELS**, E. DE CLERCQ**, J. DESMYTER**, J.
COGNIAUx"*, W. KENEALY***, 'University of Pennsylvania School of Medicine,
Philadelphia, PA, "Kathol leke Unlversltelt Leuven, Belgium, ***lnstltut
Pasteur du Brabant. Brussels, ****E.I. DuPont Central Res., Wilmington, DE
The Interaction of envelope glycoproteins of HIV (gpiio and gp41) and
their receptor(s) Is responsible for viral entry and cell fusion;
2-deoxy-D-glucose (2-dGlc) blocks the expression of HIV glycoproteins.
Uninfected MT-4 or CEM cells were treated with 5-10 mm 2DGIC for 24-96 hrs.
One-half were Infected with HTLV3_b; an untreated group of cells were simi-
larly Infected. Fresh medium (with or without 2-dGlc) was added and the
cells Incubated for an additional 72 hrs. Triton X-100-lysed cells or
glutaraldehyde-f Ixed cell surfaces were Interacted with polyclonal antibo-
dies against HIV-recomblnant proteins (p ENV9, pENV14, pENV14, pENV120,
PENV7).. Alternatively, uninfected cells were Interacted with
monoclonal antibodies against T4- J*A- T8 and th8 IL- 2 receptor. Bound
antibodies were quantified with [125l ]-F(ab' )2 fragments of antlmouse IgG or
[125l ]-ant Igoat IgG (rabbits). By trypan blue exclusion and light
microscopy, 2-dGlc-treated cells were protected against CPE by HIV.
Treatment of MT-4 cells with 2-dGlc produced a 35% decrease In the binding
of 0KT4A (to the putative receptor) vs controls. Using [3H]-Rlcln communis
or gal oxidase technique with LI3hb4, we observed a 35-60% decrease In
binding or labelling of gp41 or gp110 In dGlc-treated-cel Is; this was con-
firmed by P.A.G.E. or Western Blots. These studies support the view that
glycosylat Ion Inhibitors block the Initial steps of HIV-lnfect Ion and should
prove useful In the treatment of AIDS.
TP9fi Inhibition of HIV reverse .transcriptase activity by culture fluids
from HIV-infected, Epstein-Barr virus-transformed cells.
MICHEL TREMBLAY, M.A. WAINBERG, Lady Davis Institute for Medical Research,
Jewish General Hospital, Montreal, Canada.
Most individuals who are infected by HIV are also sera-positive for Epstein-
Barr virus (EBV) and it is important to understand potential relationships
between these two viruses. We used EBV progeny from the simian B-95-8 cell
line to infect and transform unstimulated cord blood lymphocytes. Following
the establishment of EBV-trans formed B cell lines, these cells were super-
infected with the HTLV-IIIb strain of HIV. These cultures were examined
periodically for viral reverse transcriptase activity, by means of a poly-
ethylene glycol precipitation procedure, and for the presence of intra-cellular
viral antigens, by an indirect immunofluorescence assay using mouse monoclonal
antibodies against the HIV proteins pl5 and p24 (kindly supplied by Dr. R.C.
Gallo). By 17 days after infection about 15% of cells had become positive for
HIV antigens, yet no RT activity could be detected in the culture fluids. To
investigate this further, aliquots of viral pellets from the HIV-infected,
EBV-transformed cells were mixed with equal volumes of similar material ob-
tained from H-9 cells, continuously infected with HTLV-IIIb- rt activity of
the latter preparations was inhibited by 88% when the assays were performed
immediately and by 95% if the samples were allowed to co-incubate for 3 hr at
37°C. These data suggest that EBV or EBV infection may have an inhibitory
effect on HIV RT activity.
Supported by Health and Welfare Canada and by the Medical Research Council of
Canada.
66
TUESDAY, JUNE 2
TR27
Kinetics of HIV infection after IV exposure Co blood from an
AIDS patients.
SOPHIE MATHERON*,D. DORMONT**,M. A. REY*,F. BRUN-VEZINET*, F. BOUSSIN**, A.G.
SAIMOT*,*Hopital Claude Bernard, Paris, **CRSSA, Clamart, France.
A 40 year old man was contaminated by IV injection (10 ml) of an AIDS
patient's blood, from which HIV had been isolated. He developed clinical
symptoms of primary HIV infeccion 23 weeks later. His virological status
follow up was assessed by ELISA , Western Blot (WB) and PBL cultures (PBLC).
Weeks PBLC
ELISA
*>0.30
WESTERN BLOT
25 41 55 110
Clinical symptoms-^23
8
ND
- 0.016
18
+
ND
19
+
ND
23
+
- 0.133
24
ND
- 0.103
25
ND
- 0.221
28
+
+ 0.49
29
ND
+ 0.45
32
ND
+ 0.58
33
ND
+ 0.907
/- -
+/■
/- -
+/
/- -
+
/- -
+
Our data show
positive WB at the
after contamination : 1) positive PBLC at W18 ; 2)
time of clinical symptoms (W23) ; 3) Positive ELISA at
W28. On W33, the patient had nor ARC nor AIDS.
jpqn Synergism and Antagonism In Vitro Among Various Antiviral Drugs
In the Treatment of HIV Infections.
MARKUS W. VOGT*. TING-CHAO CHOU**, KEVAN L. HARTSHORN*, LESLIE A. COLMAN* ,
DAVID A. NEUMEYER*, MARTIN S. HIRSCH*, * Massachusetts General Hospital,
Harvard Medical School, Boston; **Memorial Sloan Kettering Cancer Center,
New York
An effective therapy is urgently needed for individuals infected with the
Human Immunodeficiency Virus (HIV) Combined therapy with two antiviral
drugs that show in vitro or in vivo activity against HIV offer the
potential benefits of enhanced antiviral activity, reduced toxicity and
prevention of resistance.
We thus evaluated various combinations (Table) in vitro utilizing
different cell culture systems including peripheral blood lymphocytes, H9
cells and a human monocyte line (BT4) . HIV replication was assessed by
reverse transcriptase activity, indirect immunofluorescence, p24 capture
immunoassay and virus yield. Drug interactions were mathematically
evaluated by the median effect principle and the isobologram technique.
Drue Combination Effect
Phosphonoformate + Recombinant Interferon alpha A Synergy
Azidothymidine + Recombinant Interferon alpha A Synergy
Azidothymidine + Ribavirin Antagonism
Azidothymidine + Lymphoblastoid Interferon Synergy
Ribavirin + Phosphonoformate Synergy
Ribavirin's antagonism of AZT resulted from phosphorylation inhibition.
Other combinations are under study. Drug interactions should be considered
when planning clinical trials of anti-HIV combinations.
TP28 ft ^Pid' Simple and Economical Screening Assay for Antibodies to
the Human Immunodeficiency virus (HIV).
J.R. CARLSON*, S.CJ. MERTFNS*, q.h. YEE* , M. JENNINGS* , ^M.B. GARDNER*, E.J.
WATSON-WILLIAMS , J. GHR^YEB * AND R.J. BIGGAR***. *Uruv. of
California, Davis, CA., Centocor, Inc., Malvern, PA, Natl. Cancer
Inst., Bethesda, MD.
A dot enzyme immunoassay for the detection of anti-HIV antibodies was
developed using an antigen derived from a recombinant HIV envelop protein,
peptide 121 (Centocore, Inc., Malvern, PA). The assay can be performed in
30 minutes with a qualitative endpoint that does not require expensive
instrumentation. Antigen was spotted onto opaque, high-impact polystyrene
cards. The test was performed by adding human serum, plasma, lysed whole
blood or saliva, alkaline phosphatase-conjugated goat anti-human IgG and
substrate to the antigen spot with washing between reagents. A bright blue
color developed on the antigen spot for positive specimens, and negative
samples yielded no color. Correlations of results with western blot (WB)
were as follows:
Specimens Source No. Tested/No. WBPositive %Correlation
Serum/Plasma USA 118/60 99.2
Serum/Plasma Africa » 103/50 98.6
Whole, lysed
blood USA 115/50 98.3
Saliva USA 20/8 100
This assay may be useful for anti-HIV antibody screening for blood
donors, epidemiologic studies or initial clinical assessment in remote
areas of the world.
TP31 Regulation of mRNA Accumulation by a Human Immunodeficiency Virus
Trans- Activator Protein.
DANIEL CAPON, A. JAKOBOVITZ, D. SMITH, M. M.UESING, Genentech, Inc., So. San
Francisco, CA, USA
HIV LTR-directed expression is markedly stimulated in trans by coexpression
of a region of the HIV genome encoding a portion of the tat reading frame.
Transient expression assay analysis reveals that trans-activation of
LTR-directed expression results primarily from an increase in mRNA accumula-
tion. Deletion analysis of the LTR indicates that upstream enhancer elements
are dispensible for trans-activation, while sequences 3' of the RNA start
site displaying strict orientation and position dependence are required.
These sequences, contained in the 5' leader of all HIV transcripts, form a
stable stem-loop structure with twofold symmetry in the cognate mRNA.
Analysis of mutations in the trans-acting region demonstrates that the
trans-activator is the protein product of the tat gene. This protein has
been identified biochemically in HIV-infected and transfected cells as an
Mr 15,000 polypeptide. We discuss possible mechanisms whereby the
interaction of plStat with the dyad element promotes the accumulation of
LTR-directed mRNA.
TP2Q Attempts to Produce a Progressive Immune Deficiency and
Encephalopathy in Nonhuman Primates with the Human Immunodeficiency
Viruses. R. YANAGIHARA, D.H. ASHER, A.V. WOLFF, C.J. GIBBS, JR., D.C
GAJDUSEK, et al. National Institutes of Health, Bethesda, Md.
Of the multiple nonhuman primate species we have Investigated to date,
Including African green and marmoset monkeys, only chimpanzees (Pan
troglodytes) and rhesus monkeys (Macaca mulatta ) are susceptible to
experimental Infection with the human Immunodeficiency viruses (HIV).
Chimpanzees develop persistent Infection following Intravenous and/or
Intracerebral inoculation with strains of HIV, with brain tissues and plasma
from AIDS patients, or with blood from experimentally infected chimpanzees.
None of 24 HIV-infected chimpanzees monitored for nearly three years has
developed a wasting Illness, neoplasm or encephalopathy, despite persistent
vlremla. Signs of an Immunodeficiency syndrome, as evidenced by opportunistic
Infections and abnormalities in T-cell suhpopula tlons and in in vitro
lymphoprollferatlve responses to mitogens, have not occurred. However, a
chimpanzee, Inoculated intravenously with whole blood from an HTLV-IIIB
infected animal, has, on routine skin testing for tuberculosis, become
tuberculin-reactive 23 months postinocula tlon. Mycobacterium avlum-
ln tracellulare was Isolated from gastric washings, but no pulmonary or
gastrointestinal focus of infection was found. The animal has developed
inguinal lymphadenopathy, but Is otherwise clinically well. This
mycobacterial Infection may represent the first Indication of an underlying
immunodeficiency, and studies to determine the extent of infection are
underway.
TP32 Reactivity of HIV and LAV II Positive Sera with a Synthetic
Peptide Antigen in the p34 Nuclease/Integrase Protein.
RAYMOND L. HOUGHTON, T. SMITH, K. SHRIVER, J. McCLURE, P.C. SU, and W.L.
C0SAND, Genetic Systems Corporation, Seattle, WA, USA.
A synthetic peptide antigen has been prepared which represents a
conserved epitope in the 34kD (Nuclease/Integrase) protein present in HIV.
The peptide designated 124 was tested for its reactivity with a panel of 46
sera (35 HIV positive and 11 HIV negative). As compared to the Genetic
Systems whole virus assay (LAV-EIA) for detection of antibody to HIV,
peptide 124 showed a specificity of 100% and a sensitivity of 97%. Peptide
124 was tested against an additional panel of sera of African origin. Of 61
African sera (28 positive, 25 negative, and 8 atypical by Western Blot),
96.4% (27/28) of positives, 0% (0/25) of negatives and 25% (2/8) of atypicals
were positive. In addition, since peptide 124 represents a conserved antigenic
epitope amongst AIDS viruses, we analyzed its reactivity with 10 sera that were
characterized as positive for core and envelope antigens of LAV II by Western
Blot. As expected, 100% (10/10) reacted in an EIA using LAV II as antigen, 70%
(7/10) were positive with our standard LAV-EIA and 80% (8/10) using the single
peptide 124 as antigen. These results are consistent with cross-reactions
observed between the p34 proteins of HIV and LAV II in Western Blot analysis.
In addition, no reactivity of peptide 124 was observed with HTLV I positive
sera. These data indicate that peptide 124 will provide an additional tool
in peptide based assays for HIV antibody detection.
67
TUESDAY, JUNE 2
tooq Replicative properties of transsectional and longitudinal HIV iso-
lates from serum HIV-antigen positive and negative individuals
MATHIJS TERSMETTE, R.E.Y. DE GOEDE, J.M.A. LANGE*. J. GOUDSMIT*, J.G. HUISMAN
AND F. MIEDEMA, Central Lab. Netherl.Red Cross Blood Transfusion Service, in-
corporating the Lab. of Exp. and Clin. Immunol, of the Univ. of Amsterdam,
*Dept. of Virol, of the Univ. of Amsterdam, Amsterdam, The Netherlands
Virus replication in co-cultures of lymphocytes of seropositive individuals
and lymphocytes of healthy blood donors selected for susceptibility to HIV in-
fection was quantitated by RT activity and a HIV p24 antigen capture assay.
Virus was detected in 100% of AIDS and ARC patients (n»16) , 84% of LAS patients
(n-6) and 71% of asymptomatic individuals (n=38). Detection by antigen capture
assay was considerably more rapid than by RT assay, especially in asymptomatics
(mean: 14.0 vs. 28.1 days). HIV isolates obtained from lymphocytes collected
over a two year follow-up period in six persons, showed similar culture charac-
teristics within one Individual. No clearcut differences were observed between
serum HIV antigen-positive and -negative asymptomatic persons. Syncytia were
detected In 40% of AIDS/ARC patients, 20% of LAS patients and 20% of asympto-
matics. 8/9 Isolates that induced CPE in donor lymphocytes could be transmitted
to H9, in contrast to 0/11 non-CPE inducing HIV isolates. One asymptomatic indi-
vidual with in-vitro CPE-inducing HIV developed AIDS 16 months after first virus
isolation. These data may Imply that the probability of developing AIDS may be
partly determined by the syncytium Inducing capability of the HIV strain present
in an infected individual.
TDOg Biologic and Molecular Characterization of Human Immunodeficiency
Virus Isolated from Autopsled Brain of a Dementia Patient.
RITA ANAND*, A. SRINIVASAN*, J. MOORE*, P. LUCIW**, S. DANDEKAR**, *Centers
for Disease Control, Atlanta, GA 30333, **University of California, Davis,
CA
To study the biologic and molecular nature of human Immunodeficiency
virus (HIV) infecting patients with neurologic disorders, we isolated
HIVg£ from the autopsled brain tissue of a 57-year-old man who died of
progressive dementing illness. Isolated virus was identified as HIV by
antigenic crossreactivity and nucleic acid hybridization to HIV-apecific
antibodies and DNA probes. We studied the expression of viral proteins by
immunoprecipitation analysis of infected cells. To further determine its
biologic specificities, HIV3R, was characterized for replication and
extent of cytopathicity to 0KT4+ cells and compared with a standard HIV
(HIV451) isolate used In our laboratory. We observed that seven days
after infection HIVgR replicated 10-fold less than HIV451 but was
essentially as cytopathic as HIV451 to 0KT4+ cells. We examined the
genetic specificites of HlVg^ by molecularly cloning it and mapping it by
restriction enzymes. The restriction enzyme sites, Sac 1, Pvu II, Eco RV,
Xho I, appeared conserved in the LTR of this neurologic isolate as in some
of the previously reported HIV isolates, whereas some restriction enzyme
sites, Bam HI, Ava I, Sal I, were not present throughout the genome. For
detailed analysis of the conserved and variable domains of HIVgR, we
subcloned a 3.5 Kb fragment from 3' half of the genome encompassing env
gene. The salient features of the nucleotide sequence analysis of HIVjjr
with special reference to gp41 will be elaborated.
TP34 Comparisons of antigen detection and virus cultivation
in HIV-1-infected patients
BERND ZORR.K.O.HABERMEHL, Inst. of Clin. and Exper . Vi rol ogy, Free
University of Berlin, Hi ndenburgdamm 27, 1000 Berlin 45, Germany
All of 12 patients selected for an AZT-study gave before onset
of treatment a positive HIV-1-result by lymphocyte co-
cultivation in tissue culture. Using HIV-1-ELISA for antigen
detection (duPont) 10 patients were significant reactive, 2
patients with ARC were negative. In H I V- 1 -i nf ected children the
ELISA-antigen-detection is independent from the amount of HI V-
neutralizing antibodies. - The antigen ELISA shows a good
sensitivity with a detection limit of 20 pg/ml serum. In
comparison to a sensitive plaque titration assay on MT 4-cells
one ng corresponds to 7x10 PFU/ml .
TR37
HIV-1 and LAV-2/HIV-2 : serological cross-reactivities.
Marie-Christine DAZZA*, M.A.REY*, S.GADELLE**, J.J.MADJAR***,M.HARZIC*,
F.BRUN-VEZINET*. Laboratoire de virologie, Hopital Claude Bernard, Paris*. Diagnos-
tics Pasteur, Paris**. Universite Alexis Carrel, lyon ***. France.
A Human Immunodeficiency retrovirus named Lymphadenopathy-Associated-Virus
type 2, LAV-2/HIV-2 was isolated in 1986 from two west african patients with
AIDS. HIV-1 and HIV-2 exhibited cross-reactivity restricted to the gag and pol
gene products. No cross reactivity was demonstrated between HIV-1 (gp110, gp41
and their precursor gp160) and HIV-2 (gp130-105, gp41 -36) envelope glycoproteins.
HIV-2 antibodies were detected by Elisa using HIV-2 purified viral antigen prepared
from the CEM-infected cell line and control antigen. The diagnosis of HIV-2 infec-
tion was demonstrated by the presence of antibodies to the HIV-2 glycoproteins
by Western Blot analysis. HIV-1 antibodies were detected by Elavia and LAV Blot
(Diagnostics Pasteur). 41 HIV-2 positive sera were studied by HIV-1 Elavia : 18/41
sera were completely negative : 10/13 collected from AIDS patients, 7/25 from
asymptomatic subjects (AS) and 1/3 from ARC. 179 HIV-1 positive sera were
tested by HIV-2 Elisa. 37/179 (21%) were positive or border line : 3/42 from AIDS
patients, 20/63 from ARC and 14/74 from AS. In AS, 81% of HIV-1 positive sera
were negative by HIV-2 -Elisa whereas 28% of HIV-2 positive sera were negative
by HIV-1 Elisa (p < 10 ). Moreover these data demonstrated that cross-reactivity
between HIV-1 and HIV-2 does not allow to pick up HIV-2 seropositivity using
HIV-1 Elisa in HIV-2 AIDS patients (76% HIV-1 negative) as in HIV-2 AS (28%
HIV-1 negative). Specific HIV-2 assays are needed to screen blood donations as to
perform HIV-2 seroepidemiological surveys.
TP35
HIV tat/LTR-mediated Expression of Heterologous Genes in Transient Assays
B.Q. FERGUSON. L.L. STREHL. L.T. BACHELER. M.M. RAYNER. R. RUGER AND
S.R. PETTEWAY. E. I. Du Pont de Nemours. Medical Products Department. Wilmington.
DE.
We have used transient expression assays to study the trans-activation of
heterologous genes under the control of the HIV-IIIB LTR. Reporter genes included g.
coli p-galactosidase, chloramphenicol acetyl transferase, and human IL-2. Expression
of the reporter gene was monitored in cell lines from several species in the presence
and absence of the following viral regulatory genes: HIV tat-Ill (under SV40 early
transcriptional control), human CMV IE-I, pseudorabies virus IE. and human
adenovirus-5 El A. HIV tat efficiently induced LTR-mediated expression in HeLa cells
0400-fold) but was markedly less efficient in each of the nonhuman cell lines tested
(2 to 30-fold induction). These results suggest that a major component of Uit
function is species specific. In HeLa cells expression of the reporter gene under
tat-activated LTR control was 40-fold greater than the level expressed under SV40
early promoter control. CMV IE-I significantly induced HIV LTR expression
(-I0-fold). whereas EIA had no effect on LTR expression. These results suggest that
superinfection by CMV of a latently HIV-infected lymphocyte could result in
activation of the HIV genome.
TDQQ Virologie Endpoints in Antiretroviral Chemotherapy Trails
■'■"" WADE P. PARKS', E.S. PARKS*. M. FISCHL*. R. MAKUCH", M.
LEUTHER**, J. P. ATT.AIN*", "University of Miami School of Medicine, Miami,
FL, **Yale University School of Medicine, New Haven, CT, ***Abbott
Laboratories, North Chicago, IL.
Virologie measures may provide useful adjuncts to clinical or immunologic
endpoints to assess the efficacy of che mo therapeu t ic agents in
antiretroviral trials. Such nonclinical endpoints may be especially
important in asymptomatic or mildly symptomatic patients where clinical
endpoints are infrequent or will require prolonged observation. Two
independent virologie measures, virus recovery from peripheral blood
leukocytes (PBL) and p24 antigen detection in plasma or serum, have now
been evaluated in placebo-controlled trials of 3 '-Azido-3'-deoxythymidine
(AZT) and Ribavirin which involved a total of 72 patients. Virus recovery
was positive 92% of the total sample; detection of virus in cultures of
PBL's by a supernatant p24 antigen radioimmunoassay (RIA) varied inversely
with the absolute T4 lymphocyte count. Higher levels of T4 lymphocytes were
associated with longer time required for detection of p24 in supernatant
fluids. Direct testing of p24 antigen in serum was positive in 15/34 (44%)
LAS patients, 10/26 (69%) ARC patients and 10/12 (63%) AIDS patients
suggesting a correlation of p24 antigen positively with both clinical state
and T4 counts. In addition p24 antigen was inversely correlated to the
level of p24 antibody -measured either by a competitive ELISA assay using
rDNA antigen or I-virion p24 RIA. Treatment with AZT produced
significant diminution in virus recovery within one month of treatment and
there was a concomitant and significant decline in p24 antigen levels in
patients receiving AZT, but not placebo patients. The correlation of these
laboratory endpoints with clinical endpoints suggests that they will be
useful surrogates for efficacy studies in future antiretroviral drug
trials.
68
TUESDAY, JUNE 2
JP39 NEUTRALIZING ANTIBODIES IN HUMAN SERA BIND TO GENETICALLY
ENGINEERED NON-GLYCOSYLATED GP120 PRODUCED IN YEAST. K. STEIHER
J. STEPHANS, M. SHUH and E. MILLER. Chiron Corporation, Emeryville,
California, U.S.A.
Affinity columns of non-glycosylated genetically engineered poly-
peptides produced in yeast from defined regions of the HIV-SF2 envelope
gene were used to fractionate HIV antibody-positive sera. Pooled sera
from nine HIV seropositive blood donors were fractionated on these
columns and the affinity purified antibodies were tested for neutraliza-
tion of HIV-SF2. No neutralizing activity bound to env-5, a polypeptide
in the amino terminal one-third of gp41, composed of amino acids 557-677
of the env gene product. In contrast, env-2, a recombinant polypeptide
corresponding to amino acids 28-491 of env, bound a significant propor-
tion of the neutralizing activity In this serum pool. There were also
neutralizing antibodies that did not bind to columns of env-2. When env-
2 -specif ic antibodies were fractionated on columns of env-1 , a polypep-
tide representing amino acids 28-277 of env , the majority of the
neutralizing activity did not bind. However, there was some neutralizing
activity in the env-1-specif ic antibody fraction demonstrating that
antibodies able to neutralize HIV-SF2 can be specific for epitopes in
the amino-terrainal half of gp!20. However, this activity represented
only a minor fraction of the total env-2-specif ic neutralizing
antibodies. When the sera from the pool were fractionated individually
-on env-2 columns , all showed evidence of env-2 specific neutralizing
antibodies. We are currently assaying env-2 specific antibodies for
neutralization of other HIV isolates and attempting to identify the
target antigens for unbound HIV neutralizing antibodies.
yn in An Old Disease Meets a New Disease: Tuberculosis and the Acquired
Immunodeficiency Syndrome in New York. City
SUSAN B. MANUFF**, R.L. STONEBURNER*, J. A. MILBERG*, G.tf. CAUTHEN**,
S. SCHULTZ*, A.B. BLOCH**, et al. , **New York City Department of Health, New
York, N.Y., **Centers for Disease Control, Atlanta, Ga.
New York City (NYC) reported 1,843 tuberculosis (TB) cases in 1985, a 16%
increase over the average annual number of 1,583 cases reported from iy79
through iy84. This included increases of 32% in blacks and 19% in Hispanics,
groups with an increased incidence of the acquired immunodeficiency syndrome
(AIDS). To determine if the increase in TB was AiDS-related, we matched the
NYC TB and AIDS registries. The 266 patients common to both registries
(TB/AIDS patients) comprised 2.3% of the 11,640 TB patients reported from 1979
through 1985, and 4.8% of the 5,545 AIDS patients diagnosed from 1981 through
1985. The TB/AIDS patients included 23U (86%) men and 36 (14%) women; 49 (18%)
whites, 140 (53%) blacks, and 77 (29%) Hispanics; 81 (30%) homosexual or
bisexual men, 132 (50%) intravenous drug abusers (IVDAs), 22 (8%) patients
with both risk factors, and 31 (12%) persons with other risks for AIDS. In 175
(66%) the two diagnoses were made within a six month time span. Compared to TB
patients without AIDS, TB/AIDS patients were more likely to have extra-
pulmonary TB (46% vs. 20%, p<.001), two or more disease sites (25% vs. 4%,
p<.001), a negative tuberculin skin test (26% vs. 7%, p<.001), and were less
likely to have cavitary disease on chest radiograph (8% vs. 24%, p<.001).
Compared to AIDS patients without TB, TB/AIDS patients were more often black
(53% vs. 30%, p<.001), Hispanic (29% vs. 23%, p<.05), and IVDAs (50% vs. 28%,
p< .001 ) . These data suggest that AIDS is responsible for some of the increase
in TB in NYC, that certain presentations of TB are associated with an enhanced
risk, for AIDS, and that some AIDS patients are at higher risk for TB.
TP40 Prevalence, Incidence and Risk Factors of HIV-infection among Drug
Addicts 1n Amsterdam
JOHANNA A.R. VWiPENHOEK*, R.A. COUTINHO*, A.W. ZADELHOFF*. H.J. A. VAN HAAS*
TRECHT*. J. GOUDSMIT**, Municipal Health Service, and **Academic Medical
Centre, Amsterdam, The Netherlands
In December 1985 an epidemiological study among drug addicts in Amsterdam
was initiated. Recruitment takes place at methadone posts and the STD^clinic
for drug using prostitutes. As of 15th October 1986, 243 drug users had entered
the study of whom 80% were IV users. Prostitution was reported by 88% of 125
women and 20% of 118 men. Female prostitutes practised mainly vaginal and oro*
genital intercourse and 9\% reported frequent use of condoms. Male prostitutes
practised mainly oro-genital and manual contact. At entry into the study
66/243 (27%) were anfUHIV seropositive; 64/66 were IV users and 2/66 male
homosexuals. Antibodies to HTLV^I were found in 4/243 (1.6%), HBV-markers In
173/243 (73%) and syphilis markers in 2-1/243 (9%). HIV-seropositives reported
significantly more often enlarged lymphnodes, coughing and herpes zoster. Risk
factors significantly associated with HlV-'seropositlvity were: duration of IV
drug use, frequent sharing of needles/syringes, West-German nationality and
smoking of heroin ("protective"). No association was found with sex, age,
prostitution and methadone use. Significant changes in lifestyle were found
among participants towards a less risky behaviour (smaller proportion report-
ing daily IV use and using often the same needle/syringe; Increasing propor-
tion using needle/syringe exchange programme). However, among 50 HlV-seronega-
tlves followed up, 4 HIV-seroconvers1ons have (attack-rate 15% after 240 days),
indicating that till now the prevention measures taken in Amsterdam have had
only a limited Influence on the speed with which HIV spreads among the drug
users.
TP43 Natural History of HIV Infection in Spouses of AIDS Patients
WARREN D. JOHNSON, JR.*, M.E. STANBACK*, M-M. DESCHAMPS**,
J. SANTIL**, M. JEAN-CHARLES**, J.W. PAPE*, Cornell University Medical College,
N.Y., N.Y.*, GHESKI0, Port-au-Prince , Haiti**.
332 spouses/regular sex partners (M=53, F=279) of AIDS patients have been
followed at our clinic in Port-au-Prince, Haiti since September 1983.
Seropositivity for HIV (wv, p24, gpl20) was 53% for females (n=148) and 55% for
males (n=29) at the time of their initial visit. Ten percent of seropositive
(SP) males and 12% of SP females had either AIDS or ARC on study entry. The
seropositive asymptomatic female spouses were followed for a mean period of 15
months and male spouses were followed for a mean of 17 months (range 2-36
months for both groups) .
The proportion of those followed who developed either AIDS or ARC was
calculated using the Kaplan-Meier survival method. The percentages of initially
asymptomatic seropositive females with either AIDS or ARC at 3, 6, 12 and 24
months of follow-up were 3, 5, 10 and 26%, respectively. The percentages of
HIV-seropositive males with either AIDS or ARC at 3, 6, 12 and 24 months were
4, 13, 19 and 27%, respectively. Forty percent of the SP males and 25% of the
SP females who developed either AIDS or ARC died within 24 months of entry.
In addition, during a mean follow-up period of 14 months four initially sero-
negative asymptomatic spouses (3F, 1M) developed either AIDS or ARC.
To date, 8/29 (28%) SP male spouses and 34/148 (23%) SP female spouses have
developed either AIDS or ARC. Asymptomatic SP spouses have developed either
AIDS or ARC at a continuous rate of 1% per month over a calculated two year
follow-up period.
TR41
T.B0WRY
talet, *
gen , Den
A newl
in whole
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blood f i
found re
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Pre va
H.D.P
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mark,
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HIV a
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348 in-
TR44
of the examined Kenyan
d immunob 1 o t t ing , repre
ce limits: 0.00-0.93%).
90% of healthy children
enereal out-patients, 2
in-patients, represent
r the low prevalence of
PGL not associated wit
ults previously present
s had antibodies to HIV by both
senting a prevalence of 0.17% (95%
PGL was found in 25% of healthy
, 34% of non-venereal out-patients
1% of adult in-patients, and 50% of
ing a 44% over-all prevalence of
HIV antibodies nor the high preva-
il HIV infection is in accordance
ed from rural districts in Kenya.
AIDS-Related Immune Thrombocytopenia: HIV Expression
and Progression to AIDS. DONALD I. ABRAMS , D.W. FEIGA1
AND J. A. LEVY, San Francisco General Hospital, University of
California, San Francisco, San Francisco, California, U.S.A.
Thirty-five
thrombocytope
between 1982
390/mm3. Att
positive res
positivity (
healthy serop
pts with AIDS
(Levy and Shi
pt was trea
therapy for 2
positive at i
ITP without t
AIDS. Of th
(28.5%) have
44) after
normalization
intervention
pts. These
infectious
compared to o
progression t
seropositive h
nia (ITP) at
and 1984. Th
empts to isolate
ults in only
1556) is signif
ositives and the
and ARC employi
nabulcuro, J. In
ted with predn
yrs at the time
nitial presentat
herapy. Three c
entire 35 me
progressed to AI
ITP diagnosis,
of platelet
antedated the
data demonstrat
irus expression
thers; this find
o frank AIDS
omosexual men wit
initial presentati
eir mean T-helper
HIV from 13 patie
2 cases. This
icantly lower than
7556-90% culture po
ng identical cell c
f.Dis. 152:734, 198
isone and danazol
of culture. The o
ion in 1984 and rem
ulture negative pa
mber initial ITP
DS at a mean of 30
Five have expi
count in the absen
AIDS diagnosis in
an unusually 1
in this HIV-infec
ing does not appear
h isolated immune
on were diagnosed
cell number was
nts (pts) yielded
ate of culture
the 50% yield in
sitivity seen in
ulture techniques
5) . One positive
but had been off
ther pt was virus
ains stable with
tients developed
cohort, ten pts
months (range 16-
red . Spontaneous
ce of therapeutic
5 of 10 evolving
ow prevalence of
ted pt population
to influence the
69
TUESDAY, JUNE 2
xpjc Anti-HIV and Hepatitis B Markers in Canadian Volunteer Blood
Donors .
VITO SCALIA, J. REEVES, B.K. BUCHNER, R.Y. HARDING, Canadian Red Cross,
National Reference Laboratory, Hepatitis Section, Toronto, Canada.
This study was undertaken to compare the association of exposure to Human
Immunodeficiency Virus (HIV) with that of Hepatitis B Virus (HBV) in a
population of volunteer blood donors. Sera from donors confirmed positive
for anti-HIV by Western blot, negative for anti-HIV, and those confirmed
positive for HBsAg (hepatitis B surface antigen) by neutralization with
specific antibody were examined.
Comparison of the results for the anti-HIV positive and negative donors
indicate a greater prevalence of HBsAg in the anti-HIV positive donor
population than in the anti-HIV negative population.
Although anti-HIV testing was not initiated until November 1985, it was
possible retrospectively to determine the anti-HIV status in HBsAg positive
donors identified in 1985. The prevalence of anti-HIV in HBsAg positive
donors was higher in 1986 than in 1985, but the difference was not significant
(p < 0.05) .
The observations of this study may indicate a trend towards a positive
significant correlation of anti-HIV in HBsAg positive donors. If HIV
infections increase as predicted, our results might indicate that the
prevalence of HBsAg will also increase.
TP48 Retroviral Epidemiology in Jamaica, West Indies: the Introduction
" of HIV into an HTLV-I Endemic Island.
EDWARD L. MURPHY*, P. FIGUEROA**, W.N. GIBBS***, B. BAIN***, L. LA GRENADE***,
W.A. BLATTNER*, et al . , *National Cancer Institute, Bethesda, HD, "Ministry
of Health, Kingston, Jamaica, ***University of the West Indies, Kingston,
Jamaica.
Jamaica has a low incidence of AIDS (11 reported cases thus far on an island
of 2 million) despite much trade and travel with the U.S.A. We therefore
decided to investigate HIV seroprevalence in several large cohorts assembled
for our studies of HTLV-I epidemiology. Sera that had been stored at -80 C
were tested for antibodies to HIV using an ELISA assay (ENI). Reactive sera
were confirmed by P24 and GP120 radioimmunoassays or by Western Blot. None of
4000 healthy food service workers were seropositive. This cohort is most repre-
sentative of the general population, and has an HTLV-I seroprevalence of 5.8 %.
Three of 2400 patients from two sexually-transmitted disease clinics were HIV
seropositive; the clinic located in the tourist area did not have a higher
prevalence. Of 125 homosexual and bisexual men, 10 % had anti-HIV antibodies,
and sexual contact with Americans rather than Dromiscuity per se appeared to
be associated with increased risk of infection. 10 % of the same cohort were
HTLV-I positive, but only one man was seropositive for both viruses.
In conclusion, HIV seroprevalence is low in Jamaica, which is consistent
with the low number of reported cases of AIDS. HTLV-I infection is endemic in
Jamaica, while HIV has a very limited epidemiologic pattern suggesting limited
introduction into groups having sexual contact with Americans. Surveillance
of the local high-risk groups, combined with education, may help to limit
introduction. Finally, medical evaluation of the high-risk groups will also
provide valuable data on the consequences of infection with both retroviruses.
JP46 Understanding the Natural History of AIDS in West-
Germany. A Prospective Study in Homosexual Men.
HANS JAEGER* , C . MAYR* , L . GORTLER* * , F . DEINHARDT* * , L . ZIEGLER-HEIT-
BROCK** ,G.RIETHMUELLER** , *AIDS Study Group, Schwabinger Kranken-
haus .Munich, FRG, **Ludwig Maximilians University Munich, FRG.
Seventyfive percent of AIDS patients in West-Germany are homo-
sexual men. In 1984,93 gay men in Munich were enrolled in a
prospective longitudinal study to investigate their seroepide-
miological development in a combined biological and psychosocial
approach. Besides medical history and physical exam virological,
immunological and chemical lab data were obtained as well as data
on sexual activity and psychosocial variables. Participants were
followed for two years and classified using the Walter Reed
staging classification for HIV infections. Seroconversion rate
during the study period was 13%. HIV antibody positivity rose from
23% in 1984 to 33% in 1987. Three percent of the originally
healthy homosexual men died from AIDS during the study period. Two
thirds of HIV AB positive men showed signs of progressive
illness . Early enlarged lymphnodes were correlated with relatively
better prognosis. Condom use went up significantly .Saver sex be-
haviour characterised by protected anal intercourse or no anal
intercourse was implemented to a significant degree whereas no
significant change was seen for oral sexual activity .Anonymous
sexual contacts decreased considerably. Sexual satisfaction as
measured by a standardized test did not change with safer sex
practices.
TP.49
Projections of AIDS Morbidity and Mortality in San Francisco.
GEORGE F. LEMP, J.L. BARNHART, G.W. RUTHERFORD, T.H. PILAND, D. WERDEGAR,
Department of Public Health, San Francisco, California.
We projected AIDS cases and deaths in San Francisco for 1987 and 1988.
Cases were projected by fitting Box-Jenkins time-series models to the epidemic
curve for San Francisco. AIDS mortality was projected by applying Kaplan-
Meier survival time estimates obtained from surveillance data to the actual
and projected numbers of cases diagnosed per month. We predict that 1144 and
1222 new AIDS cases will be diagnosed in 1987 and 1988, respectively. The
cumulative number of cases predicted through the end of 1987 and 1988 is 3879
(95% C.I. = 3236 - 4521) and 5101 (95% C.I. = 3686-6516), respectively,
representing a doubling time of 26 months for the period beginning November,
1986 and ending December, 1988. A cumulative total of 2529 deaths are pro-
jected through December, 1987 (95% C.I. = 2256 - 2779), with 3552 deaths pro-
jected through December, 1988 (95% C.I. = 2854 - 4242). The proportion of
cases among non-whites is expected to increase from 13.8% at present to 14.6%
by the end of 1988, while the combined proportion of cases attributed to
heterosexual IV drug use and to heterosexual contact is projected to increase
from 1.6% to 2.0%. These projections suggest that the number of cases diag-
nosed by month will continue to increase through 1988, but that the rate of
increase will be slower than that for previous years. The distribution of
cases is expected to shift slightly, with an increase in the proportion of
non-white, IV drug user, and heterosexual contact cases.
TR47
JEANNE
Dept
Health
Pre vi
AIDS s
van ab
precis
s ur vei
be twee
e va 1 ua
AIDS-r
< NHL)
non- ac
cases
ma t c he
regist
throug
consi d
i n f ec t
wh ich
other
def i m
AIDS c
( 14%) ,
was 90
Val
Dea
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of Healt
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ur vei 11a
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luded
s sar
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on of AIDS Surveillance Through a One-Year
rtificate Review.
KUNCHES**, GR SEAGE
Hospitals. AAMassac
MA BARRY*.
:husetts Dept.
Boston
of Public
n s t
a ve
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TP5D Tne DescriPtive Epidemiology of HIV Infection in the
U.S. Army.
PATRICK W. KELLEY, L.I. GARDNER, R.N. MILLER, Walter Reed Army
Institute of Research, Washington, DC.
In October 1985, as part of a comprehensive program to control
the impact of HIV infections on military readiness, the
Department of Defense (DOD) ordered the testing of all 2.1
million members of the Armed Forces. Under the current timetable
the U.S. Army will complete screening of it's 764,000 active duty
soldiers during the summer of 1987. The DOD defines HIV
positivity as two positive ELISA tests confirmed by positive
Western Blot assay of the initial and a subsequent specimen.
Preliminary data on 135,412 soldiers tested between October 1985
and September 1986 indicate an overall HIV positivity rate of
0.98/1000. The prevalence among 19,446 officers tested is
0.51/1000; among 115,966 enlisted the rate is 1.06/1000.
Prevalence rates are 1.01/1000 for males and 0.73/1000 for
females. Rates by age are 0.23/1000 for those <20 years,
0.89/1000 for those 20-24, 1.35/1000 for those 25-29, 1.33/1000
for those 30-34, and 0.67/1000 for those 35 and older.
Prevalences by race/ethnic group are 0.44/1000 for whites,
2.19/1000 for blacks, 2.12/1000 for Hispanics, and 0.95/1000 for
other groups. Rates by marital status are 0.60/1000 for married
soldiers, 1.46/1000 for those single, and 1.22/1000 for those no
longer married. Updated figures on an estimated 500,000 tested
soldiers will be presented along with data on HIV positivity by
military occupation as well as home and assignment location.
70
TUESDAY, JUNE 2
TR51 AIDS a
Popula
GF Lemp, JL Ba
of Public Heal
To evaluate
minority commu
venereal disea
of AIDS report
Blacks, Hispan
nonwhites, 1 . 2
the incidence
among Asians,
among Blacks,
the 378 nonwhi
bisexual men.
to live outsid
bisexual men
sexuals was si
Whites (1%) .
venous drug us
44% of women a
annual inciden
significantly
White and Asia
and 20-24 year
young adult Bl
significant ri
nd the Potential for HIV Transmission in Minority
tions in San Francisco. GEORGE W. RUTHERFORD,
rnhart, PE Evans, GA Bolan, D Werdegar, Department
th, San Francisco, California.
the current and potential impact of AIDS on
nities in San Francisco, we analyzed AIDS and
se surveillance data by race. Of the 2,760 cases
ed through December 31, 1986, 378 (14%) were in
ics, and Asians. The incidence of AIDS among
1 cases per 1,000, was significantly lower than
among whites, 6.59 per 1,000; and the incidence
0.24 per 1,000, was significantly lower than
1.9 per 1,000, or Hispanics, 2.17 per 1,000. Of
te AIDS cases, 332 (88%) were in homosexual or
These men were more likely to be bisexual and
e "gay" neighborhoods than white homosexual and
The proportion AIDS cases involving hetero-
gnificantly higher in nonwhites (9%) than in
Nonwhites constituted 67% of heterosexual intra-
ers, 64% of heterosexual contact cases, and
nd 57% of children with AIDS. Additionally, the
ces of syphilis and gonorrhea among women were
higher among Blacks and Hispanics than among
n women with the highest incidences in the 15-19
old age groups. We conclude that adolescent and
ack and Hispanic heterosexuals may be at
sk for HIV infection in San Francisco.
TP54 The Geographic Distribution of Human Iiimunodeficiency Virus (HIV)
Antibodies in Parenteral Drug Abusers (PDAs) „
W. ROBERT LANGE*. B.J. PRIMM**, F.S. TENNANT***, J.T. PAYTE****, CM. LUNEY ,
J.H. JAFFE*, et al., *NIDA-ARC, Baltimore, MD, **ARTC, Brooklyn, NY,
♦♦"Community Health Projects, W. Covina, CA, ****Drug Dependence Associates,
San Antonio, TX, #DACC0, Tampa, FL.
Opioid dependence treatment programs in 5 regions of the US collaborated in
a study aimed at monitoring trends in seroprevalence of HIV antibodies. After
informed consent, 1,650 PDAs volunteered to provide blood specimens and data
on health history and patterns of drug use. While this sample cannot purport
to be representative of PDAs in the region, nor even of PDAs in treatment with-
in the region, the wide disparities in HIV seroprevalence in the face of simi-
larities in drug using behavior have important implications for prevention. In
the New York area (Harlem, Brooklyn), 61% of samples (N=230) obtained in late
1986 were positive, up from 50% of samples (N=585) from the same program taken
in early 1984. In Baltimore, 29% of samples (N=184) representing 11 programs
were positive. Significant sex and ethnic group differences were apparent. In
contrast, samples from programs distant from the Northeast corridor had far
lower rates: San Antonio, 2% (N=106); Tampa, 0%; Southern California, 1.5%
(N=413, with samples from programs from Fresno to San Diego). Contrary to ex-
pectations, there was no corresponding difference in lifetime needle sharing
experiences, which ranged from a low of 70% in New York to 99% in San Antonio.
Because needle sharing is practiced by PDAs in areas where seroprevalence is
still relatively low, these areas are vulnerable to the same catastrophic
spread seen in the Northeast. But a window of opportunity where prompt, vigor-
ous, and aggressive efforts at prevention could have major impact.
TP52 *""^ infections in the People's Republic of Congo
M. MAKUWA*, 3. MIEHAKANDA*, 3. CHOTARD**, G. DE THE**
•Public Health National Laboratory, Brazzaville, Congo ** CNRS Lab. Epidemiology
and Immunovirology of Tumors, Fac. Med. A. Carrel Lyon, France
HIV-1 prevalence was investigated in different sub-population groups in 1985-1986.
Among 50 patients suspected of AIDS in the General Hospital of Brazzaville, 28
(56Q")vere positive after confirmation by western blot in HIV-1 and 5 further had
restrictive reactivities to gag gene products. The mean age was 2* years of age for
both males and females. The prevalence rate in 1985 among 106 asymptomatic
patients in the General Hospital in Brazzaville was 7.7 %, close to that observed in
Zaire, in the general population.
In patients from neurology, oncology and infectious disease wards, but lacking signs
of AIDS, the prevalence rates were respectively 9, 4 and 8 %. In the Public Health
National Laboratory, Brazzaville, where patients are coming for sterility problems,
16.6 % were found to have antibodies to HIV-1. Possibly of greater interest was the
comparison between 1985 and 1986 regarding pregnant women coming to the Public
Health National Laboratory for screening of antibodies to German measles,
toxoplasmosis and syphilis. In mid 1985, the prevalence rate of HIV antibodies in this
group was 11 %, while in March-April 1986 18 % were positive. Such a progression of
HIV-1 antibody prevalence among pregnant women raises a critical issue for newborns
in epidemic aras. A longitudinal study of the positive pregnant mothers and offsprings
is being implemented in Brazzaville, at the Public Health National Laboratory.
TDCC Human Immunodeficiency Virus (HIV) Infection During Pregnancy: A
Longitudinal Study.
THE NEW YORK CITY COLLABORATIVE STUDY GROUP FOR VERTICAL TRANSMISSION OF HIV.
(SHARON NACHMAN. Lincoln Hospital/New York Medical College, New York, NY)
Over the past eight months pregnant women were prospectively enrolled to
study the effects of HIV infection on pregnancy. Of 71 women enrolled known
risk categories included IVDA 60%, sexual partners of IVDA 17%, both 9%, and
one other. 44% were HIV positive, 44% HIV negative and 12% pending.
Both groups (seropositive and seronegative) were identical for race, age,
income and education. Although a history of prior miscarriages was present in
33%, there were no differences in the two groups. The rates of
pregnancy-related complications, i.e., hypertension, gestational diabetes,
bleeding, concomitant infections and hospitalizations were also similar.
Only three women showed class III or greater HIV infection. None of the
others showed signs of HIV related illness, and none developed them during
pregnancy. There were no seroconversions in either group.
The immunologic profiles for the seropositive and seronegative groups were
as follows: Initial IgG (X): 1700 mg/dl vs 1096 mg/dl; T helper cells:
719/cmm vs 1107/cmm; T suppressor cells: 721/cmm vs 710/cmm; and T4/T8 ratio:
1.0 vs 1.6. At delivery: IgG (X): 1430 mg/dl vs 1114 mg/dl; T helper cells:
796/cmm vs 1172/cmm; T suppressor cells: 839/cmm vs 970/cmm; and T4/T8 ratio:
0.9 vs 1.2. An. unexpected finding was the depression of T helper cells in
mothers using methadone only (X=358/cmm for seropositives, and X=804/cmm for
seronegatives) .
Our study shows there are no significant differences between the two groups
with respect to history, obstetric history, and physical findings, and there
is no progression of illness during pregnancy.
TP53 Three-year progression to clinical AIDS in seropositive men: the
San Francisco General Hospital Study.
ANDREW R. MOSS", D. OSMOND", P.BACCHETTI* , C.CASAVANT*, J-C CHERMANN»«,
J.CARLSEN"* et al. *UCSF and SFGH,*«INSTITUT PASTEUR, *»»UC DAVIS
We examined progression to AIDS in 291 seropositive men first seen in 1983-
34. 41/291 have progressed (14%) with median followup of 30 months. 13/41 were
first diagnosed with Kaposi's Sarcoma (KS),2 with lymphoma, and 26 with 01
and/or KS. Actuarial progression rates were 6% at 12 months, 12% at 24 months,
and 24% at 36 months. There was no evidence of a declining progression rate.KS
as a first diagnosis has become rare: 11/22 men progressing in the first 18
months were KS first diagnoses but only 2/19 progressing in the second 18 months.
Rate of progression was strongly associated with abs. no. and proportion of
T4(helper) cells. 56% of men with 0-200 cells/cu.mm progressed vs. 23% of those
with 201-400 cells and 9% of those with 400+ cells. Progression was also assoc-
iated with no. of T lymphocytes and T8(suppressor) cells, Red blood count(RBC),
hematocrit, hemoglobin level, sed. rate amd beta 2 microglobulin level at base-
line but not with lymphadenopathy . In a multivariate analysis, no. of T4 cells,
T4/T8 ratio and RBC were independently associated with progression. Hepatitis
B carriers (HBsag+) were protected, 1/28 carriers progressing (3%) vs. 40/257
(16%) of those HBsag+ (p=.06).
There was a continuous loss in T4 cell population in men not progressing to
AIDS. The percentages with 0-200,201-400 and 400+ cells going from 6%, 19% and
75% respectively at baseline to 11%, 26% and 63% at two-year clinical followup.
Applying the multivariate predictor to the distribution of laboratory values at
2-year followup, the expected proportion progressing to AIDS in 5 years is 30-35%
TPSfi AIDS Incidence in Pregnant Women, Their Babies, Homosexual Men and
lr,OU Hemophiliacs. JAMES J. GOEDERT*, S.H. LANDESMAN", M.E. EYSTER***,
R.J. BIGGAR*, *National Cancer Institute, Bethesda MD, **SUNY Health Science
Center, Brooklyn NY, ***Penn State University College of Medicine, Hershey PA.
Crude and actuarial incidence of AIDS among human immunodeficiency virus
infected (HIV+) subjects was calculated for two new cohorts (pregnant women and
their babies), with 18-months additional follow-up for cohorts of hemophiliacs
in Hershey PA and homosexual men in Manhattan NY and Washington DC described
previously (Science 1986;231:992-5). Among 35 HIV+ second/third trimester
pregnant women, none has developed AIDS but median follow-up is only 7 months,
maximum 16 months. Among the 32 babies thus far born to these women, 2 (6%)
have developed histologically proven Pneumocystis carinii pneumonia, 1 of whom
died with cytomegalovirus colitis. Actuarial incidence of pediatric AIDS has
been 8%±7% (SE) at age 7 months and 19%±13% at age 10 months (median follow-up
5 months, maximum 15 months). Among the prevalent (1982) HIV+ cohorts, there
have been 2 new AIDS cases in Hershey hemophiliacs (7/50, 14X as of January
1987), 4 in NY homosexuals (17/43, 40%), and 7 in DC homosexuals (13/42, 311).
Out of 91 hemophiliacs (follow-up 6-112 months, median 56 months) there have
been 10 AIDS cases 24-94 months after HIV seroconversion, for actuarial AIOS
incidence rates of 5%±3% at 42 months and 24%*9% at 7.8 years after sero-
conversion. Among 43 seroconverters in the combined homosexual cohorts there
have been 3 cases after 28-42 months, for an actuarial AIDS incidence of 10%-8%
42 months after HIV seroconversion. These are the best incidence data available
to date and suggest: 1) that pregnant women must be evaluated further for AIDS
risk; 2) that HI V+ AlOS-free survivors can be anticipated 9 years (>108 months)
after HIV seroconversion; 3) that AIDS incidence after seroconversion may be
slightly higher in homosexual men than in hemophiliacs; and 4) that the 1-year
morbidity and mortality from pediatric AIDS will be high.
71
TUESDAY, JUNE 2
TP57 Retrospective Case Study of Presumptively Diagnosed AIDS (PDA) in
New Jersey
JOHN BEIL, E. BISHBURG, G. WHITAKER, J. MASSEY, J. FRENCH, N.J. State Dept.
of Health (NJSDH), Trenton, NJ, T. STARCHER, Centers for Disease Control
(CDC), Atlanta, GA.
Many patients with HIV infection do not meet CDC criteria for AIDS and
are not counted in AIDS statistics, but they are presumptively diagnosed as
having AIDS nonetheless. The NJSDH, in cooperation with CDC, conducted a
retrospective study of 207 patients randomly chosen from the New Jersey
registry who were entered into the registry between July 1985 and June
1986. All but three of the 207 had engaged in a known risk activity. The
goal was to determine how many of these patients could, on closer
examination, be shown to have AIDS.
Ten (5%) were diagnosed as meeting CDC criteria for AIDS; another 31
(15%) were PDA on the basis of physician opinion; and 99 (48%) met NJSDH
criteria for ARC. Forty four patients (21% of the sample) had expired by
the end of the period studied. Of the deceased, only one had been
autopsied and met CDC criteria for AIDS. Another 17 (39% of the deceased)
were judged PDA.
While the study suggests that the number of AIDS cases in New Jersey has
been undercounted, more conclusive results would depend on more frequent
autopsies of deceased PDA and more frequent attempts to make reliable
diagnoses of living PDA.
TR60 HIV High-risk Indices among Anti-HIV-negative Blood Donors
EVA A. OPERSKALSKI*, THE TRANSFUSION SAFETY STUDY GROUP* **, *USC
School of Medicine, Los Angeles, CA, **other participating institutions.
Transfusion Safety Study (TSS) is a multifaceted cooperative evaluation of
factors influencing risk of transfusion-transmitted HIV infection and progres-
sion. As part of TSS, serum samples were stored from persons who were blood
donors in September 1984 through January 1985, just prior to routine anti-HIV
screening. Data are currently available about high-risk indices (known AIDS
risk factors, hepatitis markers) for 114 anti-HIV(+) and 108 anti-HIV(-) con-
trol donors, matched to the former by sex, age, and area of residence. We
have determined relative frequencies of high-risk indices in the two groups to
assess possible discrepancies between presence of risk factors and anti-HIV
status on screening.
Among anti-HIV(+) and anti-HIV(-) males, 41% and 1%, respectively, were homo-
sexual; 42% and 0% were bisexual; and, 10% and 1% were IV drug users. Among
antl-HIV(+) and anti-HIV(-) females, 50% and 0% had a known risk factor. The
two anti-HIV (-)males with risk factors had a low intensity of exposure. For
both sexes, anti-HBc positivity at follow-up 12 to 24 months later was 55% and
1%; ALT> 45 was 7% and 5%. In neither sex were there any instances of sero-
conversion at follow-up.
These data show a high proportion of bisexuals among donor males with homo-
sexual contact; these men may be less likely than homosexual males to identify
themselves as being in a risk group. The low frequency of high-risk indices
among anti-HIV(-) donors with demographic characteristics similar to anti-HIV-
(+) donors is reassuring about the sensitivity of present anti-HIV screening.
(Supported by Contracts No. N01-HB-4-7002 and N01-HB-4-7003 of the National
Heart, Lung, and Blood Institute.)
TR58
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
TP61 Ris^ Actors for Infection by HIV and Development of AIDS in a
Cohort of Gay Men.
J. ALLEN MCCUTCHAN, D. JACOBSON, C. KENNEDY, S. SPECTOR, M. KLAUBER, D.
RICHMAN, et al . , University of California, San Diego, San Diego, CA.
To identify factors predictive of either risk of infection by human immuno-
deficiency virus (HIV) or subsequent development of AIDS, we performed two
case-control comparisons within a longitudinal study of 148 gay men. Eight
HIV-seroconverters (SC) were compared to eight seronegative controls and 15
HIV-infected men who developed AIDS (DA) after entry were compared to 15 sero-
positive men matched for clinical status who did not progress. SC had fewer
years of education (14 vs 16), whereas DA had more (16 vs 14). SC were
more sexually active, especially in the year before seroconversion. DA were
less sexually active throughout the period (1981-1984) antedating their diag-
nosis by 4-6 years. At entry, DA had lower white blood cell counts, hemo-
globins, absolute number of CD4+ lymphocytes, total area of reaction to 3
intradermal antigens, serum albumin, and lymphocyte 5' nucleotidase than
controls. IgG (ELISA) to a 20-am1no acid synthetic peptide (p 62) from the
alanine-glycine copolymer region of the Epstein-Barr Virus nuclear antigen
(J. Immunol. 134:211, 1985) was lower than controls before and after both
seroconversion and development of AIDS. We conclude that: 1) education
and recent sexual behavior is associated with risk of infection, 2) sexual
activity is diminished in Infected gay men who develop AIDS compared to
matched controls who do not, 3) multiple hematological and immunological
variables differentiate those infected men at greatest risk of AIDS, and
4) low levels of IgG to an EBNA peptide may predict both increased suscep-
tibility to HIV Infection and development of AIDS.
TDCQ Modeling the Spread of Human Immunodeficiency Virus (HIV) in the
In°3 United States
N. SCOTT CARDELL, D.E. KANOUSE, E.M. GORMAN, C. SERRAT0, P.H. REUTER, A. P.
WILLIAMS, The RAND Corporation, Santa Monica, CA USA
Despite widespread interest in the processes by which HIV infection has
spread in various U.S. populations, there have been few attempts to develop
mathematical models of the dynamics involved. Yet such models may be extremely
useful in predicting the future course of the epidemic for health services
planning purposes, identifying the most promising strategies for primary
prevention, and estimating the aggregate effects of new medical interventions
that are capable of lengthening individual survival. We have developed a
computer model of the dynamics of HIV infection that takes into account a broad
array of data on the size and sociodemographic composition of various risk
groups, estimated seroprevalence rates, the natural history of HIV infection,
and patterns of risk-related behavior. The model is fitted to the known history
of the AIDS epidemic to date. It reduces our uncertainty about the dynamics of
HIV infection and transmission by narrowing the range of possible values that
certain important parameters take on. It also allows us to identify which
uncertainties in the parameters contribute most to the uncertainties in our
forecasts. Results indicate that the future incidence of CDC-defined AIDS is
likely to be much higher than accepted U.S. Public Health Service estimates and
that a self-sustaining epidemic among heterosexuals in the U.S. is already
underway .
TPfi9 — Vivo Analysis, of AntiretroviraJ. Treatment Strategies in Mice.
1 ,f . RUTH M. RUPRECHT*. ARLENE SHARPE*'', RUDOLF , JAENISCH and DAVID
CH0UXXK, 'Dana-Barber Cancer Institute, Boston, MA, Whitehead Institute,
Cambridge, MA, Memorial Sloan-Kettering Cancer Center, New York, NY.
The reverse transcriptase inhibitor 3' -azido-3' -deoxythymidine (AZT) acts
early in the retroviral life cycle, whereas a-interferon reversibly inhibits
late events during retroviral propagation. AZT suppresses Rauscher murine
leukemia virus complex (RLV)-induced disease in adult BALB/c mice. Longterm
AZT treatment, however, leads to severe bone marrow depression. Recombinant
human interferon a-A/D (rHuIFNa-A/D) strongly inhibits RLV-induced splenomega-
ly in BALB/c mice. Combining suboptimal doses of AZT and rHuIFNa-A/D leads to
virtually complete suppression of splenomegaly without hematological toxicity.
We conclude that AZT and rHuIFNa-A/D are highly synergistic jji vivo.
We have also developed murine models to study retroviral neurovirulence, as
well as in utero and perinatal infection, by infecting SWR/J mice as midgesta-
tion embryos or neonates with Cas-Br-E virus which causes hind limb paralysis.
AZT given orally to pregnant and/or lactating females delayed the onset of
paralysis and prolonged life of infected mice in a dose-dependent fashion. We
conclude: l) AZT is active in the CNS sanctuary, 2) AZT is effective across
the placental barrier, 3) AZT is secreted into milk, and A) pre- or perinatal
infection and therapy can be evaluated in our model system. The significance
of our studies lies in the rapid and cost-effective ways in which questions
relevant to human neurovirulent retroviruses can be studied ^n vivo. Sup-
ported by a contract from the Commonwealth of Massachusetts Department of
Public Health (RMR), a Faculty Development Award from the Pharmaceutical
Manufacturers Association Foundation (RMR) and a Lucille P. Markey Charitable
Trust Scholarship (AS). AZT was a gift from the Burroughs Wellcome Co., and
rHuIFNa-A/D from Hoffmann La Roche, Inc.
72
TUESDAY, JUNE 2
TP63 EVALUATION of a NEW VIRONOSTIKA HIV CONFIRMATION ASSAY
GABY VERCAUTEREN*, W KEUR*, G VAN DER GROEN*, P PIOT*
*Institute of Tropical Medicine, Antwerp, Belgium
In the Organon anti-HIV confirmation assay (CA) wells of Vironstika anti-
HTLV III enzyme immunoassay strips (EIA) are preincubated overnight, respecti-
vely with blocking sheep anti-HIV serum, sheep anti-H9 serum and normal sheep
serum. Thus HIV antibodies from a truly positive specimen can no longer bind
to the HIV antigen. This blocking effect is compared with that of the anti-
H9 serum. If the ratio of the optical density in the presence of the anti-H9
serum versus the reaction with the anti-HIV blocking serum is greater then
2.0, the sample isconsidered positive. A ratio between 1.5 and 2.0 is inter-
preted as doubtful or "gray zone" value. In this preliminary study 180 sera
were tested in the EIA, CA and in two additional confirmation assays, indirect
immunofluorescence assay (IFA) and immunoblot assay (IBA). The EIA results
showed an overall concordance of 90.9 % with the CA. The CA revealed 4.3 %
(4/94) false positive EIA results. These 4 negative CA results were confirmed
by IFA and IBA. Concordance of the CA with IFA and IBA was 91.5 Z and 94.5 %
respectively. Two sera were negative in the CA, but positive in the IBA. One
of them was also positive in the EIA and IFA and the other one was negative in
EIA and IFA. Three sera (3.1 %) positive in EIA and CA could not be confirmed
by IFA nor with IBA. All "gray zone" CA results were negative in IFA and IBA.
An advantage of the CA is the use of the Vironostika anti-HTLV III EIA strips.
This CA may be useful to confirm the positive result of a single performed EIA.
TP6B A Method for Estimating HIV Seroprevalence Rates in Urban Areas
with High Rates of I.V. Drug Abuse: The Case of the Bronx
ERNEST DRUCKER, S.H. VERMUND, Department of Epidemiology & Social Medicine,
Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, MY, USA
In the absence of large scale seropcevalence surveys it is still possible,
using available data, to estimate the probable magnitude and geographic
localization of the AIDS epidemic in urban area with high rates of intravenous
drug abuse (IVDA). The Bronx with 1.16 million people has a distinctive
pattern of prevalence and distribution of AIDS, i.e., 69% of AIDS cases are
among IVDA's, 20% are female, 89% are Black and Hispanic, and 4.5% are
children. Local data on AIDS cases (by risk factors, age 4 sex) can be
combined with local indices of the IVDA population, e.g., drug-related deaths
and N.Y. State drug treatment data, to estimate numbers of IVDA's and rates of
HIV seroprevalence. In this application of the model, HIV seroprevalence is
calculated for Bronx males S females age 25-44, a group comprising 76% of all
Bronx AIDS cases through November 1986; and for the South Bronx area where
AIDS cases are most concentrated. Overall, the Bronx is estimated to have
between 31,300 and 46,200 IVDA's of whom 78% fall into the 25-44 age group.
30%-50% of female IVDA's and 40%-60% of male IVDA's are considered to be HIV
positive based on local sero-surveys . These figures produce a seroprevalence
range of 5.3%-11.8% for all Bronx males age 25-44 and l.l%-2.6% for females.
For the South Bronx, with 66% of all IVDA's and 38% of the population, these
rates are 9.3%- 20. 6% for males age 25-44, and 1.8%-4.3% for females. These
must be considered minimum estimates of Bronx seroprevalence in this age group
as they do not take into account the contribution of risk groups other than
IVDA's. Implications for heterosexual and vertical transmission are discussed.
TR64 Clinical and Behavioral Predictors of Developing AIDS
and Related Outcomes among Asymptomatic HIV Seropositive
Homosexual Men in Boston
KENNETH MAYER*, J. McCUSKER**, A.M. STODDARD**, S.P. SALT Z MAN * ,
M.W. MOON*, J.E. GROOPMAN*, et al , Fenway Community Health Center,
Boston and University of Massachusetts, Amherst, MA, USA.
Seventy four of 290 asymptomatic (AS) gay men enrolled in a pro-
spective study of the natural history of HIV infection between
1/85-5/86 were Ab(+) (25.5%). Of 57 followed for more than a year
(_> 1 visit every 6 months) , only 12 have remained AS, whereas 35
developed persistent generalized lymphadenopathy (PGL) , 9 thrush
(2 with PGL), and 4 zoster. All 4 of the men who developed AIDS,
had thrush first, whereas none of the men with zoster ->■ AIDS; only
1 had prior PGL. Lifetime number of sexual partners, number of
partners in the preceding 6 months, frequency of receptive ano-
genital exposure to semen, number of anogenital partners, drug use
history and prior sexually transmitted disease history were not
significantly different between men who remained AS and those with
AIDS-related clinical outcomes. Whereas the polymorphonuclear cell
count and hematocrit did not differ on the initial exam between
those who stayed AS and those who got sicker, the mean number of
lymphocytes was significantly different (p=.006) between the AS
men (2250), those who developed PGL (1722) and those who ■* thrush,
zoster or AIDS (1499). Thus, behavioral risk factors associated
with becoming infected with HIV are not predictive of the develop-
ment of PGL, thrush, zoster or AIDS; but thrush and lymphopenia
are associated with early clinical progression towards worse out-
comes.
TR67
Additional Evidence for Lack of Transmission of HIV Infection to
Household Contacts of AIDS Patients.
GH FRIEDLAND,* B SALTZMAN,* M ROGERS,** P KAHL,* C FEINER,* M MAYERS, et al.
Montefiore Medical Center/Albert Einstein Cbll. of Med., Bx. NY, "CDC, Atlanta, Ga, USA.
We report on the continuing enrollment and evaluation of non-sexual household
contacts of adult AIDS patients (pts.). 200 contacts of 85 AIDS pts. were evaluated
with detailed interviews, physical exams, and antibodies to HIV; 99 contacts
were re-evaluated 6-12 months after cessation of household contact or death of the
pt. Mean age of contacts 10.4 years; 57 under 6, U32 6-19, 41>19 years.
Median duration of household contact from 18 months prior to symptoms in pts. to
last contact, 21 months. Median time elapsed from first contact during this period to
last evaluation 35 months.
No household contact has AIDS. 199/200 are negative for serum antibody to HIV. One
HIV+ biologic child of a woman with AIDS likely acquired infection perinatally.
Sharing of selected household facilities, items and personal interaction with AIDS
patient among 199 household members:
Days Shared (Median) Days Shared (Cumulative)
586-616 102,793-106,357
397 46,777
418 36,937
108 16,402
71 17,044
84 23,964
352 55,390
352 55,70B
This study shows that household members remain at minimal to no risk for HIV
transmission (95% d, 0-1.49) despite prolonged and substantial close non-sexual
contact with AIDS patients, and after reevaluation 6-12 months after contact ceased.
Shared Activity
% Sharing
toilet, bath, kitchen
85-89
comb
69
towels
48
utensils
38
plates
51
glasses
55
hugging
76
kissing
78
TR65 Prevalence and Incidence of AIDS, ARC and HIV Infection in a Gay NYC
Cohort. JOHN L. MARTIN, Columbia U. School of Public Health, NYC, NY.
Prevalence and incidence rates of AIDS, ARC, and HIV infection (antibody)
were calculated from data collected on a cohort of 745 NYC gay men. The AIDS-
free sample was recruited and interviewed in mid-1985 in order to examine soc-
ial and behavioral risk factors for AIDS and the presence of signs of ARC. An
annual follow-up interview was completed one year later. Fourty-seven percent
of the sample (N=357) underwent an initial serologic evaluation for HIV anti-
body in early 1986 and a follow-up blood sample was obtained six months later,
at the time of the follow-up interview.
Prevalence of HIV antibody in early 1986 was 34%. Including the group of men
with- a history of sharing a needle for IV drug use increases this value to 36%.
The six month incidence of seroconversion was two out of 230 seronegatives.
Pro-rated for 12 months this represents an annual rate of 17.4 new infections
per 1,000 susceptible gay men.
The prevalence of pre-AIDS conditions or symptoms of ARC [thrush, herpes zos-
ter, lymphadenopathy, unexplained weight loss of 10 lbs (+) , persistent unex-
plained fevers of 100°F (+) , persistent unexplained diarrhea] during the 1984-
85 year was 21% for the total sample and 38% for HIV antibody positive men.
Incidence of new cases of ARC has not yet been calculated.
During the course of the one year follow-up interval, 18 incident cases of
AIDS occurred. For the total sample this represents a rate of 24 new AIDS
cases per 1,000 gay men. Using only HIV antibody positive men for the denomin-
ator, the annual incidence of AIDS is 67 per 1,000 HIV infected gay men.
The low seroconversion rate relative to the high AIDS incidence rate indica-
tes that the rate of increase of new AIDS cases among gay men should decline in
future years if sexual activity remains low or continues to decline at the rate
we have previously reported.
TP68 Western Blot-positive and -negative Sera from Harare, Zimbabwe and
New York, NY, USA are identified Equally by a Synthetic Polypeptide-
based Enzyme-Jinked Immunoassay (ELISA)
FREDERICK P. S1EGAL*, C.Y. WANG**, T. HONG**, K. SHAH*, D. IMPERAT0*, J.C.
EMMANUEL***, *Long Island Jewish Medical Center (LIJHC), New Hyde Park, NY,
**United Biomedical Inc. (UBI), Lake Success, NY, USA and ***The Blood
Transfusion Service, Harare, Zimbabwe.
Sera from 499 subjects seen at our institutions (43*t from NY, 65 from Harare)
were blindly assayed for reactivity with a new ELISA for HIV antibodies. The
antigenic adsorbent for this system is a mixture of synthetic polypeptides
representing highly antigenic epitopes of HIV gp4l and p25- Sera were selected
on clinical grounds and/or known prior reactivity with currently employed
ELISA techniques; 324 represented a wide spectrum of HIV infection (duration
and clinical stage), 175 were controls. The control sera represented normal
laboratory workers, parenteral ly and sexually exposed people, several primary
immunodeficiencies, autoimmune diseases, thymoma, classical Kaposi's sarcoma,
T and B non-Hodgkin ' s lymphomas and Hodgkin's disease. Most sera were assayed
independently at both UBI and LIJMC and all ELISA results were compared with
results from "Western" blots (WB). There were no false negatives, including
5 sera having no detectable band corresponding to gp4l , one of which (AI0S-0I)
also lacked all reactivity on WB. There were also no false positive results.
These data suggest that despite virus heterogeneity related to geographic
distances, the epitopes in question remain invariate, and the assay is
consistently highly sensitive.
73
TUESDAY, JUNE 2
to cn Prevalence and Persistence of HIV Antigen among IV Drug Users.
1 nU:' DON C. PES JARLAIS-. SR FRIEDMAN", J-P ALLAIN"*. D MILDVAN"", M
LEUTHER— , M MARMOR , S BEATRICE et al. *NYS Div. of Substance Abuse, "
NDR, Inc., "* Abbott Labs., "" Beth Israel Med. Cen., NYU Med. Cen., NYC
Dept. Health, New York NY
Recently developed tests for detecting HIV antigen in serum provide a means for examining the role
of serum antigen in the natural history of HIV infection. We examined the prevalence, persistence and
sequelae of detectable HIV antigen in a cohort of 138 intravenous drug users in New York City. No
subject had AIDS or ARC at the beginning of the study; each subject was seen twee with a mean of 9
months between the two data collection points. HIV antigen was assessed with the Abbott test,
antibody was assessed with Abbott ELISA and Western blot tests.
Antigen was detected in 5/66 (8%) of the subjects who were initially antibody positive, in 0/4 of
subjects who became antibody positive during the follow-up period, and in 1/68 (1 .5%) of the
subjects who were antibody negative at both the start and end of follow-up. All subjects who were
antigen positive at the start of follow-up were also antigen positive at the end of the period; one
antibody positive subject developed antigen during the period. Antibody to gp41 was more common
than antibody to p24 in antigen positive subjects. Antigen was associated with increased rates of T4,
T8 and B cell loss. 2/5 antigen positive, antibody positive subjects have since developed AIDS or died
with ARC, compared to 3 of 61 antigen negative, antibody positive subjects (p < .05). (Disease
incidence will be updated to the time of the conference).
Repeated ELISA antibody tests of the for one antigen positive subject were negative at both time
points; repeated Western blots for this subject showed no antibody to p24, gp41 or gp120 at either
time (additional testing is being conducted). This was the only subject for whom HIV antigen level
declined.
Presence of HIV antigen in serum of IV drug users at risk for AIDS appears to be infrequent,
relatively stable over time, and a potential marker for development of clinical disease. Further
relationships among antigen presence, presence of specific HIV antibody, and other potential markers
of disease progression will be presented.
TR72 REVERSIBILITY AND PROGRESSION OF PERSISTING AIDS-RELATED COMPLEX
BARBARA VISSCHER, R DETELS, J PHAIR, C RINALDO, R KASLOW, R FOX.
Multicenter AIDS Cohort Study, NIAID, Rethesda, MD.
A cohort of 693 HIV antibody positive homosexual men in Los Angeles were
characterized as being asymptomatic (well), having persistent generalized
lymphadenopathy (PGL) or AIDS Related Complex (ARC) on two separate visits
at least 6 months apart and were re-examined 6-12 months later. ARC was
defined as one or more of the following reported conditions: fever or diar-
rhea lasting more than two weeks or involuntary weight loss greater than 9
pounds. Men were considered to have PGL if examination revealed non-conti-
guous lymph nodes greater than 1 cm in diameter at 2 or more non-inguinal
sites. Men who had been in that same status at the subsequent consecutive
visits were most likely to remain in that same status at the subsequent
visit. The AIDS attach rate was highest for those with a diagnosis of ARC
on two consecutive visits (12%) but was lower and similar (4-7%) amnng the
other groups PGL/PGL, well/well, ARC/PGL, PGL/ARC. The ARC attack rates
were similar and lower for those with any sequential status other than
ARC/ARC. These observations suggest that persisting ARC is an unfavorable
prognostic sign, although at least some men with persisting ARC do revert to
either PGL or well, at least temporarily. PGL alone does not appear to be
an unfavorable prognostic sign over the time span studied. For the meeting,
we will have data from an additional 1000 seropositive men in Baltimore,
Chicago and Pittsburgh.
Tpyil Factors Influencing the Risk of Infection with Human Immunodeficiency Virus in a
Cohort of Homosexual Men - Denver 1983-1985
CQRNELIS A.M. RIETMEIJER. K.A. PENLEV, D.L. COHN, CR. HORSBURGH, A.J. DAVIDSON and F.N. JUDSON,
Denver Disease Control Service and The University of Colorado, Denver CO.
We studied factors associated with infection with the human immunodeficiency virus (HIV) in a
cohort of 231 gay men enrolled from November 1982 through May 1985, including 40 asymptomatic HIV
antibody negative (AS-), 21 asymptomatic antibody positive (AS+), 74 with generalized lymphadeno-
pathy (GLS), 39 with AIDS-related complex (ARC) and 57 with AIDS. Because univariate analysis did
not show significant differences between AS+ and GLS or between ARC and AIDS, these groups were
combined for analysis.
Riskfactors in
past U months
AS-
AS+/GLS
N=40 (%) N=95 (%) N=96 (X) P*
ARC/AIDS Univariate analysis Multivariate analysis
Odds ratio (C.I.)
Enemas
3 (7.5) 49 (51.5) 32 (33.3) <0. 00001
Receptive anal>30 1 (2.5) 24 (25.2) 12 (12.5) <0.005
ARC/AIDS contact 3 (7.5) 24 (25.2) 13 (13.5) <0.05
Sex partners>20 1 (2.5) 17 (17.8) 08 (08.3) <0.05
IV drug use 2 (5.0) 19 (20.0) 21 (21.8) <0.05
Insertive anal>50 2 (5.0) 43 (45. 2i 21 (21.8) <0.05
•CO. 0001 15.4 (4.1-58.3)
■CO. 05 14.6 (1.7-126.0)
<0.005 8.8 (2.2-35.3)
0.062 8.1 (0.8-75.1)
0.063 5.0 (0.9-27.5)
''AS- vs ASt/GLS: ''">AS- vs ARC/AIDS: '""'AS- vs AS+/GLS C.I.=Conf idence interval
In multivariate analysis (table) the use of enemas, number of episodes of receptive anal inter-
course and sexual contact with someone with AIDS or AIDS related conditions were all indepen-
dently associated with HIV infection. IV drug use and number of sexual partners improved the
multivariate model but did not reach statistical significance. In univariate analysis the ARC/AIDS
group did not differ significantly from AS- as to number of episodes of receptive or insertive
anal intercourse and number of sexual partners, but this most likely represents confounding that
occurs when current risk factor behavior in fatally ill men is used in place of risk factor
behavior at the time of HIV transmission. It indicates however that this group has become less
sexually active and that HIV infection is largely spread by relatively healthy infected men.
TR73
Predictors of The Hazard of AIDS Among HIV Seropositive Gay Men.
B.FRANK POLK, A.MUNOZ, R.FOX, R. KASLOW, J. PHAIR, C. RINALDO, R. DETELS,
for the Multicenter AIDS Cohort Study (MACS), NIH, Bethesda, MD.
Of 4,955 gay men who enrolled in a prospective study, 1828 were seropositive
for HIV at entry. Among the seropositives, 164 (9.0%) developed AIDS during
24 months of follow-up. Exposure variables of interest, with data collected at
entry and at three subsequent six-monthly visits, included age, race, adi-
posity, sexual activity, CBC, T-cell subsets, serum immunoglobulins, serum
antibody to CMV and HIV, serum HbsAg, and AIDS-related complex (ARC). Follow-
up data were available on 1820, 1614, 1454 and 1332 participants at the four
respective visits. We conducted a stratified analysis using a proportional
hazards regression model. In an attempt to control for the unknown time since
infection, the strata were defined by the entry CD4 number (a known marker of
disease progression) and the rate of change in the number of CD4 cells. The
estimates of the relative hazards from the multivariate analysis for those
variables that made independent significant contributions to the final model
were:
Age
log CDS
log2 IgA
Hemoglobin
HIV antibody
When Kaposi's sarcoma (KS) and opportunistic infection (01) were analyzed
separately, the hazard of KS was more strongly associated with older age, .while
the hazard of 01 was more stronqly associated with increased number of CD8
cells and decreased level of HIV antibody. In summary, after adjusting for
number at entry and change in CD4 cell number, several other variables have
predictive information regarding the development of AIDS.
AIDS
KS
01
1.51 for 10 yrs.
1779
lTFo
2.10 for twice
1.89
2.18
1.37 for twice
1.54
1.38
1.20 for -1 gm%
1.19
(NS)
1.26
1.79 for -1 O.D.
1.19
(NS)
2.02
jpy-j Mortality In AIDS in Colorado: Life-Table Analysis from the AIDS Reporting
System.
DAVID L. 00HN, A. J. DAVIDSON, K.A. PENLEY, F.N. JUDSON, Denver Disease Control Service (DCS),
University of Colorado Health Sciences Center, Denver, CO, U.S.A.
Although there have been over 30,000 cases of AIDS reported in the USA, there have been sur-
prisingly few comprehensive analyses of mortality in AIDS patients (pts). In 1985 DCS imple-
mented the computerized AIDS Reporting System (AFS), which utilizes PRODAS software program
provided by the Centers for Disease Control (CDC). From May, 1982 through December 31, 1986,
309 adult cases of CDC-defined AIDS were reported, of whom 202 (65%) had died. Follow-up mor-
bidity and mortality information was ascertained on 304 (98%). Those whose survival was not
ascertained ware censored as of the Last diagnostic entry in the ARS.
Median survival (MS) from time of diagnosis of all pts was 239 days (d), of pts who
initially presented with Pneurocystls pneuronia (PC, n=182) 257 d, Kaposi's sarcoma (KS, n=65)
293 d, PC and KS (n=10) 223 d, otter opportunistic diseases (OD, n=52) 140 d, and PC who
survived at least 60 d after diagnosis (n=115) 337 d. MS by transmission category was for
gay men (n=221) 250 d, gay men and IVDU (n=48) 236 d, heterosexual and IVDU (n»13) 251 d,
hemophiliacs (n=7) 68 d, heterosexual contacts (n«5) 293 d, transfusion recipients (n=5)
320 d, and no identified risk (NDR, n=10) 87 d. MS for pts with lymphoma at any time (n-26)
was 137 d compared with no lymphoma (n=283) 260 d; and for disseminated cytomegalovirus
(CMV, rp50) 198 d and no CMV (n=259) 255 d. MS for pts with or without mucocutaneous herpes,
M. avium-intracellulare, Candida esophagi tis, cryptosporidiosis , and cryptococcosis was not
significantly different.
Pts who present with OD have a worse prognosis than KS and/or PC, and PC pts who survive
their Initial episode have the best prognosis. NIR pts have a significantly worse prognosis
than otter transmission categories, probably because diagnoses are delayed. Lymphoma and CMV
Indicate a worse prognosis, although CMV may be underdiagnosed. ARS is useful for following
prognosis in different types of AIDS pts, and for monitoring trends over time.
TP74 Clinical Significance of Antl-HIV /Antibodies in Asymptomatic
Blood Donors: A Prospective Study.
HARVEY J. ALTER*, S.F. LETTMBN*, H.G. KLEIN*, J.J. MELPOLDER*, F. DARR**,
J.L. FOT*, et al., *Clinical Center, NTH, **Washington Region Red Cross.
88 asymptomatic Western blot + (WB+) blood donors and 51 ETA+, WB- control
donors nave thus far been enrolled in a 5-year prospective study. Compared
with the WB- controls, WB+ individuals were more frequently male (88% vs 59%)
and black (51% vs 6%). The probable source of HIV exposure was homosexual
contact, 75%; heterosexual contact, 17%; IV drugs, 1%; unknown, 7%. None were
transfusion related. On initial evaluation of WB+ subjects: 1) 38% had extra-
inguinal lymphadenopathy; 2) mean T4 cell number was 450 (range 120 to 982) and
mean T4/T9 ratio was 0.75 (range 0.26 to 1.7); 3) 47% had diminished in vitro
responses to tetanus and 25% had decreased responses to PHA and/or PVM; 4) 45%
had IgG > 1800 mg/dL; and 5) 2% had platelets < 100,000/ul. HIV was isolated
from only 8 of 88 (9%) cultured at Biotech and 7 of 74 (10%) cultured at CDC.
This is markedly lower than earlier CDC studies (57% viral isolation) and sug-
gests a change in the constituency of the WB+ donor population, as also implied
by questions relating to lifestyle.
On initial visit, 55 (62%) were CDC group II and 33 (38%) CDC group III.
During 6-18 months of follow-up, one donor progressed to group IV A and one to
group IV C-l (Pneumocystis). In these patients, the interval from enrollment
to disease was 16 and 12 months, respectively. T4 cell number and in vitro
immune responses showed progressive deterioration in these two individuals,
and virus was isolated just prior to onset of clinical disease.
None of the EIA+, WB- control donors were in known HTV risk groups and none
had evidence of HIV-related disease, immune impairraent, or positive viral cul-
tures. We believe these represent false positive reactions and support rein-
statement of such donors into the donor pool.
74
TUESDAY, JUNE 2
TD1C Heterosexual Transmission of AIDS in New York City
MARY Um CHIASSOH. R. STOHEBUBHER, A. LEKATSAS, J. WALKER.
New York City Department of Health, NY, NY.
Although heterosexual transmission of HIV is reported to be the most
common mode of transmission in Central Africa and Haiti, the extent to which
this virus will spread among heterosexuals in the USA is unknown. We
examined New York City Dept . of Health (NYCDOH) and national surveillance
data to evaluate the patterns of heterosexual risk behavior among AIDS
cases. The 8681 cases reported in NYC through 1986 account for 30X of the
total US cases. Approximately 2% of both NYC and total US cases occur among
heterosexual partners of risk group members (NYCDOH classifies persons from
Haiti/Central Africa separately) . Through 1986 , 182 sex partner cases were
reported in NYC; 3 males and 179 females . All female partners of the male
cases were IVDUs. Risks of the male partners of the female cases were as
follows: 153 (85%) IVDUs; 20 (11%) bisexual; 3 (2%) Haitian or Central
African; 2 (IX) bisexual IVDUs; 1 (IX) hemophiliac. In NYC sex partner cases
have remained at about 2% of the total cases since 1982. Infected
heterosexual IVDUs comprise the major reservoir of HIV for the heterosexual
population. While the 25 70 cases among heterosexual IVDUs in NYC account for
53% of US IVDU cases, NYC sex partner cases account for only 36% of the sex
partner cases : male cases are 3 .5% and female cases 42% of the 509 US sex
partner cases. Differences between NYC and US data may be due to better risk
identification through more thorough case investigation by NYCDOH. NYC
surveillance data suggest that heterosexual transmission does occur and
females appear to be at greater risk than males. To avoid further
heterosexual transmission in NYC, effective prevention strategies should
include a broadly based education program, but focus on the major source of
HIV in the heterosexual community, infected IVDUs.
TD7Q HIV Sero-Survey of Post-Par turn Women at a Municipal Hosptial
in New York City. S. LANDESMAN,* SUSAN HOLMAN*, S.
McCALLA*, 0. SIJIN*, J. WEBER*, H. HINKOFF* , , SUNY Health Science
Center at Brooklyn, Brooklyn, N.Y.
We performed a sero-survey of all new mothers admitted to the obstetrical
service of a municipal hospital serving the urban poor. Cord blood was
used for HIV testing; all women, on the day after delivery were interviewed
for HIV related risk factors . Blood samples and questionnaires were given
a code number and personal identifiers were destroyed prior to testing.
Six hundred women delivered: complete data is available on 527. The
remaining delivered on weekends or were discharged before interview.
One hundred twenty-three of 527 women (23%) had a self reported risk factor;
404 (^7%) had no known risk factors. All samples were tested by ELISA
and confirmed by Western Blot (WB) . Women with risk factors had a WB
done even if the ELISA was negative . Thirteen samples , 2.45% ( 1 . 4-4 . 3 , %
95% C.I.), were Western Blot postive (WB+); 11 of which were also ELISA
positive. Eight positive samples were in persons with risk factors (3
IVDA, 1 Haitian, 1 multiple sex partners 1 transfusion, 2 with a sex
partner who used drugs ) . Thus 8/123(6 . 5% ) of women with a risk factor
were positive . Five of 404 (1.2%) samples from non-risk group women
were positive.
Taking an appropriate medical history concerning risk factors for the
purpose of HIV counselling and testing during early pregnancy will only
identify 61% of the infected population at our institution. Testing of
the entire prenatal population at our hospital would be required for
identification of the remaining 39% of seropositive women.
Tp7Pi Survival Analysis of Children Reported with AIDS in New York
City, 1982-1986.
PAULINE A. THOMAS. R. E. O'DONNELL, L. LESSHER, New York City Department of
Health, New York, VY.
The incidence of Acquired Immunodeficiency Syndrome (AIDS) in children
under age 13 continues to increase in New York City (NYC) , but the course of
illness and prognosis remains incompletely described. One-hundred forty
seven children have been reported with maternally transmitted AIDS from 1982
through 1986. Median age at onset of symptoms of immunodeficiency was five
months and at diagnosis of first opportunistic infection was 11 months.
Survival analysis was performed on the 114 with either Pneumocystis carinii
pneumonia (PCP) or Lymphocytic Interstitial Pneumonitis (LIP). For 87
children with PCP, median survival from birth was 14 months (Interquartile
(10) range=29 mo.). Median survival was longer for 42 females than for 45
males (19 vs 11 mo.). Hispanic males had the poorest median survival, at six
months for 15 with PCP (IQ range=19 mo.). Median survival for 26 children
with LIP who never had PCP is strikingly different at 91 months. Numbers of
cases in different racial and diagnostic groups are too small to be compared
statistically. Seven children, aged four to nine years have survived three
or more years beyond initial diagnosis. PCP as primary diagnosis was present
in one, LIP in five, and both diagnoses in one. These data confirm the very
different course of HIV-infected children who present with LIP vs. PCP.
Differences in therapy must be examined in future survival analyses.
T***
JP79 MALNUTRITION AND HIV ANTIBODY PREVALENCE IN
THE CENTRAL AFRICAN REPUBLIC.
Jean P. GONZALEZ*, S. BIREM ETCHEBES**, C.C. MATHIOT*"", M.C.
GEORGE S-COURBOT*** and A.J. GEORGES***, *Institut Francais de Recherche
Scientif ique pour le Developpement en Cooperation, ORSTOM, Bangui,
Republique Centrafricaine (RCA), Centre de Dietetique Experimentale de
Bossangoa, RCA, Institut Pasteur de Bangui, RCA.
HIV antibody prevalence has been studied simultaneously in mothers and
their malnourished children, in a rural area of the Central African Repu-
blic (CAR). Children were selected on the basis of their nutritional status
i.e. moderate protein energy malnutrition (P E M) , kwashiorkor or marasmus.
The results obtained from rural area have been compared to those previously
obtained in an urban pediatric population as well as those recorded in the
general population of the CAR.
Elisa was used for sera screening, while Western Blot allowed us to con-
firm the presence of anti HIV 1 antibodies when reacting with either GP110,
GP41 or both.
Anti HIV 1 as well as HIV 2 antibodies are absent in the healthy control
group of children of less than 15 years, while they are found in 12. 3Z of
the malnourished children of the urban area as compared to 3.9Z in the
rural area.
These differences do not seem to be due only to environmental factors
but more likely to the way of life of the mothers of sick children under
investigation.
TP77 Fatal Unconfirmed Cases of
CHftRLES E HALEY. S H0RWITZ.
County Health Department. Dallas, Tx
The current AIDS surveillance defi
magnitude of mortality associated wi
availability of HIVab testing after
dimension that permits ar\ examinatio
Reports were obtained from physician
tioners, and other sources including
certificates. Suspects were invest ig
ogist. From 1981-86, <#7<t Dallas resi
AIDS, of whom est (59.3V.) had died b
additional 37 1 persons were reported
sources as possible cases of whom <*5
31, 1986. Two died of suicide (1 was
31* were known to be HIV positive: 15
the AIDS surveillance definition (4 i
had recei ved steroid therapy for non
disseminated infections CI TB, 3 coc
lymphomas or leukemias) . Another 19
of A I DS , but confirmatory diagnostic
underwent diagnostic procedures , no t
13 had no diagnostic procedure: none
portion of deaths possibly attribute
by 67. to 10'/ due to lack of diagnost
examinations. In the future physicia
AIDS diagnosis, resulting in greater
mor tal i t y .
AIDS in Dallas, Texas.
V REFF, K HERND0N. Dallas
nit ion underesti
th AIDS and the
June, 1985 has a
n of HIV associa
, i nf ec t ion con
rev iew of all d
a ted by a nurse
dents were rep or
y December 31 ,
by physicians a
< 1 1 .9'/. ) died be
known HIV posit
did no t meet th
ere transplant
-malignant condi
c idiodomycosis3 ,
died of ill nesse
tests were lack
resu 1 t i ng in d i
had a post -mor t
ble to HIV are
ic procedures a
ns may be less a
under est i ma t ion
mates t
idespr
dded a
ted mor
tro 1 pr
eath
epidemi
ted as
986. A
nd othe
fore De
•e> ,
e crite
recipie
t ions ,
and *♦
s sugge
i ng
agnos i s
em. The
nderest
d post-
qgress i
s of HI
he
ead
new
tal i ty.
ac t i -
ol-
having
cember
other
ria for
nts, 3
t* had
had
stive
oer sons
, and
pro-
ima ted
mor tem
in
TR80 Western-blot in HIV seroconversion : the importance of
detecting anti gp 1 10/120, the earliest envelope antibodies.
L. NOEL and the RETROVIRUS GROUP OF TnT FRENCH SOCIETY OF BLOOD
TRANSFUSION - Paris, France
¥e present a Vestern-blot (w-b) study of anti-HIY antibodies in
sequential sera collected from 25 individuals at the time of
seroconversion and beyond ¥-bs were carried out vith commercially
available kits from BIOTECH-DUPOIfT. BI0RAD and DIAGNOSTIC PASTOJR The
strips loads in gp 110/120 and gp AX antigens were systematically
controlled In 6 cases seroconversion was proved by the discovery of a
positive whole virus anti-HIV ELISA less than one month after a previous
negative test In 19 cases the incomplete pattern observed in w-b on the
first positive sample was suggestive of early seroconversion and indeed
simultaneous study with samples collected later demonstrated the
completion to a typical positive anti-HIV w-b pattern. On the first
positive samples the antibodies observed were only anti-p 25 (with the
strongest signal), faint anti-pl8 and p55 and anti- pllO/120 Anti p 41
were never detected at this early stage but appeared on samples collected
3 weeks to as long as 3 months later
Considering existing cross-reaction with gag gene products in w-b, the
criterion of anti HIY specificity relies on the detection of antibodies
directed against an env gene product ?e emphasize the importance of using
w-b filters rich in gp 110/120 in confirmatory tests to allow for an
earlier diagnosis and a better discrimination between true positives and
non HIY specific reactions
75
TUESDAY, JUNE 2
TP81 Neutralizing Antibodies against HIV in Relation to AIDS related
Diseases.
MAIKEN ARENDRUP*. K. Ulrich*. J.O. Nielsen**, B.0. Lindhardt*. C. Pedersen**
K. Krogsgaard**. *Lab. of Tumor Virology, The Fibiger Institute, **Dept of In-
fectious Diseases, Hvidovre Hospital. Copenhagen, Denmark.
Seventy consecutive frozen serum samples collected over a 1-5? year period
from 10 HIV (Human Immunodeficiency Virus) antibody positive individuals were
tested in a microplate ID^assay for neutralizing antibodies (NA) against a Da-
nish HIV isolate and the results related to disease outcome. Virusproduction
was monitored by a microplate reverse transcriptase assay. Total anti HIV was
titrated in ELISA and antibodies against core and envelope proteins detected
by Abbott's HTLV-III confirmatory assay.
One patient reached stable titers of NA > 1:640 ^ year after seroconversion,
and 3 patients around 1:100 after 2 years. One patient had titers < 1:100, and
5 patients permanently titers between 1:10 and 1:20. The 4 patients with titers
> 1:100 remained healthy during the entire observation period (2^-4^ years).
One of the 6 patients with titers < 1:100 developed AIDS, one Hodgkins Lymphoma
(HL), one ARC, and 3 remained healthy.
The titer of total anti HIV varied between 1:740 and 1:90000 and correlated
to the titer of NA. The titerratio (ID^/ELISA titer) varied appr. a 100 fold
indicating the neutralizing capacity is probably a function of quality as well
as quantity of the antibodies. In all serum samples antibodies against envelope
proteins were detected. Two patients lacked antibodies against core proteins
(CPA) (1 AIDS, 1 HL, ID <1:20). Two patients lost CPA (1 ARC, ID < 1:100, 1
healthy ID50= 1:100). The remaining 6 healthy patients had CPA during the en-
tire observation period.
In conclusion, NA may thus be a prognostic factor since patients with titers
> 1:100 in this study remained healthy during the entire observation period.
TPJM Lack of Evidence for New Transmission Modes Among AIDS Patients.
E. THOMAS STARCHER, II, TJ DONDERO, Jr., AR LIFS0N, KG CASTRO,
CR WHITE, JW CURRAN. Centers for Disease Control, Atlanta, Georgia, USA
As of January 23, 1987, 29,582 AIDS patients (29,159 adults, 423 children)
had been reported to CDC. Of these, 97% fit into risk groups that suggest a
possible means of disease acquisition. For 3%, means of acquisition is
undetermined. Of all AIDS patients initially identified with undetermined
risks and available for follow-up, 72% were reclassified because risk factors
were identified (68%) or the patient was found not to meet the surveillance
case definition (4%). Of the 932 AIDS patients with currently undetermined
risks, information is incomplete on 215 because of death (158), refusal to be
interviewed (39), or lost to follow-up (18). Of the remaining 717 patients,
523 are currently under Investigation. No risk was identified for 194 patients
who were interviewed or for whom other follow-up information was obtained.
However, 39% of the patients (52/134) answering a standardized questionnaire
gave histories of other sexually transmitted infections . Some of the patients
with undetermined risks may not have HIV infection: for those on whom
HIV-antibody information is available, 9% (32/349) tested negative compared
with 1% (103/7330) for AIDS patients with identified risks. Lack of evidence
for new transmission modes is clearest in the 5- to 15-year age group, which
makes up 16% of the U.S. population. Sixty-six AIDS cases (0.2% of total
cases) have occurred in this age group, which is exposed like other groups to
casual contact with HIV-infected persons, insects, and environmental factors.
Of these, 65 (98%) fit into established risk groups; the remaining case is
lost to follow-up. The proportion of patients with undetermined risks has not
increased significantly over time (p>0.10).
TP82 CLUSTER OF HETEROSEXUAL TRANSMISSION OF HIV IN BRUSSELS.
N.CLUMECK, P. HERMANS, H. TAELMAN, D. ROTH, G. ZISSIS, S. DE WIT
(St Pierre University Hospital, Brussels and Institute of Tropical Medicine,
Antwerp, Belgium) .
A 48y. old single central African engineer was found to have ARC in 1985.
He died in July 1986 with HIV encephalitis and pneumonia. He lived in Belgium
since 1965, travelled regularly to Central Africa and had no history of homo-
sexuality, IV drug use, or blood transfusion. Contact tracing allowed identi-
fication of 19 women (12 middle-class Europeans, 7 Africans; mean age: 35y.)
who had had sexual contacts (only vaginal) with the index case in Brussels
during the last 7 years. 8/19 women were married and mean number of children
was 1.7 (range 0-4). Number and duration of sexual contacts with the index ca-
se ranged from one to multiple contacts during two years or more. 17/19 women
have been examined and 10 of them (59?o) (7 Europeans, 3 Africans) had antibo-
dies against HIV (demonstrated by ELISA and Western blot). The index case was
the only potential source of infection for the white women for whom no sexual
promiscuity (less than 3 partners/y . ) , no travel to Africa, no sexual contact
with other men belonging to high risk groups for HIV, no IV drug use and no
transfusion was found. 7/10 seropositive women described mononucleosis-like
symptoms of acute HIV infection between 1983 and 1985. The current clinical
status of the seropositive women is presently: generalized lymphadenopathy
(n=6), AIDS-Related complex (n=2), AIDS (n=l) and unknown in one case. The
male sexual partners of these women (all Belgian) are currently under inves-
tigation.
This cluster demonstrates how HIV could spread heterosexually in an Euro-
pean area with low prevalence of HIV infection from a few number of promiscuous
men to a high number of female sexual partners without classical risk factor
for HIV infection.
TR85 Serological Analysis of HIV j»ag Reactive Sera in a Blood Donor Population
Using Both Viral and Recombinant Antigens
D. TRIBE, D. REED, P. LYNDALL*. D. WINSLOW**. S.R. PETTEWAY, etal., E.I.
DuPont de Nemours, Medical Products Department, Wilmington, DE., *Blood Bank of
Delaware, Wilmington, DE., **Wilmington Medical Center, Wilmington, DE.
Sera from a normal blood donor population that display reactivity in an HIV-ELISA
screening kit (DuPont) have been further analyzed using both viral and recombinant
antigens. Two major patterns of HIV immunoreactivity have been identified in these
HIV-ELISA reactives. The predominant class were gag reactive eny non-reactive, and
largely consisted of sera reacting with pl5/pl7 bands on immunoblot. These sera
comprise 50% or more of HIV-ELISA reactives examined. Specificity of antibodies to
HIV gag was confirmed in several ways, including competition between viral and
recombinant antigen for reaction with blood donor antibodies. Competition
experiments also provided a direct demonstration that HIV-ELISA reactivity in these
blood donors is largely caused by antibodies that react or cross-react with HIV gag.
An HIV eny reactive class of sera was also identified in this population based on
screening with both HIV immunoblots and with a recombinant (ENV9) ELISA. The gag
immunoreactivity may indicate exposure of this population to an as yet unidentified
retrovirus.
TP.83
TRANSMISSION OF HTLV III (HIV) IN INFANTS OF SEROPOSITIVE MOTHERS.
ANDREA DE MARIA, O.E.VARNIER*, G.MELICA**, F . PANTAR0TT0** ,
P.CR0VARI***, A.TERRAGNA, I Clinica Malattie Infettive, *Istituto di
Microbiologia, *'"Istituto Ostetricia e Ginecologia, ***Istituto di Igiene,
University of Genova, Italy.
HIVinfection in pediatric age occurs most frequently in children of infected
mothers by transplacental or perinatal transmission. To assess the risk for
the fetus to acquire HIV infection during pregnancy we selected and followed
up 36 infants born to HIV antibody positive drug addicts by vaginal delivery.
None of them was breast fed or received blood or blood products. All the
mothers were in WR1 or WR2 disease stages. All the infants seen at birth had
HIV antibodies at high levels, comparable to that of their mothers. 56% of
those presently older than 6 months had progressively decreasing HIV
antibodies and lost them between 7 and 12 months of age, suggesting only
transplacental maternal antibody crossing without infection. This is further
confirmed by the lack of clinical symptomatology and failure to detect HIV
antigen in serum and in peripheral blood lymphocyte culture, as opposed to
seropositive symptomatic children. The risk for the offspring of WR1 or WR2
staged mothers of acquiring HIV infection during pregnancy can be presently
estimated to be around 44%. Failure of detecting HIV antigen in serum and in
cell culture may be useful as a diagnostic tool to rule out infection.
TPRfi Prevalence of HIV antibodies in healthy subjects and groups of
patients in some parts of Tanzania
FRED MHALU, E.MBENA, U.BREDBERG-RADEN, J. KIANGOjK.NYAMURYEKUNGE,
G.BIBERFELD et al., Muhimili Medical Centre, Dar es Salaam, Bukoba Hospital,
Tanzania and National Bacteriological Laboratory, S-105 21 STOCKHOLM, Sweden.
Sera from groups of healthy subjects and from groups of patients collected
in 1986 in Dar es Salaam (the capital of Tanzania), Bukoba (the capital of the
Kagera region in the north west corner of Tanzania) and Arusha (in the north
east part of Tanzania) were screened for antibodies to Human Immunodeficiency
Virus (HIV) by ELISA (Organon-Teknika) . All screening positive sera were also
tested by a HIV competitive EtISA (Wellcome) and by Western blot analysis us-
ing disrupted virions of the HTLV-III B strain of HIV as antigen. In Dar es
Salaam Western blot -confirmed HIV antibodies were demonstrated in 3.6% of 192
pregnant women, 28.8% of 225 barmaids, 4.4% of 225 male blood donors, 9.25%
of 400 male patients attending a clinic for sexually transmitted diseases, in
86% of 35 patients with herpes zoster and in 94?o of 83 patients with clinical-
ly suspect AIDS. In Bukoba the prevalence of HIV seropositivity was higher,
namely 16?o among 100 pregnant women and 14?o among 36 blood donors while in
Arusha only one out of 144 (0.7?o) pregnant women and none of 42 barworkers
tested were positive. HIV infection seems to be newly introduced in Tanzania
and the extent of spreading of the infection differs in various parts of the
country.
76
TUESDAY, JUNE 2
TR87 Mortality, AIDS Incidence and Immunologic Abnormalities Among
Intravenous Drug Abusers (IVDA) in New York City (NYC): A 5-Year
Prospective Study. STANLEY H. WEISS*. I.B. MARGOLIS**, R. ZELNICK**, H.M.
GINZBURG*, D. FUCHS***, J.J. GOEDERT*. et al., *National Institutes of Health,
Bethesda MD, **Queens Hosp. Center, Jamaica NY,***Univ. of Innsbruch, Austria.
IVDA in NYC were among the first recognized AIDS cases. In 1981 in NYC we
initiated the earliest prospective study of IVDA to evaluate clinical and
immunologic abnormalities. HIV antibodies (Ab) were present in 46% of 54 IVDA
by 1982. At least 24% of those HIV seronegative in 1982 had seroconverted by
1986. Overall, at least 60% of the original 60 IVDA now have HIV Ab.
Seven seropositive IVDA have died, a total mortality of 42% ±15% at five
years (Kaplan-Meier method, median follow-up 46 mo., range 0-63 mo.). Deaths
were due to AIDS (3), car accident (1) , and causes still under i nvestigation
(3). By five years, AIDS has been documented in 17% ±10%.
Mortality among the seronegative IVDA also has been substantial: 9% ±6%
(median follow-up 54 mo., range 0-64 mo.), with deaths due to drug overdose
and stabbing. None of the seroconverters has developed AI0S (median
observation after seroconversion 12 mo., range 2-24 mo.).
Mean T4a counts and T4a:T8 ratios were significantly lower in prevalent
seropositive IVDA compared to seronegatives (792 & 0.95 vs. 1175 4 1.40,
p<0.02) . Immunologic pertubation was intermediate in seroconverters. Immune
activation as measured by neopterin was increased among T4a deficient IVDA.
The high mortality among IVDA from all causes makes careful prospective
follow-up of both seropositives and seronegatives essential. A review of
post-mortem material from one subject who had died of an apparent overdose
revealed AIDS (Military Med 151:M33). The excess mortality among seropositive
IVDA may indicate under-ascertainment of HIV-related disease in IVDA.
TR90
EPIDEMIOLOGY OF HIV INFECTION IN HONG KONG
PCK LI EK YEOH WK CHANG YY CHAN SH LEE KL THONG
MEDICAL & HEALTH DEPARTMENT, HONG KONG.
In a seroepidemiological study of the prevalence of HIV infection
in Hong Kong, individuals from different groups were tested for HIV antibodies
using a commercially available ELISA method. Positive results were confirmed
by immunofluorescence and Western Blot.
74 of 38,293 individuals screened between April 1985 to December
1986 were confirmed to be seropositive. Analysis of the results at 6-monthly
intervals showed no increase in the prevalence of seropositivity .
RESULTS OF HIV SEROLOGY
Tested
Social Hygiene (STD) Clinic 350
IV Drug Abusers 1127
Haemophiliacs 102
Patients with Cooley's anaemia306
Haemodialysis patients
Health Care Personnel
Sermen donors
Government HospitalsSClinics
Private Hospitals & Clinics
RISK FACTORS IN 63 INDIVIDUALS
SEROPOSITIVE EOR^ ^ ^^
Haemophiliacs
46
0
Sisexual"'
Heterosexuals 2* 1
with prostitute contact
Transfusion 2+ 0
46
12
sion
recipients
60 3
*1 practised IV drug abuse in
spSin
+Both received blood in 1984
74(0.19%)
Haemophiliacs with a history of imported factor VIII transfusion,
homosexuals and bisexuals, and heterosexuals with history of sexual contact
with prostitutes constitute high risk groups for HIV infection in Hong Kong.
The risk of transfusion-related HIV infection should be reduced by the donor
screening programme instituted since August 1985.
Tp 00 Relative Risks of AIDS for American Blacks and His panics
RICHARD M. SELIK, M.F. Rogers, AIDS Program, Center for Infectious
Diseases , Centers for Disease Control , Atlanta , Georgia, USA
Although non-Hispanic blacks and Hispanics represent only 12% and 6%, res-
pectively, of the U.S. population , they constitute 25% and 14%, respectively,
of the 29, 497 AIDS patients of known race/ethnicity reported to the Centers
for Disease Control (CDC) from June 1, 1981, to January 26, 1987. We studied
their greater risk of AIDS, compared with that for non-Hispanic whites, in
terms of their relative risks (RR) , assessed as the ratio of the cumulative
incidence of AIDS in a particular racial/ethnic group to the cumulative inci-
dence in whites. The cumulative incidence was calculated as the total number
of AIDS cases per million population of the same racial/ethnic group. Based on
AIDS cases reported to CDC and population data from the 1980 census, the cumu-
lative incidence of AIDS in whites was 98; that in blacks, 283; Hispanics,
290; and other groups (e.g., orientals), 63; these figures yielded RR of 2.9,
3.U, and 0.3 for blacks, Hispanics, and other groups, respectively, as com-
pared with 1.0 for whites. The RR for blacks and Hispanics were greater for
women (14.0 and 10.9) and children (14.0 and 9.1) than for men (2.9 and 3.1).
When the analyses were stratified by the probable means of AIDS acquisition,
the RR were greatest for transmission categories associated with intravenous
drug abuse: for heterosexual intravenous drug abusers (IVDA) (21.3 and 23.5),
for other persons whose heterosexual sex parters were IVDA (24.2 and 31.3),
for children whose mothers were IVDA (36.4 and 25.5), and for children whose
mothers had sex partners who were IVDA (14.5 and 23.1). The RR were also in-
creased in association with male bisexuality, blood transfusion, and absence
of any identified means of acquiring AIDS. Knowledge of these associations may
be important in targetting AIDS prevention strategies for blacks and Hispanics.
TP91 Modelling the Incidence of Acquired Immunodeficiency Syndrome (AIDS)
in New York, San Francisco and Los Angeles
JOHN PICKERING, J. A. WILEY, L.E. LIEB, J. WALKER, and G. RUTHERFORD, Dept. of
Entomology, Univ. of Georgia, Athens, GA; Survey Research Center and San
Francisco Men's Health Study, Univ. of California, Berkeley, CA; County of Los
Angeles, Dept. of Health Services, CA; City of New York, Dept. of Health, NY,
and City and County of San Francisco, Dept. of Public Health, CA.
With an epidemic model ve explore the biology and sociology of AIDS incidence
and forecast new cases. Our model assumes that AIDS can be modelled as a
sexually transmitted disease. Its parameters reflect (1) hov long AIDS takes to
develop after exposure to the infectious agent, (2) when infected individuals
are contagious, (3) decreases in transmission rates because of behavioral
changes, and (4) saturation — the removal of susceptible individuals through
infection. Declines in anal/rectal gonorrhea cases in New York and San Francisco
are used in modelling the impact of behavioral changes.
By November, 1986, New York, San Francisco, and Los Angeles had over 8,031,
2,546, and 2,360 AIDS cases, respectively. Each city's cumulative number of
cases doubled in the 10-13 months before July, 1985, but may not continue to
increase at this rate. The model shows how AIDS incidence in the cities could
level off and even start to drop by 1991, because of saturation and behavior.
However, a sensitivity analysis of the model's parameters shows that there are
insufficient data to choose between radically different forecasts. Before
accurate forecasts can be made, more data are needed on (1) the distribution of
development times, (2) the infectivity of individuals, (3) the proportion of
infections that develop AIDS, and (4) behavioral changes.
Judged by the model's fit to the cases reported by November, 1986, it appears
that these cases generally were diagnosed 3-4 years after exposure to the agent
and were most infectious in the months immediately after exposure.
TR89
FIve-Year (1982-1987) Prospective Clinical and Immune Evaluation
of Hemophiliacs Before and After Exposure to HIV.
CHRIS TSOUKAS*. H. STRAWCZYNSKIt, F. GERVAIS*. J. SHUSTER*, P. GOLD*,
♦Montreal General Hospital, tMontreal Children's Hospital, Montreal, Canada.
Immediately following the first appearance of AIDS among hemophiliacs in
1982 we evaluated 34 adults with severe classic hemopM 1 ta for immune defi-
ciency, all were treated exclusively with lyophilized Factor VIII concen-
trates. Initially all felt well and none had clinical manifestations related
to AIDS although 68% had evidence of cellular immune dysfunction. To deter-
mine the significance of this dysfunction and to assess the long terra clinical
.outcome of this cohort, the group was followed for the next 5 years. They were
examined and tested semiannually for T cell subsets, serum immunoglobulins,
lymphocyte responsiveness to mitogens, anergy, and viral serology. Serum
samples were sequentially frozen and stored.
Subsequent HIV serology by Western blot analysis revealed that initially 60%
were seropositive In 1982 and by 1984 33/34 had seroconverted. Although all
were Initially healthy and asymptomatic, today 90% have clinical manifesta-
tions of HIV disease. 52% (17/33) have persistent generalized lyraphadenopathy
(CDC Group III classification) and 38% (13/33) have AIDS or AIDS-related
syndromes (or Group IV). One patient has died of AIDS related disease, two are
critically ill following Pneumocystis carinil pneumonia and 5/33 have devel-
oped severe life threatening thrombocytopenia. All HIV seropositive individ-
uals currently display a spectrum of progressively deteriorating _in_ vitro
immune parameters that correlate significantly with time of exposure to HIV.
We conclude that the majority of HIV seropositive severe classic
hemophiliacs will develop severe HIV disease five years following exposure to
the human immunodeficiency virus and almost all will display a progressive and
significant deterioration of their immune status.
TPQ2 Evaluation of first and second generation (confirmatory) assays for
antibodies to HIV
P. Nico LELIE, J.G. HUISMAN et al.(l)
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service,
(CLB) , incorporating Lab. of Exp. and Clin. Immunology University of
Amsterdam.
The sensitivity and specificity of six commercial enzyme immunoassays (EIAs)
for antibodies to HIV has been evaluated in 6488 serum samples (Lancet, August
30, 1986: p. 483-486) (1). This panel and sequential sera from 12 individuals
who seroconverted for anti-HIV were used to compare the first and second
generation EIAs from three manufacturers (Abbott, Organon, Wellcome) and three
confirmatory assays, i.e. Western Blot (WB, Biotech Dupont) ; competitive
immunoassay for separate detection of antibodies to HIV envelope and core
(CIA, Abbott) and a home-made radio immunoprecipitation assay (RIPA-CLB). The
confirmatory tests and second generation EIAs were significantly more
sensitive in detecting antibodies early after HIV infection than the first
generation EIAs. The earliest detectable antibodies in the confirmatory tests
were anti-p24 and anti-gpl20/160 in WB; anti-envelope in CIA and anti-p24 in
RIPA. The anti-core CIA did not detect anti-p24 responses in approximately
10% of asymptomatic seropositive individuals. The antibody levels against
envelope proteins gp 160/120/41 persisted during transition to AIDS, whereas
antibody titers to p24 dimiminished or disappeared. Follow up studies showed
that false positive reactions were observed in confirmatory tests. The
respective frequencies in a panel of tricky sera (n=293) and of blood donors
(n-5000) were W.B.: anti-p24 1,7% , 0.18% ;CIA anti-envelope: 0,3% , 0.02% ;
RIPA anti-p24: 0% , 0-06%. The new generation EIA's are important tools to
establish early antibody responses in patients and blooddonors exposed to HIV.
77
TUESDAY, JUNE 2
TR93
PRELIMINARY RESULTS OF A SURVEILLANCE SYSTEM OF HIV PEDIATRIC
INFECTION
GIUSEPPE IPPOLITO, PEDIATRIC AIDS AND HIV INFECTIONS WORKING GROUP,
Coordinated by Latium Region Epidemiologic Unit and Children's Hospital
Bambino Gesu- Rome- Italy
A surveillance system of HIV infection, based on compulsory notification by
laboratory physicians of every positive subject together the relevant data
(place and date of birth, sex, place of residence, risk factors) was set up
in Latium, a 5.000.000 inhabitants region of Italy, in 1985.
An active working group to trace seropositive mothers, contact and perform
clinical follow up on babies at risk was established.
80 babies (1 hemophiliacs, 2 transfused and 77 child born HIV positive
mother) had a positivity for anti-HIV antibodies until October 1986.
73 seropositives have been enrolled in a follow-up study.
Mean time of observation was 10.3 months (range 1-36), for a total of 749
person/month of observation.
Nine cases of AIDS have been observed. Incidence rate, in a period of 36
months, is .123 (CI 951 .058-. 221).
Fourteen children (.122 - CI95X .109-. 301) have lost the anti-HIV antibodies
during the first year of life (mean 8 months, range 5-12).
Thirty-five children (.479 CI 95Z .361-. 600) younger than 1 year (mean time
of observation: 4.1 months) were positive at the end of the observation
time.
Six subjects (.082 CI95I .031-. 17) were seropositive and asymptomatic at the
end of an average observation period of 17.8 months.
Five (.068) children showed a persistent generalized lymphadenopathy after a
mean 12.4 months of observation and four babies (.055) costitutional
diseases and/or secondary infectious diseases.
TP96 Genetic Aspects of AIDS in Trinidad.
C. BARTHOLOMEW* FARLEY CLEGHORN*. V. WILSON*, B. MAHABIR*, AJIR00K,
A.S. FAUCI.
The University of the West Indies*, Port of Spain, Trinidad and the NIH,
Bethesda, Maryland, USA.
Trinidad has a population of 1.2 million comprising people of African descent
41%, Indian descent 41%, mixed race 16%, Chinese 1% and Caucasians 1%. To date
a total of 144 cases of AIDS have been seen in Trinidad. Of these 133 have been
in people of African and mixed African descent, 7 in people of Indian descent,
3 in Caucasians and 1 Chinese. The common opportunistic infections seen are
candidiasis, toxoplasmosis, histoplasmosis and cryptococcosis. Less commonly
seen is Pneumocystis carinii pneumonia and Kaposi's sarcoma is rare.
In a survey of 106 healthy homosexual men in Trinidad in 1983, 36/90 (40%) of
those of African and mixed African descent were HIV seropositive compared with
6/16 (37.5%) of those of Indian descent. As the prevalence of homosexuality
appears to be equal in the various ethnic groups in Trinidad the possibility of
a genetic factor associated with the relative paucity of cases of AIDS in
Indo-Trinidadians was considered. Preliminary studies of antibody dependent
cell-mediated cytotoxity (ADCC) have shown that HIV positive Indo-Trinidadians
without disease have higher levels of ADCC (mean 29.4%) than Afro-Trinidadians
without disease (mean 14.8%). Initial studies of HLA haplotypes among 130
healthy males in Trinidad have shown that HLA Dr 5, which is present in 24.8%
of black Africans is absent thus far in 70 Afro-Trinidadians while present in
8.5% of Indians. In addition, there is a relative absence of HLA Dr w6 (4.3% vs
20.2%) and particularly HLA Dr 1 (0% vs 15%) in persons of Indian descent in
Trinidad compared with those of African ancestry.
These genetic differences could possibly expain the discrepancy in the
occurence of AIDS among Trinidadians of African and Indian descent.
JP94 Surveillance of AIDS in India With Special Reference to Union
Territory of Delhi.
P.N.Sehgal.S.KUMARI.ARVIND RAI.National Institute of Communicable Diseases,
Delhi-110054 (INDIA).
Following the first confirmed evidence of AIDS virus infection in India in April,
1986, a massive surveillance campaign was launched to screen high risk Individuals
across the country. From July through December, 1986, a total of 5,000 serum
samples were collected lfrom specified high risk Individuals from Union Territory
of Delhi. Of them 3268 were from males and the rest (1732) females, mostly
between 20-45 years of age. The samples belonged to patients attending STD
clinics (2789), prostitutes (408), Jail inmates (413), drug addicts (49), professional
blood donors (1057), chronically HI patients referred from hospitals from HTLV-
III antibody screening (246), foreign students (8) and the patients who underwent
by-pass surgery abroad (30). All the samples were subjected to Wellcozyne
HTLV-III EIA. Only one sample yielded a strong positive result in ELISA confir-
med by Western blot. Samples from two male patients attending STD clinics
yielded positive ELISA results but only one gave a mild positive ( ,4 u.-j oniv)
result in Western Blot.
These findings Indicate that AIDS virus infection In this part of the country
is probably at a very low key, but continued surveillance is warranted to keep
a close vigil over the situation.
TR97
AUTOLOGOUS KILLING MECHANISMS IN HIV INFECTION. MM Lederman,
SF Purvis, Department of Medicine, Case Western Reserve
University and University Hospitals, Cleveland OH.
Longitudinal studies performed among hemophiliacs (H) infected by the
human immunodeficiency virus (HIV) reveal a progressive loss of CD4
lymphocytes and increased numbers of CD16 and activated CD8 cytotoxic
lymphocytes. We asked if lymphocytes of HIV infected H could kill
autologous cells. In 4 h. chromium release assays, unstimulated H
lymphocytes (n-9) demonstrated significant cytotoxicity against autologous
cells (5.2±2.0I lysis) (mean ± SE), whereas controls' (C) cells (n-12)
demonstrated no autologous killing (0.5±0.3X lysis, p<0.02). After culture
for seven days with irradiated autologous peripheral blood mononuclear cells
(n-7) nonadherent (NA) H cells demonstrated enhanced killing of autologous
PHA blasts when compared to C (n-7) (11.5±4.8 vs 4.1±2.0I lysis p<0.05).
After stimulation by alloantigens, H NA cells demonstrated greater killing
of autologous targets than C NA cells did (19.4±4.2 vs 10.0±2.5I lysis, p<
0.01) and were activated more than C NA cells to lyse both allogeneic
(stimulator) targets (p<0.03) and unrelated allogeneic targets (p<0.05).
Cold target inhibition studies demonstrated that K562 tumor cells and
unrelated PHA blasts inhibited lysis of autologous targets. Yet cell
separation studies revealed that autologous killing vas mediated by CD8
lymphocytes and was unaffected by depletion of CD16 cells. Enhanced
autologous killing was seen in 3 HIV-infected homosexual men but not in. 3
HIV-seronegative H. Thus, lymphocytes of HIV-infected persons possess low
levels of cytotoxic activity against autologous lymphocytes and show
increased activation by alloantigens to lyse nonspecif ically autologous and
allogeneic cells. Autologous killing may contribute to the progressive
lymphopenia of HIV infection.
TPQ5 ACTUAL SITUATION OF HIV INFECTIONS IN FRENCH POLYNESIA
E. CHUNGUE, F. FLYE SAINTE MARIE, J.L. CARTEL, G. PAP0UIN,
S. CHANTEAU and J. ROUX, Institut Territorial de Recherches Mgdicales Louis
Malard£, B.P. 30 Papeete-TAHITI
Since July 1985, a serological survey is carried out in 682 subjects belon-
ging to different groups at risk for AIDS. Positive sera in ELISA were confir-
med by immunoblotting. The sero prevalence in January 1987 is :
0/33 hemodialysis patients transfused in Tahiti
0/131 female prostitutes
1/138 male homosexual (transvestites) . He never left French Polynesia and
reported foreign sexual partners.
10/244 (9/170 M, 1/74 F) homosexual or bisexual men and patients attending
private practitioners or STD clinic for AIDS counseling. 9 of them have lived
or travelled often in countries where AIDS is endemic.
6/125 (4/54 M, 2/71 F) permanent residents operated mostly between 1981
and 1985 for heart disease and intensively transfused in other countries
(France essentially) before blood screening is established.
1/11 (5 M, 6 F) household contacts or sexual partners of 3 seropositive
cases.
The overall prevalence rate of HIV antibodies is 2.5 % in the high risk
population and 0.1 % as referred to the total population (170 000 inhabi-
tants). ARC has been diagnosed in 4 of them. Introduction of the AIDS virus
is likely recent since no instance has been found yet in more than 8 000 blood
units tested in the local transfusion center. As a matter of fact, HIV has
been brought into French Polynesia in part, by a much-travelled class of the
population involving homosexual and bisexual men essentially and in the other
hand by heterosexual patients who underwent heavy surgery in foreign country.
TP98 Persistent Co-Infection of T Lymphocytes with HTLV-II and HIV and
the Role of Syncytium Formation in HIV-lnduced Cytopathic Effect.
DAVID C MONTEFIORI*. W. EDWARD ROBINSON and WILLIAM M. MITCHELL,
Vanderbilt University, School of Medicine, Nashville, Tennessee.
We previously demonstrated a high permissiveness of HTLV-ll-transformed T
lymphocytes (C3) to human immunodeficiency virus (HIV) infection in vitro, and that
this infection results in the lysis of cells (D.C. Montefiori and W.M. Mitchell,
Virology, 155, 726-731, 1986). We now show that a small percentage of HIV
infected C3 cells resist cell lysis, grow continuously in culture and express antigens of
both viruses. High levels of reverse transcriptase activity found in the culture fluid
of these co-infected cells was associated with the presence of fully infectious HIV
and an absence of detectable infectious HTLV-II. Virus production in C3 cells co-
infected with HIV isolate HTLV-III was approximately 3-fold greater than in C3 cells
co-infected with the HIV isolate LAV, a result which suggests that HIV genomic
diversity may give rise to differences in replicative capacities. Lysis resistance was
found to be a cellular-determined function in that HIV produced in cultures of
C3/HTLV-III cells retained the capacity to elicit a lytic response upon repeated
infection. Small syncytia were rarely observed in cultures of C3 and non-lytic C3/HIV
cells whereas large syncytia were in abundance during the lytic phase of co-
infection, a result which supports a role for syncytium formation in the mechanism
of HIV-induced cytopathic effects. The results of these studies also demonstrate
that there exists a lack of HIV interference by HTLV-II infection, and that HTLV-II
transformed lymphocytes could act as a chronic reservoir for HIV in vivo. These
findings have important medical implications in view of the high prevalence of
HTLV-II antibodies in HIV antibody positive and negative individuals at risk for AIDS
(Robert-Guroffetaj., JAMA 255, 3133-31 37, 1986).
78
TUESDAY, JUNE 2
TP99 Effects of long term seropositivity to Human Immunodeficiency Virus in a cohort of
homosexual men.
MICHAEL S WEAVER, MT SCHECHTER, WJ BOYKO, B DOUGLAS, B W1LLOUGHBY, AW
MCLEOD, et al. The Vancouver Lymphadenopathy-AIDS Study, St. Paul's Hospital, University of
British Columbia, Vancouver, BC, Canada.
The long term effects of HIV infection were evaluated in a cohort of homosexual men by comparing
clinical and lab parameters obtained from 2 visits a mean of 18 months apart in groups of 148
persistently seropositive and 287 persistently seronegative men. Differences between the groups were
present at each visit with the seropositive men exhibiting lower CD4 counts, higher CD8 counts, lower
CD4/CD8 ratios, higher Clq binding, higher IgG and IgA levels, lower Hgb, and lower lymphocyte
counts. More important, comparison of the differences between visits in the positive and negative
groups, revealed that the seropositive group underwent a significant mean decline in the CD4/CD8
ratio (-0.13 vs +0.05; p=.013), and significant mean rises in the Clq binding (+4.7 vs +0.5; p<.001), in the
IgG (+92 vs -2; rx.OOl) and in the IgA (+16 vs +1; p<.001) as compared to the seronegative group.
Seropositive men were at elevated risk of developing symptoms and lymphadenopathy, though these
risks did not progress with time. Comparisons of parameters obtained a mean of 21.4 months prior to
diagnosis in 11 seropositive men who subsequently progressed to AIDS and 134 seropositive men who did
not, revealed lower CD4 counts (450 vs. 739; p<.001),lower CD4/CD8 ratios (0.65 vs 1.14; p<.001),
higher Clq binding (20.7% vs. 13.6%; p<.001), lower Hgb (14.6 vs 15.1; p=.088), and lower lymphocyte
counts (1638 vs. 2041; p=.041) in those who progressed to AIDS. Moreover, between antecedent visits,
those who progressed to AIDS experienced greater mean declines in CD4 count (-155 vs -40; p=.074), in
Hgb (-1.1 vs -0.1; p<.001) and in WBC (-1000 vs -351; p=.079) than the seropositive AIDS-free group.
Although these data document long term effects of HIV infection in a seropositive cohort, about 25% of
persistently seropositive men maintained normal CD4/CD8 ratios, suggesting the possibility of one
subgroup of men who may be resistant to the effects of HIV infection, and another who are particularly
susceptible to the progressive effects of HIV that precede the development of AIDS.
TD-ino Rapid Detection of Human Immunodeficiency. Virus Antigens in
Lymphocytes by Immunogold Scaning Electron Microscopy.
RAFAEL NAJERA, M.I. HERRERA, R. de ANDRES, I. SANTA MARIA, A. TENODIO, L. MU
Virologia e Inmunologia Sanitarias,
Spain.
NOZ. Centro Nacional de Microbiologf a,
Instituto de Salud Carlos III Majadahonda, (Madrid) ,
The observation by scanning transmission electron microscopy (STE") of —
gold immunolabelled Human Immunodeficiency Virus (HIV) infected cells might
be a new approach to rapid diagnosis of AIDS at the early phase of infecti-
on. It combines both the morphological information and rapid procedures of
scanning electron microscopy (SEM) with SEM of lymphocytes from 13 HIV posj.
tive individuals and from HIV infected cultures lymphocytes -eveals the p.-£
sence of giant cells with characteristic "spongy" surface appearance that -
suggest viral infection. In 4 patients, other unnusual spherical multiface-
ted structures (5-18 urn.) have been also found. They could correspond with
a process of gene amplification and could indicate virus production at low
level.
A more precise detection of the
cells has been achieved by their
anti-pl7 and anti-gp41 monoclonal
nm gold-labelled goat anti-mouse
STEM techniques and backscattered
vides a very sensitive technique
cell surface. Paired electron mi
"spongy" cells have a particulate
presence of HIV antigens in these "spong/"
specific indirect inmunolabelling, using -
antibodies as sprimary antibodies and -.0
IgG as secondary antibodies. The use of -
electrons imaging for gold detection pro-
for antigen detection at and below the —
crographs have been taken showing that —
gold content, indicating HIV infection.
TR100 Antibodies to the transactivating protein of HIV, tat3
and the induction of HIV antigen expression in vivo.
WILLY J.A. KRONE*. Chr. DEBOUCK**, P. HEUTINK*, J.M.A. LANGE*
F. DE WOLF*, and J. GOUDSMIT*; 'Virology Department,
University of Amsterdam, Netherlands, **Smith Kline and
French Laboratories, Philadelphia, PA, USA.
To obtain large amounts of the tat3 protein, a plasmid was
constructed in which the 3th to last tat3 codons were fused
to the first 52 codons of the E.coli galactokinase gene in
the pOTSKF33 expression vector. The fusion protein was
induced in E.coli using nalidixic acid and purified using
preparative SDS-PAGE. The purified fusion protein had a
molecular weight of 17 KD and was used as antigen for
immunoblotting and enzyme-linked immunosorbent assays (EIA).
The presence of HIV Ag was evaluated by EIA (Abbott Labs,
N. Chicago, 111.). Seguential sera of 86 individuals,
collected over a period of two years were used in this study
Twenty-one of these individuals seroconverted for antibodies
to HIV and 65 were HIV-Ab seropositive at entry in the study.
Among the HIV-Ab seropositives 21 were HIV-Antigen positive
throughout the study and 27 seroconverted for HIV-Ag.
The presence of antibodies to tat3 was closely related to
expression of HIV-Ag in serum (p<0.01). Seroconversion for
antibodies to tat3 was observed prior to or concomitant with
seroconversion for HIV-Ag. Individuals with a prolonged HIV
antigenemia showed a steady decline in antibody titers to
tat3 with time. These results present evidence for in vivo
regulation of HIV gene expression by the tat3 protein.
TP103 Normal Neutrophil Phagocytosis but Impaired Chemotaxis in Homo-
sexual Male Patients with AIDS, ARC and Neither Disorder
LAWRENCE A. CONE*, *DIVIS THIND**, MILAN FIALA*, DAVID R. W0ODARD*, DOMENIC
CASAREALE*. 'Eisenhower Medical Center, Rancho Mirage, CA.
Although the target cell for HIV infection is acknowledged to be the T4
helper cell, monocyte, macrophage and B-cell function is also adversely
affected by the retrovirus. We and others have previously reported an
increased incidence of unusual and recalcitrant bacterial infections in
patients with AIDS as well as homosexual males suggesting impairment in
neutrophil function. Chemotaxis and phagocytosis are critical events in the
effector functions of granulocytes. Thirty-one homosexual or bisexual males
were studied for neutrophil chemotaxis using zymosan-activated serum in a
Boyden chamber and phagocytosis utilizing latex spheres. Twenty-three
patients had AIDS, 5 had ARC and 3 had neither. Seventeen of 23 (74%) with
AIDS, 4 of 5 (80%) with ARC and 2 of 3 (67%) with neither disorder expressed
defective chemotaxis but normal neutrophil phagocytosis. No distinguishing
clinical or laboratory characteristics could be discerned within each group
that separated normals from those with abnormal leukocyte chemotaxis. It
is concluded that defective chemotaxis is common in patients with AIDS, ARC,
and in otherwise healthy HIV antibody-negative homosexual males. The etiology
of this defect will require additional studies, but appears to be related to
lifestyle rather than to HIV infection.
TP1H1 Characterisation of the T-lumphocyte Response to Primary
,r,,ul HIV Infection.
DAVID A. C00PER*i», B. TINDAL
AIDS Epidemiology and Clinic
for Immunology St. Vincent's
Multiple T-lymphocyte dete
sexual men for up to 500 day
In all subjects the initia
marked decrease in the total
numbers of circulating T4+ a
remained normal. Within 14
with a T8+ subset increasing
set, leading to an inverted
was followed by an increase
subsets) above base line lev
lasted up to two months and
T8+ lymphocytes, followed by
lymphocytosis. The ensuing
of the T4 + lymphocytes to ne
of a high T8 + response and a
These changes represent th
tomatic period with lymphope
lymphocytosis, and a longer
tion with a normal level of
T8+ lymphocytes and an inver
Further investigations of
the role of T8+ lymphocytes
understanding of immunoregul
L *, R. PENNY*. *N
al Research, Sydn
Hospi ta 1 , Sydney
rminations were a
s following prima
1 response to HIV
lymphocyte count
nd T8+ cells; the
days the lymphocy
proportionally m
T4+:T8+ ratio by
in the total lymp
els. This relati
the major contrib
an incomplete re
months were chara
ar-baseline level
n i nverted ra t i o .
ree distinct phas
nia, a recovery p
term period of as
T4+ lymphocytes,
ted T4+:T8+ ratio
the mechanisms of
in limiting HIV i
a tion of HIV infe
H&MR
ey.
Au
vail
ry H
inf
and
T4 +
te c
ore
day
hocy
ve 1
uti n
duct
cter
s, b
C Sp
Aust
stra
abe
IV i
ecti
i n
:T8 +
ount
than
20.
te c
ymph
g su
ion
i sed
ut a
e c i a 1 Unit in
ra 1 i a . #Cen tre
lia.
on 19 homo-
nf ec ti on .
on was a
the absolute
ratio
began to rise
the T4+ sub-
This period
ount (and
ocy tos i s
bset was the
in T8 +
by a return
ma i n tenance
es: an acute symp-
eriod with a T8+
ymptomatic HIV infec-
sl i ghtly i ncreased
these changes and
nfection may improve
cti on .
TP1(I4 In vitro synthesis of antibodies against HIV-1 components.
ALBERTO AMADORI*, A. DE ROSSI*, G.P. FAULKNER-VALLE* , C. GIAOUINTO**, E.
FRANCAVILLA***, L. CHIECO-BIANCHI*. *Inst. of Oncology, "Pediatrics Dept . ,
"'Infectious Disease Div., University of Padova, Italy.
We studied the in vitro synthesis of antibodies directed against human
immunodeficiency virus, type 1 (HIV-1, LAV/HTLV-III) components (HIV-Ab) from
peripheral blood lymphocytes of 30 seropositive individuals. A significant
amount of HIV-Ab was detected by an IgG-ELISA assay on culture supernatants of
unstimulated cultures. Mean absorbance values in the patient group was
1.104+0.381 SD, whereas in the control group mean values of 0.020+0.02 SD were
found. The phenomenon reflected a de novo Ig synthesis, as shown by the
inability of puromycin-treated cultures to produce HIV-Ab. Moreover,
spontaneous HIV production was detected within the first 24 hr of culture,
suggesting an in vivo activation of antibody-forming cells. When PBL were
cultured in the presence of pokeweed mitogen, a significant difference in
HIV-Ab production between seronegative and seropositive individuals was still
observed. When examined by the Western blot technique the supernatants from
seronegative subjects gave negative patterns, whereas all those from
seropositive individuals were reactive with different vitus proteins. A
general correlation between serum and supernatant Western blot reactivity was
observed, although in individual cases some antibody specificities were not
detected in culture supernatants. The present in vitro model could be an
useful tool to investigate the inmunobiology of HIV-1 infection.
79
TUESDAY, JUNE 2
TR105 CD4-gene transcription is not impaired by HIV replication.
P.SALMON, J.C.GLUCKMAN, D.KLATZMANN. UFR Pitie -Salpetriere, Paris, FRANCE.
HIV infected cell lines display decreased CD4 membrane expression and mRNA
levels after long-term cultures. Two mechanisms could explain such bulk reduc-
tion in CD4-gene transcription: (1) direct genomic interaction between HIV and
CD4; (2) progressive selection of individual CD4 low-producing cells. Using the
cytodot technique with a B-actin internal standard, we sequentially performed
semi-quantitative determination of CD4 mRNA levels in normal lymphocytes and
various cell lines before and after infection with HIV. Normal or slightly
elevated CD4 mRNA was observed during early (<2 weeks) HIV replication in nor-
mal CD4+ lymphocytes. CD4 mRNA remained also normal at the chronic replication
phase (>2 weeks) in CEM derived clones. In both cell types, HIV replication
led to the complete disappearance of detectable surface CD4.Low CD4- expressing
HIV-resistant cells eventually emerged from the lines while the clones subse-
quently died from cytopathic effect. Altogether all these findings rule out
any direct genomic interaction between HIV and CD4, arguing for the selection of
low CD4-expressing cells in heterogeneous cell lines. They confirm and empha-
size previous results that strong CD4 expression is a requisite for the occur-
rence of significant HIV cytopathic effect.
TP108 HIV Bln<iin8 to the CD* Molecule: Conformation Dependence
and Antibody Inhibition,
J.STEVEN MCDOUGAL, J.K.A. NICHOLSON, G.D. CROSS, S.P. CORT, M.S. KENNEDY, A.
MAWLE, Centers for Disease Control, Atlanta, GA.
The human immunodeficiency virus (HIV) binds to CD4+ T cells via a complex
of the viral envelope glycoprotein gpllO and the CD4 molecule. We treated
virus with a variety of physical, chemical, and enzymic agents to determine
their effect on the capacity of HIV to bind to CD4+ T cells. Reduction and
alkylation (but not alkylation alone) and trypsin digestion (but not
glycolytic enzyme digestions) of HIV destroyed its capacity to bind. Human
sera reactive with HIV universally Inhibited virus binding, but the binding
inhibition titers were only weakly correlated with anti-gpllO titers.
Absorption, elution, and crossabsorption of anti-HIV serum with immobilized
native or reduced and alkylated virus provided evidence for
conformation-dependent antibodies that are potent inhibitors of virus binding.
Taken together, these results indicate that the CD4 binding site of gpllO
requires a proper tertiary protein conformation that is dependent on covalent
disulfide bonds and that conformation-dependent antibodies are elicited that
are potent Inhibitors of virus binding.
TR106 Regulation of HIV Expression in Acutely Infected Promonocyte
Cells and in Chronically Infected Promonocyte Clones
THOMAS M. FOLKS*, J. JUSTEMENT*, A. KINTER*, G. POLI*, J. ORENSTEIN**, AND
A.S. FAUCI*, *NIH, Bethesda, MD, **G.W. Univ., Washington, D.C.
The monocyte has emerged as a potentially important cell in the pathogenesis
of human immunodeficiency virus (HIV) infection. Successful HIV infection of
normal monocytes in vitro has been achieved. In addition, The promonocyte
cell line, U937, has been demonstrated to be susceptible to infection with
HIV, and the level of HIV expression has been shown to be under regulatory
control with cytokines such as GM-CSF and INF-y.
The present study has investigated the effect of phorbol myri state acetate
(PMA) an inducer of monocyte differentiation, on the initial infection of U937
cells with HIV and on chronically infected U937 clones. Following acute
infection of U937 cells with HIV the cell line can be inhibited from producing
virus if treated with 10" M PMA. Concomitant with this inhibition, PMA
induces differentiation of U937 cells as manifested by adherence, granule
formation, increase in surface density of CR3, and down-modulation of CD4 (the
HIV receptor). In contrast to the acutely infected U937 cells, clones derived
from the chronically infected U937 population which manifest only a very low
level of viral productivity show an increase in the level of HIV expression
after PMA induction. EM studies of these clones indicated that PMA also
induced increased endocytotic vesicles containing many HIV particles. In situ
immunofluorescence of these clones stained with pooled sera from AIDS patients
showed an increase from 2% to 30% positivity after PMA treatment. These
studies lend insight into the role of monocyte differentiation in the
susceptibility to HIV infection as well as provide a model at the clonal level
to delineate latency or chronicity of HIV infection of monocytes and the
signals required for conversion to high level viral expression.
TPIflQ Frequency of Infected CD4 Cells After in vitro Exposure to HIV
I r. lUS Determined by Limiting Dilution Analysis.
LINDA S. MARTIN, J.S. MCDOUGAL, Centers for Disease Control, Atlanta, GA.
We developed a limiting dilution assay for determining the frequency of
infected cells (FOIC) after in vitro exposure to HIV. Cells were incubated
with HIV, washed, diluted, and cocultured with phytohemagglutinin (PHA)-
stimulated lymphocytes in microcultures. The frequency of positive cultures
conformed to a Poisson distribution. The assay was sufficiently sensitive to
detect a single infected cell as assessed by analysis of HIV-infected H9
cells. The FOIC depended on the ratio of virus to cells used for Inoculation,
i.e. the multiplicity of infection (MOI). For example, the FOIC for
PHA-stimulated CD4 cells Increased from 1 in 24 at a MOI of 0.99 to 1 in 1 at
a MOI of 99. FOIC increased with increasing time of incubation with virus and
reached a maximum of 1 in 5 to 1 in 1 at 24 hours for PHA-stimulated CD4
cells. Inoculation of unstimulated CD4 cells under the same conditions yielded
FOIC that were substantially lower (less than 1 in 100). Activated cells were
treated at various times after exposure to HIV with trypsin under conditions
sufficient to inactivate accessible HIV and to remove the HIV-blnding portion
of the CD4 molecule. There was no difference in FOIC with or without trypsin,
suggesting that the physical manipulations used remove surface-bound virus. In
contrast to these results, HIV binding to the CD4 receptor is
trypsin-sensitive, occurs much more rapidly, and is equivalent in activated
and nonactivated CD4 cells, Indicating that the limiting dilution results
reflect a more rate-limiting step in the establishment of cellular infection,
such as penetration of virus. We conclude that virtually all CD4 cells, under
optimal conditions of activation and incubation, can be infected with virus.
However, establishing infection is more efficient In activated cells, possibly
related to increased internalization and cycling of the CD4 molecule.
TR107
THE SKIN REPRESENTS A SITE OF VIRUS
INFECTION WITH HUMAN IMMUNODEFICI
E.Tschachler*.V.Groh». S . Gartner *,K . Rapper s be rge
G.Stingl**et al . laboratory of Tumor Cell
Bethesda, MD,**Dept. of Dermatologyl , +Dept . of
University of Vienna Medical School, Vienna, Aus
The skin is a heterogenous organ consisting o
ent ontogenetic origin. Epidermal Langerhans c
a persistent, distinct population of antigen
cytes within the skin. We have recently demons
HIV-infected individuals react with monoclonal
ted against HIV specific core proteins pl7 and
highly indicative for the presence of HIV withi
Extensive electronmicroscopic analysis o
biopsies from an AIDS patient with anti pl7/p2
revealed mature HIV-like virions in the extrac
rounding LC as well as developmental forms of H
budding from LC surface membranes. Moreover,
punch biopsie from normal appearing skin of-
with mononuclear phagocytes from a non-infect
in the detection of high levels of reverse-tran
in the culture supernatant. This latter fi
active virus can be rescued from the skin of H
viduals.Our findings conclusivly confirm that (
al target for HIV infection and production, su
that besides T cells , cells of the monocyte /
are a major target population of this virus
serve as a viral reservoir during the course of
REPLICATION DURING
ENCY VIRUS (HIV).
r**,P.Schenk+,
Biologie,NCI, NIH,
Oto laryngology I I ,
tr ia .
f cells of differ-
ells(LC) represent
presenting leuco-
trated that LC of
antibodies direc-
p24 - a finding
n these cells .
f skin and mucosal
reactive LC now
ellular space sur-
IV- like particles
coculti vation of a
tTils AIDS patient
ed donor, resulted
scriptase activity
nding implies that
IV infected indi-
I ) LC are an actu-
pporting the view
macrophage lineage
(II) the skin may
HIV infection.
TP110 Production of Antibody by Circulating B Cells of HIV-Seroposit ive
Subjects .
SDSAN ZOLLA-PAZNER* . H. MIZUMA*, V. GIANAKAKOS* , A. PINTER" and W. HONNEN**.
New York Veterans Administration Medical Center*, New York University Medical
Center*, and Public Health Research Institute**, New York, NY.
Cells producing antibody (Ab) do not normally circulate except during a
short time following immune stimulation. In patients infected with HIV,
however, circulating B cells were found to spontaneously secrete anti-HIV
antibodies in 20 of 22 cases. For these experiments, 0.1-5.0 x 10' peripheral
blood mononuclear cells (PBMC) were cultured in microtiter wells withont
mitogen or antigen for periods of 1-15 days. At 5 x 105 cells/well, cells
from five control subjects produced no detectable anti-HIV Ab (measured with
commercial ELISA kits) over the entire culture period; at this cell
concentration, cultures from 5 of 6 AIDS patients spontaneously produced Ab .
Cells from 11 of 11 patients with ARC produced Ab and cells from 4 of 6 HIV-
seropositive subjects without AIDS or ARC (high risk patients) also produced
Ab. Positive cultures showed the presence of detectable Ab within 24 hr.,
indicating that these cells had been stimulated .in vivo. Incorporation of HIV
viral lysates into the medium (0.125-1.0 |ig/ml) for varying periods of time
did not enhance Ab production. By a radio-immunoprec ipitat ion assay, Ab
production appeared polyclonal, with reactivity primarily directed against
gp 41, gp 120 and reverse transcriptase. When PBMC were cultured at lower
concentrations, wells containing Ab-producing cells were detected in all
experiments at 2.5 x 10J cells/well and in 75-80* of experiments at 1.0 and
0.5 x 10> cells/well. No Ab production was detected at <0.5 x 10« cells/well.
The presence of circulating Ab-producing cells may reflect continual antigenic
stimulation by replicating virus in infected subjects.
80
TUESDAY, JUNE 2
TR111 A genetlc factor affecting susceptibility to HIV infection and to
disease progression.
LESLEY-JANE EALES, KE NYE, JM PARKIN, JN WEBER, SM FORSTER, AJ PINCHING, ET
AL. St Mary's Hospital and Medical School, LONDON W2 . UK.
Whilst examining serum factors in AIDS patients, many were noted to have a
rare phenotype of Group specific component (Gc) . This prompted an Indepth
study of Gc phenotypes in 214 subjects from existing cohorts of homosexuals
at risk from, or infected by HIV, classified according to current clinical
status, compared with 122 healthy male heterosexual seronegative controls.
Sera were analysed by isoelectric focusing on thin layer polyacrylamide gels
containing ampholytes (pH 4.5- 5.4).
30.2% of AIDS patients were homozygous for Gc 1 fast (cf controls 0.8%;
p<0.001); other seropositive clinical groups also more commonly had Gc If.
Seronegative asymptomatic homosexual contacts of AIDS patients (AH-p) lacked
this phenotype. By contrast, AIDS patients lacked the Gc 2 phenotype, but this
was more common in the AH-p group (25%) than in controls (9%; p<0.01). A chi
squared trend test showed a highly significant association between the Gc 1
fast allele and progression to AIDS (p<0.0001) and the reverse with Gc 2
(p<0.05). We propose that Gc is involved in viral entry into host cells and
that the different allelic forms of Gc, which vary in sialic acid content,
dictate its ease.
Production, Characterization and Epitope Mapping of a Human
Monoclonal Antibody Reactive with the Envelope Glycoprotein ol HIV
B. BANAPOUR, K. ROSENTHAL, L. RABIN, V. SHARMA, G. REYES, JEFFREY D. LIFSON.
et al., Genelabs, Inc., San Carlos, CA.
To analyze the humoral response to HIV infection, we sought to generate monoclonal
antibodies from HIV seropositive individuals. B lymphocytes Irom an HIV antibody positive palienl
were transformed with Epstein-Barr virus, then fused to a mouse-human heteromyeloma lusion
partner. Immunoglobulin containing supematants were screened for anti-HIV reactivity by indirect
immunofluorescence analysis. Reactivity was confirmed by Western blot and
radioimmunoprecipitation analysis (RIPA). Using this approach, we have identified a monoclonal
IgG antibody, 1B8.env, reactive with the envelope glycoprotein of HIV. The antibody specifically
stains acetone fixed HIV-infected cells and is also reactive with viral antigens expressed on the
surface of unfixed infected cells. In Western blot and RIPA the antibody is reactive with the
precursor (gp160) and transmembrane (gp41) forms of the HIV envelope glycoprotein. Using a
lambda gt11 expression library, we have definitively mapped the epitope recognized by 1B8.env
to a 47 amino acid region of gp41. This epitope appears to be largely conserved among multiple
distinct HIV isolates, based on conservation of this region in published sequences of distinct HIV
isolates and on preliminary experiments with 1B8.env and a panel of viral isolates. Additional
studies of biological activity (neutralizing capacity and cytotoxicity) are in progress. These results
demonstrate the feasibility of our approach for generating human monoclonal antibodies to HIV
for analysis of the humoral response to HIV and for other applications.
TP112 Serum Non Organ Specific Autoantibodies during Infection of Human
Immunodeficiency Vitus (HIV) .
FAB 10 CASSANI, L. BAFFONI, E. RAISE", L. SELLERI, M.G. CATALINl", F.B. BIANCHI.
Clin. Med. II Universita, "Dip. Mai. Infett. Osp. Maggiore, Bologna, ITALY.
HIV infection is associated with polyclonal B cell activation and hypergamma-
globulinemia. Autoimmune features may be present. Data are lacking about the oc
currence of serum non organ specific autoantibodies. 64 HI17 infected subjects,
including healthy carriers (HC) and patients with LAS, ARC and AIDS, were scre-
ened for antibodies to: smooth muscle (SMA) , nuclei (ANA), intermediate filamen^
ts (IMF), microfilaments (MF) (IFL on rat kidney and HEp-2 cells, 1:40 serum d.i
lution) and extractable nuclear antigens (ENA) (CIE, undiluted serum).
LAS (.28)
7(25%)
9(32%)
6(21%)
0
SMA positivity showed always the V pattern and was associated with anti IMF (p<
0.01). The number of circulating CD4 lymphocytes was higher in SMA+ than SMA-
AIDS patients (p<0.05). The autoantibodies status did not correlate with: circu
lating platelets and immune complexes, serum gammaglobulins, cutaneous anergy.
Serum non organ specific autoantibodies do occur in HIV infected patients with
the same pattern (SMAV with anti IMF reactivity) of other viral infections. It is
not known whether HIV itself can trigger the process. The SMA prevalence increa-
ses with the disease progression.
TR115
Cell Li
ELLEN G
HTLV-I
Lympho
ne, AL-1
. FEIGAL
and HIV Co-seropreval ence in AIDS Non-Hodgk i n ' s
ma Patients: Characterization of AIDS Lymphoma
HC(15)
SMA
3(20%)
ANA
4(27%)
anti IMF
3(20%)
anti MF
and
anti
ENA
0
ARC(13)
AIDS(8)
tot. (64)
7(54%)
5(63%)
22(34%)
4(31%)
1(13%)
18(28%)
5(38%)
3(38%)
17(27%)
0
0
0
KAPLAN,
of Medi
HTLV-
immunop
re lat i o
non-Hod
patient
had ant
To te
lymphom
co-sero
analy s i
genomes
envelop
i nf ec te
tissue
ant igen
HTLV-I
we used
i dent i f
by the
ret rov 1
through
GREGORY
cine , San
I and HIV
recipitat
nship of
gkin's ly
s (1/20) an
i bodies t
st whethe
agenes i s .
positive
s of cell
but not
e glycopr
d mononuc
sections
AL-1
enve lope
the lamb
y a 40 am
AIDS AL-1
rus may p
a proces
PAT
R. R
Fra
ser
ion
thes
mpho
d 14
o HT
r HI
we
say
lin
HIV
otei
lear
of A
prod
gp61
da g
ino
IgM
lay
s of
RICIA
EYES,
ncisco
opreva
analy s
e re t r
ma (NH
% of h
LV-I e
V or H
establ
man wi
e AL-1
or HT
n of H
and m
L-l .
uced a
Def
tl 1 ex
acid s
The
a role
chron
V. L
MICH
, CA
lenc
es
o v i r
L) .
eal t
nve 1
TLV-
ishe
th B
DNA
LV-I
TLV-
acro
Tumo
n an
inin
pres
egme
se d
in
ic a
EKAS, J
AEL S
94110
e was e
n 3 pat
uses to
All NH
hy HIV
ope det
I might
datum
urkitt ■
revea 1
Mono
I (gp61
phage- 1
r t i ssu
t i body .
g furth
sion ve
nt with
ata sug
the gen
nt igeni
AY H. BECKSTEAD, LAWRENCE D.
MCGRATH. UCSF & SFGH, Dept.
xam i
ient
the
L pa
sero
ermi
be
or c
s ly
ed t
c Ion
/68)
ike
es w
IgM
er t
c tor
in g
gest
es i s
c st
ned b
grou
deve
t i ent
posit
nant s
direc
ell 1
mphom
he pr
al an
iden
cells
ere n
k. th
he ep
c Ion
p61 t
that
of A
imula
y Western blot and
ps to determine the
lopment of B cell
s(18/18), 5% of AIDS
ive gay men (14/100)
t ly in
ine (A
a . So
esence
t ibodi
tif ied
wi th i
egat iv
at rec
i tope
ing sc
hat wa
HTLV-
IDS as
t ion .
vol ved in AIDS
L- 1 ) from a
uthern blot
of EBV
es to the
rare (1-2*)
n lymphoma
e for HIV p25
ognized the
pecificity,
heme to
s recognized
I or a similar
sociated NHL
TR113 EVALUATION OF D/Dr Bl ,CD4 4B4, CD4 2HB4 LYMPHOCYTE SUBSETS DU-
RING THE EVOLUTION OF HIV INFECTION.
Raise E. , Gritti F.M. ,*Schiattcne M.L.*Casertano M.G.*Pulsatelli L.*Martuzzi M.
Infect.Dis.and IniiiJiapathol.Dep.-*Clinical Pathol., Osp. Maggiore-Bologna, Italy
The prognostic meaning of D/Dr Bl tCD4 4B4 ,CD4 2HB4 lymphocyte subsets during
the evolution of HIV infection was investigated in the following subjects: 13
HIV-Ab positive only, 48 LAS, 28 ARC and 9 AIDS with Pneumocystis carinii pne-
umonia. Monoclonal antibodies, wets supplied by Coulter Imnunology and Becton Die
kinson and were used with the Coulter lysing procedure. Dual-color flow cytome-
tric analyses were performed with EPICS V.
In the patients (pts) HIV-Ab positive it was demonstrated a decrease only of the
CD4 4B4 subset (388rl50/ml vs n.v. 564T233/ml: p<0.01).Tre redutimwaB more re-
markable in the further stages: LAS 343T197/ml (p<0.01), ARC 278T218/ml (p<Oj0EL)
AIDS 34*25 (p<0.01). The CD4+2H4+ lymphocytes were decreased in ARC, 170T145/ml
vs n.v. 279T165/ml (p<0.01) and AIDS 31T20/ml (p<O.Ol).The CD4+4B4+/CD4+2H4+ra-
tio showed a progressive diminution from simple HIV-Ab positive pts 1.93*1.18/
(p<0.01) toflAl blown AIDS, 1.2TO.49 (p<O.Ol). The D/Dr /Bl+ lymphocyte subset
displaied a significative decrease from the IAS to the AIDS group.
Our data suggest thet the early loss of the CD4 4B4 subset of lymphocytes is
the most consistent change in lymphocyte subpopulation and shows to be progres-
sive from siple HIV-Ab positivity to AIDS. This aspect is consistent with the
T-independent stimulation of B lymphcytes conmonly reported and appears to be
a premonitory sign of inmunological deterioration.
TP116 Loss °^ Suppressor Cell Function in HTV+ Individuals
GENE M. SHEARER and DENISE C. BERNSTEIN, NCI, NIH, Bethesda, MD .
Elevated T cell responses to HLA alloantigens ( ALLO) have been reported
in ~50Z of AIDS patients and HIV+ asymptomatic individuals (J. Immunol. 137:
2514, 1986), as well as in ~50% of HIV" homosexual men (J. Immunol. 135:
3163, 1985). In contrast, terminal AIDS patients appear to have lost ALLO T
cell reactivity. This T cell response to ALLO is not dependent on CD4 helper
cells ( Ibid , 1986) . To determine the mechanism responsible for this elevated
ALLO T cell immunity, we have identified a suppressor cell (or circuit) which
is functional in most HIV heterosexual men. This type of suppression is de-
pendent on a radioresistant macrophage that is adherent to plastic. The
suppreslon: a) appears to be HLA self restricted; b) when preactivated in
vitro, affects T cell responses to viruses as well as to ALLO; c) is most
efficiently activated in vitro by ALLO stimulation; and d) can be abrogated
in vitro by infection with influenza virus. This suppressor system is not
detected in HIV+ individuals nor in AIDS patients who exhibit elevated ALLO
T cell activity. Since a) a CDA independent pathway (detected by ALLO)
provides some immune function in AIDS patients; b) this pathway is elevated
by removal of suppressor cell activity; and c) AIDS patients appear to have
lost the suppressor function; modulation of the Immune system by this regula-
tory mechanism and its abrogation in high risk and HIV+ Individuals may
play a role in HIV susceptibility, progression to AIDS in HIV+ individuals,
and/or maintenance of some immune protection during the earlier stages of
symptomatic AIDS.
81
TUESDAY, JUNE 2
TR117
ABSOLUTE DEFICIENCY OF INTERLEUKIN 2 PRODUCTION AND IL2
RECEPTOR GENERATION IN AIDS AND ALTERED KINETICS OF GAMMA INTER-
FERON IN AIDS AND AIDS RELATED COMPLEX. R. Paganelli, MR Capobian-
chi , I. Mezzaroma, GP . D'Offizi, M. Cherchi , F.Aiuti. Dept . Clin.
Immunology and Inst, of Virology _Univ."La Sapienza"_ Rome ITALY
We evaluated T lymphocytes, CD4+ , CD8+ subsets, lymphoprolif era-
tive response, IL2 receptor expression, production of IL2 and gam
ma IFN in response to PHA in 16 patients with AIDS, 19 with AIDS-
related complex (ARC) and 15 controls. 2 AIDS were children, 14/16
AIDS had 0.1. and 3 K.S. Absolute deficiency of CD4+ cells was
present in AIDS and in most ARC, with CD4/CD8 ratio 1 in all AIDB
but only in 6/15 cases of ARC. The addition of 10 U/ml of rIL2 to
the cultures did not restore lymphoprolif eration . IL2 production
in supernatant was absent in 87$ of AIDS (mean levels 0.2U) but
near normal in ARC (4.3 U/ml vs 5.9-5.1 U/ml in controls ). IL2 rec-
eptor generation was greatly decreased in AIDS, but only slightly
in ARC( 22%vs50%of cells). Gamma IFN production was decreased in
AIDS(mean 42U/ml)but not in ARC ( 528U/ml .normal range 100-3000U/ml )
Kinetics analysis showed that some defective cases had delayed
production .reaching normal levels at 72hrs of culture in 3/11AIDS
and 5/7 ARC patients. None of the ARC patients developed 0.1. aft-
er a follow up from 18 to 30 months.
TR120 £
vitro Studies of HTLV- I I I/LAV Transmission from
Monocyte/Macrophages to Autologous T Cells.
HARTMUT P. BUCHOW, S. GARTNER, R.C. GALLO and M. POPOVIC, Laboratory of
Tumor Cell Biology, NCI/NIH, Bethesda, MD.
It has been demonstrated in patients with lymphadenopathy or AIDS
that, in addition to 0KT4+ T lymphocytes, cells of the mononuclear
phagocyte series frequently harbor HTLV-III/LAV. The longevity and
magnitude of virus expression in these kinds of cells indicate that they
represent a reservoir for virus dissemination and also play a role in the
pathogenesis of the disease. Because there is close cooperation and
interaction between cells of the mononuclear phagocyte series and T
lymphocytes, we studied HTLV-III/LAV transmission from virus-infected
monocyte/macrophages (MM) to autologous T cells using cocultivation
methods. HTLV-III/LAV was efficiently transmitted into T cells within 10-20
minutes after cocultivation with the virus-infected MM cells. Compared to
cell-free infection of T cells using culture fluids harvested from the
same MM cultures which were used for the cocultivations, virus expression
was detected earlier and virus production was significantly higher in the T
cell cultures infected by cocultivation. These results suggest that
efficient transmission in vivo from MM cells to T cells may occur.
TR118 Increase of HLA antigen in the sera of patients with
associated HIV infection disease -
P ECHANIZ.L BELL0S0.E BLASC0,J ARHIZABALAGA,P G0NZALEZ-P0HQUE ,
E CUADRADO. Hospital Ntra Sra de Aranzazu San Sebastian. C.E.
Ram6n y Ca.ia]? Madrid (Spain)
An increase of beta 2 microglobulin in the sera of patients
with AIDS or AIDS-related complex is well stablished but there
is not quantitative data about soluble HLA molecules in such
conditions. We studied the HLA antigen serum level in 14 patients
with AIDS, 9 patients with AIDS related complex and 8 with lym-
phadenopathy syndrome; 33 HIV positive and 33 HIV negative
sypmtomless intravenous drug users were included as control. Of
the 14 patients with AIDS 10 had opportunistic infections, two
B cell neoplasia, one progressive leukoencephalopathy and one
had Kapsi's sarcoma. The diagnosis was confirmed by the Spanish
Commitee for AIDS.
The amount of HLA in the sera was quantified by the method
described by Perreira et al, using the mab W6/32 bound to micro
ELISA plates and purified HLA molecules as standard. The results
showed significative increase of HLA in patients with AIDS or
AIDS related complex as compared with the observed in controls.
W-. HIVnegative HIVpositive LAS ARC AIDS
(Bicg/ml) i-v drufi users
mean+SEM 5.95±3-.^5 7.92+3.15 9+3.76 12.3+4.1 19.2+5.9
TP121 Deficiencies of Lymphocyte Proliferative Responses of HlV-Sero-
positive Men to HIV Antigens and Cytomegalovirus.
JOHN F. KROWKA*. D.P. STITES*. J. MILLS*, C. GEORGE-NASCIMENTO*. A. GYENES*. H.
HOLLANDER*, J. A. LEVY* et al . , *University of California, San Francisco and
the *Chiron Corporation, Emeryville, CA, USA.
Defects in the ability of lymphocytes to respond to antigens are character-
istic of AIDS. We therefore tested proliferative lymphocyte responses from
HIV-seronegative (HIV-) men, asymptomatic HIV-seropositive (HIV+) men and
ARC or AIDS patients to purified HIV, recombinant envelope and core proteins
of HIV, synthetic HIV envelope peptides and to CMV. Lymphocytes from HIV-
and CMV- men did not proliferate in response to any of these antigens although
recall responses to tetanus toxoid, Candida, or to PHA were detected. Only
a small percentage (<10%) of HIV+ men regardless of clinical status showed
significant (p<0.001) lymphocyte proliferation to any HIV antigens tested.
All HIV- CMV+ men showed significant lymphocyte responses to CMV. In contrast,
some HIV+ CMV+ asymptomatic men, many ARC, and all AIDS patients were hypore-
sponsive or anergic in their proliferative responses to CMV. Proliferative
responses to CMV but not to any HIV antigens could be induced or augmented
by the addition of recombinant IL2. These results indicate deficiencies in
cell-mediated immunity to HIV and CMV including but not limited to IL2 defic-
iencies in individuals exposed to HIV. The mechanisms of this immunodeficiency
including defects in antigen presentation and immunosuppression by HIV pro-
teins will be discussed.
TR119 Reactivity of Patients' Sera with HTLV-I IIrf Env Gene Recombinant
Antigens Expressed in Escherichia col i.
MICHAEL L. BERMAN AND S. CRUSH-STANTON, Bionetics Research, Inc., Rockville,
MD.
The env gene from the HTLV- 1 1 Irp strain, proviral clone AHAT-3, was
engineered as a env-lacZ gene fusion in an E_. col i expression vector.
Various 5' and 3' deletions of the env sequences were isolated. The hybrid
proteins synthesized by 11 separate fusions were characterized by Western
blot analysis and ELISA tests using sera from infected patients. The results
show that there are three immuno-dominant regions in these clones. One of
these lies within codons 54-123 of the gp41 gene sequences. The two others
map to the amino terminus and the carboxy terminus of the bacterial ly
expressed gpl20 gene sequences. The results with the gpl20 recombinants show
that hybrids carrying amino acids 30-182 or 483-520 are immunoreactive, while
a hybrid with amino acids 182-462 is unreactive.
The systematic analysis of these types of families of hybrid proteins
can help localize regions of immunological importance. This approach allows
precise mapping of areas that may be important for clinical diagnostics or
for vaccine development.
TP122 Suppression of In Vitro Hematopoiesis Following Human
Immunodeficiency Virus (HIV) Infection.
ROBERT E. D0NAHUE+, M.M. JOHNSON,* L.I. Z0N*, S.C. CLARK+, AND J.E.
GROOEMAN". +Genetics Institute, Inc., Cambridge, MA, U.S.A. and Division o£
Hematology/Oncology, New England Deaconess Hospital, Boston, MA, U.S.A.
Abnormalities including leukopenia, anemia, and thrombocytopenia are
observed in patients with the acquired immunodeficiency syndrome (AIDS) or
the AIDS-related complex (ARC). We examined the effects of two recombinant
hematopoietins, human granulocyte/raacrophage-colony stimulating factor (rGM-
CSF) and recombinant erythropoietin (epo), on the in vitro growth of bone
marrow progenitor cells from untreated AIDS or ARC patients. Bone marrow
progenitor cells from all 10 patients In the study were responsive to rGM-
CSF and epo when cultured in the presence or absence of normal human serum.
Sera or purified immunoglobulin from AIDS or ARC patients, however,
suppressed colony formation by bone marrow cells from AIDS or ARC patients
but not from healthy Individuals. Purified rabbit immunoglobulin to
recombinant HIV envelope protein (gpl20) reproduced the suppressive effects
observed with immunoglobulin from HIV seropositive subjects. HIV could be
recovered from pooled bone marrow progenitors from AIDS marrow when these
progenitors were co-cultivated with normal peripheral blood mononuclear
cells. Thus, it appears that antibody in the serum of individuals following
infection with HIV may contribute to immune-mediated suppression of
hematopoiesis in AIDS or ARC patients. In the absence of antibody, bone
marrow progenitors may be infected with HIV but they respond normally in
vitro to rGM-CSF and epo. Clinically, GM-CSF has been capable of eliciting
a leukocytosis in AIDS patients. The extent of this leukocytosis, however,
may be limited by the presence of antibody to HIV.
82
TUESDAY, JUNE 2
TP123 Membrane Markers of Bone-Marrow Cells from AIDS Patients.
HOFMANN B, 0DUM N, M0LLER J, RYDER LP, PEDERSEN C, GERSTOFT J ET AL.
UNIVERSITY HOSPITAL (RIGSHOSPITALET) , COPENHAGEN, DENMARK.
CD4 CD8
Median % : Periph.blood Bone marrow Periph.blood Bone marrow
AIDS H3 15 20 35 22
Controls N-7 41 26 23 13
The lymphocytes in peripheral blood (PB) represent only 1/1000 of all
lymphocytes, the majority of which is found in the lymph nodes, the spleen, and
in the bone marrow (BM). The lymph nodes in AIDS are depleted for CD4 cells and
invaded by CD8 cells. We have investigated and compared the percentage of
lymphocyte markers in bone marrow aspirates and peripheral blood from eight
patients with AIDS and from seven controls (donors for BM transplantation). The
analysis was made on a FACS analyzer and included both lymphocytes and mono-
cytes/blasts. Only one of seven controls had a higher percentage of CD4 cells
in BM (26S) than in PB (23!S). Two of the AIDS patients had normal fractions of
CD4 cells in PB (48K and 4950 and lower fractions in BM (33% and 43S). Of the
six AIDS patients with decreased numbers of CD4 in PB, four had higher CD4
fractions in BM (PB/BM 7K/11S, 9S/18S, 22?S/36?i, 8V22S), one had 11S in both PB
and 8M, and one had 18?i in PB and only 3% in BM. The percentage of CD8 cells
were increased in both PB and BM from AIDS patients compared to controls, but
these cells did not dominate the BM. Two of the BM from AIDS patients were CD10
(Calla) positive {M% and 2Vi) . The presence of CD10 positive blasts which are
precursors of B cells, indicates an increased turnover and may reflect the poly-
clonal activation of B cells in AIDS. None of the cells inAIDS or control BM
were IL-2 receptor positive, and the fractions of BM cells bearing HLA-DR, Ig,
or CD16 (NK cells) were similar in patients and controls. (This work was suppor-
ted by the Danish Cancer Society and the Danish Medical Council.)
TR126
Evidence far Increased circulating T6 positive cells in ARC and AIDS patients.
SYLVIE CHOLLET-HARTIN*. M. LEVAO£R«*, G. PIAL0UX", M.A. GOUGEROT-POCIDALO* - • INSERM U. 294
- CHU X. Bichat, *» INSERM u. 13 and Hopital Claude Bernard - Paris, France.
The circulating T6 bearing cells were analyzed in patients with HIV infection in order to
investigate the T lymphocyte dysbalance. Monoclonal antibody of the C01 class (I0T6) was used
in an indirect assay using a goat antimouse bound colloidal gold irrmunoglobulin as second
antibody. Patients were all seropositive for anti-HIV and were classified according to the CDC
criteria. Controls were performed in healthy volunteers and patients suffering from viral
hepatitis. Results are as follow :
cells
CONTROLS
* LS/Vn
Per^ fs/VTT
5,5
0,5
111
ARC
15
24,3
5,2
468
112
ASYMPTOMATIC
13
8,4
196
48
VIRAL HEPATITIS
9
10,0
1|7
147
11
increased
percent
AIDS
41
32,2
3,5
265
36
Variance analysis showed that the number of T6 positive cells was significantly
in AIDS and ARC patients when compared to all other groups (pOO-3) as expressed
of total lymphocytes and in absolute number per pi of blood. There was no significant
difference between controls, asymptomatics and patients with viral hepatitis. No correlation
was found between the number of T6 and T4 positive cells or the T4/T8 ratio in all HIV
positive patients. However a correlation could be evidenced between the percentages of T6
positive cells and the total lymphocyte counts per ^ul of blood (n = 69, pOo-1).
Since I0T6 monoclonal antibody is known to recognize T lymphocytes precursors, this
increase of circulating I0T6 positive cells could be the consequence of the regeneration of T
cells in these lymphopenic patients. Further studies are actually done to evaluate a possible
pronostic value of this parameter.
TR124
HLA Al, B8, DR3 as a Risk Factor for the Development of Clinical
Sequelae to HIV Infection in the Edinburgh Haemophilia Cohort.
DIANNE BEATSON**, R.J.G. CUTHBERT*, J.F. PEUTHERER*** , C.A. LUDLAM*. CM. STEEL**
*Dept. of Haematology, Royal Infirmary of Edinburgh, **MRC Clinical and Popula-
tion Cytogenetics Unit, Western General Hospital, Edinburgh, ***Dept. of
Bacteriology, University of Edinburgh.
Several reports have suggested that HLA antigens may influence the response
to HIV infection. We have carried out a study of the distribution of serolog-
ically defined HLA antigens in a group of haemophiliacs. Thirty-two patients
not previously exposed to HIV received a batch of locally produced FVIII
contaminated with HIV; 18 became seropositive and 14 remain seronegative. In
addition we have typed 28 other haemophiliacs not exposed to this batch; 6 are
seropositive and 22 seronegative. Using a standard 2-stage complement-dependant
microcytoxicity assay these patients have been typed for 17 alleles at the
HLA-A locus, 32 private and 2 public alleles at the HLA-B locus and 8 alleles
at the HLA-DR locus.
We found no significant association between any one HLA antigen and the risk
of seroconversion following exposure to HIV. However the HLA antigens Al,
B8 and to a lesser extent DR3 were over-represented in the subgroup who sero-
converted. Among 7 patients with clinical progression following seroconversion
(1 with AIDS, 3 with ARC, 2 with PGL and 1 with thrombocytopenia) the
combination Al, B8 was present in 5, 4 of whom also carried DR3, the 5th not
yet having been typed at the DR locus. The Al, B8 combination was found in only
2 of 13 seropositive patients without evidence of clinical progression. Neither
patient has yet been typed at the DR locus. Al , B8 was present in 3 of 14 sero-
negative aptients exposed to the contaminated batch of factor VIII. One
patient is DR3+; the DR type of the other two is not yet known.
TR127 Normal antibody-dependent cellular cytotoxicity (A0CC) mediated by
effector cells defective in natural killer (NK) cytotoxicity in
patients with acquired immunodeficiency syndrome (AIDS). JONATHAN D . KATZ ,
RONALD MITSUYASIT, MICHAEL S. GOTTLIEB*, LAURA TIMARES LEBOW\ and BENJAMIN
B0NAVIDA*> *Dept. of Microbiology and Immunology, and +Dept. of Medicine, UCLA
School of Medicine, University of California, Los Angeles, CA
We have recently reported that the depressed NK cytotoxic activity in AIDS
may be due to a defective "trigger" required for activation in the lethal hit
stage of the NK lytic pathway. NK effector cells can mediate antibody dependent
cellular cytotoxicity (ADCC) through the use of the FCT receptor (FCrR).
Therefore, it was important to delineate whether the defect in AIDS NK cells
affected the ADCC activity observed by these cells. The ADCC cytotoxic activity
of AIDS PBL was found to be within the normal range despite the absence of
significant NK activity. Depletion of FCTR bearing cells resulted in elimina-
tion of both the ADCC and NK cytotoxic functions. The frequency of ADCC target
conjugates and the frequency of killer cells from AIDS PBL were comparable to
normal controls. Furthermore, the frequency of two-ADCC target cells killed by
a single effector was comparable that of the controls. However, when mixture
of NK and ADCC targets were used to form two-target hetroconjugates, the AIDS
effector cells lysed only the bound ADCC target. Furthermore, AIDS effector
cells stimulated with ADCC targets, but not with NK targets, were shown to
release natural killer cytotoxic factors (NKCF), postulated mediator of the NK
CMC reaction. These findings indicate that the NK/K cells in AIDS are triggered
normally for ADCC activity but are not triggered for NK activity. Furthermore,
the results indicate that the lytic pathway is not impaired in the AIDS NK/K
cells. Supported by the AIDS Task Force and in part by the NCI tumor immunology
training grant CA-09120.
TD19K Molecular Analysis of Growth Factor (s) Produced by HTLV-II Trans-
formed Cell Lines and Cell Clones Developed From Kaposi 'Sarcoma <KS)
BARBARA ENSOLI,* S. NAKAMURA, * P. BIBERFELD,** Z. SALAHUDDIN,* F. WONG-STAAL*
and R. C. GALLO,* *Laboratory of Tumor Cell Biology, National Cancer Institute
NIH, Bethesda, MD, **Department of Pathology, Karolinska Institute, Stockholm,
Sweden .
Human T-cell Lymphotropic Virus Type II (HTLV-II) transformed CD4+ cell
lines produce a strong growth stimulating factor (S) inducing KS-derived cell
lines to proliferate. This factor (S) is heparin independent and stimulates
preferentially KS cells, but it is also active on normal endothelial cells.
Interleukin-1 (IL-1) induces the proliferation of KS cells, but the mitogenic
response plateaus earlier than the factor (S) from HTLV-II transformed cell
line and IL-1 has a very low effect on normal cells. In contrast classical
growth factors: e.g., human endothelial growth factor (ECGF) and fibroblast
growth factor (FGF) induce proliferation of normal endothelial cells, but do
not seem to stimulate KS cells. Molecular analysis confirmed the novelty of the
factor (S) released by HTLV-II transformed cells. Parallel studies indicate that
KS-derived cell clones also possess a growth factor specific for endothelial
cells. The KS-derived cells contain abundant levels of mRNA which hybridize to
probes derived from the FGF cDNA sequences. However, differences are evident by
Northern blot analysis in the species of RNA expressed in these cells as com-
pared to the messages found in human hepatoma cell lines and in bovine hypo-
thalamus for FGF. The biological data and the molecular characteristics suggest
that the factor produced may be FGF or a related protein. Further experiments
may determine whether this factor has a role in an autocrine stimulation which
leads to the abnormal cellular proliferation found in KS.
TplOQ HIV Glycoprotein (gpl20) Serves as Target for Antibody-Mediated
IT. ICO Cytolysis. H. KIM LYERLY*, T.J. MATTHEWS*, A.J. LANGLOIS*. P.
AHEARNE*, D.P. BOLOGNESI*, and K.J. WEINHOLD*, *Department of Surgery, Duke
University Medical Center, Durham, North Carolina, USA
Patients infected with HIV produce antibodies against the major envelope
glycoprotein gpl20, which have been shown to exhibit virus neutralizing
activity and may be involved in preventing further spread of the virus.
Anti-gpl20 antibodies in patient sera as well as sera from immunized animals
show extensive cell surface reactivity against both virus infected cells and
purified gpl20 complexed with the CD4 molecule on uninfected lymphocytes.
Such observations led to an investigation of whether these cytophilic
antibodies could mediate the destruction of virus infected and/or antigen
coated target cells.
Antibody-Dependent,- Complement-Mediated Cytolysis (ACC) was evaluated in a
series of 90 minute Cr release assays in which gpl20-coated, normal CDA
lymphocyte targets were incubated with either patient sera or immune goat
serum in the presence of rabbit complement. Although goat anti-gpl20 serum
directed the lysis of gpl20 coated targets, none of the patient sera contained
significant lytic activity. In contrast, patient sera, in combination with
normal donor lymphocytes, effectively directed Antibody-Dependent Cellular
Cytotoxicity (ADCC) of gp!20 coated CD4 cells In 4 hour Cr release assays.
Goat anti-gpl20 serum failed to mediate ADCC. The finding that patient sera
can direct the cell mediated destruction of gpl20 bearing cells indicates
the presence of an additional barrier to HIV infection.
83
TUESDAY, JUNE 2
TP129 The Immunopathology of Peripheral Nerve Disease in PIDS
S. M. DE Lfl MONTE. D. H- GABUZDA, D- D- HO, E. T HEDLEY-
WHYTE, M.S. HIRSCH, MD; ft. K- BHftN. Massachusetts General Hospital
Harvard Medical School, Boston, Mft. USft.
Peri pheral neuropathy in ft IDS is of unknown pathogenesis. In
our series, histopathologic evidence of peripheral neuropathy
with demy el inat ion (78%) , axonopathy < 31%) , or mononuclear eel 1
inflammation (40%) was observed in 19 of £0 (95%) patients. De-
my e 1 i nat i on was pa t chy and assoc i at ed with endoneur i a 1 f i bros i s.
Axonopathy was characterized by attenuation and fragmentation of
fibers and axonal spheroid formation. Immunohistochemical stain-
ing demonstrated a 4. 5— fold increase in the density of endoneu—
rial mononuclear inflammatory cells relative to controls. 60% of
the inflammatory cells were identified as Leu— 4+ T lymphocytes or
Leu— M3+ macrophages. The remaining 40% of mononuclear inflamma-
tory cells, not identified immunohistochemical ly, were also pro-
bably macrophages based upon their cytomorphology. T8+ (cyto—
toxic/suppressor) cells predominated among the T lymphocyte
subsets. B cells were not identified in the nerves. Diffuse
immunostaining for HLft— DR was present on endothelial cells,
mononuclear inflammatory cells, and Schwann cells, and variable
patchy immunostaining for HLft— DR was present on nerve fibers. In
contrast, control nerve specimens showed staining for HLft— DR lim-
ited to endothelial and a few scattered mononuclear cells. The
findings suggest that the peripheral neuropathy of AIDS results
from specific T cell and macrophage— mediated tissue destruction
as occurs in viral infections.
TR132 Humoral and cellular responses to HIV and polypeptides in a model
system.
BRITTA E, Uahren1 , E.M. FENYO2, F. CHIODI2, R. KURTH3, J. GHP.AYEB4, S. PUTNEY5,
R. GALLON & D. BOLOGNESI7, National Bacteriological Laboratory and 2Karolinska
Institute, Stockholm, Sweden, 3Paul Ehrlich Institut, Frankfurt, FRG, ^Cento-
cor, Malvern, PA, 5Repligen, Cambridge, MA, ^National Cancer Institute, MD,
Duke University, Durham, NC.
A model system was established for studies of humoral and cellular immunity
to HIV antigens in primary and reactivated infection and after vaccination.
Macaques (Macaca fascicularis) were immunized with purified HIV, a cell extract
rich in gpl20 or polypeptides of cloned genes for parts of p24, gp41 and gp!20
(pE3). Western blots best showed the appearance of antibodies to nucleocapsid
protein while antibodies to higher molecular weight envelope glycoproteins were
better demonstrated by radioimmunoprecipitation. With whole HIV, antibodies to
p24 appeared first, and sometimes were the only ones to be demonstrable. Seve-
ral immunizations with HIV were required to obtain antibodies to gpl20, and
the response was weak. (g)p41 also had a poor immunizing effect. IgG synthesis
from B-cells in vitro was well demonstrable to whole HIV, and generally paral-
leled the antibody titers of sera after multiple immunizations. The HlV-speci-
fic lymphocyte proliferation response as measured by DNA synthesis was best
seen with p24, followed by (g)p41, pE3, gp!20 and whole HIV.
TP130 Human Monoclonal Antibodies Directed Against gag Gene Products of
the Human Immunodeficiency Virus (HIV) .
LOUISE EVANS, J. HOMSY, I. GASTON, J. MORROW, C.D. SOOY , J. A. LEVY, Cancer
Research Institute, and Department of Otolaryngology, School of Medicine,
University of California, San Francisco, CA.
Tonsillar B lymphocytes from a patient infected by the human immuno-
deficiency virus (HIV) were transformed with Epstein Barr virus obtained from
the B95-8 marmoset cell line. Three cloned lymphoblastoid cell lines secreted
human monoclonal antibodies that specifically reacted with HIV as detected by
immunoblot analysis. The monoclonal antibodies recognized proteins of 55, 41
and 25 kd.
Serum antibody responses to the p55 gag precursor protein and the p25 core
protein of HIV have been well documented. The reactivity of these human
monoclonal antibodies suggests that individuals naturally infected with HIV
also respond to a p41 gag gene product. This p41 protein is probably a
processing intermediate generated from the p55 gag precursor. Caution should
therefore be exercised when examining Western blot profiles and designating
an anti-p41 response as anti-gp41. This report is the first description of a
human monoclonal antibody directed against gag gene products of HIV. The
effect of this newly identified human monoclonal antibody on viral replication
will be discussed.
TP133 Interleukin 2 (IL2) Receptor Gene Expression in Human Monocytes
Infected with Human Immunodeficiency Virus (HIV)
NANCY MCCARTNEY-FRANCIS, DIANE MIZEL, JANICE ALLEN, LARRY WAHL, PHILLIP SMITH,
THOMAS FOLKS et al. , NIDR and NIAID, NIH, Bethesda, MD 20892
Circulating monocytes recruited to sites of inflammation undergo phenotypic
and functional changes characteristic of activated macrophages. We
investigated the role of IL2 receptor expression in activated monocytes in
vitro and then examined the effect of HIV infection in vitro and in vivo on
monocyte IL2 receptor expression. We first demonstrated IL2 receptor gene
expression and synthesis of the receptor in activated monocytes. The addition
of recombinant IL2 to suboptimally activated IL2 receptor-positive monocytes
enhanced both the production of reactive oxygen intermediates and cytotoxic
activity and also regulated interleukin 1 (IL1) production. Normal monocytes
cocultured with HIV in vitro also expressed increased surface receptors for
IL2, and the addition of recombinant IL2 to these cells caused an increase in
reverse transcriptase activity, suggesting that IL2:IL2 receptors may play a
regulatory role in the infective process. We next examined the effect of HIV
infection on IL2 receptor expression in monocytes from AIDS patients.
Peripheral blood monocytes from patients with AIDS expressed increased levels
of IL2 receptors as well as HLA-DR antigens. In addition, Northern blot and
in situ hybridizations demonstrated an increase In the level of IL1 and IL2
receptor mRNAs In the circulating monocytes from these patients, indicating
the prior in vivo activation of these cells. These studies suggest that HIV
infection may contribute to the in vivo activation of monocytes in AIDS
patients and that these activated cells may play an important role in the
pathogenicity of the disease.
TP131 Prognostic Importance of Presence of NAb and Anti-pl7/24 Antibodies
in HIV Infected Individuals.
YOSHITATSU SEI , R.J. PETRELLA, M.M. YOKOYAMA, J.G. BEKESI, Mount Sinai School
of Medicine, New York, New York.
We have serially tested for antibodies directed against HIV antigens and for
the presence of neutralizing antibody (NAb) activity in the sera of 149 pro-
dromal homosexual males, 36 patients with AIDS, and 33 heterosexual males under
double blind conditions in 1985-1986. Presence of anti-HIV antibodies was
determined by ELISA and Western blot methods. All AIDS patients and 101 of 149
(67.8%) prodromals were found to be HIV (+) . All heterosexual subjects and 48
of 149 (32%) prodromals were HIV (-). The neutralizing activity of the sera
was tested by a newly-developed micro-culture assay system using H9-HIV sus-
ceptible cells. Study subjects were devided into NAb+ and NAb- groups. During
the 18-months observation period, 2/80 (3%) HIV+ NAb+ prodromals progressed to
AIDS and died, as compared -to a significantly greater ratio, 5/21 (24%) of HIV+
NAb- prodromals whose conditions thus progressed. Similarly, among the NAb+
AIDS patients, 8/23 (35%) patients died, while 10/13 (77%) NAb- patients died
from the disease. In both these groups, lack of neutralizing capacity in the
serum, was directly related to rapid disease progression. In addition, absence
of anti-pl7 and p24 antibodies as well as the lack of the NAb appears to be
closely related to clinical progression of the disease. These observations
could be a useful tool in the clinical management of patients.
TP134 Modulation of T Cell Proliferative Responses by Envelope
and Core Antigens of the Human Immunedef iciency Virus.
JAMES REUBEN*, A. RIOS*, P. NAYLOR**, G. BREWTON* , A. L.
GOLDSTEIN** and P.W.A. MANSELL* . *M.D. Anderson Hospital and
Tumor Institute, Houston, TX, and **George Washington University,
Washington, DC, U.S.A.
We studied the ability of the recombinant envelope protein,
P121, and two synthetic core proteins, HGP-18 and HGP-30, to
activate peripheral blood lymphocytes (PBL). P121 is a 82 amino
acid peptide corresponding to the env-lor region of HIV. HGP-18
and HGP-30 are protein analogues that share 100% homology with
the gag protein, P17, of HIV; HGP-30 also shares 50% homology
with thymosin-alpha-1 .
PBL from control and symptom- free subjects ( SF) , cultured for 5
days with each of these antigens, resulted in minimal
proliferation (SK5.0). The addition of HGP-30 to PBL cultures
containing PHA did not appreciably affect proliferation. In
contrast, HGP-18 added to PBL cultures containing PHA
significantly augmented the PHA responses of SF( p=0 . 04 ) but not
of controls. Unlike the gag proteins, the envelope protein, P121,
suppressed the PHA responses of both the SF and controls by 36.3%
and 24.1%, respectively.
These results suggest that the gene products of HIV elicit
different but specific host cellular immune responses.
Experiments are in progress to study the mechanism of these
interactions and to determine if these responses differ
quantitatively or qualitatively from SF to more symptomatic
individuals .
84
TUESDAY, JUNE 2
TR135 Relationship Between Skin Test Reactivity and T4 Counts in
Screened Human Immunodeficiency Virus (HIV) Seropositive Active
Duty and Marine Corps Personnel
KENNETH F. WAGNER*, D.L. MAYERS*, S.W. BERG**, W. HARRISON**, T.R. ZAJOWICZ***,
M.J. CHANG,****, et al. , Naval Hospitals *Bethesda, MD, **San Diego, CA,
***Portsmouth, VA, and ****Oakland, CA, USA.
0KT4-positive lymphocytes (T4 counts) and delayed hypersensitivity skin test-
ing (DHS) are major parameters used in the staging and evaluation of HIV sero-
positive patients. We evaluated the relationship between T4 counts and DHS re-
sults in 600 patients identified by the HIV screening program mandated by the
Department of Defense (DOD) . The skin tests were applied by the Allergy De-
partment at each hospital. Three hospitals used the Merieux multitest and one
used intradermal injection of a panel of 5 antigens. For data comparison, nor-
mal is defined as reactivity to 2 or more antigens; hypoergic as reactivity to
1 antigen; and anergy as no skin test reactivity. Summary data is presented
below.
T4 Counts Skin Test Reactivity Results(%) ^Patient
Anergic Hypoergic Normal Evaluations
0-100
i 00-200
200-300
300-400
>400
73
17
10
50
18
32
17
29
54
11
25
64
13
21
66
29
44
90
96
418
Skin test reactivity remains stable down to T4 counts of 300, with a sharp
decline in reactivity observed at counts below 200. Nevertheless, great
individual variability is seen with 27% of HIV seropositive patients with T4
counts less than 100 still able to mount some skin test reactivity.
TP138 Diagnosis and Investigation of Hairy Leukoplakia Using Non-Invasive
Techniques
3.S. GREENSPAN*, D. GREENSPAN*, Y. DE SOUZA*, and U.K. FREESE**,
♦University of California, San Francisco, CA, and **Deutsches Krebsforschungs-
zentrum, Heidelberg, FRC.
A high proportion of HIV seropositive individuals with oral hairy leukoplakia (HL)
subsequently develop AIDS. Diagnosis of oral hairy leukoplakia currently requires
biopsy, a procedure which may not be readily available or may be contraindicated, for
example in hemophiliacs. We have investigated the use of two non-invasive techniques
directed towards establishing the presence of EBV in the epithelial cells of HL
lesions. Filter in-situ hybridization (FISH) involved the use of the pBgl2U probe for
the IR-I sequence of EBV, hybridized to cells obtained from smears applied to filters
under suction, and visualized autoradiographically. Cytospin in-situ hybridization
(CISH) involved the same probe, used on cells applied to glass slides by
cytocentrifugation and visualized using a multistep biotin-enzyme technique. Twenty
cases of biopsy-confirmed HL were studied to compare the ease and accuracy of FISH
and CISH. Both techniques showed the presence of EBV-DNA in all cases. FISH
showed very high sensitivity but was technically more demanding and involves the use
of radioisotopes. CISH allowed identification of single positive cells, was quick and
relatively simple. Both techniques permit confirmation of EBV infection in HL with
high accuracy and may obviate the need for biopsy in some cases.
Supported by the University of California Systemwide Task Force on AIDS and by the
Deutsche Forschungsgemeinschaft.
TR136 EVIDENCE OF HUMAN IMMUNODEFICIENCY VIRUS ENCEPHALOPATHY
IN THE ABSENCE OF OVERT NEUROLOGICAL DISEASE
JOSEPH R. BERGER, MARGARET FISCHL, LIONEL RESNICK, RICHARD DIX, WADE
PARKS, University of Miami School of Medicine, Departments of Neurology, Internal
Medicine and Microbiology, Miami, Florida.
Twenty five HIV seropositive, male homosexuals with AIDS related complex (16) or AIDS
(PCP within 90 days)(9) had neurological assessment upon entry into an antiviral protocol
which excluded patients with overt CNS disease. Review of systems revealed complaints
of memory loss and poor concentration (11), peripheral paresthesias (5), headaches CO,
altered mood (4), and hallucinations (1). Abnormal recent memory and trail making tests
were noted in 9 and 12 patients, respectively.. Examination revealed a pathologically
brisk jaw jerk and/or frontal release signs (13), hyperreflexia or asymmetric reflexes (12),
postural tremor (10), incoordination CO and diminished distal sensation (3). The
neurological assessment was completely normal in only 4 patients.
CT scan revealed cortical atrophy in 4/6. MRI demonstrated diffuse hyperintense white
matter lesions on T2 weighted images in 3/*. CSF examination in 16 patients disclosed a
mononuclear pleocytosis (6-200 cells/mm3) in 6, increased protein (46-79 mg%) in 7, and
glucose 60 mg% in 12. CSF HIV cultures were positive in 4/7. Intrathecal synthesis of
HIV specific IgG was detected in 11/14. All 14 had antibody to gp41, whereas only 6 had
antibody to p24. No herpes viruses, adenoviruses or enteroviruses were isolated from the
CSF.
Evidence of an underlying HIV encephalopathy in ARC and AIDS in the absence of
readily identifiable neurological disease is extremely common. Over S096 exhibited
abnormal neurological findings and 78% had intrathecal antibody synthesis to HIV. CSF
studies and neuroimaging complemented the neurological examination in confirming the
presence of HIV-related CNS abnormalities.
TP.139 Evaluation of a Clinical Case Definition of Pediatric AIDS in
Africa.
ROBERT L. COLEBUNDERS*, A. GREENBERG**, P. NGUYEN-DINH**, K. NDOKO***,
I. LEBUGHE*, P. PIOT***« et al. , * Projet SIDA, Kinshasa, Zaire, «* CDC,
Atlanta, *** Mama Yemo Hospital, Kinshasa. **** Institute of Tropical
Medicine, Antwerp, Belgium.
To determine the accuracy of the clinical case definition for AIDS in
children which was proposed at the second meeting of the WHO collaborating
centers of AIDS December 1985, we examined and carried out HIV serology on
all 15S children hospitalized at Mama Yemo Hospital between July 5 to 7,
1986. Nineteen (12%) of the 15S children examined were HIV(+). Symptoms
and signs significantly associated with HIV seropositivity included:
diarrhea lasting for at least one month, chronic or recurrent otitis
(p=.03), generalized lymphadenopathy (p=.007), oral candidiasis (p=.03),
hepatomegaly (p=.03) and splenomegaly (p=.02). Illness of the mother (p
.0001) and presence of HIV associated symptoms or signs in the mother
(p=.0001) were also strongly associated with HIV seropositivity. The
provisional WHO clinical case definition of pediatric AIDS was found to have
a specificity of 88 4, a sensitivity of 40%, and a positive predictive value
for HIV infection of 30*.
Our study suggests that the use of the proposed WHO pediatric clinical
case definition for surveillance of AIDS in African children will result in
significant underreporting.
TP.137 Clinical Features of Transfusion-Associated Human Immunodeficiency
Virus (HIV) Infections in Children. JOSEPH A. CHURCH, Childrens
Hospital of Los Angeles and USC School of Medicine, Los Angeles, CA, USA.
Blood transfusion (tx) represents the risk factor in over 50% of HIV patients
(pts) at Childrens Hospital of Los Angeles (CHLA). Of 17 pts (15 M, 2 F) with
AIDS or documented HIV infection acquired through blood transfusions, 10 had
AIDS, 5 AIDS-related disorders and 2 were asymptomatic. Ages at diagnosis (Dx)
varied from 8 months to 4i years (mean 3.7 years). Ten pts (9 M, 1 F) received
Tx as premature infants; 5 other symptomatic pts (4 M, 1 F) received Tx at 2
days to 6 years of aqe. The 10 pts infected as prematures were compared to the
5 other symptomatic pts transfused later.
The time (in years) from Tx to development of symptoms (Sx) was 1.6 for pre-
matures and 1.7 for the others, from Tx to Dx of AIDS or HIV infection was
2.7 and 2.8, respectively; and from first Sx to Dx 1.2 and 1.2, respectively..
Failure to thrive, chronic oral candidiasis and hepatomegaly were seen in
both qroups. Recurrent or persistent otitis media or sinusitis was seen in 9
of the prematures and 2 of the others. Interstitial pneumonias including P.
carinii, lymphoid interstitial pneumonitis and pulmonary fibrosis were seen in
8 prematures and only 1 of the other pts. Four of 10 pts infected as pre-
matures have died; 1 of 5 pts infected later has died.
In summary, Tx-associated HIV infection in premature infants was no more
aggressive than that seen in pts transfused at older ages. The high prevalence
of interstitial pulmonary disease in post-prematures may reflect microanatomic
damage and/or local host defense disruption associated with the respiratory
distress syndrome seen in these pts.
TP140 Painful Sensory Neuropathy (FEN) in Patients with AIDS
' DAVID R. Q3MHLAHL* J.C. M3KIHJR,* N.E. FANCE,** J.W. GRIFFIN,*
Departments of "Neurology and ""Neuropathology, The Johns Hopkins University School
of Msdicire, Baltimore MD.
Paresthesias and dysesthesias oonfined to the feet are uluihii symptoms in patients
in the pre-terminal stages of AIDE. This cJ inirai picture has been called PSN. Ten
patients with those complaints uere studied shortly before death. Fxaminaticns
revealed elevated vibratory thresholds, increased sensitivity to pinprick, and
reduced ankle reGeoES. Electii iliagrpstical ly, sural sensory responses were absent
in 6 and reduced in amplitude in 4. Peroneal motor evoked amplitudes were absent in
2 and reduced in 8. Three demonstrated carpal tunnel entrapnents, and ulnar sensory
potential amplitudes were reduced in 4. Conduction velocities were normal or
slightly reduced in proportion to the reductions in amplitude. DG demonstrated
acute denervation potentials confined to distal leg nuscles. These studies are
typical of a distal awnopathy.
In a retrospective study of AIDS autopsies, we previously reported four man
with severe degeneration of the gracile tract of the spinal aord (Faroe et al, Ann
Neuro 1986, 20:146). All developed prominent distal paresthesias and dysesthesias,
vhich increased in severity over 3-6 months. Vibration sensation was impaired in the
feet, ankle jerks were depressed or absent, and plantar responses were flexor. In
one, dorsal root ganglia revealed evidence of demyelination and remyelination with
infiltrating lymphocytes and macrophages. No viral inclusions or perivascular
inflammation were identified in the spiral cards.
The clinical and physiological picture of the 10 PSN patients and the character
and distribution of the lesions in the gracile tract in 4 other patients with
symptoms of PSN suggests a "dying bade" ^uwh of the primary sensory awn. This
may represent a degeneration in the d » w<l root ganglion oells, possibly fran direct
HIV infection.
85
TUESDAY, JUNE 2
TR141 Alterations in Sleep Architecture in Asymptomatic HIV Seropositive
Patients
LIONEL RESNICK, S. NORMAN, M. SHAUKAT, K. NAY, J. HERBST, M. COHN , et al . ,
Mount Sinai Medical Center, Miami Beach, FL.
HIV infection is associated with neurologic disease. Data on sleep are
scarce and suggest that subjective complaints of initiating or maintaining
sleep are secondary to anxiety or depression. No polysomnography data ex-
ploring sleep architecture in HIV infected individuals exists.
A pilot study was conducted to evaluate sleep physiology in asymptomatic
HIV seropositive patients. Eight HIV seropositive (western blot analysis)homo-
sexual males (mean age of 37.6 years) (Group A) and 3 HIV seronegative homo-
sexual men (mean age 28 years) (Group 3) volunteered to complete a sleep his-
tory questionnaire and a polysomnogram (PSG). Both groups did not differ in
their sexual practices or lifestyles. Two patients in Group A and none in
Group B had sleep complaints ,i .e. sleep onset and maintenance difficulty and
daytime fatigue. Mean sleep efficiency index was less in Group A indicating a
poorer quality of sleep (mean 87%, range 71-96%) compared to Group B (mean 94%,
range 90-96%). Six of 8 Group A patients had above normal predicted percent
slow wave sleep (%SWS) (mean 21. 8%, range 16-32%) .whereas this occurred in only
1 Group B patient. Also,%SWS in the second half of the night in Group A (mean
12. 7%, range 2.2-25.1%) was greater than Group B (mean 5. 3%, range 0-8.9%).
We hypothesize that sleep disturbances can be caused by altered biological
processes and not just psychological factors. Early alterations in sleep
architecture may be an early marker of CNS involvement in HIV infected
patients.
TP144 Failure to Maintain Normal Growth Pattern in Pediatric Hemophilia:
Possible Predictor of Progressive Immunodeficiency.
DOREEN B. BRETTLER*. A.D. Forsberg*, P.H. Levine*, F.E. Brewster**, C.
Andrews**, J.L. Sullivan**. *Worcester Memorial Hospital and **University of
Massachusetts Medical School, Worcester MA, U.S.A.
Standard growth charts and clinical, serologic and immunologic measurements
were carried out over 3 years (1983-85) on a cohort of 37 HIV-antibody positive
hemophiliacs, aged 2-15. Seven patients (group A) failed to maintain a normal growth
curve for at least 2 years, while 30 (group B) grew normally. The mean ages of group
A and B were 11.5 years (range 2.8-15) and 8.1 years (range 2.5-14.9) respectively.
All had previously used non-heat-treated concentrate and were HIV antibody positive
by 1984. There was no significant difference between the amount of factor concentrate
utilized by each group.
In 1983 there was no significant difference between the 2 groups in any of the
immunologic or clinical parameters studied. By 1985 those who had failed to maintain
a normal growth pattern had developed: 1) a significant decrease in the number and
percentage of absolute T helper cells: 253/uI vs 813/ul, p<.01; 16.896 vs 30.496, p<.01;
2) a decreased T helper/suppressor ratio: .37 vs .86, p<.01; and 3) decreased skin test
reactivity. One patient who failed to grow has developed AIDS and 1 patient has had
chronic diarrhea and weight loss; another has persistent oral candidiasis and recent
severe weight loss. No patient in the control group is ill. Since those who failed to
maintain a normal growth pattern exhibited significantly greater deterioration in
immune studies than those who continued to grow and since cessation of normal growth
often preceded laboratory or clinical deterioration, it is possible that a period of
lack of growth could be predictive of more severe progression of clinical manifestations
in children with HIV infection. It is also likely that growth failure is another sign
of clinically symptomatic HIV infection in children.
TP142 Is cytomeftalovirus (CMV) a cause of pneumonia in AIDS 7
DANIEL VITTECOQ, S. DURAND, MC. MAZERON, A. HIRSCH, Y. PEROL,
St. Louis Hospital, Paris, France.
In order to investigate the incidence of CMV (frequency and prognosis) in
the lungs of AIDS patients we examinated broncho alveolar lavage (BAL) fluid
in 80 AIDS and 20 preAIDS patients observed during 14 months. BAL was
performed either for pulmonary symptoms or unexplained fever (>3 weeks).
CMV was isolated by culture in 29 patients (32 BAL) and was the only
microbiological agent In 14 BAL, and was associated with other agents in 18
BAL (14 Pneumocystis, 3 Mycobacterium avium intra cellulare (MAI), 1
Cryptococcus neoformans). 2 preAIDS patients had CMV in BAL and AIDS was
diagnosed 6 months later in 1 of them admitted for an unexplained fever
which was due to pericardial tuberculosis. CMV was observed in 13 AIDS
having had at least one opportunistic infection (01). It was also isolated
in 14 AIDS during the first 01. 5/29 patients with CMV died of the
pneumonia which required BAL, but no death seems to be specifically linked
to CMV, since another agent was found in these cases: Pneumocystis (3), MAI
(2) associated in 3 cases to pulmonary kaposi sarcoma. No patient died of
pneumonia when CMV was the only microbiological agent.
CMV is frequently isolated in BAL during AIDS (301). CMV seems to be
isolated more often in advanced stages of the disease. The pathogenic
significance of CMV is unclear in this disease.
TR145 Evaluation of the WHO Case Definition of AIDS in Rural Zaire.
KEVIN M_^ DE COCK, R. COLEBUNDERS, N. NZILAMBI, H. FRANCIS, P.
PIOT, J.B. MCCORMICK, et al. Division of Viral Diseases, Centers for
Disease Control, Atlanta, GA, U.S.A.; Project SIDA, Kinshasa, Zaire;
Institute of Tropical Medicine, Antwerp, Belgium.
The World Health Organization (WHO) has proposed a clinical case
definition for AIDS for use in areas where medical facilities are inadequate
to confirm AIDS as defined by the Centers For Disease Control. In these
areas the clinical definition can only be evaluated against human
immunodeficiency virus (HIV) antibody status; this evaluation is therefore
one of the case definition as an indication of symptomatic HIV infection.
Seventy-seven patients in 4 rural hospitals in the Equateur Province of
Zaire were examined and had sera tested for anti-HIV. Fulfillment of the
clinical criteria was compared with anti-HIV status. Twenty-one (271)
patients were anti-HIV seropositive, and 22 (29%) fulfilled the criteria.
For diagnosing symptomatic HIV infection, the WHO criteria performed as
follows: sensitivity 521; specificity 80%; positive predictive value 50%;
negative predictive value 82%. The clinical spectrum of HIV infection is
broad, and determining the amount of HIV related disease and deaths is more
relevant in Africa than strictly defining AIDS. We propose the case
definition be assessed accordingly.
Tp-MO Increased Risk of Cervical and/car Vaginal Squamous Atypia in Women
1 r" "" Infected with HTV.
LEWIS SCHRAGER, GH FRIEDLAND, RS KLEIN, D MAUDE, K SCHREIBER, LG KOSS, et al.
Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NX, USA.
We studied women with AIDS as well as female sexual partners (SPs) of male AIDS
patients to determine the prevalence of cervical and/or vaginal squamous atypia and
its relationship to HIV infection. Si±>jects underwent standardized interviews
regarding demographics and sexual history, complete physical exams including pelvic
exam, and assay for HIV serum antibodies and T4 cell counts. Samples of cervical
epithelium for cytologic evaluation were obtained and read by one cytopathologist
blinded to the subject's HIV status. 35 HIV antibody + (HTV+) women (28 SPs and 7
with AIDS) and 23 without HIV infection (HIV-) (all SPs) were evaluated.
11/35 (31%) HIV+ subjects had evidence of squamous atypia compared with 1/23 (4%)
of HIV- women (p=&019); Compared to HTV- women, HIV+ women had a significantly
increased frequency of venereal disease, decreased use of barrier contraceptives and
fewer months 3ince last sexual contact with an AIDS patient (p<0.05). HIV+ women
also had significantly lower absolute T4 counts,
HIV+ women with atypia compared to mv+ women without atypia had no significant
differences with respect to any demographic, sexual or immunologic variables, except
for more children among those with atypia (pt.05).
We conclude that HIV+ women have a significantly increased prevalence of cervical
and/or vaginal squamous atypia compared to HIV- women. In the HTV+ group atypia was
not associated with variables relating to sexual experience. Hypotheses to explain
these findings include increased susceptibility of HIV+ women to agents which may
potentially promote cervical or vaginal atypia (e.g. papillomavirus), a direct
effect of HIV infection, or increased susceptibility of women with preexistent atypia
to HIV infection. Additional epidemiologic, pathologic and virologic studies are
required to explore these possibilities.
TR146 Examination of Neurodeveloproental Outcome in Congenital HIV
Infection: Heterosexual vs. IVDA Transmission
Gary W.Diamond*,A.L.Belman**,A.A.Wiznia j. Kashkin , H.J.Cohen*, A. Rubinstein.
Albert Einstein College of Medicine, Department of Pediatrics , *Rose Kennedy
Center, Bronx, N.Y. , **SUNY, Stony Brook, N.Y.
Previously described neurodevelopmental impairment in infants and chil-
dren with AIDS includes a variety of cognitive deficits, motor delay, enceph-
alopathy, acquired microcephaly, spasticity and dementia. Most cases of con-
genital AIDS to date have been traced to maternal IV drug abuse. Drug abuse
during pregnancy is associated with greater fetal wastage and less favorable
neurodevelopmental outcome in the newborn. A pilot study for a long term
multidisciplinary prospective project was conducted to delineate those per-
nicious neurodevelopmental effects which were disease induced and those drug
induced.
Sixteen HIV-antLbody positive pediatric patients under the age of 2%
years were examined by raters blind to the etiology of the infection, using
standardized cognitive measures and neurological assessment. A group of 10
were the offspring of confirmed maternal TV drug abusers; another 6 were in-
fected in utero from heterosexual contact.
Statistical analysis using the Fisher exact test shewed no significant
differences between the 2 groups on either the neurological or cognitive
(Bay ley MDI scale) measures. Earlier onset of CNS symptoms was associated
with a poorer long term developmental prognosis and a higher score on the
AIDS embryopathy rating scale for related dysmorphic features.
Lack of significant differences between the groups suggests how severely
the HIV infection affects the developing nervous system regardless of
exposure to other potentially toxic environmental factors.
86
TUESDAY, JUNE 2
TP147 Diarrhea in Patients with AIDS/ARC.
SAUL J. RODRIGUEZ, M.M. HERNANDEZ, K.V.I. ROLSTON. Institute for
Immunological Disorders and U.T.S.C.C. M.D. Anderson Hospital and Tumor
Institute, Houston, Texas, U.S.A.
Diarrhea is a common problem in patients with ARC and AIDS. Much time and
effort is spent in evaluating these patients. We examined the records of
230 HIV antibody positive (53% AIDS; 47? ARC) patients. Of these, 64 (28%)
had diarrhea and 63 were male homosexuals. Conventional work-up (stool smears
and culture, ova and parasites, mycobacterial smear and culture, and viral
culture) revealed causative organism(s) in 19 patients (29%). Eleven patients
had infection with one and 8 with more than one organism. Thirteen different
pathogens were recovered including Cryptosporidia (5), Giardia and CMV (4),
Shigella flexneri (3), Entameba coli and Entameba hartmani (3), Isospora
belli , Blastocystis hominis, ji. histolytica, Salmonella typhi , Camphylobacter
spp. , and Pseudomonas putrefaciens (1). Seventeen of these 19 patients received
specific therapy with 11 complete and 4 partial responses. Of the remaining
45 patients 22 (49%) had self-limited disease which required no therapy.
Fifteen of these had ARC. Twelve others responded completely and 6 partially
to non-specific anti-diarrhal agents (Imodium, lomotil). Only 5 patients had
persistent diarrhea requiring further evaluation. Endoscopy and intestinal
biopsy was diagnostic in 3 of 5 patients. Our data suggest that the majority
of ARC/AIDS patients do not require endoscopy and intestinal biopsy for the
evaluation of diarrhea since it is often self-limited or may respond to
non-specific therapy.
TR150 Prognostic Indicators of Survival in AIDS Patients with Pneumocystis
carinii Pneumonia: A Biostatistical Analysis
N.A. LEE*, E. BELLIN*, L. FRAULIN0+, WARREN A. AN0IMAN*+. *Yale University
School of Medicine, +Yale-New Haven Hospital , New Haven, CT.
In order to identify prognostic indicators of survival from Pneumocystis
carinii pneumonia (PCP) we studied retrospectively our first 48 adult AIDS pa-
tients with PCP. We determined which clinical and laboratory features present
early in the course of treatment were predictive of prolonged survival from an
initial episode of PCP. Statistical evaluation of uncensored (followed to
death) and censored (followed to date last seen) patients was accomplished
using the survival analysis method of Kaplan and Meier. The Cox-Mantel test was
used to determine whether the difference between separate Kaplan and Meier
survival curves was significant.
Seven variables emerged as significantly associated with prolonged survival:
an initial positive response to therapy, the presence of night sweats, a normal
or near-normal chest Xray, an arterial oxygen tension >50mm Hg in room air, a
TH/TS ratio? 0.25, either no alteration of PCP therapy or alteration because of
adverse reaction only and the absence of respiratory failure requiring artifi-
cial ventilatory support. The singlemost important indicator was the patient's
initial response to anti-PCP therapy and emphasizes the importance of the clin-
ician's assessment during the first 7 days in estimating the ultimate length of
survival .
The presence of dyspnea on exertion and significant recent weight loss, a re-
spiratory rate >30/min, fever, and a widened A-a gradient were associated with
a general reduction in survival.
Familiarity with specific indicators of survival from PCP assists the physi-
cian in providing realistic information to the patient and his/her family re-
garding prognosis and guides decisions about future care.
TP148 Renal Tubular Nephropathy in AIDS Causing Volume Depletion and Mal-
nutrition.
J.K. MAESAKA, A.J. CUSANO, F.P. SIEGAL, H.L. THIES, L.I. Jewish Medical Center,
New Hyde Park, N.Y.
Weight loss and cachexia often accompany AIDS. We did renal clearance studies
in 4 patients with AIDS.wt loss, cachexia and clear evidence of severe hypovol-
emia(postural hypotension, reflex tachycardia, high plasma renin and ADH levels,
cvp 0),but no evident fluid losses. Renal tubular defects were shown in all pts
by high renal excretion rates (RER) of uric acid(UA) and various amino acids (AA)
despite low blood levels and volume depletion. Salt therapy did not correct vol-
ume depletion, but further increased RER of UA and AA,and showed abnormal RER
for sodium, potassium and phosphorus. Also, one pt returned to baseline volume
depleted state when extra salt was stopped. These data highlight the magnitude
of the tubular defects since similarly volume depleted pts with normal tubular
function markedly reduce RER and retain augmented salt intake. All pts had nl
creatinine, urinalysis(no protein, glucose) and adrenal function. Opportunistic
illnesses or drugs did not cause these effects. Conclusion: HIV infection ap-
pears to cause renal tubular defects which produce severe hypovolemia due to
renal salt wasting, and also significant renal losses of other minerals and
amino acids that worsen when replacing salt. Low plasma AA resulting from renal
losses may partially account for the cachexia in AIDS. Salt therapy to replete
volume given without other nutrients will aggravate malnutrition by increasing
renal losses of amino acids and other nutrients.
TP1R1 Neuromuscular Complications of Human Immunodeficiency Virus (HIV)
1 '• '" ' MARIN OS C. DALAKAS*, G.H. PEZESHKPOUR**, 31. SEVER*, *NINCDS,
NIH, Bethesda, MD., **Armed Forces Institute of Pathology, Washington, DC.
We have seen the following neuromuscular complications in patients infected with HIV:
I. Peripheral Neuropathies of the following subtypes: a) Acute demyelinating
inflammatory sensorimotor polyneuropathies identical in presentation and course
to Guillain-Barre syndrome with occasional cytomegalovirus (CMV) inclusions in
the Schwann cells; b) Mononeuropathy multiplex which can remit spontaneously
or evolve into a distal symmetric polyneuropathy; c) Chronic, slowly progresive
sensorimotor demyelinating polyneuropathy with CSF pleocytosis and elevated
protein; d) Small fiber, distal, symmetric sensory neuropathy, due to a distal
axonopathy; and e) Large fiber sensory ataxic neuropathy due to
ganglioneuromas. Nerve biopsy shows demyelination with inflammatory
infiltrates (la, lc), vasculitis (lb), axonal loss (Id), inflammation in the ganglia
(le), or a combination of findings.
II. Polymyositis as described (Dalakas et al. JAMA, 1986).
III. Type II muscle fiber atrophy, as the only morphological finding in the weak
muscles due to poor nutrition, rapid weight loss or remote effet of lymphomas.
Amyotrophic Lateral Sclerosis (ALS) in one case.
Although some neuropathies and the type n atrophy can be due to nutritional
factors, there is evidence that the majority of the cases are due to HIV
infection, co-infection with other viruses, i.e. CMV or due to immunopathologic
mechanisms. Based on our experience, a neuromuscular disease may be the
presenting sign of an ARC or developing AIDS or the only clinical manifestation
of HIV seroconversion. Patients at risk who present with neuropathy or
myopathy, should therefore be screened for HIV.
IV.
TP14Q
ii.i-tj Distribution of HIV Message in Postmortem Brain
THOMAS A^ ESKIN and M. H. STOLER, Department of Pathology, Uni-
versity of Rochester, Rochester, NY, U.S.A.
The in situ hybridization technique has the potential for al-
lowing very precise localization of the replicating human immuno-
deficiency virus (HIV) in the brains of AIDS patients who suffer
from neurologic complications. We preliminarily tested the util-
ity of this approach as applied to routinely fixed and processed
tissues CStoler et al (1986) JAMA 256: 23603 and here report ad-
ditional studies of similarly processed brain tissue from autop-
sied AIDS patients. In this study we examined cases with, and
cases without typical histopathological evidence of "AIDS enceph-
alitis", but in either case with additional ongoing or potential
complicating CNS pathology (eg. primary CNS lymphoma, systemic
CMV infection). Our conclusions are: (1) that HIV can replicate
in brain concurrently with other complicating CNS processes and
k2) in situ hybridization applied to routinely processed autopsy
(as well as surgical) tissue, provides the potential for direct
study of the topographic distribution of HIV infection in brain,
for correlation with specific neurologic impairment in life.
TR152 Tne Control of HIV Transmission ■ A Public Health Challenge Requiring
the Maximum of Foresight. Courage and Reassessment and Flexibility.
DONALD P. FRANCIS. Centers for Disease Control. Berkeley, CA
It is clear that, because most (>90%) HIV transmission in the United States is
through behavior that can be modified, HIV transmission can be controlled. The
marked behavior changes of San Francisco homosexual men and the resulting
decreased infection rates attest to the potential success of behavior modification.
Yet, despite some local successes by-and-large our AIDS prevention efforts are
failing. Why? First, our political, budgetary, and public health managerial systems
are not geared to such long term emergencies and. as a result, have largely been
paralyzed by the day-to-day chaos of AIDS Second, we as a society have not
developed the courage to move ahead with the difficult issues involved with fielding
an AIDS prevention program.
With recent publications (Surgeon General's Report, NAS Report, Francis and Chin)
there are prevention plans around which local programs can be designed The
message to be promulgated by these programs is rather simple: Dangerous virus -
take personal responsibility to protect yourself: 1) If you are (joing to have sex. use
a condom 2) Don't use drugs: if you must, don't share unsterilized needles/syringes.
3) If you are going to get pregnant and possibly have been exposed, be tested before
and if you are positive, don't become pregnant.
In the absence of effective vaccines or therapeutic agents, the extent of spread of
HIV will be determined by the effectiveness of changing at-risk behavior. That
effectiveness will require an immense short term 'catch up" program of adult
education, motivation and skill building followed by "maintenance" programs through
schools and adult updates In addition, prevention centers where indrvxiuals and
families can find information, testing, and support groups will be increasingly
important. Finally, assessment by periodically determining prevalence and incidence
of infection, behavior changes and STD rates will be critical in evaluating the
success or failure of the program so that appropriate changes can be instituted.
87
TUESDAY, JUNE 2
TR153
H1V-1 and 2 are present in Ivory Coast in AIDS patients
TR156
Asymptomatic Myositis in HTV Antibody-positive Men
A. OUATTARA*. GROUPE IVOIRIEN DE TRAVAIL SUR LE SIDA*, M. A. REY**, F.
BRUN-VEZINET**, C. DE-THE*** - *Pasteur Institute, Abidjan, Ivory Coast
**Hopital Claude Bernard, Paris, France ***CNRS Laboratory, Fac Med A. Carrel,
Lyon, France
Investigation of AIDS in Ivory Coast showed that the disease became clinically
evident by the end of 19S5 and took epidemic proportions in 1986. Sera collected in
June 1986 from patients with AIDS, according to the WHO Bangui definition, showed
in 30 % of the cases antibodies to HIV-1 alone, in 20 % antibodies to HIV-2 and in
50 % antibodies to both HIV-1 and HIV-2 env and gag antigens. Sera considered as
HIV-2 positive exhibited however weak and variable cross reactivities to HIV-1 gag
products (pi 8, p26, p55). Survey of prostitutes in Abidjan showed that about half of
them had antibodies to both HIV-1 and 2. These results indicate that both viruses are
present in Ivory Coast, that they are associated with AIDS and that infection by one
HIV strain does not protect from the other.
Prior sero-epidemiological investigation (Ouattara et al, Ann. Inst. Pasteur
(Virology), 1986, 1 37E: 303-310) showed a low prevalence of infection by HIV-1 in
the general population of northern, eastern, western and southern regions of Ivory
Coast in mid-1985. Prevalence of HIV-2 antibodies in these sera is being
investigated.
WILLIAM 0. HARRISON, S.W. BERG, CM. COUNIHAN, United States Naval
Hospital, San Diego, CA.
Among the first 500 active-duty naval personnel identified as HIV anti-
body-positive and evaluated at the Naval Hospital, San Diego, 17 were noted
to have creatine phosphokinase (CPK) levels more than 50% above the normal
range for the hospital laboratory. All were asymptomatic with regard to
musculoskeletal problems. After bed rest 4 of these individuals continued to
have markedly elevated enzyme levels. CPK isoenzyme determination was 100%
MM (skeletal muscle-related) in each case. Muscle strength testing and
electromyography were normal in 3 men. Muscle biopsies of 3 of the 4 showed
acute myositis. Only one of the 4 developed AIDS. His myositis regressed
during treatment for PCP but recurred when his pneumonia recurred. Two
others were in DoD (Walter Reed) Class 1 and the third in Class 3. These 3
have remained well, with persistent moderate-to-marked CPK elevations.
A recent paper reports acute symptomatic polymyositis in association with
AIDS. It further implies that the use of steroids as therapy for myositis
may enhance the onset of AIDS. We present these cases as the opposite end of
what may be a spectrum of HTV-associated myositis. Only one of the 4
developed AIDS. He was not treated with steroids, but eventually died of
AIDS. The remaining 3 show no evidence of progressive KEV-associated
disease. Further study will be necessary to confirm an association between
HIV and myositis in asymptomatic antibody-positive individuals.
TP154 Limited Value of Mycobac
of Pulmonary Tuberculosi
NATALIE C. KLEIN*, F.P. DUNCANSON*
EY*, G.P. WORMSER**, *Metro
dical College, New York Cit
S. BAIL
York Me
New Yor
Tuberc
phic ar
studies
patient
the maj
mul tisy
with TB
1, 1985
York Ci
Over th
Of thes
(22).
with pu
bacteri
f requen
sputum
(76%)
We con
certain
pulmona
sputum
suspect
terial Smears in the Diagnosis
s in AIDS/ARC Patients.
, T.H. LENOX*, R. VOGEL*,
politan Hospital Center, **New
y., New York, and Valhalla,
k, U.S.A.
ulosis (TB) is increasing in incidence in certain geogra-
eas where both TB and HIV infections are endemic. Prior
have emphasized the presence of extrapulmonary disease in
with both infections. Less well known is the fact that
ority of such patients have pulmonary TB as a component of
stem tuberculous infection. We reviewed our experience
diagnosed by culture over a two year period from January
to December 31, 1986 at a metropolitan hospital in New
ty serving East and Central Harlem and the South Bronx,
is time period 104 hospitalized patients had pulmonary TB.
33 (32%) were known to have or develop AIDS (11) or ARC
Of these 33 patients 94% were male. Of the 71 patients
lmonary TB without AIDS or ARC, 75% were male. Myco-
al smears of pulmonary secretions were significantly less
tly positive in AIDS/ARC patients 16/33 (48%) (mean 2.5
smears examined/patient range 1 to 9) compared to 54/71
n patients without AIDS/ARC (p< .05).
elude that about one third of pulmonary TB
areas of New York City have AIDS/ARC. The
ry TB should not be excluded on the basis o
smears. Empiric anti-TB treatment is warra
ed in the AIDS/ARC patients pending culture
patients in
diagnosis of
f negative
nted when TB is
results.
TPffl The
IK10# WILF
H.D. POHLE**,
gen, ** Rudol
Germany
In order to
sis of HIV-en
10 with ARC a
methods that
immune respon
- the quantit
in CSF (IgG,
- the compara
in CSF ans se
centrations
compensates i
- the confirm
trum in CSF a
A CSF/serum
strongly sugg
According to
patients show
very early HI
70 % (7/10) o
tients with A
production of
apparent neur
cerebrospinal fluid diagnosis of HIV-encephalitis
RIED LUER*, W. BUTTNER* S. POSER*, D. EICHENLAUB** ,
K. Felgenhauer* , * Georg-August Universitat Gottin-
fTVirchow Krankenhaus Berlin, Federal Republic of
est
ceph
nd 3
have
se w
atio
IgA
tive
rum
This
mpai
ativ
nd s
rat
esti
this
ed i
V-in
f th
IDS
imm
olog
abli
alit
1 wi
bee
ithi
n of
and
qua
by a
met
rmen
e ev
erum
io o
ve f
cri
ntra
feet
e pa
show
unog
ical
sh a reliable procedure for the early diagno-
is, 56 patients - 15 HIV-antibody positive,
th AIDS - were examined with the following
n recently developed to evaluate the humoral
n the central nervous system:
the locally produced immunoglobulin fractions
IgM ) by an empirical dif f erentation diagram,
ntitation of HIV-specific antibody activity
modified ELISA based on identical IgG-con-
hod avoids the calculation of indices and
ts of the blood-CSF barrier,
aluation of the HIV-specific antibody spec-
by Western blot,
f the specific antibody activity above 2 is
or an intrathecal HIV-antibody synthesis,
teria 46 % (7/15) HIV-antibody positive
thecal antibody synthesis indicative of a
ion of the central nervous system, whereas
tients with ARC and 65 % (20/31) of the pa-
ed evidence for HIV-encephalitis. The local
lobulins, however, does not correlate to
symptoms .
TR155 *10Srases°a
feet of R
PETER KERN*, W. ME
Nocht-Institut, Ha
Georg, Hamburg, Ge
Twenty-eight pat
treated with inter
of 18x 106 Units w
administrations su
according to the W
tients is given in
WR5 (11), and WR6
ly intervals. An a
served in 9 patien
stitution and tenia
servatior, time of
tients died 11, 15
portunistic infect
less favorable sco
of patients in the
(1) , UR4 (4), HR 5
peated episodes of
the median observati
Some patients achi
of IFN together wi
sarcoma and HIV in
2 or 3 may have a
ciated Kaposi's Sarcoma: Antiproliferative Ef-
ecombinant Interferon Alpha.
IGEL**, T. DETTKE**, M. DIETRICH*, *Bernhard-
mburg, Germany, **Allgemeines Krankenhaus St.
rmany .
ients with biopsy-proven Kaposi's sarcoma were
feron alpha 2a. Daily intramuscular injections
ere given for 3 months, followed by 3-weekly
bsequently. Staging of patients was performed
alter Reed classification: the number of pa-
brackets: WR1 (0), WR2 (6), WR3 (3), WR4 (4),
(4). Response to treatment was judged in month-
ntiprolif erative effect of interferon was ob-
ts (32S) during the first 3 months of IFN sub-
ined so for at least 6-9 months. The median ob-
the responder group was 11.5 months. Three pa-
, 17 months after start of treatment due to op-
ions or tumor progression. All of them had a
re in the WR classification (WR3-5). The majority
nonresponder group had a higher WR score (WR2
(10), WR6 (4)). Host patients suffered from re-
opportunistic infections. Seven out of 18 died,
on perioH was 6 months, ranging from 2 to 18.
eved stabilization by the combined treatment
th vinblastin. Thus, patients with Kaposi's
fection classified according to WR into stage
favorable response to interferon alpha 2a.
TR158 Patterns of Magnetic Resonance Brain Scanning of Lesions in AIDS
and ARC Patients.
JERRY JARVIK, J. HESSELINK, C. KENNEDY, R. TESCHKE, C. WILEY, O.A. MCCUTCHAN
et al., University of California, San Diego, San Diego, CA.
Magnetic resonance (MR) brain scans of 30 patients with either acquired
immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) were reviewed.
Twenty patients had focal ly abnormal neurological examinations at the time of
scanning. Pathological diagnosis was available in nine. Four patterns of
abnormality were observed on T2-weighted Images. Multiple discrete high
signal foci (Type A) were found in patients with toxoplasmosis and progres-
sive multifocal leukoencephalopathy (PML). Large, bilateral patchy to con-
fluent high signal areas within the white matter (Type B) represented a
white matter encephalitis secondary to cytomegalovirus (CMV) or human
immunodeficiency virus (HIV). Generalized enlargement of the cortical sulci
and ventricles (Type C) reflect atrophic changes probably from the chronic
HIV infection. Solitary high signal intensity lesions (Type D) suggested
a focal (VZV and coccidioidomycosis in our series) opportunistic infection.
Differential diagnosis of brain abnormalities in patients with AIDS can be
assisted by recognition of these characteristic patterns.
TUESDAY, JUNE 2
TR159 Central Nervous System Reactions to Trimethoprim-Sulfamethoxazole
in Acquired Immunodeficiency Syndrome (AIDS) Patients.
MICHAEL J. BORUCKI, D.S. MATZKE, R.B. POLLARD, Division of Infectious Diseases,
The University of Texas Medical Branch, Galveston, TX
Adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMZ) therapy, espe-
cially leukopenia, thrombocytopenia, and rash, occur with increased frequency
in patients with AIDS. Only one CNS reaction (seizures) to TMP/SMZ in this
population has been reported. The CNS side effects of TMP-SMZ reported in nor-
mals include headache, depression, and hallucinations. Three patients who had
tremor as a prominent manifestation of TMP-SMZ therapy were observed in an 18-
month period. One patient also developed hallucinations, another a wide-based
gait and dysmetria. Two of the patients were noted to appear apathetic at the
time of the reaction. Symptoms occurred 4-9 days after the onset of therapy
and were co-incident with the development of leukopenia. All three patients
had a mild hyponatremia (127-130). The tremor, hyponatremia, and leukopenia
resolved after discontinuance of the TMP-SMZ with marked neurologic improvement
evident in the first 24 to 48 hours. During this same interval 27 additional
AIDS patients were treated with TMP-SMZ for Pneumocystis carinii pneumonia, 25
of whom were treated with both Pentamidine and TMP-SMZ, either concurrently or
sequentially. Laboratory investigations failed to implicate alternative eti-
ologies for the tremor. This experience suggests that not unlike the increased
incidence of other toxicities previously reported, neurotoxicity to TMP-SMZ may
be more frequent in the AIDS population than is generally appreciated.
TP162 Routine Blood Cultures in AIDS Patients. TJ SPECH, MC MCHENRY,
TF KEYS, C KARAFFA-MYLES, DL LONGWORTH, SJ REHM. Department of
Infectious Disease, Cleveland Clinic Foundation, Cleveland, OH.
Blood cultures (BCs) for bacteria are commonly drawn in the febrile
AIDS patient Cpt) despite the relative infrequency of bacteremia versus oppor-
tunistic and non-bacterial infections. This observation prompted an analysis
of the utility of BCs for 'routine' bacterial pathogens in AIDS patients.
The charts of 65 of the 68 pts with AIDS followed at the Cleveland Clinic
from 1981 through 1986 were available for review with attention to the number
of positive and negative BCs, presence of central venous catheters, clinical
diagnoses, and pt outcome. A total of 710 BCs for aerobic and anaerobic bac-
teria were drawn on 60 patients. Only 13 episodes of bacteremia were detected,
and 5 of these were due to staphylococcal infections of central venous cathe-
ters. The remaining 8 episodes were primarily due to gram-negative bacilli
from various sources: E. coli urosepsis, K. oxytoca pneumonitis, K. oxytoca
biliary sepsis, E. coli of unknown source, and S. pneumoniae pneumonia. Two
pts had polymicrobial bacteremia (due to paratracheal abscess and to sinusi-
tis).
Non-catheter related bacteremia was seen in pts with far-advanced AIDS,
always occuring several months after diagnosis (mean 358 days, range 169-898
days). Gram-negative bacteremia usually signified terminal disease with only
one of 6 pts surviving beyond one month (mean 17 days, range 1-65 days). These
data suggest that routine bacterial BCs in AIDS pts are of low yield except
in the presence of central venous catheters or far-advanced disease.
TR160 RETINAL DETACHMENT IN TREATED CYTOMEGALOVIRUS RETINITIS.
Dennis M_. Causey. W.R. Freeman, D.E. Henderly, W.L. Wan, N.A. Rao,
J.M. Leedom, et al. University of Southern California, Los Angeles, CA USA.
Despite the frequent occurrence of cytomegalovirus (CMV) retinitis in AIDS
patients, associated retinal detachment has not been reported. We treated
twenty-five patients with AIDS and CMV retinitis with ganciclovir. Each
patient was treated initially with 2.5 mg/kg every 8 hours for 10-20 days
(induction) and then was placed on a maintenance regimen of 5 mg/kg/day 5-7
days/week. Every patient showed evidence by funduscopic exam of regression of
the retinitis after the initial induction dosing. Ten eyes of six patients
developed retinal detachment during maintenance ganciclovir treatment. Retinal
detachments presented clinically as acute, sudden loss of vision in the affec-
ted eyes. Multiple breaks in areas of peripheral, healed, atrophic retina
accounted for the detachments. All eight eyes undergoing surgery had exten-
sive retinal detachments that were reattached with vitrectomy and silicone
oil. In the fellow eye of one patient, laser treatment was used prophylacti-
cally to wall off a peripheral patch of healed retinitis. Endoretinal biop-
sies and culture were taken in five eyes; evidence of persistent CMV was seen
in two cases despite concurrent and clinically effective ganciclovir therapy.
We conclude that retinal detachment is a frequent complication of treated CMV
retinitis. These detachments are often surgically correctable. Because of
the propensity of these eyes to develop proliferative vitreoretinopathy,
vitrectomy and the use of silicone oil may offer long-acting tamponade to the
extensive areas containing retinal breaks as well as preventing potential
future retinal breaks in zones of healed retinitis. The possible effective-
ness of laser prophylaxis to surround areas of thin healed retina warrants
further evaluation.
TDHCO Prognostic factors for Pneumocystis carinii pneumonia requiring
mechanical ventilation.
WAFAA EL-SADR, and MICHAEL S. SIMBERKOFF, VAMC, New York, N.Y.
Mechanical ventilation (MV) has been reported to be associated with a poor
prognosis in Pneumocystis carinii pneumonia (PCP) . Records of 19 patients (pts)
requiring MV in association with their first episode of PCP were analyzed.
Group A (GA) consisted of 8 pts who survived; group B (GB) of 11 pts who died.
The mean ±SD of the duration of symptoms was 13±10 days and 23±19 days for GA
and GB respectively (p=.03). Arterial oxygenation deteriorated and A-a gradient
widened more precipitously in GA. The time from diagnostic bronchoscopy to
initiation of MV was 1.5±0.5 days and 6±7 days for GA and GB respectively
(p=.001). MV was necessary for 6+4 (range l-6)days in GA and 19±16 (range 6-60)
days in GB pts. Admission and peak serum LDH concentrations were similar in the
2 groups. However, LDH decreased by at least 40% from the peak level in all pts
in GA by 5 days after intubation while it fell in only 4 of 11 GB pts. Con-
comitant early infections were seen in 3 pts of GA (1 S. epid. sepsis,
1 salmonella sepsis and 1 mycobacterial isolate from the sputum) and in 7 pts
in GB (3 S. aureus sepsis, 4 S. aureus pnemmonia and 2 mycobacterial sputum)
(p<.05).
We conclude that 42% of pts with PCP may recover from required MV. Factors
associated with recovery include short duration of symptoms prior to admission,
need for intubation shortly after bronchoscopy, early improvement in serum LDH
levels and the absence of concomitant bacterial infections.
TP161 Prevalence of hairy leukoplakia and oral candidiasis among HIV-
infected Danish hemophiliacs.
MORTEN SCHIODT, J.RINDUM, E.SCHEIBEL, J. J.PINDBORG, Royal Dental College,
Department of Oral Medicine & Oral Surgery and East Danish Hemophiliac Center,
University Hospital, Copenhagen, Denmark.
Oral hairy leukoplakia (HL) and candidiasis occur frequently and early among
seropos. homosexuals cut are largely undescribed among hemophiliacs. All known
patients with severe hemophilia (90) in Eastern Denmark were invited for oral
examination. Seventyseven (85%) responded, and the oral examination was con-
ducted without knowledge of the HIV-antibody status. Of the 77 patients 42
(55%) were seropos. .Only one had AIDS.
Erythematous (atrophic) oral candidiasis was found in 4 seropos. (10%) and
in one seroneg. patient (3%). No cases of pseudomembranous candidiasis were
seen. HL was found in 6 seropos. patients (14%) and in no seroneg. patients.
Among the 6 HL patients 1 had AIDS with PCP and 1 non-diagnosed lung symptoms.
The mean T-helper:T-suppressor cell ratio of the HL patients was 0.3 whereas
tha same ratio was 1.0 for the 36 seropos. qnon-HL patients (p=0.0013). The
mean number of T-helper cells was 0.2 x 10 and 0.8 x 10 among the HL and
non-HL seropos. patients, respectively (p=0.0001). Thus, seropos. hemophiliacs
with HL have more impaired immune system than seropos. hemophiliacs without
HL. The observed prevalence rates appear to be lower than those so far re-
ported among seropos. homosexuals. The prognostic significance of these
findings has to be elucidated.
This study has been supported by the Danish Hemophiliac Society (Danmarks
blederforening) .
TP164 Muco-cutaneous Manifestations in HIV Positive Subjects
MARCO CUSINI, ROBERTO ZERBONI , GUIDO CARMINATI , ELVIO ALESSI -
1st Clinic of Dermatology - AIDS Screening Centre - University of Milan -
Via Pace 9, 20122 Milan - Italy
We studied the muco-cutaneous lesions in 310 HIV positive patients
attending our AIDS screening Centre. Two hundred seventy-seven were
homosexuals, 30 were intravenous drug abusers, 3 were heterosexual males.
Fifty-four were asymptomatic carriers (Walter Reed 1), 137 had persistent
generalized lymphadenopathy (WR 2), 98 had ARC (WR 3,4,5) and 11 had full
blown AIDS (WR 5K,6). Among this group 93 patients (301) had mucocutaneous
lesions. We considered 3 main categories: infective, tumoral and other.
Morphological, histological, imrounohistochemical and electronmicroscopic
studies were performed.
Viral infections were caused by herpes virus in 30 patients (9.67X), human
papilloma virus in 20 (6.45X) and by both viruses in 10 patients with Oral
Hairy Leukoplakia (3,221). Only 3 patients were affected by bacterial
folliculitis. Oral thrush was present in 12 subjects (3,821) while other
dermatomycosis were found in 7 subjects (2,151). Five patients (1,61!) had
muco-cutaneous Kaposi's Sarcoma.
An important role was played by Seborroehic Dermatitis that was present in
26 patients (9,381) often with widespread lesions resistant to therapy. We
also observed subjects with Yellow Nail Syndrome, Immune Complex Vasculitis,
severe Psoriasis.
Some of the skin diseases we observed had a strong relation to the
clinical stage of immune-depression; five out of 12 patients with oral
thrush also had Candida Esophagitys and 5 out of 10 patients with Oral Hairy
Leukoplakia developed full blown AIDS within the year.
89
TUESDAY, JUNE 2
TP165 Pneumocystis Carinii Pneumonia (PCP) : value of Pulmonary Function
Tests (PFT) follow up.
FRANCOISE CAMUS, S. MATHERON , P.M. GIRARD , E. AOUSSI , J.F. FOULT, A.G. SAIMOT
et al. HSpital Claude Bernard. PARIS. FRANCE.
Among 52 AIDS patients (pts) admitted from 7/84 to 9/86 with BAL proved 1st
episode of PCP, 19 were followed up by serial PFT over a mean period of 10.2 -
4.2 months. Tests were : transfert lung capacity for carbon monoxide (TLCO)
(N > 80% of the predicted value by steady state method, corrected for anemia)
and alveolar arterial gradient for partial pressure of oxygen (A - a)0_ (N ^
20 torrs) . PCP relapse occured in 6/19 patients. None of them had specific
maintenance therapy.
At the time of 1st PCP, PFT revealed significantly low TLCO (49.8 - 12.5)
and major hypoxemia (A - a)0 = 41.4 - 13.7). In all 19 cases, PFT values
1, 2 and(5 - 1) months after 1st PCP episod were subnormal (TLCO = 85.6 - 21
(A - a)0 = 16.9 - 9.64); with no significant difference between patients with/
without relapse.
Relapse was suggested within 8.8 - 1.6 months after 1st PCP by sudden de-
crease in TLCO (53.75 - 5.85) and severe hypoxemia (40.2 - 11.7) in &i& sribr.pts.
Three of them had no radiological changes at that time. TLCO and (A - a)0_ one
month later were 68.5 - 20.9 ; 22.6 ± 9.5).
PFT follow up in these pts showed : 1) normalisation of both TLCO and (A -
a)0 one, two and five months after 1st PCP, and no predictive value for PCP
relapse ; 2) sudden deterioration preceeding X Ray changes in 3/6 cases, at the
time of relapse ; 3) More severe changes in TLCO and (A - a)0_ one month after
relapse/one month after 1st PCP.
TPIfifi Serum Adenosine Deaminase Level; A Simple Screening test for
Disseminated Mycobacterial Disease in Patients Seropositive
for Human Immunodeficiency Virus
DEBRA FERTEL, K. MILLER, R. UTTAMCHANDANI , A. PITCHENIK, G. BAUM. University
of Miami/Jackson Memorial and VA Medical Center, Miami, Florida.
Adenosine Deaminase (ADA), an enzyme of purine metabolism, is produced by
activated T- lymphocytes and plays an important role in T-cell maturation.
Surprisingly , this enzyme has been reported to be normal in the T- lymphocytes
and high in the null lymphocytes of patients with the Acquired Immune
Deficiency Syndrome (AIDS). We measured the serum levels of ADA in 32
hospitalized patients with positive serology for Human Immunodeficiency Virus
(HIV) and 33 age matched control subjects (hospital personnel) . ADA was
analyzed by the standard Giusti and Galanti colorimetric method. Among the
seropositive patients, 12 had Pneumocystis carinii pneumonia, 13 had
mycobacterial disease (9 with histologic or culture proven disseminated
disease and 4 with pulmonary tuberculosis), 2 had Kaposi's sarcoma and 5 met
the criteria for AIDS related complex. The mean serum ADA was 74.78 IU/L
(range 64.1-103.1) among the patients with disseminated mycobacterial disease;
72.7 IU/L (range 27.9-102.7) among the patients with pulmonary tuberculosis;
38.9 IU/L (range 17.1-56.1) among the 19 HIV seropositive patients without
mycobacterial disease and 21.8 IU/L (range 11.9-42.6) among the healthy
control subjects. The ADA level among the HIV seropositive patients with
mycobacterial disease was significantly greater than that of the HIV
seropositive patients without mycobacterial disease (p<.0001) and also greater
than that of the healthy subjects (p<.0001).
Measurement of serum ADA is a simple test which may prove clinically useful
in screening for the presence of disseminated mycobacterial disease among
patients seropositive for HIV.
I r. 100 Chemoprophylaxis Prevents Recurrence of Pneumocystis
carinii Pneumonia (PCP) in Retrovirus Induced Immunodeficiency (AIDS)
D CRAIG WRIGHT*, JL RHOADS, J MCNEIL, DS BURKE, RR REDFIELD. WRAMC*.
WRAIR, Washington DC
Fifteen patients with biopsy proven PCP and HIV Induced immunodeficiency
(AIDS) were evaluated. After recovery from the initial episode of PCP,
two patients received no chemoprophylaxis while 13 patients received
chemoprophylaxis with either one tablet weekly of pyrimethamine-
sulfadoxine (FAN), or one tablet trimethoprim-sulfamethoxazole 80mg/400mg
twice daily (TMP-SXT) . Recurrence of biopsy proven PCP was noted in both
patients who did not recieve chemoprophylaxis, 4 and 8 months after
original PCP episode. These two patients were subsequently placed on
chemoprophylaxis after their second episode of PCP. No patient (0/15)
recleving prophylaxis redeveloped PCP. Six of fifteen died during follow
up period (mean time to death 10.3 months, range 2-31 months). Three of
these six had post mortem examination; none had histological evidence of
PCP. Nine of fifteen still survive (mean follow up 13.7 months, range
6-22 months). Chemoprophylaxis was highly effective in preventing
recurrence of PCP (p <0.001). Although both regimens were effective In
preventing recurrent PCP, a trend toward increased mortality was suggested
In the TMP-SXT group. In the FAN regimen group there were 1 death/ 104 man
months of follow up as compared to the TMP-SXT group with 5 deaths/91 man
months of follow up ( p*>0.07). A placebo-controlled trial is currently
In progress to determine the efficacy of FAN chemoprophylaxis prior to the
Initial episode of PCP in Walter Reed stage 5 and 6 patients.
TP1RQ Splenomegaly and Extrapulmonary Disseminated Pneumocystis carinii
Infections in Patients with AIDS
A.M. MACHER*, C. STEIGMAN**, L. PASTORE**, D. KAHN***, J. GARFINKLE*** , M.L.
DEVINATEA*, et . al . , *Registry of AIDS Pathology, AFIP, Washington, D.C.,
**Fairfax Hospital, Falls Church, VA, ***Sherman Oaks Community Hospital,
Sherman Oaks , CA
We studied the clinical course, surgical and autopsy pathology of 2 patients
with AIDS who developed pulmonary and extrapulmonary disseminated infections
caused by Pneumocystis carinii.
Patient 1: A 32 year old white male homosexual with left upper quadrant pain
had splenomegaly and inguinal lymphadenopathy and was HIV sero-positive. He be-
came febrile and an abdominal CT scan revealed focal defects in the spleen. At
splenectomy, the spleen weighed 2000 grams and contained grey-white nodules;
microscopic examination revealed foci of eosinophilic foamy necrosis containing
cysts of P_. carinii. He died 1 month later and autopsy revealed necrotic foci
containing P_. carinii in lymph nodes, liver, kidneys, ureter, jejunum, omentum,
mesentery, appendices epiploicae, pancreas, adrenals, heart, thyroid, bone mar-
row, choroid and lung.
Patient 2: A 48 year old white male homosexual with fever, cough and progres-
sive dyspnea was bronchoscoped and £. carinii pneumonia was diagnosed. He was
HIV sero-positive and died 6 days later. At autopsy there was a 250 gram spleen
containing white nodules and microscopic examination revealed P. carinii in
spleen, lymph nodes and lung.
Although infection with P. carinii is typically confined to alveoli of the
lung, in the immunodeficient host it may disseminate. The patients in this re-
port developed splenomegaly as part of their disseminated extrapulmonary P_.
carinii infections. Clinicians and pathologists should be aware that £. carinii
may infect organs other than the lung.
TP167 Esophageal Candidiasis in High-Risk Patients for AIDS.
ses Unity Gastroenterology and Hematology*"*"* Hospital de Badalona "Germans Trias
i Pajoln«Badalona«Baroelona«Oatalonia.3pain
Esophageal candidiasis may be asymptomatio and not associated with oral thru-
sh. To evaluate its prevalence in high-^sk groups for AIDS we endosooped 50 P*"
tients(45 intravenous drug addiots and 5 homosexuals)through 19o6#None had 0-
ral thrush or esophageal syraptoras.Forty had generalized lymphadenopathy* None
fulfilled AIDS criteria at admis3ion.AH but 2 had antibodies to HIV detected
by BLISA method.In 9 of them esophagosoopy showed plaques of white exudate, soa-
tered in some«Cytologio examination of esophageal brushings demonstrated candi-
diasis in all thenUBLopsy was positive only in 2 oases probably because of sam-
pling error in dealing with scattered fool of fungal involvement* In these 2 oa-
ses biopsy showed only moderate.not invaaivetesophagitis.One out of nine was
negative for HIV antibodierf.Patients with esophageal candidiasis have been ad-
mitted beoause of idiopathio thrombooytopenio purpura In 2*right-^ided endocar-
ditis in 2(in 1 associated also to a pulmonary tuberoulosis), constitutional di-
sease(group XV«subgroup A)in 2 and gonococcal sepsis»pneumonia and left arm ce-
llulitis In the rest •The median T4/T8 ratio in this group was 0*53 (range 0*13
to *U13)»The follow-up during this year has not shown the evolution to AIDS, In
2 oases(l of them with positive biopsy )we demonstrate d, by esophagosoopy, sponta-
neous resolution without treatment at 10 days interval.The other patients rece-
ived a 10 days course of oral ketooonazol.Asymptomatic Candida infection of tie
esophagus is not an uncommon disease in patients at risk for AIDS, it may dis-
appear spontaneously, Is not associated with unfavorable outcome and should
not be considered a criterion for AIDS unless shown dearly Invasive by biopsy.
TR170 Congestive Cardiomyopathy in Association with Acquired Immune
Deficiency Syndrome in Children
V. JOSHI, CHARLES GADOL, E. CONNOR, J. MENDELSON, J. MARIN, J. OLESKE
Children's Hospital of New Jersey, UMD New Jersey Medical School, Newark, NJ
At autopsy in 5 children with AIDS, dilated cardiomyopathy characterized
by a) enlargement of heart with biventricular dilatation, b) rare foci of
myocardial necrosis with minimal to mild inflammatory infiltrate, cj hyper-
trophy, d) interstitial edema and myxoid change, 3) mild focal interstitial
fibrosis, f) vacuolation due to fatty change, gj focal pericardial inflammatory
infiltrate and h) endocardial fibrosis was seen. Two of the patients had de-
veloped congestive heart failure. Candidiasis, Aspergillosis, CMV or M. avium
intracellular infection was present in one patient each; mild focal calcifi
cation of small branches of coronaries without luminal narrowing was present
in one patient and noneof the patients received any drugs commonly associated
with hypersensitivity reactions. These factors are unlikely to be related to
pathogenesis. Anemia, nutritional deficiency, infection and undetermined type
and immunologic factors may play a role in the pathogenesis of cardiomyopathy
in these children.
90
TUESDAY, JUNE 2
TR171 Factors Distinguishing Homosexual Males Practicing Safe and Risky
KAROLYNN SIEGEL, F. MESAGNO, J.Y. CHEN, G. CHRIST, Memorial Sloan-Kettering
Cancer Center, New York, NY, USA.
A longitudinal study of patterns of sexual behavior among asymptomatic,
homosexual males (N=161) in New York City was conducted. Participants were
interviewed at two time points six months apart. Based on their reports of
sexual behaviors during a recent "typical" month, respondents were classified
at each time point as engaging in safe (or low risk) sex versus risky sex
(e.g., unprotected anal intercourse or oral-anal contact).
Discriminant analysis was employed to distinguish the 48 males classified as
safe at both Tl and T2 from the 58 males classified as risky in both periods.
Statistically significant discrimination (Wilks1 lambda = .675) was parsimo-
niously achieved through the use of seven predictor variables: drug use during
or in anticipation of sexual activity; living with lover; number of years
engaged in regular sexual intercourse with males; perceived emotional support;
fewer friends or acquaintances with AIDS; self-esteem; and alcohol use. Of
the predictors, drug use within sexual contexts is particularly noteworthy,
since it provided the greatest relative contribution to the discriminant
function and appears to be an important candidate for educational interven-
tion.
Among the variables which did not significantly contribute to this discrim-
inant function were: gay network affiliation, denial of AIDS threat and com-
fort negotiating sexual limits.
The significance of these findings for public health efforts will be
discussed.
TR174
Determinants and Effects of HIV Antibody Test Disclosure.
JANE MCCUSKER*, J.G, ZAPKA*. A.M. STODDARD*, K.H. MAYER**, J.S. AVRUNIN*,
S.P. SALTZMAN***, et al., ^University of Massachusetts/Amhers t, Amherst, MA,
U.S.A., **Memorial Hospital and Brown University, Providence, RI, U.S.A.,
***Fenway Community Health Center, Boston, MA, U.S.A.
The role of HIV antibody screening of high-risk groups is an unresolved
public health issue. This study identifies the differences between individuals
who choose to know vs. not to know their results and explores the impact of
knowledge of HIV antibody test results on subsequent behavior. In a
longitudinal study of initially asymptomatic homosexual/bisexual men (N=290)
at a Boston community health center, 23% of the participants chose not to
know their initial test result during the following six months. Antibody
positive and negative men were equally likely to be informed. Multivariate
analysis determined that the following variables were associated with the
decision not to be informed: greater perceived severity of AIDS, lower
reported effort to change sexual behavior, greater exposure to informational
activities, and age 25-29. Significant differences were found by antibody
status and test disclosure in emotional reactions (anger and depression) during
the six months following test disclosure. Both emotional reactions and
correlates of the decision to be informed should be considered in
interpretation of subsequent behavior.
TR172
A National Survey of Public Concern Regarding AIDS
SHIRLEY DAMROSCH and B. BAUSELL, K. SOEKEN AND P. PARKS University of Mary-
land School of Nursing, Baltimore, MD.
A survey on acquired immunodeficiency syndrome (AIDS) was conducted using a
national random sample of 1,256 adults; the poll utilized random digit dialing
and achieved 70% participation. Those with higher levels of education (at
least a high school diploma vs. those without diploma) were somewhat more
optimistic that AIDS would be under control five years from now (48% vs. 40%)
and less pessimistic that AIDS would become a major epidemic (12% vs. 21%) .
Although only 10% of the sample perceived themselves at any risk of catching
AIDS, 41% reported taking special precautions to avoid catching the disease.
Perceptions of risk were highest among college graduates (16%) , those aged
30-39 (16%), and those living in the East (16%). Blacks (61%) and Hispanics
(58%) were more likely to report special precautions than were whites (37%) .
Of the total sample, 79% agreed either strongly (47%) or somewhat (32%) that
the government should spend whatever it takes to find a cure or vaccine.
Seventy percent of the total agreed either strongly (50%) or somewhat (20%)
that the government should impose restrictions on gay bars and bath houses
during the epidemic; there were educational differences on this issue, with
77% endorsement among those with high school or less, dropping to 62% for
those with at least same college. Highest endorsement (97%, 88% strongly and
9% somewhat agreeing) was given to the proposal that individuals should take
extra care in sexual relations and personal preventive habits.
TP175 Campaign to Promote Safe Sexual Practices in the Montreal
Homosexual Population - Quebec
ALIX ADRIEn/1'2), J . CARSLEY, ( 1 , 2) , S , IOANNOU , ( * ) , ( 1 ) : Community Health
Department, Montreal General Hospital, (2): Departments of Family Medicine,
Epidemiology and Biostatistics , McGill University, Montreal, Quebec, Canada.
With an AIDS community group (C-SAM) we developed a program to promote safe
sexual practices among Montreal ' s homosexual population. Focus groups were
used to review educational materials and extensive coverage by various gay
media was provided. During a one week educational campaign, ten thousand
health education pamphlets on "Safe Sex" and the same number of condoms were
distributed in 27 gay bars and clubs, and 5 saunas by 30 trained health
promotion volunteers.
A month later , a self -administered questionnaire was distributed in six
representative establishments. The response rate was: 77.9%. Of the 839
respondents 79.3% had heard about the campaign and 50.9% had read the
campaign pamphlet. Of those who read the pamphlet, 57.1% thought it had
influenced their sexual behaviour. 45% of those who reported the campaign had
an influence on their behaviour reported condom use compared to 19.6% of
those who denied an influence of the campaign (X2=49.03, pCO.001).
18.9% of those who denied influence could not identify passive anal
intercourse without a condom as high risk while only 10.8% of those reporting
influence could not .
This project shows the feasability of a community preventive intervention
in a population at high risk for AIDS.
TP173 AIDS and the College Campus: A model Prevention Program
CATHY K0DAMA,MPH, MARY O'DONNELL, MPH, Cowell Hospital, University
of California, Berkeley, CA.
Approximately 12 million students are enrolled in colleges and universities
in the United States, representing about 5% of the population. In California
alone, between 9,000 to 45,000 students currently enrolled in institutions of
higher education can be expected to develop AIDS or ARC.
Upon entering college, the sexual networks of young people suddenly expand
and experimentation with a variety of sexual practices, including bi-sexuality
is common. A significant number of students also drink alcohol excessively
and engage in recreational drug use. This leads to impaired judgment regard-
ing sexual behavior and responsibility. For the most part, the threat of AIDS
and death does not seem real to college students who believe themselves invin-
cible.
The purpose of the poster session is to present a model for campus-based
AIDS prevention. The model was developed and tested at the University of Cali-
fornia, Berkeley in 1986-87. The State of California Department of Health Ser-
vices contracted with Berkeley to design and disseminate this model. It is
currently being replicated at other institutions of higher education. The
poster session will highlight theoretical principals of AIDS education for this
target group, with an emphasis on community organization and peer education.
A 60 page training manual for campus AIDS educators wil be showcased along
with institutional guidelines for policy development .
TP176 "AIDS Community Outreach for Intravenous Drug Users" Harvey W.
Feldraan, Ph.D. & Patrick Biernacki, Ph.D. YES Project, 1779
Haight St., San Francisco, CA 94117.
In May 1986, a community health education/outreach program was created in
San Francisco to stop the spread of AIDS among intravenous drug users
(IVDUs). Currently, the program employs eight workers who provide AIDS
education, counseling and referral to drug users in those areas of the city
that contain the highest concentrations of IVDUs . This paper describes and
analyzes the maj or stages undergone since the program' s incept ion and
addresses problems encountered. The analvsis will help other communities to
develop similar outreach efforts.
The program developed in the following stages: 1) Formation of the overall
strategy guiding the program effort toward the major goal of stopping the
spread of AIDS among IVDUs; 2 ) Ethnographic studies of target areas to map
out & analyze the needle-using scenes and drug-using practices; 3) Recruit-
ment & training of an outreach staff component; 4) Successful entree into
the target community; 5) Development & distribution of health promotion
materials, condoms and small bottles of bleach; 6) Use of indigenous field
assistants, who are natural leaders, to help promote safe health practices;
7) Utilization and management of the media to promote the project's goals;
8) Evaluation and reassessment of project plan and ensuring compl lance with
health messages, & 9) Entry into new IVDU scenes, when and how to move
beyond the original target groups .
An administrative proj ect evaluation indicates that, contrary to popular
wisdom, IVDUs will change their behavior, especially in relation to sani-
tizing their shooting paraphernalia.
91
TUESDAY, JUNE 2
JP"|77 Utilization of HIV Alternate Testing Sites in Upstate New York
JOHN C. GRABAU, M.P.H., PH.D.,* BENJAMIN I. TRUMAN, M.D., M.P.H.,**
DALE L. MORSE, M.D. , M.S.,** AIDS Institute* and Bureau of Communicable
Disease Control,** NYS Department of Health, Albany, NY
In June and July, 1985, the New York State Department of Health established
HIV Counseling and Testing sites throughout New York State exclusive of
New York City. Between June, 1985, and October, 1986, 7,608 persons received
pretest counseling at the sites. Just over 69% of those being counseled
elected to have the HIV antibody test (N=5,283). Of the 5,161 persons
receiving posttest counseling during the 17 month period, 13% were positive
via ELISA and Western Blot for HIV.
Individuals submitting blood for HIV testing were asked to voluntarily
complete a questionnaire assessing demographic and HIV associated variables.
Of the 2,788 (53%) completing the questionnaire 70% were males. The ages
ranged from less than 15 to greater than 55 with 89% falling in the 15 to 44
year age group. The preponderance of those using the alternate site considered
themselves to be white (84%). Of the 1,833 who considered themselves to be a
member of a risk group: 44% were homosexual; 21% were bisexual, and 24%
reported IV drug use. The two most common reasons for wanting to be tested
were risk group membership and sexual contact with a risk group member. Nearly
80% considered themselves physically well at the time of testing.
TR180
Attitudes towards HIV antibody testing among General Practitioners.
V6ron1quer1ASSARI« , J B BRUNET** , E BOUVET** , A-J VALLERON * ,
* Unite* de Recherches Blomathematlques et Biostatlstlques ( URBB) INSERM et Unlversltfi
Paris 7 , ** Direction 06n6rale de la Sant6 , Bureau des maladies transmlsstbles, Paris.
In order to evaluate the use of HIV antibody testing by general practitioners (GPs), a specific
questionnaire was set up on the French Communicable Diseases Network in November 1 986. This
network , established in 1 984 for the surveillance of certain communicable diseases, links 250
sentinel general practitioners ( SGPs), by electronic mail to a central computer. These 6Ps were
asked to report all prescriptions made for HIV antlbooy testing and to provide, for each case, the
following information : person requesting test ( I.e. patient or GP), reason for test, characteristics
of patient, result of test and diagnostic method(s) used.
After one month of the study, preliminary results indicate that 1 4S ( 36/250) SGPs had
prescribed at least once a test for a total of 65 subjects. The overall percentage of patients
spontaneously asking for the test was roughly 50%. However this percentage was higher in male
homosexuals (69$) than In (V drug users (338). demonstrating the striking difference in the
attitude in these two groups. Thirteen subjects were anti HIV positive, 7 of these being IV drug
users.
Routine collection of Information will provide further data on GPs" attitudes towards HIV testing,
characteristics of tested subjects and help in adapting educational programs devoted to health care
professionals.
TR178 HIV Antibody Testing and Community Mental Health:
Qualitative Outcomes of a Collaborative Model
ttlCHAEL GROSS, Ph.D.*, MARSHALL FORSTEIN, M.D.*,**, *Gay and Lesbian
Counseling Service, Boston, MA, **The Cambridge Hospital, Cambridge, MA
Despite near universal opposition by the gay community in April 1985 to AIDS
antibody testing the Gay and Lesbian Counsel ing Servi ce (GLCS) took a pro-
active stance, working with the state Department of Public Health to design
and implement a network of alternative testing sites. We describe the
rationale for that decision and outcomes of two years of participation.
By participating in program design GLCS fostered principles fundamental to
the Massachusetts program: ( 1 ) total anonymity, (2 ) an emphasis on education,
especial ly about risk reduction, rather than on testing, and (3) access to a
network of AIDS-aware medical and mental health providers sensitive to issues
specific to high risk populations.
A key contractor with the Department in staffing/supervising several sites,
GLCS also created and maintains a statewide provider referral list. Within
its service region, GLCS provides both acute and long-term mental health
services to test site clients wit hut regard for their ability to pay.
The changing compos i tion and issues of test site clients forecast trends in
service needs. GLCS flexibly responded to program needs by: (1) adding a
voluntary (anonymous) second follow-up visit several weeks after individuals
testing positive learn their status, for further help with referrals; (2)
creating a "Safer Se;< Psychoeduct ional Group" for ATS cl ients and others in
the community; <3) sponsoring a support/educational group for pregnant women
at risk through needle shar ing or a sexual partner who has shared needles.
Other needs identified concern links between drug/alcohol use and unsafe
sex, specific issues for bisexual men in long-term relation hips with women,
and short- and long-term adverse sequelae of learning one's antibody status.
TR181 JUNIOR AND SENIOR HIGH SCHOOL STUDENT'S KNOWLEDGE ABOUT AIDS:
THEY WANT TO LEARN MORE AND WANT TO LEARN IT AT SCHOOL
STEVEN D. HELGERSON, and the AIDS Education Study Groups, Yale University
Department of Epidemio.logy and the Connecticut State Department of Health
Services, including William Sabella.
We assessed knowledge about AIDS from 657 junior and senior high school
students randomly selected from required English classes in two Connecticut
school districts. Although many students had some factual knowledge about
the virus that causes AIDS, many students were misinformed about methods of
viral transmission, high risk groups for developing AIDS, and methods to avoid
acquisition of the virus. Importantly, 58% did not recognize the existence of
an asymptomatic carrier state; and 63% and 59% respectively did not recognize
the potential for vertical transmission from fathers or mothers infected by
I.V. drug use. Responses from students of different grades, ages, sexes, races
and school districts, differed rarely and without apparent pattern. Students
reported they had learned about AIDS mostly from television or radio (57%) or
magazines or newspapers (16%); while few had learned from persons with whom
they had frequent contact, such as parents (6%) or teachers (4%). Seventy-
four percent of students said they wanted to learn more about AIDS, and 49%
said they wanted to learn it in school. We conclude that students' knowledge
about AIDS is not adequate, students wish to learn more, and information about
AIDS should be presented in public schools.
TR179 The AlternaCive Test Site (ATS) in Rhode Island
JACK BRONDUM, B. DEBUONO, L. DONDERO, J. HODGE, A. JOHNSON, Rhode
Island Department of Health (RIDH) , Providence, Rhode Island, USA.
An ATS was established at the RIDH in June, 1985, to provide anonymous test-
ing and counseling for Human Immunodeficiency Virus (HIV) infection to persons
who might otherwise have gone to blood donation centers to be tested. As of
January 28, 1987, 862 persons had attended. Median age was 31 years; 644 (75%)
were male. 835 (97%) persons had their blood tested, 794 (95%) of whom belonged
to groups at high risk for HIV infection. 406 (63%) males cited homosexual
activity as a risk factor, and 116 (53%) women cited sexual contact with a high-
risk individual.
HIV infection was confirmed in 74 (9%) persons; 71 (96%) belonged to high-
risk groups. 65 (88%) were male, of whom 55 (85%) were homo/bisexual and seven
(11%) were intravenous drug abusers (IVDA). Five (56%) women were IVDA, three
(33%) were sexual partners of IVDA.
Among non-infected persons, 139 (54%) seen at the ATS from July through
December, 1985, would have donated blood to determine their HIV antibody status
if the ATS had not been available, while only 106 (40%) seen from July through
December, 1986, would have done so (X2 test for trend=10.2, p=0.0014). 23 (31%)
infected persons would have donated blood.
The ATS in RI serves a population at high risk for HIV infection and plays an
important role in monitoring HIV seroprevalence in this population. It has also
served to divert infected potential donors from blood donation centers.
TR182 The AIDS/STD EDUCATION PLAN - An Innovative, Effective and Cost Ef-
ficient Program for Schools to Teach AIDS Education and Achieve the
USPHS 1990 STD Education Objective
STEPHEN R. SROKA*, L.CALABRESE**, T.JONES***, Cleveland State University and
Cleveland Public Schools, Cleveland, OH, **Cleveland Clinic, Cleveland, OH,
***Wisconsin Dept. of Hlth, Madison, Wise.
The AIDS/STD EDUCATION PLAN is a response to the Surgeon General's Report on
AIDS and to the USPHS 1990 STD Education Objective which encourage educators to
teach students AIDS and STD education.
The AIDS/STD EDUCATION PLAN is a teacher training program based on the Educa-
tor's Guide to AIDS and STD's, a behavioral approach to teaching AIDS and STD educa-
tion in a communicable disease conceptual framework, which is easily implemented
in all schools.
Over 2450 educators who teach over 700,000 students in 3 states use the AIDS/SID EDUCATION PLAN.
Educators (N= 520) Evaluation Data:
Objective: (% educators responding "agree"):
offered effective methods and materials
to teach students how to:
- recognize symptoms (103%)
- find, use clinics (9C%)
- refer sex partners for medical care (89^)
- follow treatment instructions (93%)
- avoid STD's (97%)
. made STD's easier to teach (98%)
produced significant educational
gains in students':
- knowledge (98%)
- attitudes (81%)
- behavioral intentions (77%)
will use the Guide apfvin
The AIDS/STD EDUCATION PLAN is cost efficient. Ohio achieved the 1990 STD
Education Objective for less than It per students.
The AIDS/STD EDUCATION PLAN offers a prototype for schools to teach AIDS edu-
cation and achieve the 1990 STD Education Objective at the city, state or
national level .
92
TUESDAY, JUNE 2
TP183 Lessons of History: An Examination of the US Army Pre-Antibiotic
Venereal Disease Control Program and its Application to HIV.
CHARLES F. CLARK, M.D., AUSTIN C. KUHN , MSW, SHAPE Hospital, Casteau, Belgium,
RAY MOEHRING, Boulder, CO, EDMUND C. TRAMONT, M.D., Walter Reed Army Institute
of Research, Washington DC.
The venereal disease control program instituted by the United States Army
in 1911 contained the following elements: Monthly lectures by medical
officers about human reproductive physiology, the transmission and course of
venereal diseases and an explanation of why sexual intercourse was not
necessary to a healthy body, commanding officers expounding on the duty to
remain healthy, chemical prophylaxis within two hours after fornicating,
chaperoned social activities on Post, and pay withheld while in treatment.
The Army applied this program to every command on every Post in every part
of the world where there were soldiers. The full program was applied
regardless of variations in local circumstances and regardless of the ethnic,
educational or cultural background of the troops. This Army wide program
does appear to have caused a slow, progressive decrease in the venereal
disease rate in the Army as a whole, but the reduction of the rate varied
enormously with racial, geographic, and cultural factors.
History has for us an important lesson. A single massive aggressive
intense repetitive educational campaign to control the spread of HIV in the
United States will not be effective in stopping the HIV epidemic, and will
slow it only modestly. There must be a campaign of a thousand parts, each
directed towards a specific racial, economic, intellectual, social, political
group and addressing specifically the issues critical to that group's sexual
behavior. We need a rapid, rigorous rethinking of our educational programs
and other efforts.
TR186 flI0S KntMled9e ln Urban us Rural Washington State High School Students.
SHARON HOPKINS, A. DOWNER, L. MILLER. Seattle-King County Department of Public
Healthi Seattle, Washington, U.S.A.
Ue surveyed 11th-grade students to assess AIDS knowledge as a basis for curricula development
and to compare urban and rural students. Of 502 students surveyed, 214 were from urban King
County (pop. 1,350,000! 300 AIDS cases); 268 were from rural Clallam County (pop. 52,000; 1 AIDS
case).
Practically all students (96?) identified blood and semen as likely to spread HIV, but 39?
thought saliva a likely source. Students recognized male homosexuals and IV drug users as risk
groups, yet 48? thought female homosexuals at high risk. One in 5 thought living in the same
household as someone with AIDS was risky, 32? thought AIDS could be acquired while donating
blood; 27? thought mosquito bites a transmission source. Responses to individual knowledge
questions varied little between urban and rural students. When the 2 groups were compared for
percent correct responses on 34 knowledge questions, there was no difference (72? vs 74?
correct). Significantly more urban than rural students wanted to know more about AIDS (70? vs
55?).
We concluded: 1) Both urban and rural students have basic knowledge of AIDS 2) The same
misconceptions were prevalent in both groups 3) Rural students may not feel the need for AIDS
education as acutely as urban students 4) One curricula is suitable for both urban and rural
Washington State students.
TP184 Sharing of Paraphernalia in Intravenous Drug Users (IVDU): Know-
ledge of AIDS is Incomplete and Doesn't Affect Behavior.
NEIL M. FLYNN», S. JAIN", S. HARPER", V. BAILEY", R. ANDERSON", G. ACUNA",
et al. "Univ. Calif. Davis, "Sacramento AIDS-IVDA Taskforce, Sacramento, CA.
Transmission (T) of HIV among IVDU in the U.S. is occurring rapidly. Ef-
forts at reducing thi3 spread have been ineffectual. The potential for
heterosexual and vertical T by'this population is enormous. To determine
causes of rapid spread we examined knowledge and behavior of 200 IVDU at-
tending Sacramento(S) drug abuse clinics. Most addicts believed that: HIV
was present in IVDU in S (90$); they would eventually acquire HIV if they
continued sharing paraphernalia (P) (93$); HIV can be transmitted hetero-
sexually (91$), vertically (100$); condoms can prevent sexual T (61$). 95$
wanted to avoid acquiring HIV. With respect to behavior last time they shot
up, however: 75$ used own P, but 77$ shared it; 87$ cleaned P between users,
but only with water, rarely disinfectant; majority (70$) had potential disin-
fectant solution readily available (bleach 35$, rubbing alcohol 56$, peroxide
31$, wine 23$). Addicts expressed: surprise at rate of HIV spread; ignorance
of potential disinfecting agents, methods for cleaning P; reluctance to carry
P because of criminal possession laws; strong desire to continue sharing P.
We conclude: some knowledge of HIV epidemiology exists among IVDU; IVDU are
not aware of imminent risk of infection; knowledge of disinfection is dismal,
rarely acted upon; sharing is likely to continue because of social aspects,
criminal possession statutes. Immediate intervention, emphasizing AIDS risk,
practical P disinfection methods and condom use is warranted. Failure to
effectively intervene will result in rapid heterosexual and vertical T of HIV
from this population.
TR187 Prevalence of Antibodies to HIV in Prostitutes and Dominican and
Haitian Cane Cutters in the Dominican Republic .
R .ELLEN KOENIG* L,DE CASTRO", J. ACRA"*,3.CASASN0VA"*,C. CU>OLLERA*" and
J.A.LEVY****, *Laboratorlo Naclonal de Salud Publico, "Univ. Autonoma de Santo
Domingo, ***Univ, Nac. Pedro Henrlquez Urefia, ""Cancer Research Inst,, Univ.
of California, San Francisco, California
In recent nonths,i0 female prostitutes have returned to the Dominican Republic
from neighboring islands and their seropositlvlty to HIV confirmed at the
National laboratory of the Public Health Ministry.
To examine the extent of AIDS seropositvlty ln resident Dominican prostitutes
and heterosexual rural agricultural workers known to associate with prosti-
tutes, two studies were undertaken using commercial ELISA kits and lmmunflor-
escence or Western blot to reconfirm.
One hundred thirty nine prostitutes in Santo Domingo were questioned and
bled. Two individual were seropositive. No correlation wa3 found with kind and
extent of sexual activity, VD, or relations with non-Dominicans.
Two hundred cane cutters of Dominican or Haitian origin residing within a 20
km radius were studied. Although they work in the same fields, these men live
ln separate areas, depending on nationality. The same female prostitutes,
though, do intermingle with both groups. The health of the Haitians was consid-
erably better than the Dominicans, using AIDS symptoms as criteria. More Domin-
icans reported venereal diseases. Nevertheless, 2 Haitians and no Dominicans
were seropositive. No significant factor could be found to explain the sero-
positlvlty in these two. It is therefore assumed that they were Infected through
heterosexual sex ln the Dominican Republic or Haiti.
These results Indicate that heterosexual transmission from local prostitutes
does not represent a serious threat now, but the international trade could pro-
vide a way for HIV to enter the rural and urban heterosexual population.
TR185 Follow-up to Ensure Counseling of HIV-Ab Positive Volunteers to
HIV Test Sites (HTS)
NANCY E. SPENCER. B. DILLON, G. WARE, J. LESLIE, Colorado Department of
Public Health, Denver CO , U.S.A.
Confidential post-test counseling of volunteers for HIV-Ab testing gives
positive persons an opportunity to learn their antibody status and receive
personalized instruction on methods to prevent HIV transmission. Subsequent
practice of safer sex and no needle share behaviors should reduce community
transmission of HIV. Confidential (non-anonymous) testing and reporting
allows public health follow-up of positives who fail to return for test
results and counseling. Public Health can ensure (with provider consent)
knowledge of test results and appropriate counseling for positive
individuals. During 1986, 109 HIV-Ab positive individuals for whom there
was no record of post-test counseling were followed by the Colorado
Department of Health. The results were; 20 (19%) were brought to
counseling, 33 (30*) had been previously counseled, 47 (43*) were not
located, and 9 (8*) refused test results and counseling. Follow-up revealed
that 82 (75*) positives provided accurate locating information at the time
of test, but the proportion located and counseled decreased as the time
interval between test and follow-up increased. Assuming that without
counseling, each positive would transmit to 1 other individual, and that
40* of HIV-infected individuals experience some serious HIV-related
morbidity, 20 new HIV infections, 8 of which may have developed AIDS or
ARC, may have been prevented through this activity. Confidential testing
and reporting, coupled with rapid and active follow-up of uninformed
seropositives by public health can affect counseling and help reduce
community transmission of HIV.
TP188 Perceived Changes in Sexual Practices Among Homosexual Men
" DON JOHNSON and H. M. MCGRATH, The University of Texas Health
Science Center at San Antonio, TX.
The study surveyed 343 gay men in three Texas cities regarding their
sexual practices during the last 30 days of this year (current sexual
practices) compared with their sexual practices the same 30 day period one
year ago (past sexual practices). The survey consisted of 16 items
regarding current sexual practices and the same 16 items regarding past
sexual practices. Behaviors were rated from 0 (low risk) to 5 (high risk).
The mean scores of each current sexual practice were compared to each past
practice using the Wilcoxon Matched-Pairs Signed-Ranks Test. Results
indicate that the present sexual practices compared to past sexual
practices are significantly less risky for contracting AIDS. Significant
differences were found in the following high risk behaviors: anal receptive
sex (Z = -4.1969 p = <0.0000); anal insertive (Z = -4.9605 p = <0.0000);
oral receptive (Z = -5.0503 p = <0.0000); oral insertive (Z = -5.2322
p = <0.0000); location of meeting partners (Z = -5.9669 p = <0.0000);
rimming (Z = -4.7041 p = <0.0000); swallowing of semen (Z = -7.8294
p = <0.0000); use of intravenous drugs (Z = -14.3138 p = <0.0000) number of
sexual partners (Z = -6.9269 p = <0.0000); anonymous sexual partners
(Z = -6.0697 p = <0.0000); sharing of anal sex toys (Z = -2.8571
p = <0.0043).
Although there are significant differences between current and past
sexual practices, the study shows that 25.1% (N = 85) are continuing to
have anal receptive sex without the use of condoms and 38.8$ (N ■ 132) had
two or more sexual partners within the last thirty days; and 24.41 (N = 83)
had anonymous sexual partners.
93
TUESDAY, JUNE 2
TR189 The Minnesota AIDS Media Campaign Consortium (MAMCC) - An Inter-
organizational Approach
KAREN A. HECKERT, M.E. MOEN, Minnesota Department of Health, Minnesota AIDS
Media Campaign Consortium, Minneapolis, MN, USA.
During 1986, the Minnesota Department of Health developed a statewide
health education and risk reduction plan to control transmission of HIV
in Minnesota. One objective of the plan was to develop a statewide mass
media campaign and to evaluate its success. In February, 1986 the Minnesota
Poll, (a random statewide telephone survey) demonstrated that 90% of those
surveyed considered mass media to be their primary source of AIDS information.
To ensure statewide coordination of media efforts, the efficient mobilization
of resources and the development of the most effective messages, we developed
the MAMCC. The MAMCC is represented by two state public agencies (MN Dept.
of Health, Dept. of Human Services), four local public health agencies
(Hennepin Co. Community Health Dept., Mpls. Health Dept., Ramsey Co. Health
Dept., St. Paul Div. of Public Health), three state and national private
non-profit agencies, (MN AIDS Project, MN Medical Assoc, American Red Cross
- St. Paul) and one private for-profit agency (MN Insurance Information
Center). Marketing data from the statewide MN Poll, the Ctr. for Health
Statistics, the MN AIDS Project surveys of youth and gay men guided the
development of effective messages. Messages that have been developed promote
the elimination of risk and utilization of services. A Twin Cities
communications firm was selected in a competitive process to develop a
creative strategic plan and media products for the media campaign. The
MAMCC development, the ad agency selection process, the strategic plan,
the media products and the evaluation techniques may have application value
for other low prevalence states.
TP192 Contact Tracing for STD's : A Review
MICHAEL L. REKART, UBC School of Medicine, Vancouver, B.C., Canada
Contact tracing is an integral part of the standard public health approach
to the control of sexually transmitted diseases (STD'S). It needs to be con-
sidered in the control of AIDS but can only be objectively evaluated when its
definition and history are examined. Three distinct types of contact tracing
exist. First, 'formal contact tracing' is a system in which specially trained
staff interview patients, obtain names and addresses of sexual partners, lo-
cate these partners, and offer them examination and treatment. This is the tra-
ditional method used for gonorrhea and syphilis. Second, 'simplified contact
tracing' refers to a variety of methods by which patients identify, locate
and insure the examination of their own sexual partners without specifically
naming them to the health worker. Last, 'conditional contracting' is a sys-
tem in which contact information is given to the interviewer in trust and the
patient contracts to notify these partners within a specified period of time.
If this fails, the interviewer must seek out the sexual partner for assess-
ment. All of these methods have clear advantages and disadvantages. Simplified
contact tracing is the method usually used for AIDS and HIV seropositivity.
W. L. Munson in 1932 was the first to demonstrate that contact tracing was
possible and effective in finding new Infectious cases of syphilis. This
'sole-leather epidemiology' works as well for gonorrhea and has contributed
significantly to the control of both.
TP190 flI0S: What You Need to Know: A Teaching Unit for Secondary Schools.
ANN DOWER. Seattle-King County Health Department and L. Wilier, University of
Washington. Seattle, Washington, U.S.A.
We developed an AIDS curriculum to enable high school students to make informed decisions
about AIDS as a public health issue and to make safer choices in risk-taking behavior. The
curriculLHn covers AIDS epidemiology and projections, etiology, pathogenesis, blood-testing, and
prevention.
The curriculum can be modified to suit the teaching situation. Depending upon the level of
student knowledge and classroom constraints, any of the modules may be used. Assessment of
student comprehension can be accomplished with evaluation modules consisting of learning-check
questions and an exam for measuring objective learning.
we tested the curriculum on 240 eleventh graders. The test results revealed a significant
increase in student knowledge, which corresponded with a positive change in students' attitudes
about the disease. We conclude that exposure to a curriculum which impacts upon knowledge and
attitude will enable young people to make informed public health decisions about AIDS.
TP193 T^e bl-ooa donor perspective on false positive test results: The im-
pact of anti-HIV test procedures
A.P.M. LOS*. M. VONK**, L. ACHTERHOF**, TJ . TIJMSTRA*, T.B.P.M. SUURMEYER*.
C.TH. SMIT SIBINGA**, * Div. of Medical Sociology, University of Groningen,
** R.C. Blood Bank Groningen-Drenthe, Groningen, NL
For confirmation of initial findings on ELISA tests a fresh blood sample is
needed, and the donor has to be called back. Of over 97,000 donations tested
since May '85, 64 (0.076%) turned out to be false positive. With focused inter-
view technique donors (n=30) were asked whether they associated the recall with
AIDS or the anti-HIV test, how they handled the information about the test pro-
cedure, and what their reactions and feelings were.
Results: 19 Indicated to be upset by the recall. The thought of AIDS was
mentioned by 17 although immediately rejected as considered impossible for
themselves. Only 2 associated the recall with the anti-HIV test and 20 were
ignorant of the existance of the test. 18 Indicated to pay hardly any attention
to information related with AIDS because they have no risk factors. Ignorance
of which tests actually are done made 16 upset by the thought of leukemia and
cancer. 13 Associated the recall with their health at the moment of donation,
and another 13 were very surprised by the recall because they felt healthy. 20
Indicated to consider blood screening as a very important check on their health.
Conclusion: Misunderstanding and anxiety can be relieved by carefully infor-
ming donors about meaning and content of donor screening. Information about im-
portant and new aspects of AIDS and screening procedures should preferably be
included in this general information, rather than be given separate attention.
TP191 Distribution of Free Condoms as a Technique to improve Acceptance
of Condom Use.
ARTHUR STUTSMAN. B.M, Branson. J. Stein. D. Vaughan, Health Education
Resource Organization, Baltimore, MD, USA.
A survey was conducted to identify factors that might discourage the use of
condoms. Respondents frequently cited interference with sensation, lack of
familiarity and embarassment when purchasing condoms as important reasons
for not trying them. A majority were not familiar with proper use of condoms,
and personnel in STD clinics were rarely trained regarding procedures for
proper application and use.
A graphic, pictorial brochure with step-by-step instructions for condom use
was developed. A sample packet, including the brochure, safer sex informa-
tion and condom samples wasdesigned, labeled "A Healthy Gift from HERO."
Cay-patronized retailers such as bookstores and gift shops were solicited to
distribute these with customer purchases. Additional samples were prepared
in a matchbook-cover package design, with the message "Stop Transmission
Fluid Leaks" or "Life Preserver" imprinted on the cover.
Each of the sample packets were well received, and proved popular with both
retailers and the general public. Samples became sought after, and proved to
be an incentive, attracting targeted at-risk individuals to neighborhood edu-
cational presentations in order to obtain condom samples.
TR194 Assessment of the AIDS Public Information Campaign in the
HILARY
I nf orma
The U
and mag
a leafl
telepho
campaig
any oth
In ge
in the
and tak
mi tting
as to t
contact
any cla
tion, (
spite o
(6) the
campaig
UK
PICKLES
tion , Lo
K AIDS P
azine ad
et del iv
ne advic
n has be
er gover
neral , t
subject
en note
HIV wer
he dange
were wi
imed rec
5) offen
f mentio
re was e
n of thi
and G
ndon ,
ubl ic
verti
ered
e ser
en su
nment
his r
of AI
of AI
e wid
rs of
despr
ent c
ce wa
n of
xtens
sor
.Bond*,DH
England .
Inf ormat
sement s ,c
to all ho
vices hav
bject to
-run publ
esearch h
DS, with
DS public
ely under
blood do
ead but d
hanges in
s not cau
matters s
ive suppo
t.
SS AIDS Unit and *Central Office of
ion Campaign has involved newspaper
inema, radio, street posters, TV and
useholds. A detailed leaflet and
e also been made available. This
a larger programme of research than
icity campaign.
as shown (1) there was great interest
high percentages claiming to have seen
ity, (2) the main methods of trans-
stood (3) misconceptions, for example
nation and transfusion and of casual
iminished over the time of study (4)
behaviour were in the desired direc-
sed by the material presented, in
uch as anal sex and drug injecting,
rt for a government-conducted
94
TUESDAY, JUNE 2
TP195 Intravenous Drug Abusers Infected with Human Immunodeficiency TR198 Delivery of
Virus: Details of Behavioural Patterns over the Period of an using a mod
Epidemic MARGARET NICHOLS*, S.
J.R. ROBERTSON, CAROL A. SKIDMORE, A.B.V. BUCKNALL , J.J.K. ROBERTS, New Jersey
W.B.F. GALLOWAY, C.A. FOSTER, Edinburgh Drug Addiction Study, Scotland AIDS Health-care e
Intravenous drug abusers infected with AIDS virus and those apparently non psychosocial support
infected were part of a cohort of 250 individuals followed over a 2 year New York and Shanti
period. Retrospective data was available on 117 individuals 683 men (71%) in a highly cost-eff
Ik women (29%) with a duration of heroin use of 3.6 years (SD 2.28, range programs have been i
0.2-1^.8) . Importantly the length of time of intravenous drug use to Foundation is one of
presentation to medical intervention was 1.25 years (SD 1 . A3 , range 0-7.75). rural setting as wel
The group had been in contact with the doctors for 12.8 years (SD 8.h+, the different issues
range 0.1-28.6). including such topic
Case record search and detailed interview data was used to validate and the need for decentr
corroborate the information as well as the subjective analysis of physicians greater stigma and s
with clinical responsibility. concammitant need fo
Results demonstrate a peak of heroin use in 1981-1983, 60% of study group these patients requi
commencing use during these years. Subsequent heroin use was subdivided patients in suburbia
into Abstinent, Dependent and Non-Dependent use, most individuals demonstrat- issues present as we
ing change between these patterns of behaviour every 0.A8 years. As expected
the total number of episodes correlated with duration of use (r=0.*»25,
p< 0.001).
In the total of *»995 months of heroin use 39% was spent in abstinence, 10%
in non-dependent and k8% dependent use. No correlation between groups and
HIV seroposi ti vi ty was demonstrated.
Conclusion: Drug users demonstrate varying patterns of use amongst
individuals over time and in a group.
Psychosocial Services in a non-urban area
el of Volunteer Efforts.
FLACK,* Hyacinth Foundation, New Brunswick,
xpert
prog
Pro je
icien
nstit
the
I as
that
s as :
alize
hame
r ext
re ; d
We
II as
ge
rams
ct
t an
uted
few
in u
fac
1)
d pr
that
reme
eali
will
pot
neral
such
n San
d sue
prim
progr
rban
e ser
deali
ogram
subu
conf
ng wi
disc
entia
ly agre
as Gay
Franci
cessf ul
arily i
ams ope
centers
vice pr
ng with
2) h
rban AI
identia
th fami
uss the
1 solut
e tha
Men '
sco c
mann
n urb
ratin
. Thi
ovide
geog
andli
DS pa
lity,
lies
prob
ions .
t vol
s Hea
an de
er. H
an ar
g in
s pap
rs in
raphi
ng th
tient
even
of or
lems
unte
lth
live
owev
eas .
a su
er d
sub
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s fe
sec
igin
each
er-bas
Crisis
r serv
er
Hyaci
burban
escrib
urban
stance
nerall
el and
recy
of AI
of th
ed
in
ices
ch
nth
/
es
areas
s and
y
the
that
DS
ese
TP196 Intergrating Positive Attitudes and Healing with the Expression of
Painful Emotions and Dying in a Client Support Group
JIM GEARY, Executive Director, Shanti Project
In facilitating a support group for people with AIDS/ARC group leaders and
members often find themselves in conflict regarding some members' desire to
maintain a positive attitude and other members need to express depression,
grief and/or concerns regarding dying. These needs can also be present con-
currently in any one individual. Often members will not return to group
because they find the group process too depressing or positive to the point
where they feel unable to deal with difficult emotions.
Having facilitated a group for people with AIDS/ARC for 5 years, I have
learned ways to support certain group members in maintaining a positive
attitude, while assisting others dealing with painful emotions. These methods
have resulted in a more intergrated approach to facing one's illness. I have
found that when people realize that they can express strong emotions, yet still
maintain an overall positlveness that this empowers them to handle whatever
emotions they feel, rather than be controlled my them.
I have concluded by the success of my support group, measured in terms of
longevity of attending members, that both metaphysical as well as more common-
lly accepted approaches to dealing with illness can be combined and mutually
supported for the benefit of everyone.
TR199 Mul tidisciplinary Planning for the Psychosocial and Legal
Needs of Persons with AIDS and their Families
LAUREN GORDON, CSW, C. ZUCKERMAN, JD, Monteflore Medical Center,
rs and attorneys, as members of a multi-
ve jointly addressed psychosoc ial-legal
1 out of every 3 persons with AIDS and
the team. Timely and sensitive planning
and death and the continued lives of fa-
Bronx ,
Sine
dlscip
proble
their
for th
mily m
Our
and f e
ing th
ven tio
dren o
3 . Lac
t ional
by the
agnos i
ienta t
accept
legal
Earl
lble u
wills
and so
erwise
famlll
NY,
e 19
Una
ms o
fami
e pa
embe
cl in
male
e na
n: 1
rot
k of
sho
ill
s , e
ion)
ed p
res p
y r
ses
and
cial
ove
es h
USA
85,
ry AID
f appr
lies f
tient
rs is
leal e
, AIDS
ture o
. Rela
hers f
econo
ck and
ness ;
thnic
; 7. N
a t tern
ons ibi
cognl t
of sue
child
plann
rwhelm
elps
clal
S te
oxim
olio
s de
nece
xper
pop
f fu
tive
inan
mic
cha
6. S
or r
a tur
s of
liti
ion
h le
cus t
ing
ed b
urvi
worke
am , ha
ately
wed by
c 1 ine
ssary .
i ence
ula tio
ture p
you th
cially
resour
os f ol
ocle ta
acial
e of 1
ex ten
es )
of spe
gal me
ody an
provid
y thei
with
n , ha
lanni
of p
and
ces a
lowln
1 bia
s ta tu
lvlng
ded f
a p
s i
ng
ati
emo
mon
d
ami
redominantly minority, both male
dentlfied 7 major issues affect-
and the options for legal lnter-
ents ; 2. Existence of minor chil-
tionally dependent on patients;
g patients and families; 4. Eroo-
iagnosis; 5. Time limits imposed
ttached to patients (due to di-
drug abuse history or sexual or-
rangements (unconventional but
lies which confuse traditional
cific problems requires novel and flex-
chanisms as durable powers of attorney,
d guardianship procedures. Advance legal
es security and control to patients oth-
r Illness. Ongoing assistance offered to
n coping with the loss of loved ones.
TP197 ^en ^^ Is°lated Thrombocytopenic Purpura - The Impact of
Psycho-Physiological Intervention on Platelet Count
Inge B. Corless*
0. Abrams**, E. Biglieri**, M. Dodd**
♦University of North Carolina, Chapel Hill
"university of California, San Francisco, California
A psychophysiological intervention composed of relaxation, imagery and
therapeutic touch was investigated as to its effect on platelet count,
helper: suppressor ratio, and adrenal function, in eight males with Isolated
Thrombocytopenic Purpura. Individuals in the experimental group received a
sixty minute psychophysiological intervention thrice weekly supplemented by
an audiotape three times per day. After the five week intervention period
participants used the audiotape alone. In a delayed start design, control
group patients also received the intervention. This paper reports the
psychological findings and their relationship to hematological and immunogical
status. Control group patients exhibited an increase in tension and
depression as measured by the Profile of Mood States from the baseline
measures to the time of intervention. This same pattern was not observed in
the experimental group. The experimental patients who showed decreases in
tension, depression, anger, confusion and fatigue in the first five weeks
exhibited further gains in the next five weeks. A trend was observed between
decreases in depression and tension and an increase in platelet counts in two
patients. Only one of the eight individuals had a normal H:S ratio.
Increases and decreases in these ratios over the ten weeks were not
remarkable. Five of the eight men had adrenal responses requiring further
evaluation.
TR200 Behavioral, Immunological and Biochemical Patterns in ARC and AIDS.
ROBERT M. SCHMIDT'. V. I KVITASH". 'San Francisco Stale University.
""Medical Research Institute of San Francisco at Pacific Presbyterian Medical Center.
San Francisco, CA USA
Potential markers for predicting development of AIDS were studied in 33 men with
ARC. Thirty -eight healthy controls and 1 1 AIDS patients were also evaluated. Seven
behavioral parameters (medical events, general well-being, psychological well-being,
nutrition, tobacco use. alcohol use. physical activity) 6 immunological and 9
biochemical parameters were analyzed with the assistance of a computerized
technique permitting pattern cognition and graphical representation of relationships
among these 22 variables.
During 30 months of follow-up, 4 men with ARC developed AIDS, 15 remain
healthy or have not progressed with additional ARC symptoms; 14 men were lost to
follow-up. No healthy controls developed ARC or AIDS. AIDS-resislant ARC patients
had a higher cholesterol (1733). HDL (450). T4/T8 ratio (0.78) and alcohol score
(80,3) compared to the pre-AIDS ARC patients (149.5). (30.0). (0.31). (70.5).
Although no single variable permitted discrimination among AIDS-resistant and pre-
AIDS individuals with ARC. composite computor generated patterns of multiple
intersystem regulatory abnormalities at the time of initial presentation provided
clear separation without overlap. We conclude that definitive early identification of
pre-AIDS individuals among ARC patients is possible using routine clinical
laboratory tests when combined with behavioral data
95
TUESDAY, JUNE 2
TP201 Predictors of chronic psychosocial disturbance arising from the
threat of HIV infection: Lessons from Heterosexual, Bisexual and
Homosexual Worried Well patients.
DAVID MILLER, The Middlesex Hospital Medical School, London, England.
Twenty patients presenting with high-level psychological distress in
response to the threat of HIV infection were assessed on 16 psychosocial
variables. All presented conspicuous management difficulties. There was a
striking consistency in the presenting and background histories of patients
within this group. These consistencies concerned the appearance of misinter-
preted somatic features, numbers of negative antibody tests undertaken,
difficulties in sexual adjustment and self-acceptance of sexuality, poor social
integration, previous psychiatric/psychological history, level of physician
attendance, problems of sexual expression, previous low experience of sexually
transmitted diseases, obsessive-compulsive disturbances, anxiety, depression
and suicidal planning.
The consistencies found in this group enable future managment requirements
in this and other groups to be predicted. In addition, this analysis provides
a measure of the impact of the threat of HIV in sections of low-risk heterose-
xual communities. It appears that 'worried well1 persons with the lowest
levels of objective risk frequently require a much larger amount of clinical
involvement and present with a greater threat for suicidal activity than
people from other groups. This is due to their higher levels of social
isolation, psychological vulnerability, sexual maladjustment and guilt.
TR204 The ResP°nse °f Philanthropy to AIDS: A Survey of Private Giving
Trends Between 1982 and 1986 to AIDS-related Issues and Implications
and Considerations for Future Support
GEORGE MARSHALL WORTHINGTON, Worthington and Associates Worldwide, New York
City, New York
Most philanthropy is an unimaginative, dutiful, and largely dubious process.
Nearly half — $21.7 billion — of America's philanthropic contributions in 1984
went to religion; another $7.6 billion went to health care, nearly one quarter
of which was used for hospital consruction — and this in a country with a sur-
plus of hospital beds. In general, projects involving social change issues of
any kind — research, conferences, publications, legal suits, large "pilot pro-
ject" service organizations, and occasional grassroots groups — got less than
2.8 percent of the total. Even the Ford Foundation, considered the most adven-
turous of the large foundations, gave only 8 percent of its money to projects
concerned with social issues. With respect to AIDS, in particular, the picture
is considerably less optimistic by comparison. But the situation is changing.
Oral abstract will present a complete and current information survey on fi-
nancial support for AIDS education, research, and related fields with emphasis
on foundations and corporate giving programs. The survey will include the out-
comes and follow-up to the five Regional Associations of Grantmakers which held
meetings on AIDS in 1985. Presentation will include information on foundations
and corporations which have expressed an interest in AIDS with emphasis on
their giving interests: research/treatment; services; public policy, community
and public education; housing and hospice programs; advocacy and civil rights
for persons with AIDS. Information will also be provided about grants made-to-
date, including foundation or corporation with amounts, grantee, project or
purpose. Also included will be guidelines for grantmakers and grantseekers, in-
cluding where support is needed plus a suggestive list of funding opportunities.
TP202 Social Support in gay men with the Acquired Immunodeficiency
' Syndrome (AIDS).
BECHTEL, G. A. Auburn University School of Nursing, Auburn, AL 36849
Social Support is a core requirement for human survival and it assists an
individual in recovering from a major life crisis. Because most individuals
diagnosed with AIDS are already partially isolated from society due to the
stigma attached to homosexuality, social support networks have limited
functional ability. The problem of the study sought to determine if differences
exist in social support systems between gay men diagnosed with AIDS and those
at high-risk for developing AIDS.
The sample consisted of 67 gay men from a metropolitan area of a conservative
southern state. Thirty-six of the respondents were diagnosed with AIDS and 31
at high-risk for developing AIDS based on their sexual lifestyle. Each
participant was given the Norbeck Social Support Questionnaire (NSSQ) which
measures both social support networks and functional support systems.
The Mann Whitney U-Test showed no significant difference between groups in
either subscale of the NSSQ. However, social network scores were far below the
"norm" although functional support scores fell within normal ranges.
Social support scores from both subscales were significantly correlated with
income for individuals diagnosed with AIDS and perception of health status for
individuals at high-risk for developing AIDS. Neither support subscale was
significantly correlated with the amount of support lost although both groups
reported losses from lovers, friends, and family.
The study suggests that immediate intervention to develop and encourage
social support systems is not as important as the maintenacne of support
systems which are already in place.
TR205 HIV SEROPOSITIVE MOTHERS AND THEIR BABIES - DELIVERY OF
HEALTH CARE.
J MOK, S Davidson, RP Brettle, City Hospital, Edinburgh.
An epidemic of HIV began in Edinburgh amongst heterosexual
intravenous drug misusers in August 1983 and had reached 50%
seropositivity by 1985. Only 40% of the individuals are currently
abusing and one third are female.
With the introduction of the HIV antibody test in October 1 985
families with one seropositive individual and newborn babies were
detected. Previous experience of this group in delivering health
care had revealed default rates of 30-40%. On the 1st January,
1986 we established a separate hospital based out patient service
specifically for at risk mothers and babies. This involved:
1 ) the joint attendance of mother, baby and/or father for health
care assessment, counselling and education. 2) the service was
provided by a consultant paediatrician in community health, a
midwife/counsellor and a consultant in Infectious Diseases. 3) a
liaison health visitor coordinates the care in the community and
the referrals from 4 obstetric services. 4) where necessary the
problem of non attendance has been overcome by home visiting.
To date 38 families have been enrolled in this service which
consists of 3 monthly assessments. Twenty-five infants were born
to 24 seropositive mothers, of whom 58% attend hospital regularly,
42% consistently utilise home visits. One family needed home
visits to establish contact and encourage hospital visits. No
families have been lost to follow up to date but despite intensive
counselling and education 2/24 or 8% of the mothers became
pregnant and required terminations.
TP203 AIDS Educat'°n 1" Medical and Nursing Students: Knowledge and Attitude Correlates
HARVEY BARTNOF MP*, Jeffrey Mandel*, Margaret Grade*. Leonard Zegans*, Barbara
Faltz**, et al, *UCSF School of Medicine, »*UCSF School of Nursing, San Francisco, CA
Health care provider students are often thrust Into clinical environments with HIV-infected
persons prior to having adequate knowledge about AIDS or HIV. In attempt to obviate this
problem, a thirteen hour multldlsclpl Inary survey elective course on AIDS-HIV was designed
at UCSF and led to an enrollment of 139 medical, nursing, and pharmacy students. Prior to
the first lecture, students were asked to complete an anonymous questionnaire on AIDS knowledge,
attitudes, and personal demographics to determine the level of knowledge about AIDS, and
to ascertain any stlgmaphoblas and demographic correlates which might detract from optimal
clinical Interactions with AIDS and ARC patients. An Identical post-course questionnaire
will be administered In March, 1987 to ascertain any changes.
Pre-course questionnaires Indicated that 26* of medical students (MS) thought AIDS could
be transmitted by mosquitoes and 18* believed AIDS could be transmitted by sweat or urine.
Self Identified gay/bl/lesblan (SIG8L) nursing and pharmacy students achieved slightly higher
knowledge scores (97* and 88$ respectively) than did their heterosexual counterparts (HO
(871 and 75X1 whereas SIGBL and heterosexual MS scored equally high (88? vs. 85*). Interestingly,
significantly more SIGBL medical and nursing students (60* and 100*) agreed or strongly
agreed (AOSA) they had a lot of knowledge about AIDS than did their HC (16* and 28* each).
18-29* of all students AOSA that hospital employees should be allowed to refuse to care
for persons with AIDS (PHA). 5-33* of all students would prefer to avoid caring for PWA.
Generally, there were low rates of homophobia and ethnlphobla. Post-course questionnaires
will be completed In March 1987; those data will enable us to ascertain pre- and post— course
correlations between demographics, knowledge, and attitudes. Verbal feedback to date Indicates
that AIDS education of student health care providers further decreases stlgmaphoblas and
maximizes knowledge on AIDS and HIV. In turn, this will optimize patient care.
TR206 A Conceptual Model for a Transitional Self -Help Residence for IVDA
with AIDS/ARC
J.PERRY, G.RODRIGUEZ, L. ROTKIEWICZ, S.YOUNG, New Jersey State Dept. of
Health (NJSDH), Trenton, NJ.
Temporary housing is needed for AIDS/ARC patients who are ambulatory and
able to provide self-care but currently lack stable housing and thus,
appropriate discharge and referral from inpatient settings. The NJSDH has
identified an urgent need for such a resource in the Newark/Jersey City
area, where most AIDS/ARC cases are related to IV drug abuse. It is
hypothesized that cost-effective and humane care can best be provided in a
small-scale residential facility that houses 20 persons reimbursed at a per
diem rate through state funds.
To facilitate negotiations with local community groups, a conceptual
model was developed. Resource development is based on the nature of the
disease and the risk group to be served and is structured as part of a
continuum of post-hospitalization care. Components of the model include
eligibility criteria, staffing patterns and job responsibilities, daily
activity schedules, rules and regulations geared toward self-care,
requirements for monitoring and reporting to the funding source, and a per
diem reiinbursement rate lower than that for acute long-term care or
residential drug treatment.
A flow chart illustrates potential patient transfers among alternative
levels of care. This process is facilitated by case management.
96
TUESDAY, JUNE 2
TR207 ™he Attitudes and Knowledge of Health Care Professional
Working with Patients with AIDS and How They Impact on
Their Professional Behavior. WILLIAM J. NELSON, W. C.
HOLZEMER, M. 0 ' ROURKE , San Francisco General Hospital,
San Francisco, California U.S.A.
A survey was conducted in 3 cities of the United States . The
survey was a post-test for 3 workshops on AIDS given in
Anchorage, AK , Eureka, CA and So. San Francisco, CA. Sample
surveyed consisted entirely of registered nurses . These nurses
had worked with as few as 0-1 patients with AIDS, to 10 pts with
AIDS . Academic preparation of nurses was varied . Not all nurses
performed bedside care . Majority of respondants were Caucasian
women. A majority of nurses received their nursing education in
the U.S. Purpose of the pilot study was twofold. We were
piloting a new survey tool based on the works of Rubin &. Peplau
(1975) and Herek (1984). Main thrust of the pilot study was to
look at nurses ' responses to attitudinal/knowiedge questions and
compare those responses to questions which required a
professional judgment . The null hypothesis states that
essential ly no differences exist between nurses in outlying areas
and those closer to a major metropolitan area where AIDS was more
commonplace . Early analysis of the data show: 1 ) nurses are
open to learning about AIDS and dealing effectively with those
patients, irrespective of how they may feel about homosexuality
or I . V . drug use ; 2 ) that nurses are not as homophobic as may
have previously been thought ; 3) that nurses work effectively
with AIDS ir regardless of how much exposure to AIDS the nurses
have had .
TP91A Survey of United States Nursing Schools' Guidelines/Policies on AIDS
CHERYL L. BOWLES, V.L. CARWEIN, Department of Nursing, University of
Nevada, Las Vegas.
A descriptive survey of 242 NLN accredited schools of nursing was conducted
to identify guidelines and methods used to deal with both student assignment
to AIDS clients and students who are antibody positive or diagnosed with AIDS.
In the absence of existing guidelines responses were based on personal
thoughts or feelings.
Results indicated 95% of the schools of nursing have no guidelines for deal-
ing with infected students, 76% have no guidelines for dealing with student
assignments to AIDS clients and 49% have no plans to develop guidelines.
Thirteen percent felt HIV antibody testing should be required of all nursing
students and 81% disagreed.
While 66% responded that another assignment would be made if a student
refused to care for an AIDS client, 45% added "other" comments, primarily
student conferences and further AIDS education.
In response to dealing with antibody positive students who are not ill, 84%
felt students should remain in theory and 64% in clinical. Regarding who
should know the student is antibody positive, 62% felt the student health
center, 35% only nursing faculty in direct contact and 51% the nursing school
administration. When asked about students diagnosed with AIDS, 79% would allow
theory attendance while only 31% would allow clinical attendance. Regarding
who should be notified, 67% indicated the student health center, 41% only
nursing faculty in direct contact and 61% the nursing school administration.
Results demonstrated few schools of nursing have existing guidelines, many
have no plans to develop them and uncertainty abounds in the resolution of
these issues.
TR208
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TR211 HIV Infected Patients with Pulmonary Tuberculosis: Risk of Exposure
for Health Care Workers (HCWs)
S.OFFUTT, ROBERT B. NADELMAN, G.P. WORMSER, NY Medical College, Valhalla, NY.
Recently, the association of TB with HIV infection has been noted. Since TB
is potentially communicable to HCWs and since respiratory isolation is not rou-
tine for patients with HIV infection, we reviewed our experience with patients
who had both infections. Mycobacterium tuberculosis infection was documented
by culture for 35 patients at our hospital between 1/1/85 and 12/31/86. Seven-
teen of 18 of these patients who were tested for HIV demonstrated presence of
serum antibody. Nine of these 17 patients (53%) had extra-pleural pulmonary TB
(PTB) with or without other + culture sites. Six of 9 patients had sputum
smears + for AFB. Respiratory isolation was instituted on admission for 4/9
(44°/) of the patients, but in the other 5 (56%) PTB was not initially suspec-
ted. Time to institution of isolation ranged from 2-41 days with a mean of 8
days. Delay in instituting respiratory isolation resulted from a lower index
of suspicion for TB in HIV infected patients who were initially believed to
have had an alternative diagnosis. No patient had cavitary disease and only 2
had upper lobe infiltrates. Other CXR findings included 2/9 patients with only
lower lobe infiltrates, 1 with only adenopathy, 1 with apical scarring, 1 pleu-
ral effusion, and 2 with a normal CXR. Six patients with PTB had a + PPD.
TB's resurgence in the HIV infected population has been characterized by ex-
trapulmonary and non-classical infection. The frequently atypical CXR and the
occurrence of skin test anergy may mask the diagnosis of PTB in the HIV infec-
ted patient. The lack of early institution of respiratory isolation in these
patients may pose an increased risk of transmission of TB to HCWs. A high index
of suspicion for TB in HIV infected patients will be essential in preventing
nosocomial outbreaks of TB.
TP209 Designated AIDS Centers/AIDS Intervention Management System (AIMS)
IRA FELDMAN, R.F. HUMMEL, JUDITH SIMMONS, M.D., NYS Department of
Health, Albany, NY
In January, 1986, New York State amended pertinent regulations in order to
allow for the designation of acute hospitals as AIDS Centers for the care and
treatment of AIDS patients. The Designated AIDS Center concept is based on a
continuum of care/case management model designed to meet and/or arrange for
all levels of care and needed services required by AIDS patients. This model
will allow for increase access by persons with AIDS to essential health care
and community resources so that AIDS patients are able to maintain the quality
of their lives in a home environment as long as possible.
In conjunction with the AIDS Center process, New York State solicited
competitive applications from qualified organizations for the design,
implementation, and operation of an oversight system to review the performance
of the comprehensive AIDS Centers, conduct a comparative review of AIDS
patients, and ensure that appropriate standards of utilization review, quality
assurance and case management are established and met. This oversight system
is referred to as the AIDS Intervention Management System (AIMS) . AIMS will
centrally coordinate the retrieval of data from the multihospital treatment
of AIDS patients under the case management, discreet unit model. Information
concerning inpatient/outpatient services and costs as well as diagnostic and
demographic data will be retrieved and analyzed in order to provide new
information concerning the impact of AIDS and HIV related illness on the health
care delivery system.
TR212 Orthopaedic Surgeons' Attitudes and Practices Concerning Treatment
of Patients with Human Immunodeficiency Virus (HIV) Infection
PAUL ARNOW, L. POTTENGER, C. STOCKING, H. OE LEEUU, '!. SIEGLER. University of
Chicago, Chicago, IL.
Concern regarding a possible occupational risk of acquiring HIV infection
has made some health care workers reluctant to treat AIDS patients and may in-
fluence surgeons' willingness to operate. To assess attitudes and practices of
a group of surgeons that treats young and middle aged males, we conducted a
questionnaire survey of all orthopaedists in the five cities with the most
AIDS cases. Topics included experience, knowledge of HIV transmissibil ity,
precautions during surgery, HIV testing of patients and surgeons, and ethical
obligations of surgeons. Questionnaires were mailed during March-July 1986 and
were completed anonymously by 325 of 510 orthopaedists. In the previous year,
142 (43%) had examined or operated on an HIV-infected patient, and 90" of re-
spondents who evaluated HIV-infected patients for surgery chose to operate.
Decisions to operate appeared not to be based on hospital requirements, per-
ceived ethical obligations, or knowledge of HIV transmissibility. About half
of the orthopaedists who operated considered HIV to be more transmissible than
it is. Most orthopaedists felt they had the right to require preoperative HIV
testing of all patients (71%) and high risk patients (85%), but such testing
was ordered infrequently. Forty-three percent of orthopaedists felt patients
have a right to know if their surgeon is HIV-positive, and 51% felt restric-
tions on the professional activities of infected surgeons were necessary. Al-
though orthopaedists reserved broad rights for themselves, they almost always
were willing to treat patients with HIV infection.
97
TUESDAY, JUNE 2
TR213 Psychological problems in nursing patients with AIDS
Seidl,0. , Goebel , F. -D. ; Medizinische Poliklinik, University
of Munich, West Germany
Nursing the patients with AIDS causes a lot of problems which
are not comparable with those in nursing other patients with a
terminal illness . Health-care personnel experience* many sources
of stress leading to an emotional exhaustion.
To understand the emotional reactions and to help the staff
members we performed "training cum research"groups (Balint) once
a week over a half year period.
In the first months an imposing feeling of hostility against
the patients with AIDS predominated. They were experienced as self-
willed, demanding and conceited in a strong difference to other
patients. The nurses had difficulties to assert themselves, and if
they could, patients raised the feelings of not being a good nurse.
Within the hospital nurses felt themself stigmatized because of
nursing stigmatized patients with a stigmatized illness. The fee-
lings and the reactions could be interpreted in the group-process
as a consequence of the more or less unconscious negative attitu-
de to the patients on one side and the identification with the
mostly young, intelligent and alert homosexuals on the other side.
The perception, that nearly all patients shall die let to interpre-
tation of all their wishes as last wishes, leading to the difficul-
ty to say "no". The more the motives of nurses became conscious, the
more stress in nursing was reduced.
"Training cum research" groups seems to be a possibility to
minimizestaf f stress , especially the chronic professional stress
syndrome . • c j r
TR216 Treatment of AIDS-related Kaposi's Sarcoma (KS/AIDS) by Alpha-2-
recombinant Interferon and Bleomycin.
L.J. COUDERC*, S.MATHERON2, M. JANIERl, P.M. GIRARD2, M. SELIGMANNl,
J. P. CLAUVELl. 1 : Hopital Saint-Louis 75010 Paris. 2 : Hopital Claude Bernard
75019 Paris -FRANCE-
The efficacy of recombinant leukocyte A interferon (Roferon) treatment of
KS/AIDS has been previously evaluated. We have showed response of KS/AIDS to
bleomycin alone (Second Intern. Conf. on AIDS. Paris 1986). In a pilot study,
we evaluated Roferon in combination with bleomycin. Roferon was given I.M. at
18 Mu daily for one month and was continued at the same dose three times weekly.
A slow continuous infusion of bleomycin was given I.V. at 6 mg/m2 daily for 3
days each month. Treatment was continued unless tumor progressed.
In October 1985, the first 9 patients were enrolled in this prospective study.
All patients were homosexual men with disseminated KS. No patient had received
treatment for KS. Preliminary results indicate that 2 had a complete response,
3 a partial response, 3 a stable disease. One patient developed Pneumocystis
carinii pneumonia. Final results will be presented on all the patients treated
for more than 3 months.
TR214 A Survey of Residency Programs for Persons with AIDS
H. Monroe Wright, M.Div., S.T.M., the United Methodist
Church, Branford, CT.
Lack of alternative housing represents a growing financial and social problem
within the context the the AIDS epidemic in the US. For hospitals there is the
accumulation of "Administrative Necessary Days" and for Persons with AIDS (PWAs)
there is the burden of institutionalization. Various urban centers have estimat-
ed that 30% of PWAs lack appropriate alternative housing. There are several
causes: patients' ostracism by family, roommates, lovers; evictions; financial
straits and refusal of nursing homes and hospices to admit.
This paper is a survey of eight urban residency programs for PWAs. Half are
in areas with high concentrations of PWAs. Various models are presented: small
group homes, "hotels," foster homes and rent subsidies. The common thread is
that while no direct health care is provided by the sponsoring organizations ex-
tensive psychosocial and spiritual support is rendered directly and health care
is coordinated from hospital discharge planning through to Visiting Nurse ser-
vices.
Emerging issues include IV drug abusers and neurological/physiological limi-
tations of residents. Thus there is a need for an increase in supportive ser-
vices and direct health care services. The first such programs have garnered ex-
tensive support from the Gay community and Federal demonstration grants. Future
needs demand more through planning at all levels. The PWAs residency programs'
home care approach provides a cost effective alternative to chronic hospitaliza-
tion and an enhanced psychosocial/spiritual environment.
TR217 INHALED PENTAMIDINE AS EXCLUSIVE THERAPY FOR PNEUMOCYSTIS CARINII
PNEUMONIA (PCP) IN THE ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS).
J. A. Golden, H. Hollander, J.E.Conte.Jr. University of California, San Francisco,
CA. The treatment of PCP is associated with side-effects in over 50% of AIDS
pts. We therefore assessed the efficacy of inhaled pentamidine (P) in AIDS pts
with mild PCP (defined as P02>60mm Hg). Pts inhaled P (4 mg/kg) daily for 14
days by nebulization ("Ultra Vent," Mallinckrodt, St. Louis). P levels by HPLC
were assessed in bronchoalveolar lavage (BAL) and plasma. Nine pts were entered
into they study. Six pts favorably responded to inhaled therapy with resolution
of dyspnea, fever, and improved chest x-ray and arterial blood gases. One pt
failed after 5 days of inhaled P; two pts became ineligible for the study after
less than 48 hrs when they clinically deteriorated and were no longer consider-
ed mild PCP. There were no serious adverse effects of inhaled P although 2 pts
had P-related cough. Inhaled P resulted in P base concentrations (see table) in
BAL that were higher and plasma levels significantly lower than levels in our
pts treated with intravenous P (BAL P level 7.15+5.3 ng/ml ; plasma level
286+171 ng/ml) consistent with the efficacy of inhaled P and lack of adverse
effects in this study. Inhaled P should be further investigated.
Pt # P1 Concentration in BAL (ng/ml) Day3 Plasma (ng/ml)4
1 ND2 - 3.1
2 55.3+17.1 1 14.7
3 28.6+10 4 16.9
4 66.8+16 3 0
5 16.8+7.3 1 2.5
6 30.6+27.5 14 32.8
1. Mean + SD; 2. Not done; 3. day(s) of therapy prior to BAL; 4. peak
concentration measured post inhalation, day 1
TP215 Improving Utilization of Services by Families of Children with
AIDS/ARC
MARY BOLAND, E. CONNOR, P. EVANS, J. KERESZTES, S. MORRISON, J. 0LESKE
Children's Hospital of New Jersey 8 UMD-New Jersey Medical School, Newark, NJ
In 50 families with 57 children with AIDS/ARC, one or both parents are in-
fected with HIV. Maternal risk factors were: intravenous drug use (28/50),
sexual partners with AIDS or at increased risk for AIDS (16/50), maternal blood
transfusion (3/50), Haitian (2/50), and no identified risk factor (1/50) .
42/57 children reside in a single parent family headed by a woman. 2/57 chil-
dren were cared for by their fathers. 17/50 families were known to family
protective services agencies prior to the diagnosis.
HIV infection is a family illness. 10/57 children have at least one parent
who has died from AIDS. Only 3/36 parents received regular medical care. The
remainder (33/36) received episodic care for acute symptoms. Illness in a
parent decreased the amount of physical and emotional energy available for
parenting. The combination of drug use, poverty and illness stressed an al-
ready weakened family unit.
Hospital based care services were poorly utilized. Initial home visits by
a nurse and social worker lead to the development of a relationship with the
family. Subsequently, 32.57 children received the following services in the
home: nursing care (32/32); homemakers and home health aids (6/32); physical
therapy (9/32), and speech therapy (4/32). The family with HIV infected
members deals with multiple stresses on a daily basis. Assuring continuity
between hospital and home while providing care in the home can result in
improved utilization of services in both settings.
TP218 Use of Imuthio:L (Diethyldithiocarbamate, DTC) in
Symptomatic HIV Infection.
GARY W. BREWTON*, E. HERSH**, P. MANSELL* , A. RIOS*, J. REUBEN*.
*Univ. Texas System Cancer Center/Institute for Immunological
Disorders, Houston, TX **Univ. Arizona Cancer Center, Tucson, AZ
To determine whether Imuthiol improves clinical and immunologic
status, we studied the drug in symptomatic AIDS and ARC patients
(pts). 44 pts were stratified and randomized to receive either
200 mg/m IV weekly for 4 months or no therapy, followed by
crossover to the opposite arm for an equal period. Both groups
have been followed with the same clinical and immunologic para-
meters, and all pts had evidence of severe immune deficiency at
entry. No significant toxicity has been observed. Analyses of
results from the first 4 months prior to crossover indicate that
treated pts show a trend towards reduced progression (p=.231)
and are significantly more likely to show improvement in symptoms
(p=.002) and reduction in lymphadenopathy (p=.005) than untreated
pts. One treated pt each showed disappearance of marked spleno-
megaly, hairy leukoplakia, and intractable perianal monilia. One
pt with Kaposi's sarcoma confined to lymph nodes showed partial
histologic remission. No significant changes in lymphocyte
surface markers, lymphocyte blastogenesis, or skin test reactiv-
ity were seen.
These results indicate a possible role for immunorestorative
therapy in symptomatic HIV infection. Double-blinded, placebo-
controlled studies are under way to confirm and extend these
findings .
98
TUESDAY, JUNE 2
TP219 Use of Hi8n Dose Oral Ketoconazole in AIDS patients for Prevention
of Relapse in Cryptococcal Meningitis. TIMOTHY P. MESS, WK Hadley
CB Wofsy. San Francisco General Hospital, San Francisco, U.S.A.
From April 1985 to December 1986, 35 patients with cryptococcal meningitis
(CM) were seen at SF General Hospital. 22/35 patients (.637.) completed 6-8
weeks of induction treatment with Amphotericin B with or without 5-FC. 13 died
during induction. Because recurrence is high (30-60%), an open study with high
dose (lOOOmg) oral ketoconazole (KCZ) was begun in June 1985 for patients who
had completed an induction treatment with Amphotericin B. 20/22 patients who
completed induction were offered KCZ prophylaxis, a demented patient and a non-
compliant patient were excluded. 15/20 eligible patients chose KCZ.
Of the 15 patients who received KCZ, 7 are still alive without evidence of
relapse, range 4-11 months post diagnosis of AIDS and CM. 6 patients have died
with a range of survival post diagnosis of CM of 6-11 months (median 7.5) and
a range of survival post diagnosis of AIDS of 8-14 months (median 8.5). One of
these patients relapsed after 5 months of KCZ therapy and died 2 months later
due to active CM. One had an excellent clinical response during 4 months of
KCZ and died 1 month after discontinuing KCZ. The other 4 deaths were unre-
lated to CM. One lost to follow-up was still free of CM after 7 months of KCZ.
2 patients stopped KCZ secondary to toxicity. One stopped KCZ after 2 weeks
due to a >10-fold increase in LFT's and died 2 months later. The other stopped
KCZ after 3 months due to abdominal pain and died 5 months later without evi-
dence of relapse. 3/13 remaining patients had mild nausea. MIC's to KCZ were
available on 13 patients with a median value of 1.56ug/ml (range 0/39-3.13).
12 serum KCZ levels on 8 patients were available with a median value of
3.79ug/ml (range 2.24-15.0). CSF KCZ levels on 2 patients failed to detect KCZ.
Only 1/12 (8.8%) patients had evidence of CM relapse while on KCZ. Whether KCZ
is as effective or as toxic as weekly Amphotericin remains to be studied.
TDOOO Phase I Tolerance Study of HPA-23 in Patients with AIDS and
'"•£££ Preliminary Data of Anti-HIV Activity
HPA-23 COOPERATIVE STUDY GROUP. (BRUCE 1. MOSKOVITZ, Rhone-Poulenc , Inc.,
Monmouth Junction, N.J.)
The heteropolyanion HPA-23 is active against HIV in vitro and was selected
for study as a potentially effective antiviral compound for patients with AIDS.
Sixteen, 16, 23 and 14 patients with AIDS received, respectively, 0.25, 0.5,
1.0 or 2.0 mg/kg daily doses of HPA-23, intravenously-administered, five days
weekly (Monday-Friday) for up to eight weeks to assess the tolerance of HPA-23.
Clinical changes and anti-HIV activity were monitored periodically.
Forty-three of the 69 patients completed the entire eight-week course.
Thirteen discontinued because of a concurrent illness, six discontinued because
of a clinical adverse event, and seven discontinued because of laboratory test
abnormalities ( thrombocytopenia-6 , 4+ proteinuria-1) .
HPA-23 produced a dose-dependent decrease in platelet count and increase in
SGOT values. Other adverse events included leukopenia, granulocytopenia, fever,
diarrhea and nausea.
Over the eight-week course of treatment, no improvement in immunological
function, measured by total lymphocyte count, T^ cell count, and T^/Tg ratio,
was observed.
No changes in clinical symptoms, development of new opportunistic infections,
or occurrence of Kaposi's sarcoma lesions were apparent.
Qualitative results of reverse transcriptase activity assays suggested a
dose-dependent anti-HIV effect.
We conclude that the toxicity of HPA-23 is predictable and acceptable.
Longer-term studies to assess drug concentration-effect relationships, in vivo
antiviral activity, and clinical efficacy of HPA-23 are warranted.
TR220 D-penicillamine(DPA) Treatment for Lymphadenopathy Syndrome (LAS)
and AIOS-Related Complex (ARC)
DAVID H. PARENTI*,R. SCHEIB*,G. SIMON*, P. CHANDRA**, P. SARIN***, R. SCHUL0F*,
*George Wash. Univ. Hed. Ctr. .Wash. ,DC, **Frankfurt Univ. Med. Sch.,
Frankfurt, West Germany, *** NCI .Bethesda, MD.
DPA has been shown to inhibit HIV replication in vitro. We assessed the
clinical, virologic and immunologic effects of 3 different daily oral regimens
of DPA in 24 HIV-infected homosexual men who had: (1) HIV isolated from
peripheraUblood mononuclear cells (PBMC), (2) T4/T8 <1.0, (3) absolute T4
100-500/mm , and (4) depressed lymphoprol iferative responses (LPRs). 19
patients had LAS, 5 had ARC. 10 PTS received oral high dose (HD) DPA (2 gm)
for 2-6 wks. 7 were treated with low dose (LD) DPA (0.5 gm) for 12-18 wks. 7
PTS are receiving intermediate, intermittent dose (ID) DPA (1 gm), alternating
4 weeks on drug with 4 weeks off. One PT each in the HD and LD groups stopped
therapy because of a drug induced skin rash. Therapy was discontinued in 8
HD, 2LD and 2 ID PTS because of a decrease in T4 or LPR of > 50*. HIV
expression was assessed by measuring reverse transcriptase activity and by
detection of pi 7 and p24 antigens in PHA-activated PBMC co-cultured with H9
cells. HIV expression in LD PTS was unchanged whereas all HD PTS had reduced
HIV expression. Complete inhibition was seen in 3/5 HD PTS who received DPA
for 6 weeks, without re-expression for at least 6 weeks after stopping
therapy. Two patients treated for at least 4 weeks had detectable serum p24
antigen before treatment which decreased by 20% and 60% respectively with
treatment. Reversible depression ( > 20%) of T4 counts was seen in 5/10 HD,
4/7 LD, and 4/7 ID PTS; depressed LPR ( £ 40%) in 7/10 HD, 2/7 LD, and 2/7 ID
PTS. DPA has promising in-vivo anti-HIV activity, but further study is needed
in order to define a regimen which both inhibits HIV replication without
depressing T-cell numbers or function.
Tpppo Open Study of AL-721 in HIV-infected Subjects with Generalized
Lymphadenopathy Syndrome (LAS).
MICHAEL H. GRIECO, M. LANGE, E.B. KLEIN, A. ENGLARD, G.F. McKINLEY, K. ONG,
et_al. , St. Luke's/Roosevelt Hospital Center, New York, N.Y.
Eight subjects with LAS associated with HIV infection consented to an open
8-week trial to evaluate the antiviral and immunologic effects of AL-721.
CD4/CD8 ratios were less than 0.7 and CD4 counts below 550 cmm. The drug
was administered in 10 gm frozen sachets and reconstituted twice daily in 10
ml chilled orange juice before a fat-free breakfast and after a low fat
dinner. Surveillance studies were conducted of clinical state, serum lipids,
lymphocyte subsets, lymphoproliferative responses, and reverse transcriptase
assay (RTA) following cocultivation of peripheral blood mononuclear cells.
There were no significant drug-related clinical events during the 8 weeks
of drug and the 8 weeks follow-up period. Seven patients remained
clinically stable throughout the study and follow-up period. One patient,
however, who always had less than 35 CD4+ cells, developed disseminated CMW
after 4 weeks off drug and cerebral toxoplasmosis after 10 weeks off drug.
Serial RTA were performed in 7 with detectable RT at baseline having an
initial mean level of 73,419 cpm decreasing to a mean 44,653 at 6 weeks and
27,419 at 8 weeks. These changes in mean values resulted from decreasing
levels in 5 of the 7 subjects. Pokeweed mitogen responses increased in 5 of
8 so that the baseline mean of 18,000 cpm rose to 30,300 at 4 weeks and at
28,923 at 8 weeks and then subsequently decreased to 18,223 at 4 weeks
following treatment. No significant effects on serum lipids or T
lymphocyte subsets were noted.
The results of this study suggest that AL-721 may exert an anti-HIV
effect and augment immune responses in subjects with LAS.
TR221 Faniidar prophylaxii o f Pneumocyitii carinii pneumonia
in aiymptomatic HIV + penoni and penoni w-c-th ARC.
Jeffrey Vieira, MP. The Brooklyn Hoi.pi.tal, Brooklyn, NY, USA.
Pneumocyitii carinii pneumonia ii the mat common initial,
ti&e.-th>ie.ate.nj.ng oppoitu.nt.itic infection in penoni with AIDS.
Mortality from the fint epiiode of, PCP ii ai high ai 20-30$.
Safe and elective prophylaxii would be worthwhile to prevent
the morbidity and mortality aaociated with PCP.
30 patienti with T4 cell counti 250 wete randomized to
receive Faniidar 1 7 tablet weekly) or placebo. Patient groupi
were comparable in termi of age, T4 counti, baietine hematology
and chemiitriei . All were followed every three weefei .
There wete 4 epiiodei of PCP during the mean follow-up
period of 7 monthi, all occurring in the placebo group. One of
theie wai fatal. In the placebo group lab itudiei mete itable
except for increaiei in LVH and decreaiei in Hgb and leukocyte
counti in patienti developing PCP. In the Faniidar recipienti
mild toxicitiei included nauiea (4/15) and raih (l/!5) not
requiring dii continuation of drug. Progreaive anemia (2/Z5)
and ieveie leukopenia (3/15] required doiage modification or
dii continuation of the drug in 1 patient.
In iummary , Faniidar may provide effective prophylaxii
for fint epiiode PCP. Bone marrow iuppreaion may be a
iignificant limitation to prolonged u4e in iome patienti. The
uie of folinic acid iuppltmentation may help reduce thii drug-
induced morbidity .
TP224 Combination Chemotherapy and Interferon in Kaposi's Sarcoma (KS) and
AIDS. F.A. SHEPHERD, M.B. Garvey, W.K. Evans, M.M. Fanning, M.
Kline, and S.E. Read. University of Toronto, Toronto, Canada.
Thirteen males, median age 37 years (range 28-46), with extensive KS and AIDS
were treated with combination chemotherapy and Interferon. There were four
patients with stage III and 9 with stage IV disease (one pulmonary and 8 G.I.
involvement). Treatment consisted of monthly courses of act inomycin-D, 1 mg/m2
and vinblastine, 6 mg/m2 , day 1; bleomycin, 10 rag/m2 , day 1 and 8; and human
lymphoblastoid Interferon, 10 million units/m2 i.m. 3 times per week x 6 doses
starting day 14. Forty-one treatment cycles were administered (median 3, range
1-12). Complete response was seen in one patient (24 weeks), and partial
response in 4 patients (14-44 weeks). One patient had mixed response with re-
gression of extensive skin involvement, but progression of pulmonary disease.
Median survival of the group was 48 weeks (4-143+ weeks). Eleven patients
died of progressive KS, one with lymphoma, and one with Pneumocystis pneumonia.
Nausea and vomiting was mild to moderate and easily controlled. All patients
had slight temperature elevation and muscle aches while receiving Interferon,
both easily controlled with antipyretics. The median granulocyte and platelet
nadirs at day 14 prior to starting Interferon were 600 x 109/L and 134,000 x
10^/L, respectively and did not fall further while on Interferon. Four
patients required hospital admission for neutropenia associated fever. Compar-
ison of pre- and post-treatment T-cell subsets, 2'5'A synthetase levels, and
mitogen responses demonstrated no improvement while on Interferon.
Although a significant number of patients achieved response with this com-
bined modality therapy, we feel that the duration of response, survival, and
toxicity suggest that this form of therapy is not appropriate for patients
with KS associated with AIDS.
Supported by Pacific Isotopes and Pharmaceuticals Ltd. Vancouver, Canada.
99
TUESDAY, JUNE 2
TR225 Effect of AZT Therapy on Quantitative Serum HIV Antigen.
JOEL SPEAR*. H. K.ESSLER*, J. POTTAGE*, C. BENSON*, D. PAUL**, L.
FALK**, et al. Rush-Presbyterian-St. Luke's Medical Center*, Chicago, IL, U.S.A. and
Abbott Laboratories**, North Chicago, IL, U.S.A.
To determine the effect of AZT therapy on quantitative serum HIV antigen (Ag), we serially
studied 18 HIV culture positive AIDS patients treated with AZT in accordance with the BW-
AZT protocol. HIV Ag was determined prior to therapy and weekly thereafter using a
commerically available enzyme immunoassay (Abbott Laboratories) which detects the p24 gag
gene product. T-cell subset analysis was determined monthly. Ten of 18 patients were HIV Ag
positive prior to the initiation of therapy. There was no significant difference in mean T-
helper cell counts (67 vs 109/mm ) or T-suppressor cell counts (412 vs 1012/mm ) between
HIV Ag positive and negative patients, respectively. In 9 HIV Ag positive patients with a
mean pre-therapy quantitative Ag of 253 pg/ml (range: 23-804), the Ag decreased by a mean
of 223 pg/ml (92% reduction) with a range of 56-731 pg/ml (range: 56-100% reduction) after
one week of AZT (1200 mg/day). In one patient HIV antigen decreased by 1961 pg/ml (80%
reduction) after 4 weeks of AZT (1200 mg/day). Dose reduction of AZT (600 mg/day) in 2
patients was followed by slight increases in HIV Ag. AZT had to be discontinued in 7 patients
after 12-46 days (intercurrent opportunistic infection, 3; toxicity, 3; progressive deterioration,
1). HIV Ag increased by a mean of 721 pg/ml (range: 30-2927) within a mean of 6.6 d
(range: 2 to II) of discontinuing AZT. Four of 8 patients who were HIV Ag negative at
initiation of therapy became transiently HIV Ag positive within 3 weeks of beginning AZT.
Initiation of AZT therapy in HIV Ag positive patients with AIDS is followed by a rapid
decline in HIV Ag which rapidly returns to pre-therapy levels after AZT is stopped. This
suggests that serial quantitation of HIV Ag may be a useful parameter by which to monitor
AZT therapy. The clinical significance of this is as yet undetermined.
TR228 Clinical and Immunological Response to IMREG with ARC/AIDS
Patients. S, LANDESMAN*, ADRIEN MARCEL*, M. MURALI*, H.
DREW*, M. GOTTLIEB**, A. GOTTLIEB**. SUNY Health Science Center at
Brooklyn*. Brooklyn, N.Y., IMREG Inc.**, New Orleans, La.
Sixteen patients with HIV disease (12 with AIDS related complex (ARC)
and 4 with AIDS) received 6 biweekly intradermal injection of IMREG-I
in a phase II clinical trial. IMREG-I is an immune modulator comprised
of a small molecular weight peptide prepared by a series of dialysis
and HPLC separations from human leukocytes. At entry the average T4
cell numbers for ARC and AIDS subjects were 309(62-761) and 51(0-71)
respectively. Seven ARC and four AIDS subjects were anergic to PPD,
tetanus toxoid and Candida. Three ARC patients had minimal skin test
reactivity (<5mm induration) to tetanus toxoid alone.
Nine of the 10 anergic ARC and 2 AIDS subjects regained full skin
test reactivity to tetanus toxoid (8-30mm induration).
While there was no change in absolute numbers of T4 cells in these
subjects, the response to 1.0 ug/ml of PHA (studied sequentially in
9 subjects) increased 2 to 4 fold in 7 patients and was unaltered in
two.
Associated with therapy was the resolution of constitutional symptoms
such as fever and night sweats in 9 patients. There was no loss of
body weight in any patient. The hematocrit and platelet counts were
stable. No toxicity was noted with use of IMREG-I. These data suggest
that IMREG-I has some reconstitutive effect on the cell mediated immune
response in these patients as judged by skin test reactivity and pHA
responsiveness. No conclusion as to the long term efficacy of IMREG-I
can be made based on this limited trial. Further studies are in progress.
TR226 Preliminary Data From a Phase I Study of Oral Ribavirin (RIB) in
Children with AIDS-related Complex (ARC).
EDWARD CONNOR, S. MORRISON, A. MINNEF0R, J. KERESZTES, T. DENNY, J. 0LESKE ET
AL. Children's Hospital of NJ & UMD-NJ Medical School, Newark, New Jersey.
We are presently conducting a Phase I study to determine safety, tolerance,
and pharmacokinetics of single and multiple doses of oral RIB (1-beta-D-ribo-
furanosyl-l,2,4-triazole-3-carboxamide) is stable children with ARC. This is
an open study with sequential dose escalation. Patients were excluded if they
had severe or progressive end organ disease. Five patients were enrolled in
the first group (3 female, 2 male); mean age 26.2mo (16-61mo). Six mg/kg RIB
was dissolved in 3ml water and given po after 6-8hr fast. Safety parameters
included: vital signs, physical exam, stool guiac, CXR, EKG, CBC, platelet ct.,
reticulocyte ct., SMA-18, urinalysis, PT/PTT. Patients readily took the drug
and all tolerated it well. All parameters remained stable except HGB which de-
creased, mean 0.78gm (0.1-1.5gm). This was greatest for the smallest children,
could be accounted for by blood drawing and was associated with appropriate in-
crease in reticulocyte ct. One patient developed mild eosinophil ia. Following
a single 6mg/kg dose mean peak plasma RIB concentration was 2.5uM (1.02-3.96uM)
and occurred l-2hr post dose. During multiple dosing the range of trough cone,
at steady state was 2.05-2.8uM at 30 days and 1.85-2.9uH at 60 days.
During the two months of this study parents reported decreased night sweats,
increased activity and improved appetite. In addition, lymphocyte phenotyping
was performed at baseline and after 30 and 60 days of daily RIB administration.
There was a general trend toward increase of absolute number and percentage of
T-helper cells with improvement in helper:suppressor cell ratios. We are
now proceeding with dose escalation.
TR229 L0NG TER1VI F0LL0W-UP OF-82PATIENTS TREATED BY RECOMBINANT ALFA 2
INTERFERON IN AIDS RELATED KAPOSI 'S . SARCOMA.
WILLY ROZENBAUM, S. GHARAKHANIAN , B. DUFLO, M. STENBERG , G. BRUCKER , M. GENTI-
LINI. PITIE-SALPETRIERE HOSPITAL. PARIS FRANCE
Over a 4 years period, 82 male: patients (homosexual or bisexual) with a
mean age of 38.7 years (range : 24-55) with AIDS-related Kaposi's Sarcoma
(KS) were treated (83 courses) with recombinant leucocyte interferon alfa
2A (r IFN alfa 2A ) . Two types of dosage regimen were used : 36 million unites
(n=l6) and 18 mu (n=67).
43 patients had cutaneous and/or lymph node KS , 30 had cutaneous and/or mu-
cosal KS, 10 cutaneous and/or visceral KS. 24 patients (29$) had a complete
response ( CR ) with a mean duration of 10.6 months (range :l-36 months). 6"
of them relapsed within 12.5 months (r : 4-28 months) after discontinuation
of treatment, 2 responded completely with a new course of IFN. 9 patients
had a partial response, 5 of them relapsed. None of the patients died in these
group*.
The CR rate was higher in the group of patients who had only cutaneous and/or
lymph node KS (37%) in comparison with the group who also had mucosal (23%)
or visceral lesions (10%).
None of the patients with prior or concomitant opportunistic infection had
a CR, neither did patients who had a positive CMV blood culture. Other factors
which seem to be of relevance for the responding groups are: lymphocyte count,
absolute number of auxiliary (CD4) cells, CD4/CD8 ratio, response to recall
antigens, serum B2-microglobuline level, serum IgA. r IFN alfa 2A is efficient
in controlling AIDS-related KS, its- effect on life expectancy should be eva-
luated.
TP227 * phase II Study of 8etaser Interferon Given Subcutaneously to
Patients With AIDS Related Kaposi's Sarcoma.
STEVEN A. MILES, E CORTES*, SG MARCUS**, J CAROEN*, R RUDD*, and RT
MITSUYASU*. *UCLA School of Medicine, Los Angeles, California and **Triton
Biosciences, Alameda, California, USA.
Betaser Interferon has shown antiproliferative activity in several
neoplasms and has in vitro antiviral activity against the human immuno-
deficiency virus (HIV). To date we have treated 15 patients with AIDS
related Kaposi's Sarcoma subcutaneously with 90 x 10° IU qd x 5 each wk.
for 12 wks. Two patients had prior Pneumocystis carinii pneumonia. Five
had received prior chemotherapy, and 12 had positive culture for HIV prior
to starting treatment and are evaluable for antiviral activity. Fourteen
patients were stage II and one was stage IV. Of 15 evaluable patients, 3
had partial responses, 5 have stable disease and 6 had progressive
disease. One patient had an opportunistic infection (M. Tuberculosis)
diagnosed while on study. To date, 2 of 4 patients who have had sequential
HIV cultureshave become culture negative. Toxicity has been mild with no
grade 2 toxicity seen in any patients. Side effects have been limited to
fever, chills, malaise and local skin reactions at the site of injection.
Preliminary results of T-cell subsets are presented below.
Time on Study (months)
1 (n=13) 2 (n=10) 3 (n=4) 4 (n=2)
pre Rx 1048+628 1151+680 991+274 957+378
post Rx 747+500 905+611 1208+830 1301+535
pre Rx 220+203 273+201 384+187 236+69
post Rx 156+150 148+167 348+173 202+44
Betaser Interferon appears to be a well tolerated treatment with in
vivo activity against AIDS related Kaposi's Sarcoma.
Leu 3
Leu 2
TP230 Treatment with high doses of immunoglobulins in HIV-rela
ted thrombocytopenia.
ADRIANO LAZZARIN*, L. VOLTOLIN* , C. NEGRI*, P. CROCCHIOLO* , M.
GALLI*, S. CENZUALES** , *Milan University Clinic of Infectious
Diseases; "Blood Transfusion Centre - "L. Sacco" Hospital, Milan,
Italy.
In our Clinic a severe idiopathyc thrombocytopenia (<15.000 PLT
x mm ) was observed during the early phases of HIV infection in
21 out of 451 patients affected with LAS. These patients were in
the most part asymptomatic. We treated with human immunoglobulins
(0.4 g/kg daily for 5 days - Venoglobulines Merieux) 10 thrombocy_
topenic patients (7 males, 3 females; age 20 to 27) presenting
with hemorrhagic symptoms (3 purpuras, 3 metrorrhagias, 2 epista-
xis and 2 hematomas due to microtraumas). A rise of platelets
count was recorded since the third day of treatment; by the fifth
day nine patients were showing a four-fold increase of their pla-
telets (PLT x mm 55000 + 9000). Platelets, however, returned to
initial values 3 to 4 weeks after therapy was discontinued. In all
but one patient (a woman with metrorrhagia) clinical symptoms sub
sided. In conclusion, i.v. infusion of immunoglobulins at high
doses in HIV-positive patients with thrombocytopenia seems to re-
present a rather effective therapeutic approach; in our view, how
ever, it should be considered in symptomatic patients only.
100
TUESDAY, JUNE 2
TP231 Pharmacokinetics of Oral Azidothyraidine (AZT) in 5 AIDS Patients.
BARBARA J. CHINNOCK. C. FLETCHER, F. RHAME, B. CHACE. C. SULLIVAN,
H.H. BALFOUR, JR., University of Minnesota, Minneapolis, MN.
Limited pharmacokinetic data are available on AZT. We studied 5 AIDS
patients (4 male, 1 female; age range 19-32 years) receiving AZT after
recovery from an initial bout of Pneumocystis carinii pneumonia. 200 mg AZT
was administered PO every 4 h. Patients had sera drawn for pharmacokinetic
analysis on the first dose according to the following sampling scheme: pre-
treatment, 10, 20, 30, 45, 60, 90, 120, 180, 240 mins . Fifty sera were
analyzed for AZT by HPLC . AZT serum cone. (Cp)-time data were subjected to
model independent pharmacokinetic analysis. Mean pharmacokinetic parameters
(n - 4) were: AUC, 4.09 + 1.29 /M hr; T 1/2, 0.6 + 0.25 hr; TBC/F. 3260 +
896 ml/min. The average Cp max was 3.54 ^M, which occurred 0.75 - 1.5 h
post AZT dose. Cp min at 4 h. was < 0.5 jiM in 4/5 patients. One patient
was treated separately. His AUC (10.18 /iM hr) and TBC/F (1230 ml/min) were
substantially different (by a factor of >2) than the other 4 patients. This
could not be explained on the basis of renal or hepatic dysfunction and may
be a result of concurrent drug therapy affecting AZT metabolism. Further
investigations are in progress. The previously estimated minimum level for
in vitro antiviral effect with AZT is 1 /iM. In our 5 AIDS patients
receiving 200 mg PO q 4 h, AZT Cp were only above 1 /iM for 1-1 1/2 h out of
each 4 h dosing interval. This may not be sufficient to control viral
replication in all patients and, if dosage is reduced due to toxicity we
predict Cp will almost always be below 1 jiM.
TP234 Tne Inactivity of Anti-HIV Positive Blood Components
STEVEN KLEINMAN*, THE TRANSFUSION SAFETY STUDY GROUP**,
♦American Red Cross, Los Angeles, CA, **other participating
institutions.
To determine transmissibility of HIV by transfusion, the Trans-
fusion Safety Study retrospectively tested donor sera collected in
late 1984 and early 1985 in five areas with high AIDS prevalence.
The rate of anti-HIV positivity among 91 recipients of blood com-
ponents from anti-HIV (+) donors (by EIA, IB, and RIP) was 89%
12-18 month post-transfusion. The 10 anti-HIV(-) recipients did
not differ from the anti-HIV (+) by age or underlying disease. By
blood component type, positivity rates were 91% (51/56) for RBC,
100% (10/10) for platelets, 83% (5/6) for WB, 100% (2/2) for leu-
kocyte poor blood, 85% (11/13) for FFP, and 100% (2/2) for cryo-
precipitate. One anti-HIV (-) recipient and one anti-HIV (+) reci-
pient received components from the same donation. Two of two re-
cipients of washed RBC were anti-HIV(-); recipients of previous
donations by the same donors were anti-HIV (+), indicating the
potential infectivity of these donors. A third anti-HIV(-) reci-
pient received only a few ml of RBC. Two other anti-HIV (-) reci-
pients received components (FFP and RBC) from the same donor, sug-
gesting that this donor was not infectious. These findings have
important implications for assessing the importance of anti-HIV
screening, the risks to recipients of components from anti-HIV(+)
donors, and for establishing lookback policies.
(Supported by Contracts No. N01-HB-4-7002 and N01-HB-4-7003 of
the National Heart, Lung, and Blood Institute.)
TR232 The Efficacy of Azidothymldine in the Treatment of Patients with AIDS
and AIDS-related complex: a double-blind placebo-controlled trial.
THE AZT COLLABORATIVE WORKING GROUP.
To determine the efficacy of Azidothymldine, AZT, a double-blind placebo-
controlled trial of oral AZT was conducted in 282 patients with AIDS and AIDS-
related complex at 12 medical centers. Patients were prestratified according
to CD4 cell numbers and randomly assigned to receive a capsule containing
either 250 mg of AZT or placebo every 4 hours for a total of 24 weeks. The
study trial was terminated prematurely in September, 1986. One-hundred forty-
five patients received AZT, and 137 patients received placebo. Twenty-seven
patients had completed 24 weeks of the study; the remainder had completed at
least 8 weeks. Nineteen placebo recipients and 1 AZT recipient died during the
study (p<0.001). This increased likelihood of survival was comparable for
patients with AIDS and AIDS-related complex who received AZT. Forty-five
patients receiving placebo developed opportunistic infections compared to 24
receiving AZT (p<0.001). Six AZT recipients and 10 placebo recipients
developed Kaposi's sarcoma (p>0.20). A statistically significant increase in
the number of CD4 cells was noted in patients receiving AZT compared to those
receiving placebo (p<0.001). After 12 weeks, the number of CD4 cells among AZT
recipients with AIDS returned to pretreatment values. Similar trends in CD4
cell numbers were also noted among AZT recipients with AIDS-related complex
but were less prominent. Twenty-nine percent of patients receiving AZT
developed cutaneous hypersensitivity reactions compared with 9% receiving
placebo (p<0.001). AZT appeared to prolong and Improve the quality of life in
a select group of patients with AIDS and AIDS-related complex over a 24 week
period.
TR235 Improved Anti-HIV Screening Assay Using Recombinant Antigen
Based Conjugate
LARRY MIMMS, B. BRAUN, S. W0R0BEC, L. PAUL, S. EARLE and L. VALDIVIA,
Hepatitis/AIDS R4D, Abbott Laboratories, Abbott Park, Illinois 60064
Two major antigenic proteins of HIV, ENV and CORE, have been cloned and
expressed in E. coli by recombinant DNA (rDNA) methodology and purified
by immunoaffini ty chromatography. These purified antigens were coated
onto polystyrene beads which are used to capture anti-HIV from the
specimen. Anti-HIV bound to the beads was detected in the assay using a
probe solution containing rDNA HIV antigens coupled to horseradish
peroxidase (HRPO). Unlike currently licensed anti-HIV tests, this assay
requires no sample dilution and is capable of detecting IgG, IgM and
IgA. This recombinant antigen based screening assay is 8 to 64 fold more
sensitive than current anti-HIV tests and shows significantly improved
specificity. When 125 sera reactive by the current anti-HIV test but
negative by Western Blot were tested, all were negative in this assay.
68 AIDS sera and 250 sera testing positive by current EIA and Western
Blot were reactive in this assay.
Serial bleed studies indicate that the rDNA based screening assay can
detect anti-HIV seroconversions significantly sooner than current tests.
As configured, this assay does not allow differentiation between
anti-CORE and anti-ENV reactivity. rDNA CORE and ENV may be separately
coated onto beads and coupled to HRPO to make tests which will
discriminate anti-CORE and anti-ENV positivity.
TP233 Anti-HIV Seroconversion in Haemophiliacs Receiving Heat-Treated
Concentrates.
E.J. MILLER, P. A. LILLEY, D.S. THOMPSON, P.D. GRIFFITHS, P.B.A. KERN0FF.
Departments of Haematology and Virology, Royal Free Hospital, London, and
Luton and Dunstable Hospital, UK.
In the UK, about two thirds of factor VIII used is imported commercially
from the USA. The remainder, and all factor IX, is derived from domestic (NHS)
volunteer plasma. In December 1984, when heated concentrates were first
introduced, 78?o of patients attending the RFH Haemophilia Centre who had been
exposed to US commercial factor VIII in the preceding six years were anti-HIV
seropositive. All 52 patients who had only received NHS concentrates were
seronegative. At that time at least, therefore, HIV contamination appeared
much less likely in domestic products. 82 patients seronegative at the time
of their first exposure to heated products have been followed to December 1986.
Of the 30 who received factor IX concentrate, all remain seronegative (total
35 exposure years). Of the 52 who received VIII concentrate (31 'wet heated'
commercial, 18 'dry heated' NHS, 3 'dry heated' commercial) 49 remain sero-
negative (64 exposure years). 2 patients receiving 'wet heated' commercial
VIII seroconverted within 4 months of starting treatment with heated product.
However, both had received incriminated lots of unheated NHS VIII before
changing to heated factor VIII. A third patient, treated with 'dry heated'
commercial VIII derived from non-anti-HIV screened donors, seroconverted 8-10
months after starting heated product. Although this patient had also
previously received an incriminated lot of unheated NHS concentrate, HIV
transmission by the'dry heated' commercial concentrates seems more likely.
Tppoc Prognostic Importance of Western Blot HIV Antibody Patterns in HIV
Antibody Positive Hemophiliacs
MARGARET V. RAGNI*. T.A. O'BRIEN**, J.A.SPERO*, J.H. LEWIS* *Department of
Medicine, University of Pittsburgh School of Medicine, Central Blood Bank of
Pittsburgh, Pittsburgh, PA, and **DuPont Co., Wilmington, DE.
Antibodies to specific HIV viral antigens were measured by a Western blot
system using biotin-avidln detection (Biotech Research Labs, Rockville MD) on
36 HIV antibody positive hemophiliacs (HTLV-III ELISA, DuPont) on whom serial
samples were available between 1977 and 1986, representing 2 to 8 years
following seroconversion. Of these, 20 were Class IV (9 AIDS, 7 ARC, 4 other)
and 16 were asymptomatic. At seroconversion, antibody to p24 (gag) appeared
first, followed by antibody to gp41 (env); antibody to p55 (gag) was weak or
absent at seroconversion in 26, developing one to three years after
seroconversion in six of 26 or not at all in three of 26. Thirteen of 20 Class
IV (8/9 AIDS, 2/7 ARC, 3/4 other) hemophiliacs lost (or never developed)
antibody to one or more HIV gag (pl5, 24, 55) or pol (p31, 53, 64) antigens,
as compared with one of 16 asymptomatic hemophiliacs (X = 12.81, p<-001).
The development of AIDS was preceded (one to four years) by the loss/lack of
antibody to pl5 (in 5 AIDS patients), p53 (in 4), p24 (in 3), p55 (in 3), p64
(in 3), and p31 (in 2), each p < . 05 as compared with non-AIDS patients.
Absence of antibody to more than one (2-5) HIV antigens occurred in five of
eight AIDS patients. The single AIDS patient with no loss/lack of antibody
was the only one with lymphoma and no opportunistic infection. In conclusion,
the loss or lack of antibodies to gag (pl5, 24, 55) or pol (p31, 53, 64) HIV
gene products appears to be associated with and occurs within one to four
years before the development of AIDS in HIV antibody positive hemophiliacs.
101
TUESDAY, JUNE 2
TP237 Frequency of Recent Blood Donation in HIV Infected Soldiers
* JOHN G. MCNEIL*, J. WHAUN**, P. RENZULLO*, J. BUNIN*. J. BRUNDAGE*,
*Division of Preventive Medicine, ** Department of Virus Diseases, Walter
Reed Army Institute of Research, Washington, D.C.
In October 1985, the Department of Defense mandated screening all active
duty soldiers for the presence of antibody to human immunodeficiency virus
(HIV). Data assessing frequency of recent blood donation by HIV infected
soldiers and rate of infection in product recipients has important disease
control implications.
One hundred seventy-four HIV infected soldiers from a broad geographic dis-
tribution were ascertained through general (not blood bank) screening. Each
soldier was evaluated for a history of blood donation between March 1983 and
April 1985. Twenty-six percent (45/174) reported donating at least once
during that period; a rate almost ten times higher during this interval than
reported for persons subsequently diagnosed with ARC and AIDS. A centralized
effort to "look back" at living recipients of components donated by HIV-Ab
positive soldiers ascertained through blood bank screening is in operation.
Seven living recipients have been evaluated; 5 (71%) are HIV-Ab positive by
western blot. Two recipients were infected as long as 22 months before deter-
mination of positivity in an asymptomatic donor. Although 70% of HIV infec-
tions in the Army are determined by methods other than blood donor screening,
"look back" does not currently include prior donations from soldiers deter-
mined HIV-Ab positive by other than blood bank screening.
These data describe a situation with far-reaching disease control conse-
quences. Increased effort to evaluate and improve donor self-deferral and
"look back" is essential.
Tp240 Confidential Exclusion of Donated Blood: Evidence for Donor
Compliance. J. PINDYCK, B. HOSEIN, A. WALDMAN, W. YING, M. LOWY,
and C. BIANCO, The New York Blood Center, New York, N.Y. 10021.
Recognition that AIDS was a disease transmissible by blood necessitated
introduction of stringent measures to ensure safety of the blood supply.
Early in 1983, The New York Blood Center Introduced a questionnaire which
allows individuals who appear medically acceptable as blood donors to review,
before their donation, information about high risk of exposure to AIDS. They
are then asked confidentially to designate their donations "for transfusion"
or for "laboratory studies only". This system has been maintained in addition
to the ELISA assays for antibodies to HIV, introduced in April of 1985,
because the population of self-excluders may contain individuals who are
exposed to HIV, but have not yet developed detectable antibodies.
Analysis of results from 459,165 blood donations show that the 98.2% who
designated their units "for transfusion" had HIV antibody prevalence of
0.09%, while the 1.8% who designated their units "for studies only" had a
prevalence of 2.1%. The prevalence of Hepatitis B surface antigen was 9
times higher among "for studies" donors than among "for transfusion" donors.
These differences were highly significant (p<0.001) Indicating that many
donors are aware of their higher risk of exposure to HIV, find it difficult
not to donate at a blood drive, and therefore designate their units "for
studies only", in compliance with systems designed to improve the safety
of the blood supply.
TDOQA HIV Infection in the Edinburgh Haemophiliac Cohort
CHRISTOPHER A. LUDLAM* , R.J.G. CUTHBERT*. D. BEATSON***, F.A.
LAINSON**, J.F. PEUTHERER**, CM. STEEL ***. *Dept. of Haematology, Royal
Infirmary Edinburgh. **Dept. of Bacteriology, University of Edinburgh. ***MRC
Clinical Population and Cytogenetics Unit, Western General Hospital, Edinburgh.
We previously reported on a cohort of 33 haemophiliacs who were transfused
in April 1984 with a single batch of factor VIII contaminated with HIV. In
our initial study we found that 15 patients had developed anti-HIV antibodies,
but we have since identified 3 later seroconverters. We now report a 4 year
follow up of this cohort.
Patients who became seropositive received significantly more bottles of the
contaminated batch of factor VIII. All patients receiving more than 30 bottles
became seropositive. The annual factor VIII consumption was significantly
greater in the seropositive group. Thirteen patients developed HIV-specific
antibodies within 15 weeks of exposure to the contaminated batch, whereas 4
patients developed antibodies more than 20 weeks after exposure, and one
patient between 11 and 36 weeks after exposure. There were no differences in
total dose of batch received, annual factor VIII consumption, pre-exposure
T4/T8 ratios or absolute T4 counts between early and late seroconverters.
Mean T4 counts in the seropositive group have declined from 0.73 x 10 /l before
exposure to 0.33 x 10 A at the time of writing. Mean T4 counts in the sero-
negative group have remained static at 0.77 x 10 /l . In the seropositive group
one patient has AIDS, 3 have ARC, 3 have PGL and one has thrombocytopenia. Ten
seropositive and all the seronegative patients remain asymptomatic.
TR241
UNIVERSI
In a p
IgG leve
1986) we
HIV posi
In all
T cell d
hi gher 1
nega t i ve
PWM stim
Staph. An
posi ti ve
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MEC
RAJ
TY DE
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Is in
have
ti ve
posi
epend
evel s
pati
u 1 a t i
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pati
ief.
HANISM
AN MAD
PT. OF
us stu
HIV p
i n v e s
(asymp
tive p
ant B
of sp
ents r
on was
Cowan
ents.
of .57
OF B
HOK,
MEDI
dy we
o s i t i
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ontan
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The
wi th
HIV POS
UNSTIM STIM
320 290
CELL DYSFUNCTION IN HAEMOPHILIA
JAGRACIE GDO LOWE CD FORBES
CINE GLASGOW ROYAL INF .SCOTLAND
showed a significant increase in serum
ve haemophiliacs ( INT. CONG. AIDS PARIS
ed the mechanism of this increase in both
ic) and HIV negative haemophiliacs,
ts the increase was polyclonal. Using the
mitogen PWM our results show significantly
eous IgG secretion in both positive and
ve to normals. No further increase on
Using the T independent B cell mitogen
n 1, no significant change was seen in
T 4 cnt in HIV positive pts. showed
spontaneous IgG secretion.
CONTROL
UNSTIM STIM
97 110
HIV NEG
UNSTIM STIM
115 128
97
80
STAPH 320 370 115 115
medians are shown Non parametric stats.
The B cell dysfnc. in HIV positive haemophiliacs appears to b'e
both due to T4 cell depletion and a intrinsic B cell defects.
TP23Q Transfusion-Associated Transmission of Human Immunodeficiency
virus (HIV) from a Seronegative Donor - Coloraoo
CATHY A. RAEVSKY*. B. DILLON*, A. SCOTT*, F. WOLF*, D. COHN**, *Colorado
Department of Health, **Denver Disease Control, Denver, Colorado, U.S.A.
In November 1985, a male donor at a Colorado blood collection facility
was seropositive for HIV antibody (ELISA and Western Blot) although
previously donated units (August and April 1985) were ELISA negative.
Recipients of the April 1985 donation were seronegative by ELISA when
tested in May 1986.
The 2 recipients of the August donation were subsequently found to be
seropositive. Recipient #1, who had no other risk factors for HIV
infection, received units from 15 different donors. Recipient #2, who
had other risk factors for HIV infection, received units from 3
different donors. Another donor (seronegative April 1986) was common to
both August recipients. Of the remaining 14 donors, 12 resided in
Colorado and were seronegative when retested 5 months or more after the
August donations. Two donors outside Colorado have not been tested.
Interviews of the seropositive donor and recipients suggest donor
infection through sexual contact 12 weeks or less prior to his August
donation when he may have been falsely negative on ELISA or viremic but
without detectable antibody. Sexual contacts (18) of the seropositive
donor and 2 recipients were identified. Of those in Colorado (11), all
were located, 9 tested and 2 seropositive. Contacts outside Colorado (7)
have not been notified.
This is the first reported case of HIV transmission from a sero-
negative blood donor since screening for HIV antibody in blood
collection facilities.
TP242 Detection of Human T-Cell Lymphotroplc Virus-I (HTLV-I) Antibodies
by an Enzyme Immunoassay (EIA). A.J. B0DNER*. A.J. CORRIGAN*, S.S.
ALEXANDER*, T.S. CLEMENT*, T.A. O'BRIEN**, W.R. FREDERICK***, et al., *Biotech
Research Laboratories, Inc., Rockville, MD, **Du Pont, Wilmington, DE, ***
Howard University Cancer Center, Washington, D.C.
An EIA has been developed to screen blood components for antibodies to
HTLV-I, the virus linked with Adult T-Cell Leukemia (ATL) and implicated in
other diseases as well. The format of the HTLV-I test is identical to that of
the Du Pont HTLV-III antibody screening test, allowing the two tests to be
used simultaneously. Simultaneous testing for HTLV-I and III antibodies may
become necessary if the risk of contracting HTLV-I infection from contaminated
blood products is eventually judged unacceptably high. Simultaneous screening
may also become common clinically if the prevalence of dual infection with
HTLV-I and III increases, either through HTLV-III infection of previously
HTLV-I infected individuals or through spread of HTLV-I by the same risk fac-
tors as for HTLV-III. Preclinical evaluation of the HTLV-I EIA confirms that
it is both sensitive and specific. 24 of 24 ATL patients were reactive, while
only 4 of 1,752 (0.2%) individuals at low risk for HTLV-I infection were re-
active. HTLV-III antibodies are not reactive in the HTLV-I EIA. Sera from a
group of intravenous drug abusers were screened with the HTLV-I and III EIAs
and western blot (WB) tests. 10 individuals reactive on the HTLV-III WB were
nonreactive on the HTLV-I EIA but reactive on the HTLV-III EIA. 9 individuals
reactive on the HTLV-I WB are reactive on the HTLV-I EIA but nonreactive on the
HTLV-III EIA. Another 10 individuals reactive on both HTLV-I and III WB were
reactive on both the HTLV-I and III EIAs. The HTLV-I EIA and a confirmatory
WB test are currently being clinically evaluated at several blood research
centers in the United States.
102
TUESDAY, JUNE 2
TP243 SCREENING OF VOLUNTARY BLOOD DONATIONS FOR ANTIBODIES TO HUMAN
IMMUNODEFICIENCY VIRUS (anti-HIV) - EIGHTEEN MONTHS EXPERIENCE
S. Mankikar, J.B. Derrick, B.K. Buchner, P. Humphreys, M.G. Davey, Canadian
Red Cross Blood Services, National Headquarters, TORONTO, ONTARIO
By November 1986 the Canadian Red Cross had screened 1,25 million blood
donations for anti-HIV using the Abbott enzyme Immunoassay (EIA) . Blood found
repeatedly reactive by EIA is discarded and the antibody status is confirmed
by Western blot (WB) . The data Indicate that during the first six months of
testing, initially EIA reactive, repeatedly EIA reactive and WB positive rates
gradually decreased. During the subsequent seven months, however, there was
a gradual increase in all three rates. It is not clear whether this Is due to
modifications in the test system or to changes in the donor population. Data
was also analyzed In terms of geographic location, sex, age and frequency of
donation. Prevalence of anti-HIV in urban donors was approximately four times
greater in rural donors. Although the highest incidence of AIDS is reported in
the Province of British Columbia, the highest anti-HIV prevalence was observed
in the Province of Quebec. The highest anti-HIV prevalence was in male donors
between 30-39 years of age. Nationally, the WB rate fluctuated from a high
of 0.034% in November 1985, to a low of 0.008% in May 1986. The. data indicate
that in spite of the inherent problems with the WB system it is still very
important in establishing the donor antibody status. Data which will have been
accumulated on the screening of over 1.82 million donations by the end of
April 1987 will be analyzed for presentation of additional Information.
TP246 FOLLOW-UP OF WESTERN BLOT POSITIVE BLOOD DONORS- VICTORIA AUSTRALIA .
*K.McGrath, **A.Mijch, **W.Maskell, **T. Howard, *J. Morris,
**C. R.Lucas et al. (**Fairfield Hospital, Melbourne Australia. *Victorian
Blood Transfusion Service, Victoria Australia.)
Nationwide blood donor screening was introduced in Australia on 1st May 1985.
In Victoria sera repeatedly reactive by Enzyme Immuno Assay (EIA) (Electro
Nucleonics Inc.) were referred to the State Reference Laboratory for
confirmatory testing by Western Blot (WB) . Sera were regarded as positive if
precipitin bands were detected at p24 and/or at p41 as recommended by C.D.C.[]
Of 214,699 donors screened in the first 12 months 924 (0.4%) were repeatedly
reactive by EIA; 15 of these(0 .0065%) were positive by WB (p24 in 5, p41 in 2,
p21 plus p41 in 7) . (] Fourteen were referred for clinical assessment (10F &
4M) . Their ages ranged from 21 to 49 years. No donor admitted to risk factors
for HIV infection; 10 were married (8F & 2M) and one divorced (F) . All were
asymptomatic. One donor had generalised lymphadenopathy and physical
examination was normal in the others. [] Among spouses, tests for anti-HIV by
EIA were negative in all 10 and by WB in the 7 tested. [] Of 27 cultures for
HIV from 14 donors only one, from the donor with lymphadenopathy, was positive.
[J The 14 WB positive donors have been reviewed on 3 to 8 occasions over 4 to
17 months. Each has remained well and lymphadenopathy has not been detected in
the follow-up examinations of the donor in whom it had been initially present.
[] In subsequent serological testing 5 have become negative by EIA and 13 of
14 remain positive by WB (p24 in 7, p41 in 2, p24 plus p41 in 4 ) .
Our experience suggests that in this population the majority of donors reactive
by WB test are not infected with HIV. This has resulted in modification of both
WB interpretation criteria and blood donor notification policy in Victoria.
TP244 HlV-seroposi tive hemophilia cohort in follow-up since 1983:
Virologic, immunologic and clinical relationships.
GAETANO GIRALDQ*. E. BETH-GIRALDO*, R. DE BIASI**, E. MIRAGLIA**, G. CASTELLO*
S. CEPARANO* et al . , *Ist Naz Tumori , **Ctr Med Soc Hemophilia, Naples, Italy.
Since longitudinal studies are needed to establish the effect of HIV infec-
tion on the immune system, we have chosen to follow-up a cohort of patients
with coagulation defects (>245 subjects). While 41.5% of 79 HIV-seropositive
hemophiliacs have a LAS and 11.4% (9 patients) a lesser AIDS, 5.1% (4 patients)
have come down in 1986 with AIDS (3 AIDS/001, 1 AIDS/KS). Comparison of case/
control matched HIV-seropositive, symptomatic subjects with seronegative,
asymptomatic ones revealed a significant reduction of T-helper to T-suppressor
ratio (p<0.001) and absolute T-helper cell counts (p<0.001) as well as an in-
crease of T-suppressor cells (p<0.01) in the seropositive group. Furthermore,
a significant increase of urinary neopterin levels was observed in that group.
Analysis of the antibody profile to herpesviruses showed elevated anti-EBV-VCA
titers (IgG) with a 4-fold increase of geometric means in case/control matched
seropositive subjects. Moreover, they have significantly more (p<0.005) IgM
antibodies to EBV-VCA. There was no association however with antibodies to CMV,
HSV-1 and HSV-2. These findings strenghten the concept that LAS may be the
result of an important interaction between EBV and HIV in hemophiliacs, since
both viruses may be responsable for polyclonal B-cell activation.
Furthermore, data will be presented on correlations between neutralizing
antibodies to HIV, antibody detection by 1 1 F and Western blot analysis com-
pared to immunological profiles and clinical evolution of this AIDS risk groupi.
TP247 Risk Factors for Antibody to HIV in New York Blood Donors:
Validation of AIDS Risk Classification and of Confidential Donor
Self-Exclusion at the Time of Donation
CHARLES S. RABKIN*, N. VAN DEVAMTER**, W. E. EWING***, and J. PINDYCK** ,
*CDC, Atlanta GA, **NY Blood Center, ***NYC Dept. of Health, New York NY.
We studied blood donors in the New York metropolitan area, a region of high
incidence of AIDS, to determine prevalence of antibody to HIV, risk factors
for seropositivity , and potential sexual transmission. From April 1985 - May
1986, the Greater New York Blood Program collected 470,000 blood units, 8000
of which were confidentially donor-designated to be used for laboratory
studies only. Anti-HIV by Western Blot was present in 337 (0.08%) units
donated for transfusion and in 133 (1.6%) units donated for studies (relative
risk = 20). Two hundred-fourteen seropositive donors from both groups have
been interviewed, 169 men and 45 women. One hundred twenty-nine (90%) of 144
donors for transfusion and all 70 donors for studies had known risk factors
for AIDS: male homo- or bisexuality (62%), intravenous (IV) drug use (4%),
male homo- or bisexuality and IV drug use (6%), blood transfusion (1.4%), and
sexual contact to a member of an AIDS risk group (15%). Fifteen seropositive
donors, 12 men and 3 women, had no known AIDS risk factors. None of the 15
had received hepatitis B vaccine, acupuncture , or artificial insemination,
and none was a health care worker; 2 had received immune globulin since 1978,
and 5 reported prostitute contact 1 to 5 years before interview. Twenty-two
sex partners of seropositive blood donors of opposite sex were also studied;
anti-HIV was detected in 2 of 3 bisexuals, in 1 of 2 IV drug users, and in 1
transfusion recipient , but not in 16 heterosexual partners without other
risk. Despite a high endemic incidence of AIDS in the New York area, anti-HIV
is rare in blood donors, most seropositives are in known AIDS risk groups,
and new risk factors are not apparent in seropositives not in risk groups.
TP245 UV-Laser Inactivation of Virus in Blood Products.
KRISTINA N. PRODQUZ*. J.C. FRATANTONI*, N.A. LOWEN* ,
P. ALBRECHT* and R.F. BONNER**, FDA* and NIH**, Bethesda, MD.
Evaluation of UV radiation to selectively inactivate virus in
blood products was conducted by uniform treatment of attenuated
poliovirus, platelets and plasma with 40 nsec pulses of 308 nm
(UVB) radiation emitted by a XeCl excimer laser. Dose rates and
doses of UVB were varied from 0.1 to 1.3 MW/cm2 per pulse and
0.51 to 53.7 J/cm2, respectively. Virus and platelet samples
were prepared in isotonic phosphate buffer containing 5% albumin.
Biologic activities measured included: 1) cytopathic effect of the
virus; 2) platelet aggregating activity; 3) spontaneous release of
serotonin from platelets; and 4) plasma prothrombin time (PT) and
partial thromboplastin time (PTT) . Poliovirus showed a dose-
dependent titer decrease of 4 to 6 log10 with UVB=10.8 to 21.5
J/cm2. Although rate and amplitude of platelet aggregation
decreased in a dose-dependent manner over the range of UVB doses
used, at UVB=10.8 to 21.5 J/cm2 aggregation amplitude was
decreased 20-30%. At UVB=10.8 J/cm2 serotonin release was 5%
above control, while at the highest dose of UVB (53.7 J/cm2)/
10% was released from irradiated platelets. Plasma proteins were
minimally affected by UVB=10.8 J/cm2: PT 10% above control, PTT
7.5% above control. With UVB=21.5 J/cm2, PT and PTT of irradi-
ated plasma were <20% above control. The observed inactivation of
a hardy virus by doses of UVB which do not abolish the biological
activity of platelets or plasma proteins suggests that UV-laser
treatment is a potential method for diminishing the viral
bioburden of blood products containing anucleate cells.
TP?dft Analysis of discrepant anti-HIV ELISA reactives. D. THOMAS,
IT.LHO F K^ nujjdqj^ n> ZIMMERMAN, D. LARSON, L. COWAN, and S. W1LHELM,
Electro-Nucleonics, Columbia, MD 21046.
Conflicting results are sometimes obtained in tests for the presence of
antibody to HIV in plasma and serum samples, depending on the particular kit
being used in the screening test. We examined samples from thirty-three blood
bank donors with histories of repeatedly reactive plasma. Of 33 samples
received, 19 were reported to be repeat positive when analyzed In a
competitor's test at the blood bank. Comparative testing with reagents from
two other manufacturers showed that Inconsistencies were present within the
ELISA data generated from the different kits. We have used 3 independent
methods (Western blot, IFA, and competition with labelled anti-HIV human
antiserum) to further analyze these plasma samples. For seven of the eight
samples which demonstrated Western blot reactivity, the results indicated the
presence of antibody only to a protein with M = 24,000. The eighth sample
(sample 5) contained antibody to other HIV proteins in addition to p24. Only
2 of the 33 samples appeared positive by IFA. These IFA results were
confirmed independently by an outside laboratory. The IFA-negative samples
could not compete with authentic anti-HIV human antlsera for binding to plates
that contained bound HIV protein. In this same competition assay, however,
sample 5 showed complete inhibition of binding; sample 14 showed partial inhibi-
tion. We conclude that the use of Western blot as a confirmatory test may
be misleading in the case of "p24 only'1 reactivity, and all but 2 of the 19
samples originally designated as repeat reactives must be considered to be
false positives.
103
TUESDAY, JUNE 2
TR249 AIDS STUDIES IN KENYAN HAEMOPHILIACS
Dr. G.M. Kltonyl. M.R.C.Path., Prof. T. Bowry, M.R.C.Path
Prof. E.G. Kasili, M.D., M.R.C.Path., University of Nairobi, Kenya.
Fifty one consecutive black Kenyan patients with haemophilia A
CtO), Christmas disease (8) and Von Willebrand' b disease (3) were
tested for HTLV-III antibodies uith an ELISA test. Positive resultB
were confirmed by Western blot analyais. 12 of the UO patients (30%)
with haemophilia A were seropoaitlve. None of the patients uith
Christmas disease or Won Willebrand ' s disease were seropositive. Our
results indicate a link between the use of commercial factor UIII
concentrates and seropositivity.
These studies also indicate that the rate of exposure of the
Kenyan haemophiliaca to the HLV-III virus is not as high as reported
elsewhere. ThiB is probably related to limited use of factor con-
centrates in Kenya due to the prohibitive cost of the concentratea.
done of the 51 patients has clinical AIDS but k seropositive patients
have extrainguinal lymphadenopathy.
Although there are many studies on sexually transmitted AIDS in
black Africa, there are very few reports on AIDS studies on haemo-
philiacs. This paper represents one of the few reports on AIDS
studies in black African haemophiliacs.
Ongoing work includes T-cell subset studies and attempts to
isolate the AIDS virus from the patient.
TP250 HIV Infection: Surveillance of Heat Treated Factor VIII in the UK
Criteria Based on Retrospective Studies of Unheated Factor
J. CRASKE* , T. SNAPE**, C.R. RIZZA, ROSEMARY SPOONER***, ANDREW PEARSON****,
*PHLS , Manchester, **Blood Products Laboratory, Elstree, Herts, ***Haemophilia
Centre, Churchill Hospital, Oxford and the UK Haemophilia AIDS Group,
****CDSC, PHLS, London.
Criteria are given for defining a transmission event of HIV from heat
treated factor VIII and IX concentrates to man. Retrospective information
was obtained appertaining to the use of seven batches of unheated factor VIII
and one batch of factor IX concentrate in patients from England. Seven out
of 22 (32%) patients seroconverted with the batch of factor VIII for which
most information was available. The attack rate of HIV antibody negative
haemophiliacs receiving this batch was seven out of 12 (58%) . There were 13
seroconversions amongst the 179 (7.3%) haemophiliacs who had received
factor VIII concentrates from one of seven batches. One patient seroconverted
of 24 (4%) who had received factor IX concentrate from one batch for which
there was information. Three individuals had HIV antibody before exposure to
this batch so the TRUE ATTACK RATE was 1 in 17 (6%) . The batches of unheated
concentrate were used between 1981 and 1985. Testing of recipients started
in the autumn of 1984. The total number of seroconversions was 14 out of
203 patients (7%) and the attack rate corrected for known prior exposure in
36 individuals was 14/167 (8%) . A strategy for the surveillance of heat
treated factor is proposed.
104
WEDNESDAY, JUNE 3
Plenary Session IV
W.I.I public Health Measures for Prevention and Control of AIDS
DONALD R. HOPKINS, M.D., Centers for Disease Control, Atlanta, Georgia, USA
Epidemiological surveillance, epidemiological research, and laboratory
research are the basis for existing and potential interventions to help
prevent and control the unprecedented threat posed by AIDS and HIV
infection. Dissemination of information to the public, health education,
individual counseling and testing of persons whose actions or
circumstances put them at Increased risk of infection, prevention and
treatment of I.V. drug abuse, and serological screening of donated blood,
sperm and organs are the main public health measures which are now
available. The extent of application of these measures varies widely in
different target U.S. populations. All require thorough evaluation.
Asymptomatic infectious persons are the largest source of new infections;
they need to know that they are infected, and be counseled as quickly as
possible. Even partly successful drugs to delay onset of symptoms in
infected persons would provide a significant new incentive for potentially
infected persons to be tested voluntarily, but the scope of this pandemic
will be decided before any vaccine or curative therapy is available for
general use, if ever. Strong informed leadership is required at all
levels to minimize irrelevant distractions and keep attention focused on
the most important issues in this life and death struggle .
W.1.4 Research on HIV infection among intravenous drug users:
State of the art and state of the epidemic.
Don C. Des Jarlais, New York State Division of Subtance Abuse Services,
New York, N.Y.
As the largest group of heterosexuals infected with HIV in the United States
and Europe, intravenous drug users will play a key role in the future of the
AIDS epidemic in those regions. This presentation will review emerging
critical issues in HIV infection among IV drug users. In epidemiology there
is not yet a satisfactory explanation of the great geographic variation in
seroprevalence rates nor a good understanding of the efficiency of
heterosexual transmission to non-IV drug users. In natural history, HIV
infection appears to lead to a variety of fatal outcomes in addition to
surveillance definition AIDS; co-factors for infection outcomes need more
intensive study. In prevention, basic AIDS education does lead to risk
reduction, but methods of increasing risk reduction have not yet been fully
assessed.
Epidemiology — Heterosexual Transmission
W.1.2
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
Multicenter Study of HIV Antibody in U.S. Prostitutes
H.W. DARROW, J.B. COHEN, J. FRENCH, P. GILL, R.K. SIKES, J.
WITTE,
W.2.1
et al., CDC Collaborating Group on HIV in Selected Women, Atlanta, GA, USA.
To assess seroprevalence of antibody to human immunodeficiency virus (HIV)
and risk factors for a positive anti-HIV test, we are studying women who have
engaged in prostitution since 1978. Prostitution is defined as the exchange of
oral, vaginal or anal sexual exposures for money or drugs. Serum is tested for
HIV antibody by an enzyme immunoassay supported by Western blot assay, for
hepatitis B seromarkers by radioimmunoassay, and for antibody to syphilis by
RPR and MHA-TP, confirmed by FTA-ABS . As of January 28, 1987:
Number positive/Number tested' (percent)
Research Site
Anti-HIV
Hepatitis B
4/20 (20.0)
12/54 (22.2)
26/82 (31.7)
78/109 (71.6)
41/102 (40.2)
93/169 (55.0)
12/12 (100.0)
Syphilis
0/18 (0)
0/52 (0)
11/87 (12.6)
38/119 (31.9)
9/102 (8.8)
81/179 (45.3)
2/13 (15.4)
Las Vegas 0/26 (0)
Colorado Springs 1/67 (1.5)
Atlanta 1/92 (1 .1)
Los Angeles 7/136 (5.2)
San Francisco 7/126 (5.6)
Miami 40/210 (19.1)
Newark-Jersey CI ty-Paterson 9/13 ( 69 . 2)
Women with antibody to HIV tended to have seromarkers for hepatitis B
(odds ratio=4.6; CI=2.3-9.2) and antibody for syphilis (0R=2.1; CI=1.2-3.8).
Measures of parenteral drug use, especially "shooting gallery" attendance
(0R=4 .0; CI=2 .1-7.5), and unprotected sexual exposures with many "nonpaying"
partners (r=.124) were associated with a positive anti-HIV test, even after
effects of place were statistically controlled. About 80% reported using
condoms, but only 8 women had used them with each vaginal exposure. All 8 were
anti-HIV negative. Treatment for drug addiction and the proper, more frequent
use of condoms should reduce risks of HIV infection in female prostitutes.
W.1.3 Significant Contributions of Community Organizations
PAULA VAN NESS, Former Chair of National AIDS Network; Centers for
Disease Control, Atlanta, GA, USA.
The AIDS crisis has presented multiple challenges to communities
throughout the world. In the United States a network of community-
based organizations, now spanning all 50 states, has developed over
the past few years. In the absence of a vaccine and effective
treatment for the infection, these community-based organizations
have borne the brunt of developing and maintaining cost-effective
social service programs and educational efforts to reduce
transmission of the virus and to counter unwarranted fear in the
general public. Working in conjunction with other public and
private organizations on the community and national level, these
organizations have also contributed significant leadership in
identifying community needs and promoting other groups' involvement
In providing information/education and vital human services to their
constituencies. Specific examples of the significant accomplish-
ments of these organizations will be discussed and analyzed.
Ill O 9 Human Immunodeficiency virus (HIV) among Female Prostitutes in South
Florida.
MARGARET A. FISCHL, GM DICKINSON, S FLANAGAN, MA FLETCHER. University of
Miami, Miami, Florida.
To evaluate the prevalence of HIV infect ion among sexual ly active
heterosexuals, prostitutes in south Florida were evaluated. Prostitutes from
an economically depressed Inner city area and a middle class urban area were
recruited. Ninety prostitutes from an inner city area were studied. All were
between 17 and 28 years of age, from the lower soc ioeconomic group, had less
than 12 years of education, and had arrest records. Sixty used Intravenous
drugs. Thirty-seven (417.) had anti-HIV antibody. Of the 63 who used
intravenous drugs, 29 (467.) had antibody to HIV, and 8 (307.) of the 27 who did
not use intravenous drugs had antibody to HIV. Factors associated with HIV
antibody (p<0.05) included a greater number of clients per week (28.7 _ 5.2,
seropositive group; 20 _ 11.7 seronegative group), number of black clients
(497. vs. 15%), participation in vaginal Intercourse (607. vs. 267.), hepatitis B
antibody (587. vs 237.), syphilis (681 vs. 301), number of pregnancies (3.8 *
2.0 vs. 1.8 _ 1.3), and gynecologic surgery (877. vs. 377.); whereas, a negative
as soc at ion (p>0.05) occurred with length of prostitution, out of town clients,
repeat clients, working outside the south Florida ares, and fellatio.
Twenty-five women from escort services were also studied. All were between
21 and 32 years of age, from the middle socioeconomic group, and were high
school graduates. None had anti-HIV antibody.
These data suggest that inner city prostitutes in south Florida have a high
prevalence of HIV antibody and that the major risk factors for infection
appear to be both Intravenous drug use and multiple heterosexual partners from
an area with a high incidence of AIDS.
105
WEDNESDAY, JUNE 3
\U O 3 AIDS and HIV Infection, Belle Glade, Florida.
KENNETH G. CASTRO*, S.LIEB**, C. CALISHER*, J.WITTE**, H.W. JAFFE*,
THE FIELD STUDY GROUP, *Centers for Disease Control, Atlanta, GA, & Fort
Collins, CO, **Florida Department of Health & Rehabilitative Services,
Tallahassee, FL, USA
We studied the occurrence of AIDS and HIV infection in Belle Glade,
Florida, because of the high cumulative incidence rate of AIDS (375/100,000)
and high proportion (8/62; 13%) of AIDS patients with no identified risks.
Most of the AIDS patients resided in an area characterized by high rates of
intravenous (IV) drug abuse and sexually transmitted diseases. Nineteen
(32%) of 59 adults with AIDS could be directly linked to at least one other
reported AIDS case by sexual contact, sharing of needles during IV drug
abuse, or both. From February through September 1986, we conducted a
community-based seroepidemiologic study to identify risk factors for HIV
infection. Twenty-nine (3%) of 844 adults tested had antibody to HIV,
including 17 (4%) of 441 men and 12 (3%) of 403 women. The highest
age-specific rate (6%) was among persons aged 18-29; no person over age 60
was seropositive. None of 144 children aged 2-10 years had antibody to HIV.
No clustering of infected persons within households occurred, except for
infection in sex partners. Compared with adults who were seronegative for
HIV antibody, adults with HIV antibody were more likely to have antibodies
to hepatitis B virus (56% vs. 25%, p<0.001) and to Treponema pallidum (58%
vs. 22%, 0R= 5.0, p<0.001). The presence of antibodies to five arboviruses
prevalent in south Florida or the Caribbean was not significantly correlated
with HIV infection. In Belle Glade, the high cumulative rate of AIDS appears
to be the result of HIV infection in IV drug abusers and their sexual
partners; transmission through mosquito vectors is unlikely.
W O fi Heterosexual Transmi ssion of Human Immunodeficiency Virus (HIV):
Association with Severe T4-Cell Depletion in Male Hemophiliacs.
JAMES J. GOEDERT*, M.E. EYSTER**, R.J. BIGGAR*, *National Cancer Institute,
Bethesda, MD, **Pennsyl vania State University College of Medicine, Hershey, PA.
Since 1984 this cohort study has evaluated risk factors for HIV infection in
the female sexual partners of HIV+ men with hemophilia. Of the 38 known female
partners, 24 (63%) participated in the 1986 follow-up. Of 14 non-participants,
1 had AIOS 2 years after her husband, 1 was tested HIV+ after her husband had
AIDS, 5 were clinically well, and 7 could not be contacted. HIV antibody
prevalence in participating women increased from 0/10 in October 1984 to 4/24
(17%) by September 1986. Three of the 4 HIV+ participating women had
documented HIV seroconversion more than 4 years after their male partner's
seroconversion, and the fourth was sexually exposed to an HIV+ hemophiliac for
only 5 months. The dominant risk factor for HIV infection appeared to be the
male partner's most recent T4 count (Table, trend p = .01) :
HIV infection was not inevitable, in that 5/5 T4 cells/ul HIV in
women were HIV- after more than 5 years of sex with in male female
an HIV+ hemophiliac. All 4 HIV+ women had vaginal 0-99 3/6
intercourse without a condom, but risk of HIV did 100-349 1/7
not appear to be affected by frequency of sex or by 350-549 0/6
hysterectomy. Other sexually transmi tted diseases, >550 0/5
anal intercourse, or sex during menstrual periods were not necessary for HIV
infection. Thus, HIV transmission can occur after years of routine vaginal
intercourse especially once the male has severe immune deficiency. These
findings suggest that rapid replication of HIV and death of T4 cells may be
linked in vivo, with low T4 counts heralding a high risk of both AIDS and
sexual infectivity. If true, effective antiviral drugs may reduce not only
AIDS but also incident HIV infections.
Virology — Vaccines
W.2.4 Case control study of HIV-seropositive versus HIV-seronegative
European expatriates in Africa
LUC BONNEUX, H TAELMAN, CORNET**, G VAN DER GROEN, P PIOT. Institute of
Tropical MEdicine, Antwerp; Ministry of Foreign Affairs, Brussels.
Of 3805 European expatriates screened at the Medical Center, Ministry of
Foreign Affairs, Brussels or the Hospital for Tropical Diseases, in Antwerp,
27 (0.7 %) were HIV-antibody positive in 1985, and of 4398 European expatria-
tes tested in 1980, 46 (1 %) were HIV seropositive, including the 27 of 1985
(38 M and 8 F) . A standardised questionaire was offered to 30 seropositives
(24 M and 6 F) between June and December 1986, asking for residence, sex-
life and other risk-factors. 49 (39 M and 10 F) sero-negative European ex-
patriates were recruited as controls at teh same centers in November and
December 1986, and matched for age, sex and residence. European male sero-
positive expatriates had significantly more sex-partners (p^ 0.0001), more
contact with prostitutes (p^ 0.001), and more injections (p<* 0.05) by less
qualified personnel (p/ 0.01) than seronegative controls. There was no
significance in dental interventions, use of condoms, ano-rectal sex, and
a history of STD.. There were no active homosexuals, IVD addicts or blood-
recipients amongst this group. There were no significant differences between
the 6 female seropositives and their controls, exception made for having
seropositive (promiscuous) partners. It is concluded that HIV infection in
European expatriates in Africa is mainly heterosexually acquired, and that
prostitute contact is a major risk factor.
lil Q -i Expression of HIV Genes by Recombinant Vaccinia Viruses
P. Earl, T. Fuerst, C. Flexner, F. Falkner-Gunter,
S. Chakrabarti and B.. Moss. Nat. Inst, of Allergy and Infectious Diseases,
Bethesda, MD.
Recombinant vaccinia viruses that express HIV env, gag, pol and tat
genes were made. When the entire open-reading-frame for the env gene was
expressed, gpl60 was synthesized, cleaved to form gpl20 and gp41, and
transported to the cell surface. Both gpl60 and gp41 were exclusively cell
associated whereas approximately half of the gpl20 was in the medium.
Exclusive synthesis of gpl20 was obtained by introducing a stop codon before
the cleavage site. The majority of gpl20 made under these conditions was
extracellular and the electrophoretic mobility of the protein was similar to
that of the cleaved product of gpl60 indicating that the transmembrane and
anchor sequences were not necessary for glycosylation or transport. Enhanced
expression of the entire gpl60 gene and the truncated gpl20 form were
obtained with a newly developed hybrid vaccinia virus/bacteriophage T7
expression system. The entire gag-pol region was expressed by recombinant
vaccinia virus, as an immunoreactive protein of approximately 55,000 daltnns.
Neither frame-shifting nor proteolytic processing occurred to a detectable
extent. Active reverse transcriptase was made by a recombinant vaccinia virus
that contained a pol gene engineered to contain a translation initiation
codon at its start, tat expression was achieved by still another recombinant
vaccinia virus.
These recombinant vaccinia viruses are being used to produce
neutralizing antibody, determine cytotoxic T cell targets, investigate
proteolytic processing and transport, study receptor binding, and analyze
inhibitors of enzyme activity.
W 2 5 Heterosexual Transmission of Infection and Disease by the Human
Qmunodeficiency Virus (HIV).
NEAL H STETGBIGFL*. D.W. MAUDE*. OJ. FEJNER*, C.A. HARRE*. B.R. SALTZMAN*, R.S. KLEIN* et
al.,«rbnrpfinre Med. Ctr., *A. Einstein Coll of Med., Bronx, NY.; (DC, Atlanta, GA; NTH,
Bethesda, MD; USA.
We report on a longitudinal prospective study, Initiated in July, 1982, of the potential
far the heterosexual transmission of HIV infection and disease. Thus far, 100 steady
heterosexual partners (HP) (88 females, 12 males) (with no other AIDS risk factors) of 97
pts. with AIDS or ARC have had detailed st'dized interviews, physical exams, immunologic
studies and tests for HIV antibody by EIA, confirmed with Western blot. Screening was
repeated every 4-6 mos. HP were followed for a median of 10 mos. (range 1-44). Median number
of estimated sexual encounters was 152 (range 8-945) (during period from 18 mos. prior to
symptom onset in pt. to last sex).
48 of ICO HP (48%) had antibodies to HIV: 41 of 88 females (47%) and 7 of 12 males (58%).
Of sero(+) HP, 20 (42%) had clinical or lab. AIDS-related abnormalities: 2 had ATX6 (1 died),
another died with persistent generalized lymphadenopathy (LA) and dissan. the., 14 had LA
with low T-4 cells (one had oral rmMMasdn and one H. zoster), 3 had either LA or low T-4
cells.
There were no significant assoc's. between serologic status and duration of relationship,
number of episodes of sexual contact, sex during menses or serologic markers for Of/ or
hepatitis B.
Anal intercourse was significantly assoc. with seropositivity (p-,02). Female sero(+)'s
were recipients of analingus (p<.Gl) and oral semen ejaculate (p<.Cfl.) mare often than sero(-)
women. However, none of these activities were required for serojxMitivity. Sero(-) HP used
barrier contraceptives significantly more often than those who were sero(+) (p <.G5), but 49%
of HP who did not use them remained sero(-) .
This study indicates that both male and female steady HP of pts. with AIDS cr ARC are at
substantial risk for HIV infection and related <
w 3 9 A Neutralizing Monoclonal Antibody Reactive against an External
" * Envelope Glycoprotein of HTLV-III/LAV (Human Immunodeficiency Virus)
SHUZO MATSUSHITA*, A.K0IT0*. H.SUT0H*, T.HATT0RI*, M.R0BERT-GUR0FF**,
K.TAKATSUKI*, ^Second Division of Internal Medicine, Kumamoto University
Medical School, Kumamoto 860, Japan. "Laboratory of Tumor Cell Biology,
National Cancer Institute, Bethesda Maryland, USA.
We report the production and characterization of a monoclonal antibody
reactive against an external envelope glycoprotein (gpl20) of human
T-lymphotropic virus type I II(HTLV-II I/LAV) . Gpl20 has been associated with
virus infectivity and cytopathology including cell fusion. We immunized mice
with glycoprotein fraction of viral antigens (HTLV-IIIB isolate) and obtained
a clone (designated as 54'C), which was secreting monoclonal IgGl antibody
reactive against 120 kilodalton(kd) molecule of the purified virion in a
Western blotting assay. This antibody (designated as 0.56) bound to the
surface of HTLV-III infected H9/IIIB cells but not to uninfected H9 cells.
0.5B immunoprecipitated 160 kd and 120 kd molecules from extracts of endo-
genously radiolabeled H9/IIIB cells. 0.5B crossprecipitated gpl60 and gpl20
recognized by antibodies in the serum from patients with AIDS. Gpl60 and
gpl20 have been identified as virus encoded envelope gene products of
HTLV-IIIB. Neutralizing activity of the antibody was evaluated by infecting
the susceptible T-cell line with cell free virion. 0.56 inhibited the
infection of HTLV-IIIB in a dose dependent manner as detected by immuno-
fluorescence assay. We also tested the antibody with syncytia induction
inhibition assay using virus producing H9/IIIB cells. Inhibition of syncytia
formation was observed in the presence of 0.56 antibody. These results
suggest that 0.56 antibody reacts with an external envelope protein of
HTLV-III. 0.56 antibody may have diagnostic or therapeutic value.
106
WEDNESDAY, JUNE 3
Uf Q O Extensive heterogeneity of HIV genomes in vivo.
MICHAEL SAAG* , J. GIBBONS*, W. PARKS**, E. PARKS**, F.
WONG-STAAL*** , R.C. GALLO***, G. SHAW*, and B. HAHN* . ^University of Alabama
at Birmingham, Birmingham, AL, **University of Miami, Miami, FL, and ***Labo-
ratory of Tumor Cell Biology, NCI, Bethesda, MD.
The AIDS virus, HIV, has been shown to exhibit striking genomic variation
when isolates obtained from different individuals are compared. To assess
the extent of genetic variation present iji vivo we isolated HIV from periph-
eral blood mononuclear cells of two infected patients (RJS and MPF), generat-
ed large recombinant lambda phage libraries, and identified and characterized
multiple clones of HIV to search for evidence of genomic diversity in vivo.
Thirty full-length viral clones from the RJS library and 16 full-length viral
clones from the MPF library were obtained and analyzed via restriction
endonuclease mapping using Sst I, Eco RI, Bgl II, Hind III, Pvu II, and Pst
I. Out of 30 RJS clones, 13 highly related yet genetically distinct
genotypes were evident. Of the 16 MPF clones, 9 highly related yet distin-
guishable genotypes were apparent. Certain genotypes were represented by
more than one clone and these, in turn, were evident as predominant species
on the original Southern blot patterns of infected cellular DNA. HIV
passaged in vitro by sequential limiting dilutions requiring multiple rounds
of replication did not exhibit similar degrees of genomic variation. These
data indicate that (i) extensive genetic variation is generated in vivo; (ii)
the degree of viral heterogeneity has heretofore been underestimated; (iii)
many different viral forms coexit in persistently infected individuals, and
thus, "isolates" obtained from such persons for use in the study of HIV
biology and immunology, unless cloned, are actually complex mixtures of
genetically-distinct viruses.
W3 6 Group specific T cell response to HIV in chimpanzees
Immunized with external glycoprotein gpl20 of HTLV-IIIB
KAI. J.E. KROHN*. W.G. ROBEY** , A. RANKI*, T.A. PANAVELIL», P.J.
FISCHINGER** and R.C. GALLO*, *Laboratory of Tumor Cell Biology,
NCI, Bethesda, MD and *#0fflce of the Director, FCRF. NCI,
Frederick, MD
In a pursuit of an effective and safe HIV vaccine, chimpanzees
were Immunized with purified external envelope glycoprotein,
gpl20 from HTLV-IIIB, and the immune response towards HIV was
monitored. Neutralizing antibodies were measured with the ATH-8
assay, based on the cytolytic effect of HIV on this target cell
line. Cellular Immune response was followed by T cell
proliferation assay, IL-2 measurements and by assessing the
capacity of Immune lymphocytes to suppress the expression of HIV
In cultures of Infected autologous cells. All Immune animals, but
not the controls, showed an antibody response towards gpl20 In
Western blot. Neutralizing antibodies were strictly type specific
to HTLV-IIIB. In contrast, T cell IL-2 production and
proliferative response to whole heat killed virus was group
specific, seen with three different HTLV-III Isolates (B, MN,
RF). The proliferating cells were CD-4 or CD8 +ve and -ve for B
cell markers. When Immune lymphocytes, stimulated with gpl20 were
added Into cultures of autologous lymphocytes Infected in v i tro
with HTLV-IIIB, the percentage of cells expressing viral antigens
fell from 5-10% to 0-2%. The above results demonstrating group
specific cellular Immune response to HIV even when a vaccine
candidate representing only one Isolate Is used raises hope for
the development of a vaccine against HIV Infection.
Blood and Blood Products — Screening and
Donor Characteristics
III Q A Full-length and truncated HIV Envelope Polypeptides Produced in
an Insect Cell Expression System Elicit High Titer Neutralizing
Antibodies in Animals.
Gale Smith*,. M.A. Cochran*, B.L. Ericson*, M. O'Shaughnessy**, T. Folks***,
M. Martin***, et al., *MicroGeneSys, West Haven, CT, **Laboratory Centre for
Disease Control, Ottawa, Canada, *** NIAID, Bethesda, MD.
Recent efforts to develop subunit vaccines against the human acquired
immune deficiency syndrome (AIDS) have focused on the HIV envelope proteins.
Sera from individuals infected with the HIV virus often contain high titer
antibodies directed against the viral envelope; however, these antibodies
are not protective and usually exhibit low- level neutralizing activity in
vitro . This apparent contradiction may in part be due to immunodominant
determinants on the envelope being physically separate from important
protective and neutralizing sites.
Full-length and various truncated forms of the HIV env gene have been
inserted into Baculovirus vectors and recombinant glycoproteins of 15,000 to
160,000 molecular weight have been expressed in insect cells . Of more than
600 sera from clinically-diagnosed AIDS patients, all had antibodies that
recognized a recombinant gpl50 polypeptide using an immunoblot assay .
However, when measured by immunoblot, ELISA, and RIP assays many of these
same sera had low or undetectable antibodies against a recombinant
glycoprotein (gpl20*) which represents more than 90% of the amino- terminal
portion of HIV gpl20.
Animals immunized with gpl20* or recombinant HIV proteins that include
this region of the envelope produced high titer antibodies that recognized
the native viral envelope . Unlike the serum antibodies found in the human
AIDS patients we tested, animal sera against these recombinant proteins have
high titer antibodies against the portion of the envelope included in
gpl20*. Also, unlike most sera from AIDS patients, sera from animals
immunized with these recombinant envelope proteins contains antibodies that
neutralize HIV in vitro at high dilutions. Our data indicate that the
apparent lack of a protective immunity in infected humans may in part be due
to a misdirected immune response to the viral envelope.
\kl A 1 Epidemiologic Characteristics of Blood Donors Who Have Antibody to
the Human Immunodeficiency Virus
JOHN W. WARP*, S KLUINMAN**, D DOUGLAS***, A GRINDON****, S HOLMBERG* , AIDS
Program, *Center for Infectious Disease, Centers for Disease Control, Atlanta,
GA, USA **American Red Cross Blood Services, Los Angeles, CA, ***American Red
Cross Blood Services Baltimore, MD, ****American Red Cross Blood Services,
Atlanta, GA
The demographic and epidemiologic profile of donors with antibody to the
human immunodeficiency virus (HIV) is useful for educating donors and studying
the prevalence of HIV infection. We examined persons positive for HIV antibody
who donated blood from March 1985 to July 1986 at three major U.S. blood
centers. Of 818,629 donations, 450(0.05%) were HIV-antibody-positive ;
decreasing from 0.07% to 0.04% during the study period. When compared with
seronegatives , HIV-seropositive donors tended to be 20-40 years of age (81%),
male (88%), and black (47%). HIV seroprevalence among white donors (2/10,000
donations) was lower than among black (31/10,000 donations) (p<0.0001) and
Hispanic (9/10,000) (p<0.0001) donors. Seventy-seven percent of seropositive
males reported sexual contact with men; 41% were bisexual. Although 44% of
seropositive females had apparently acquired infection from heterosexual
contact , an equal percentage denied having risk factors for HIV infection. A
small but decreasing number of HIV-infected persons continue to donate blood.
Black and Hispanic communities may have an increased prevalence of HIV
infection in donor populations and /or may have received less information
concerning donor self deferral. The high proportion of bisexual men suggests
these men may be unaware of their risk for infection. Donor education efforts
should be targeted toward minority and bisexual men who may not consider
themselves at risk for HIV infection.
W 3 5 CORRELATION OF CLINICAL STATUS AND NEUTRALIZING ACTIVITY OF SERA
OF PATIENTS INFECTED WITH HTLV-II I/HIV . DAVID LQQNEY , A
Fisher**, R Redfield*, D Burke*, R Gallo**, & F Wong-Staal . Walter
Reed Army Institute of Research, Washington, DC 20307. **Laboratory of
Tumor Cell Biology, NIH, Bethesda, MD 20205.
Neutralizing activity (NA) in the sera of patients with AIDS, ARC, and the
lymphadenopathy syndrome has been described extensively (Robert-Guroff 1985,
Weiss 1985, Ho 1986, Rasheed 1986). Some investigators have found NA in sera
of most patients with ARC {27/27,28/35 - Ho, Guroff) and AIDS (26/31,21/35),
whereas others have found few AIDS sera possessing NA (Weiss, Rasheed).
The role of neutralizing antibodies in preventing or retarding the progression
of disease is of paramount importance in ascertaining the desirable target
response of candidate vaccines. Indications that NA may play a beneficial role
include the observation that 12/12 clinically stable children with AIDS, but
only 1/12 children with a rapidly deteriorating clinical course exhibited NA
in the serum (Robert-Guroff). We examined NA in a panel of sera, including a
number of serial specimens, fom patients categorized according to the Walter
Reed Staging Classification (Redfield 19861 against a number of viruses
derived from molecular clones of HTLV-III/HIV (HX10, HXB2D, & others). We
failed to find a significant correlation of the NA of individual sera against
any clone or clones with respect to stage of disease (p=0.578,n=26) , and
found NA to differ substantially even between very similar strains. These
results suggest that determining the clinical sionificance of the presence of
N<\ against d.iy sinjlj s^i-i >• ;l)sely r*lit*1 sfcrti i; >r HTLV-III/HIV may
be difficult.
W 4 2 Risk of HIV Transmission by Anti-HIV Negative Blood
STEVEN KLEINMAN, American Red Cross, Los Angeles, CA
Because anti-HIV does not develope until several months after
HIV exposure, anti-HIV screening of donated blood is not expected
to eliminate HIV transmission via transfusion. We have estimated
this risk, by analyzing the results of anti-HIV testing of 676,000
donations (dona) over a 21 month period. We have found 17 donors
(.003% of dona tested) who have had an anti-HIV(-) dona followed
by an anti-HIV (+) dona. The intervals separating these dona were
a) 3 months (mo) for 8 donors, b) 3 to 6 mo for 5 donors and c)
6 mo for 4 donors. We have tested 4 recipients of anti-HIV (-)
blood from 3 Group A donors. Two tested ' anti-HIV(+) , having re-
ceived blood 2 and 4 months prior to the donor's seroconversion.
Donors in Groups A and B gave 16 anti-HIV(-) units; with an assum-
ed 50% infectivity rate, we estimate the risk of HIV acquisition
from anti-HIV(-) blood to be 1 in 84,000.
When compared to anti-HIV (+) donors who did not seroconvert (n=
323), seroconverting donors were less likely to be gay (44% vs.
86%, p=.01) and more likely to have possible heterosexual exposure
or no identified risk (44% vs. 9%, p=.01). In late 1986, serocon-
verting donors comprised 14% of all anti-HIV ( + ) donors as compared
to 2% in 1985 (p=.002) and 6% in early 1986 (p=.l). Our data sug-
gests that the risk of HIV transmission from anti-HIV(-) units may
increase unless donor deferral and screening methods are improved.
107
WEDNESDAY, JUNE 3
W 4 3 Serologic and Culture Follow-up Study of Anti-HIV Reactive Blood
Donors
MICHAEL BUSCH*, J.SHIOTA*, M.NASON*, S.SAMSON*, G.VYAS**, H. PERKINS*;
*Ir\vin "Memorial Blood Bank , **University of California, San Francisco, CA.
As of December 1986, 473 donors had been repeatedly reactive by EI A for anti-
HIV. Of these, 119 were Western blot positive (WB+), 334 were Western blot
negative (WB-), and 20 were considered equivocal (WBeq) based on the presence
of weak p24 and/or p55 bands only. We have enrolled 75 of these donors in 3 to
6 month follow-up studies. The initial and follow-up sera were tested by 6
different EIA screening tests for anti-HIV*, by 2 anti-HIV tests using recombi-
nant antigens**, by 2 HIV-antigen assays**and by screening for anti-HLA anti-
gens. Lymphocytes from WB+ and WBeq donors were cultured for HIV by standard
techniques; cells from WB- donors were pooled prior to culture. Cultures were
monitored by reverse transcriptase, in situ hybridization, in vitro DNA amplifi-
cation***,immunocytochemistry, and HIV-antigen assay**.10/10 WB+ donors (7 with
risk factors) were positive by all EIA and recombinant antibody assays on both
samples, 2/10 had detectable plasma HIV-antigen, and HIV was cultured from8/10.
50 WB- donors with both index and follow-up sera were negative by at least 7/8
antibody tests and by both antigen tests; HIV was not detected in pooled cul-
tures from these donors; the majority tested had HLA antibodies. Whereas 11/15
WBeq donors were negative on all follow-up testing, 4 had persistent atypical
antibody profiles; none were HIV culture positive. These results confirm per-
sistent infection of most WB+ donors, and demonstrate the value of follow-up
HIV test panels to clarify the status of WB-/eq donors. (Supported by NHLBI:
1-P01-HL36589-01; HB-6-7024).
♦Abbott, Genetic Systems, Dupont, Burroughs-Well come, ENI, Chiron
**Abbott, Chiron ***Cetus
W 4 6 HIV Blood Screening in Africa: Are there no Alternatives?
" * NZILA N2ILAMBI*. R.L. COLEBUNDERS* , J.M. MANN*, H. FRANCIS*,
K. NSEKA**, J.W. CURRAN***, et al., *Projet SIDA, ** Mama Yemo Hospital,
Kinshasa, Zaire, *** CDC, Atlanta.
Screening potential blood donors using the presently available ELISA
methods is not feasible in many African countries. To determine the
percentage of HIV(+) blood donors which could be excluded by simple history
and physical exams, we screened for HIV antibody and conducted physical
examinations on all J25 blood donors (307 men and 18 women) who donated
blood at Mama Yemo Hospital, Kinshasa, between March 3 to April 4, 1986.
Sixteen (5%) donors (14 men and 2 women) were HIV(+) by ELISA and Western
blot (a rate similar to the one previously observed in the adult population
of Kinshasa). No significant differences in clinical findings or exposure
to established HIV risk factors between HIV(+) and HIV(-) blood donors were
found. Two-hundred and twenty-seven (70t) of 325 units would have been
rejected if we had used the following exclusion criteria for screening blood
donors: 1) paid donor 2) symptoms suggestive of HIV infection 3) abnormal
physical examination 4) history of tuberculosis, herpes zoster or venereal
disease within the past year 5) transfusions during the past 5 years 6)
receipt of injections during the past 6 months. Of the 99 units not
rejected by these criteria, one was HIV(+). Because of the persistent blood
shortage in Africa such a high rejection rate is unacceptable.
Use of a lab test -independent clinical screening profile to reject high
risk donors in Africa is not possible. An inexpensive, highly sensitive,
rapid, simple machine independent laboratory test for detection of antibody
to HIV is urgently needed.
Clinical Management — Pulmonary, Pediatric
and Neurologic Implications
W.4.4 Characteristics of EIA and Western Blot Positive Blood Donors in a Milticenter
Study
JOEL N. KURITSKY*. J. C. FRATANTONI**, H. W. DREIS*, D. J. GRAHAM*, and the FDA Blood Donor
Study Group, Food and Drug Administration*, Office of Epidemiology and Biostatistics**, Office
of Biologic Research and Review*, Rockville, HD, USA
In December 1985, a prospective study was begun at 11 geographically different blood
collection centers in the U.S. to: (1) characterize risk factors of EIA-positive donors; (2)
assess the EIA ratio as a predictor of Western blot (WB) status; and (3) determine the ability
to isolate virus from EIA positive patients. Blood specimens from EIA positive donors were
obtained for T-lymphocyte testing, WB analysis, and viral cultures. As of November 1986, 658
EIA positive donors were enrolled in the study. Of these, 52 (8%) were WB positive (34 males,
18 females), and 5 were culture positive. There were geographic differences in the proportion
of EIA positive donors tested positive by the WB test. WB positive donors were more likely to
have T4/T3 ratios below 1 than were WB negative donors (21 of 45 versus 31 of 521; pe.0001 ).
WB positive males were more likely to have had sex with a male than WB negative males (18 of
33 versus 4 of 284; pc.0001). WB positive females were more likely to have a history of sexual
contact with an IV drug user than WB negative females (3 of 13 versus 2 of 279; p<.001).
Analysis of EIA OD ratios confirmed that higher ratios were better predictors of a WB positive
test. These data indicate that individuals at risk for AIDS continued to donate blood at some
centers during this period.
yy R -J Predictive Value of Chest X-rays (CXR) for Lymphocytic Interstitial
' " Pneumonitis (LIP)/Desquamative Interstitial Pneumonitis (DIP) in
Pediatric Patients with AIDS
SUSAN MORRISON, E. CONNOR, J. MARQUIS, J. OLESKE, V. JOSHI, B. HOLLAND, ET AL
Children's Hospital of New Jersey & UMD-New Jersey Medical School, Newark, NJ
LIP/DIP is the most common pulmonary disease in children with HIV infection.
Currently, diagnosis requires biopsy (BX) of lung tissue. To evaluate the
value of CXR in identifying LIP/DIP, we compared pre-Bx CXR with pulmonary
histopathology. 32 children (15 male, 17 female) with HIV infection underwent
lung BX. Mean age at BX was 26.4 mos (3.5-120 mos). Medical records were re-
viewed to determine respiratory status, results of CXR and histopathologic
diagnosis. All children presented with respiratory symptoms: rales>retractions
cough>clubbing,>rhonchi>wheeze. Histopathologic results follow: 23/32 LIP/DIP;
7/32 Pneumocystis carinii pneumonia (PCP); 1/32 Cytomegalovirus (CMV) pneumonia
1/32 nonspecific inflammatory disease. Pre-BX CXRs were read by one pediatric
radiologist. Nineteen of 32 CXRs had linear/nodular pattern (LN); 8/32 conso-
lidation, and 5/32 were normal. Of patients with LIP/DIP, 18/19 had LN, 1/8
consolidation and 4/5 normal CXR. We evaluated LN CXR as a predictor of LIP/
DIP. Sensitivity 0.78, specificity 0.89, positive predictive, value 0.95,
negative predictive value 0.62. When a second pediatric pathologist blindly
read the same CXRs, sensitivity 0.52, specificity 0.78, positive predictive
value 0.86, negative predictive value 0.39.
These data suggest that LN on CXR in this cohort is highly predictive of
LIP/DIP. Further studies will be necessary to confirm these observations.
Among HIV infected children with chronic respiratory symptoms, LN CXR may
prove sufficient for diagnosis of LIP.
W 4 5 Human Immunodeficiency Virus (HIV) Cultured from Limiting Dilutions
of the Peripheral Blood Mononuclear Cells (PBMC) of Asymptomatic
Seropositive Persons
P.P. ULRICH*, T. EL-BEIK*,M.P. BUSCH**, E. DQNEGAN*,GIRISH N. VYAS*. et al.,
*UCSF School of Medicine, San Francisco, CA, **Irwin Memorial Blood Bank, San
Francisco, CA.
To determine the prevalence of HIV infection in seronegative blood donors,
we propose to culture the PBMC from 200,000 donors using pool sizes of 20-200
specimens. In this pilot study the proportion of HIV-infected PBMC from 10
asymptomatic anti-HIV(+) persons has been defined using two separate approach-
es: (1) Direct probing of the uncultured PBMC for viral nucleic acids and
antigens using _in_ situ hybridization (ISH) and immunocytochemistry (IC) analy-
ses, respectively; (2) Limiting dilution of the HIV-infected PBMC in cocultures
with PHA-stimulated normal PBMC assessed by reverse transcriptase (RT), ISH and
IC. The dilutional studies revealed a higher proportion of HIV-infected cells
ranging from 1:100 to 1:10,000 in comparison with exceedingly rare (less than
1:10,000) HIV-positive cells detected either by direct ISH or IC analyses.
Thus, a large proportion of _in_ vivo-infected cells are not producing detectable
levels of HIV-RNA or proteins without jji vitro stimulation in the coculture
procedure, suggesting that they are latently infected and require _in vitro
stimulation for the expression of viral gene products. Because 10- to 10,000-
fold dilution of HIV-infected PBMC coculture with normal PBMC leads to virus
recovery, it may be possible for us to grow the virus out of HIV-infected cells
from a single individual when mixed with cells from uninfected donors and the
pool of 100 PBMC specimens is cocultured in an analogous procedure. (Supported
in part by the NHLBI Contract HB-6-7024, Grant P01 HL-36589 andcarried out in
conjunction with the SFMHS supported by NIAID Contract N01 AI-32519.)
W 5 2 Retroviral antigenemia in children with HIV infection.
" W. BORKOWSKY, K.KRASINSKI, D.PAUL*, R.LAWRENCE, T.MOORE, and
S.CHANDWANL NYU-Bellevue Hospital Medical Ctre. New York, N.Y., *Abbott
laboratories. North Chicago, TL.
A selected group of 35 children with suspected or documented HIV infection were tested
for plasma HTV antigen using an ELJSA antigen capture assay. Plasma from 33 of these
were antigen positive at some time in their life. Antigen concentrations were determined
in those with AIDS (range of 18-3026 pg/ml; mean + S.D. of 573 + 404); in those with ARC
(range of 0-2143 pg/ml; mean + S.D. of 499 + 202); and those without symptomatology
(range of 0-175 pg/ml; mean + S.D. of 55 + 213). The latter group had significantly lower
HIV antigen levels than those with clinical illness. Two sets of HTV antibody positive
twins were also antigen positive. One of each twin set developed severe HIV related
illness in the first 4 months of life. Within each set, the affected twin had the higher
titre of antigen. Plasma from 8 high risk maternal-infant (Ml) pairs was assayed for HIV
antigen at the time of delivery. Three antigen positive babies were bom to antibody
positive but antigen negative mothers. One MI pair was concordantly antigen positive and
1 MI pair was concordantly antigen negative. Three antigen positive mothers delivered
antigen negative babies, however, 2 of these babies developed antigenemia at subsequent
evaluations during the first year of life. These data suggest that (1) prenatal HTV
infection may occur; (2) passive transfer of HTV antigen across the placenta need not
occur; and (3) that natal infection with subsequent antigenemia is possible. All the
children from the MI pairs are im munologically and clinically well bo date but continued
foJJowup is necessary. HIV antigen testing of plasma may help explain patterns of vertical
transmission of virus and possibly predict clinical manifestations of disease.
108
WEDNESDAY, JUNE 3
ui c o Pediatric AIDS: Neurologic Syndromes
'"■0-0 Anita L. BELMAN*, G. DIAMOND**, D. DICKSON**, G. LANTOS**, A.
RUBINSTEIN**, *SUNY, Stony Brook, N. Y. ,**AECOH, Bronx, N.Y. U.S.A.
To further delineate the spectrum of central nervous system [CNS] syndromes
in pediatric patients with HIV infection we have followed 63 infants and
children [ages 6 weeks to 13 years] in an ongoing study. Forty-eight children
had AIDS and 15 ARC. CNS dysfunction was documented in 61. Manifestations
included microcephaly, cognitive deficits, encephalopathies and corticospinal
tract signs. The neurologic course in 5 AIDS patients was rapidly
progressive. Ten patients [9 AIDS, 1 ARC) had a subacute but steadily
progressive course with loss of cognitive skills, progressive long tract signs
and movement disorders. In 28 patients [25 AIDS, 3 ARC) the course was
punctuated by plateaus during which no new milestones were attained.
Cognitive assessments, revealed mild to severe mental retardation and long
tract signs were common. Of these patients, 10 (9 AIDS, 1 ARC) had further
neurologic deterioration. CT examinations revealed marked white matter
abnormalities, cerebral atrophy and calcification of the basal ganglia. These
CT findings correlated well with recovery of HIV from CSF, and with
neuropathology findings of myelin pallor, inflammatory responses with
multinucleated giant cells, calcific vasopathy, and corticospinal tract
degeneration. Six patients [4 AIDS, 2 ARC] with plateaus improved but
remained mentally retarded. Eighteen patients [7 AIDS, 11 ARC) had a static
encephalopathy: moderate to borderline mental retardation with varying degrees
of stable motor deficits. CNS lymphoma, cerebrovascular accidents, and CNS
infection by conventional pathogens occurred in 8 children [11%]. We conclude
that (1) CNS involvement with progressive encephalopathy occurs frequently in
children with HIV infection; (2) unlike adult AIDS patients, CNS opportunistic
infections are uncommon; [3) In neurologically stable children, morbidity
includes mental retardation.
W 5 6 Serum Glutamic Acid as Potential Marker for Pneumocystis carlnil
Pneumonia in AIDS.
JOHN R0B02, D. KAPPATOS , D. MILDVAN, M. CHUANG, AND J.F. HOLLAND,
Mount Sinai School of Medicine, New York, NY, 10029.
Current diagnostic techniques, open lung biopsy and bronchoscopy, are highly
invasive and cannot be used to monitor therapy. Objective: to find a circulat-
ing serum marker that could be used repeatedly for both diagnosis and monitor-
ing. Identification: computer comparison of gas chromatographic-mass spectro-
metric (GC-MS) profiles of the trimethylsilyl (TMS) derivatives of aqueous
extracts from PCP Invaded lungs and normal lungs revealed a potential marker,
the presence of which was also confirmed in PCP serum samples. The marker was
identified as L-glutamic acid (glu) by both low and high resolution mass
spectrometry (electron and chemical ionization) using TMS and acetyl-methyl
derivatives and also by using L-glutamic decarboxylase to remove glu. Quanti-
fication in serum: GC-MS (int. std.: deuterated glu); analyses were also made
using colorimetry and liquid chromatography. Glu cone. >108 pM (mean of normal
+2s.d.) considered elevated. Of 103 patients (70 coded) containing 73 indepen-
dently confirmed PCP cases (45 coded) sensitivity: 81%, specificity: 86%. Of
22 patients with blood taken within 3d of bronchoscopy: 15 of 20 with proven
PCP were positive. Two true negatives and 5 PCP cases were negative. No false
positives were found. This suggests that invasive testing need be performed
only in those who do not have elevated glu cone. Preliminary results revealing
concurrent changes in serum glutamine (gin) cone, suggest that chenges in glu
may result from physiological changes caused by PCP, resulting in an altered
glu/gln ratio.
(Supported by AIDS Institute, State of New York, and the T.G. Martell
Memorial Foundation for Leukemia and Cancer Research) .
Roundtable Discussions
W.5.4 Objective Clinical and Histological Prognsotic Factors for Patients with Pneumocystis
carina Pneumonia and the Acquired Immunodeficiency Syndrome.
MATTHEW BRENNER. F.P. OGN1BENE, E.E. LACK, H.C. LANE. A.S. FAUCI. H. MASUR. et a!., From
the Critical Care Medicine Department, National Institutes of Health. Belhesda, Maryland. USA.
Pneumocystis carinii pneumonia (PCP) is the- most frequent life- threatening opportunistic infection occurring in
patients with the acquired immunodeficiency syndrome (AIDS). In this study, objective clinical and
histopathological characteristics were analyzed to assess acute and long term prognostic significance in 43 patients
with AIDS and PCP. Survival data, alveolar-arterial oxygen (A-a) gradients, clinically blinded graded chest
radiographs and scored transbronchial biopsies were analyzed for all 43 patients.
Prognostic factors for survival for the acute episode differed from factors correlating with long term survival
following the diagnosis of PCP. Thirty of 43 patients (70%) survived the acute episode. Decreased ability to
survive the acute episode of PCP was associated with widened A-a gradients (>30torr) and more severe
abnormalities on iniual chest radiographs (p<0.05). Histopathologic specimens were semi -quantitatively scored
for severity of 5 separate components of alveolar damage. Cox proportional hazards analysis revealed long term
survival following the diagnosis of PCP correlated with the severity of edema on biopsy (z=2.25, p<0.05), and the
extent of A-a gradient at the time of iniual diagnosis (z=2.88, p<0.05).
Repeat bronchoscopy with re-biopsy was performed in 27 of the 43 patients following an average of 3 weeks of
therapy. The persistence of pneumocysts on follow-up bronchoscopy was associated with significantly decreased
long term survival (p<0.05 at 8 months following the diagnosis). Patients diagnosed more recently (July
1985-July 1986) has less severe pulmonary disease at the time of diagnosis (possibly due to earlier, more
aggressive evaluation) by the parameters examined in the study and a belter prognosis for survival the acute
episode (p<0.05) than patients diagnosed earlier (January 1983 to June 1985).
Thus, important prognostic information can be derived from objective clinical and histopathologic data obtained
at the time of diagnosis and at follow-up bronchoscopy in patients with AIDS and PCP. The improved survival
in patients with less severe disease as measured by these objective parameters suggests that early detection and
iherapeulic intervention for patients with PCP may improve chances for survival.
W.6
Heterosexual Transmission of the AIDS Virus
Panel Organized By: Dr. Tim Dondero
Centers for Disease Control
Atlanta, Georgia
H. Hunter Handsfield, Seattle-King County Department of Public Health
and University of Washington, Seattle, Washington
Peter Piot, Institute of Tropical Medicine, Antwerp, Belgium
Robert Redfield, Walter Reed Army Institute of Research, Washington, D.C.
Niel Steigbigel, Montefiore Medical Center, Bronx, New York
Rand Stoneburner, New York City Health Department, New York, New York
W 5 5 Serum Lactate Dehydrogenase levels (LDH) in
Pneumocystis carinii pneumonia (PCP) in AIDS: Possible
Indicator and Predictor of Disease Activity.
ILEANA MEDINA, MILLS J, WOFSY C, UCSF School of Medicine, San
Francisco General Hospital, San Francisco, CA, USA.
Seventy-eight AIDS patients with first episode PCP and
moderately well (95* had pO >.60) had LDH determinations on days
0,1,3,6,14,18,21, one and 3 months after end of treatment.
During the acute phase significant elevation of serum LDH
activity was noted in ail patients. The LDH followed a specific
pattern beginning to increase one week prior to diagnosis: the
peak was usually on day 6 to 8 and declined to normal levels
within one and a half months. In 67 patients with good outcome
(survivors without respiratory failure) the mean initial LDH was
355.9 U (150-520). Eleven patients had a poor outcome
(respiratory failure or death w/o intubation); the initial LDH
was significantly higher in these patients with a mean value of
710 ' (450-977) . All the survivors with or without respiratory
failure showed a decline in LDH levels after 5-6 days of therapy.
All nonsurvivors had a progressive increase in their LDH levels
after day 6 to 8. LDH isoenzymes were performed in 19 patients.
In all but 2 LDH fraction 3 was abnormally elevated ^26*}.
These findings suggest that serum LDH activity is a useful
indicator of the severity of PCP in AIDS patients and that it may
be utilized to predict disease course and monitor response to
treatment .
W.7
Vaccine Related Issues
Panel Organized By: Gerry Quinnan
Food and Drug Administration
Bethesda, Maryland
Patricia Fultz, Centers for Disease Control, Atlanta, Georgia
Fritz Deinhardt, Max v. Pettenkof er-Inst itut , Munich, Federal Republic of
Germany
Dani Bolognesi, Duke University Medical Center, Durham, North Carolina
John La Montagne, NIAID, Bethesda, Maryland
Richard Kaslow, NIAID, Bethesda, Maryland
109
WEDNESDAY, JUNE 3
Poster Session
W.8
Legal, Ethical and Public Policy Issues:
The American Perspective
Panel Moderator: Gene Matthews
Legal Advisor
Centers for Disease Control
Atlanta, Georgia
Earl Shelp, College of Medicine, Houston, Texas
June Osborn, University of Michigan, Ann Arbor, Michigan
Carol Levine, The Hastings Center, Briarcliff Manor, New York
Harold Edgar, Columbia University School of Law, New York, New York
Joan B. Campbell, World Council of Churches, New York, New York
Alvin Novick, Yale University, New Haven, Connecticut
Larry Gostin, American Society of Law and Medicine, Boston, Massachusetts
U/P1 Enhanced J_n Vitro Suppression of HIV Infectivity by a Combination
of Nucleoside Analogs
LIONEL RESNICK*, A. M. MIAN**, *Mount Sinai Medical Center, Miami Beach, FL,
"University of Miami School of Medicine, Miami, FL,
Azidodeoxythymidine (AZT),a nucleoside analog with anti-HIV reverse trans-
criptase (RT) activity in vitro has been found to have clinical toxicity that
limits drug dose. 6 thio-deazaguanine (6TDG),a nucleoside analog with anti-
viral properties, was tested individually and in combination with AZT to deter-
mine if HIV inhibitory activity occurred in vitro. A drug screening assay was
developed to evaluate the antiviral activity of compounds at drug levels
causing no target cell cytotoxicity over a broad range of multiplicity of in-
fectious units (MOI) and over prolonged periods of time. Evidence of HIV in-
fection and replication in culture was monitored by RT assays .immunofluores-
cense cellular assays with anti-p24 monoclonal antibody and cell-cytopathic
effects. At an MOI of l.AZT (2ug/ml) and 6TDG (,0.3ug/ml) individually exhibi-
ted suppressive effects on HIV expression throughout the 20-day experiment.
The HIV infected culture without drug (control) revealed the presence of HIV on
day 10. At an MOI of 100, HIV replication was detected at day 10 with 6TDG
(0.3ug/ml), day 20 with AZT (2ug/ml) and day 14 with AZT (lug/ml) (control-
presence of HIV on day 7). The utilization of AZT (lug/ml) and 6TDG (0. lug/ml)
in combination, at lower doses .achieved complete suppression of viral replica-
tion at an MOI of 100 over the 20-day period. The combination of nucleoside
analogs, AZT and 6TDG, appear to enhance the inhibition of HIV infectivity in
vitro. Combination antiviral therapy may be important in maintaining efficacy
at non-toxic drug levels.
W.9
Assuring an Adequate Blood Supply of Healthy Blood Donors
in This Age of AIDS
Panel Organized By: Gerald Sandler
American Red Cross
Washington, D.C.
Gordon T. Archer, Australian Red Cross, Sydney, New South Wales, Australia
Richard E. Counts, Council of Community Blood Centers and Puget Sound Blood
Center and Blood Program, Seattle, Washington
Lewellys F. Barker, International Society of Blood Transfusion and American
Red Cross National Headquarters, Washington, D.C.
Joseph R. Bove , American Association of Blood Banks and Yale-New Haven
Hospital, New Haven, Connecticut
Anthony F.H. Britten, League of Red Cross and Red Crescent Societies,
Geneva, Switzerland
WR2 In Vitro Infection of Glial Cells with Diverse HIV Isolates
JONATHAN WEBER*, E. R0BEY**, R. AXEL**, R. WEISS*, *Chester Beatty
Laboratories, Institute of Cancer Research, London, **College of Physicians
and Surgeons, Columbia University, New York, 10032.
The susceptibility to HIV infection of 6 established malignant glioma cell
lines was investigated, using a diverse range of characterised HIV isolates.
The results were contrasted with the susceptibility of 50 primary cultures from
malignant glioma tissue. One line, U 138. MG (Westermark) was susceptible to
infection with diverse characterised HIV-1 and HIV-2 isolates, including HIV RF,
HIV Illb, HIV RUT and LAV-2. Infected cells do not demonstrate indirect immuno-
fluorescence for HIV antigens, and cultures were negative for antigen ex-
pression (Dupont), and only occasionally positive for reverse transcriptase;
however, infected cells consistently produced syncytia with a T-cell line,
C8166, which were specific for HIV. There was no evidence of the CD4 antigen on
the cell surface, or in the cytoplasm, in infectable cells by immunofluorescence
with several monoclonal anti-CD4 antibodies. However, CD4 mRNA was detected in
these cells by northern blot with a CD4 probe; even so, it was not possible to
block infection of glial cells with anti-CD4 monoclonals. The infected glial
cells were not lysed by HIV, and grew normally. The possibility remains that
HIV infected glial cells may be a target for lymphocyte cytotoxicity in vitro,
and data on this will be presented.
Jonathan Mann, World Health Organization, Geneva, Switzerland
W.10
Meeting Gaps in Medical Needs
Panel Moderator: Reed Tuckson
Commissioner of Public Health for
the District of Columbia
Washington, D.C.
Joseph A. Nkwanyuo, Internal Medicine, Baltimore, Maryland
Elmer W. Smith, Health Care Financing Administration, Baltimore, Maryland
Paul A. Volberding, San Francisco General Hospital, San Francisco,
Cal if ornia
James M. Graham, Whitman-Walker Clinic, Inc., Washington, D.C.
A Representative of the Robert Wood Johnson Foundation
WR3 Persistent HTLV-IIIb and LAV Infection in Chimpanzees. Its Effect
on Virus Biochemistry and Serology.
PETER L. NARA* , L.O. ARTHUR**, W.G. ROBEY* , P.J. FISCHINGER* , and D.M.
ASHER*** ,*Office of the Director, Virus Control Unit, NCI-Frederick Cancer
Research Facility (FCRF), Frederick, MD 21701, **Program Resources, Inc., NCI-
FCRF, Frederick, MD 21701, NINCDS, NIH, Bethesda, MD 20205, USA.
The chimpanzee has been shown to be capable of persistent infection by HTLV
III/LAV. This state of persistent viral infection can thus be utilized for
biochemical and serological investigations. Three chimps were given either
HTLV-IIIb-infected cells (#525), HTLV-IIIb virus only (#525), and LAV from a
previously infected animal (#524). Virus was reisolated from all animals 1 1/2
years later and purified viral envelopes were compared to the original virus
inoculum by oligo-chymotryptic peptide mapping methods. In the 2 cases where
the original isolate was mapped (HTLV-IIIb), a difference in 2 peptides was
detected in the reisolated virus. Viral maps from the LAV animal were similar
to the reisolated HTLV-IIIb maps suggesting a host-induced modification. All
animals developed progressively high titered, initially type-specific, neu-
tralizing antibody response which progressively broadens after 2-4 months to a
group-specific response. Maximal titers were found between 1 and 2 years
following virus inoculation. Also, virus reisolated from each chimp was
neutralized by each others sera, as well as their own. All animals' sera
contain antibodies which recognize p24, Ag 121, gpl20, and exhibit antibody-
dependent, complement-mediated cytolysis (ACC). Human sera from healthy AIDS
and ARC patients were found to be negative for ACC. Thus, it appears that
chimpanzees persistently infected by one virus isolate undergo an in vivo
expression to yield alternate form(s) of the envelope which leads to a group-
specific response. Research sponsored, at least in part, by the NCI, DHHS,
under Contract Number NO1-CO-23910 with Program Resources, Inc.
no
WEDNESDAY, JUNE 3
Wp4 Membrane Immunoassays for the Detection of HIV Antibody and Antigen
CELIA M. CRANE and KEVIN J. REAGAN, Medical Products Dept., E. I.
Du Pont de Nemours and Co., Inc., Glasgow Research Laboratory, Wilmington, DE
19898.
The likelihood of HIV transmission through donor blood has been greatly
reduced by the introduction of enzyme immunoassays (EIA) which monitor the
presence of antibody to virus. In addition to an antibody assay, Du Pont has
released as a research product an EIA designed to detect HIV core antigen.
These assays are highly sensitive though their requirement for automation
limits their application to modern clinical or research settings. Studies were
initiated to adapt several methods to membrane surfaces designed to function
without automation yet provide sensitive and specific detection of HIV antibody
and antigen.
HIV antibody was monitored using two recombinant proteins, one specific for a
portion of the viral envelope (gp41) and the other for core (pl7,24,15). The
recombinant antigens were placed on separate areas of a nitrocellulose strip.
Diluted patient samples were incubated with the strips, and bound antibody was
detected using alkaline-phosphatase-conjugated anti-human antibody and bromo-
chloro-indolyl phosphate/nitroblue tetrazolium substrate. Excellent sensitiv-
ity was noted in a 40 minute assay using a visual read-out.
HIV antigen was monitored by sandwich immunoassays on nylon membranes. Two
assays were devised, one to detect the major core protein, p24, and the other
to detect envelope glycoproteins, gpl20 and gp41. Measurement of p24 has been
the more sensitive method with a detection limit of approximately 0.3ng/ml of
p24. Nylon membranes having a large surface area permit a high concentration
of capture IgG as well as dynamic sample flow-through.
W/P7 MT~4 pla<lue Assay Distinguishes HIV Serotypes and Distinct
Biologic Isolates
MASATOSHI TATENO, C. CHENG-MAVER, J. A. LEVY, Cancer Research Institute, UCSF
School of Medicine, San Francisco, CA.
The MT-4 plaque assay, as described by Harada et al (Science 229:563, 1985)
was used to quantitate infectious HIV. Six out of fourteen HIV isolates tested
formed plaques. Titers were in the range of 5 X 10 to 2.5 10 pfu/ml. Plaque
formation did not correlate with ability of the fourteen HIV to replicate in
established cell lines. Studies with the plaque-forming HIV isolates indicated
the presence of neutralizing antibodies in many HIV-positive individuals.
Neutralizing antibody titers as determined by the MT-4 plaque assay correlated
well with those determined by reduction in reverse transcriptase acitivity in
infected cells. The presence of these antibodies did not reflect a particular
disease state.
During this study, it was noted that HIV . did not form plaques in MT-4
cells. However plaqueswere induced by both HIV , an isolate obtained
5 months later from the same individual yielding HIV » , and HIV . , an
isolate recovered from a chimpanzee inoculated one year previously with HIV -.
The results of these studies suggest biologic changes in HIV over time in
the same individual and in a new host. Comparative serologic studies and
restriction enzyme and envelope gene analyses of HIV
should indicate the extent of antigenic and molecular1 changes1
occurred in these HIV isolates.
1IVSFl^tardHIVSF2A
have
WR5 Development of clonal cell lines from Kaposi's sarcoma (KS) lesion
(AIDS-KS) and their biological properties
ZAKI SALAHUDDIN*. S. NAKAMURA*, P. BIBERFELD , and R. GALLO*. * National
Cancer Institute, Betheda, MD . ** Karolinska Institute, Stockholm, Sweden.
AIDS-KS is an aggressive disease of young people and has a multifocal and
histologically complex nature. So far, its origin and pathogenesis remain
unknown, in part due to the lack of in vitro long-term culture system to pro-
duce large quantities of cloned cells. We report the isolation of KS cells,
their long-term culture and their morphological and biological characteris-
tics. They were isolated and cloned from KS lesions obtained from the lung of
AIDS-patients. These cells gave only a low response to classical endothelial
cell growth factors. However, conditioned medium from HTLV-II-transformed
cell 1 ines(HTLV-II-CM) supported the growth of KS cells for over 9 months and
large quantities were harvested for study. Immunocytological ly and morphologi-
cally, they shared the properties of lymphatic endothelial cells. CM from
these KS cells(KS-CM) were tested for activity on normal endothel ial (NE) cell
growth, IL-1, colony stimulating activity and other growth factors. KS-CM pro-
moted NE cell growth and it also had some effect on KS cell growth. NE cell
growth promoting activity in KS-CM differes from HTLV-II-CM. Molecular analy-
sis suggested similarity between basic fibroblast growth factor and KS-CM but
not with HTLV-II-CM. It also contained IL-1-like factor as measured by thymo-
cyte co-mitogenic assay. Because IL-1 could stimulate KS cell growth, it was
suggested that a autocrine mechanism of the IL-1-like factor was related to KS
cell growth. KS-CM has a potent neo-angiogenic activity. KS cells also induce
KS like lesion, when they are transplanted in athymic nude mice. No viruses
have been detected in cultured KS cells. In summary, our results are consistent
with the idea that pathogenesis of KS may depend on the production and response
to soluble factors.
B
WP8 Cyclosporine A (CSA) prevents infection of healthy T cells by HIV
but has no effect on pre-infected cells
MARK A. WAINBERG, N. BLAIN, Lady Davis Institute, Jewish General Hospital,
Montreal, Canada.
In order to determine the effect of CSA on ability of HIV to infect healthy
peripheral blood lymphocytes (PBL's), these cells were stimulated with PHA
for 48 hr, after which they were co-incubated with an excess of the HTLV-IIIn
strain of HIV, in the presence of polybrene (2ug/ml). CSA (0.5ug/ml) was
added to cultures after either 2 hr, 24 hr, or 72 hr. Infection of cells was
monitored both by an indirect immunofluorescence assay, using monoclonal
antibodies against viral proteins pl5 and p24 and by measuring reverse
transcriptase activity. In control cultures, untreated with CSA, the
percentage of positive cells after 5 days was about 25%. The addition of CSA
at 2 hr completely prevented viral infection in PBL's over 21 days. However,
if the addition of drug was delayed either 24 hr or 72 hr after infection,
the results showed that 1% and 15% of PBL's became positive for viral
antigens after 12 days and 5 days respectively. CSA had no effect on the
ability of HTLV-III -infected T cell line, H-9 cells, to replicate or to
express viral antigens. HIV was able to infect PBL's obtained from each of 6
kidney allograft recipients on long-term CSA anti-rejection therapy, as long
as CSA was not included in the culture medium. In addition, we were able to
repeatedly isolate HIV from patients entered into a Canadian therapeutic
protocol, in which CSA was used to treat AIDS patients with advanced disease.
Supported by Health and Welfare Canada and by the Medical Research Council of
Canada
lA/PR Role of synthetic peptide analogs of HIV on T-lymphocyte cells
and on virus replication.
S. CUMMING*, P. MCPHEE*. D. STAPLETON**, B. KEMP** and R. DOHERTY*.
*Virology Department, Fairfield Hospital, Fairfield 3078, and
**Department of Medicine, University of Melbourne, Repatriation General
Hospital, Heidelberg 3081, Australia.
Biological activity of HIV proteins is being studied by examining the
effect of synthetic peptide analogs on lymphocyte proliferation and on
virus replication in T4+ cell lines. Synthetic peptides from gpl20
(aa 2-13, 55-65 and 192-200), from gp41 (aa 582-596, 579-600, 659-670, and
766-778), and from ptat (aa 46-58 and 60-72) were synthesized using the
Merrifield procedure with COOH-terminal cysteine residues. One gpl20
peptide (192-200) has been found to be a potent inhibitor of virus
replication for isolate HTLV-IIIb (PNAS, 83, 9254-8, 1986) and a gp41
peptide (582-596 and extended peptide 579-600) has been found to be highly
antigenic (PNAS, 83, 6159-63,' 1986). Additionally the latter peptide has
sequence homology to other retroviral transmembrane proteins that are
known to suppress lymphocyte proliferation (Science, 230, 453-5, 1985).
Our results indicate that peptides 582-596 and 579-600 both suppress
lymphocyte proliferation with all other peptides having little or no effect.
Replication in T4+ cell lines of an Australian isolate, in the presence of
the above peptides, was compared with that of HTLV-IIIb. The results
indicate variable effects on virus replication. Thus these regions in
gpl20, gp41 and/or ptat proteins may play important roles In virus
replication at least 'in vitro'.
WR9
Correlation of Serum HIV Antigen Detection with Isolation of HIV from Patients
with AIDS and Patients at Risk for AIDS.
BONNIE DITTEL*. L.FALK", D.PAUL", J.SPEAR*. H.KESSLER*, and A.LANDAY*
•Rush Medical College, Chicago, 1L and v'* Abbott Laboratories, North Chicago, IL.
HIV isolation was attempted with peripheral blood mononuclear cells (MNC) from AIDS
patients (n=41), ARC patients (n=28), HIV seropositive asymptomatic homosexual males (AHM
(n=37), and HIV seronegative AHM controls (n=29). All samples were obtained from
individuals who were hospitalized or seen by a private physician. Cultures were performed
using peripheral blood MNC from healthy heterosexuals which were stimulated with PHA
(PHA-MNC) and cocultured with MNC of the above patient groups after addition of 1L-2 and
polybrene to the medium. Virus was isolated from 39 of 41 AIDS (95%), 16 of 28 (57%) ARC.
and 22 of 37 (59%) asymptomatic antibody positive homosexual males. All control patients
were culture negative. The association between HIV-Ag detection and virus isolation is shown
in the following table:
HIV
D24 Act
Culture Results Amona Patient Grouns
AIDS ARC AHM
Pos Neq Pos Neq Pos Neq
+
18 0 12 3 15 2
21 2 4 9 7 13
There was no significant association noted between detection of HIV-Ag and virus isolation
among AIDS patient. In contrast, there was a significant association (p<0.01) between HIV-Ag
in serum and positive cultures among ARC and AHM patients. Detection of HIV-Ag in the
serum of patients with ARC or asymptomatic HIV antibody positive individuals may be
predictive for isolation of HIV from MNC.
Ill
WEDNESDAY, JUNE 3
WP10 DETECTION OF DIFFERENT TYPES OF OLIGOSACCHARIDES IN ENVELOPE
GLYCOPROTEINS OF HIV/HTLV-III VIRUS
C.A. Abel, M.D. , C.H. Mielke, Jr., M.D., and J.C. Klock, M.D.
Institute of Cancer Research, Medical Research Institute, San Francisco, CA.
The envelope (Env) structures of the HIV/HTLV-III virus (gpl60 , gpl20) have
been defined as glycoproteins on the basis of their ability to bind Lens
Culinaris Lectin (LCL) , incorporate radiolabelled glucosamine in cell
cultures, and display a significant reduction in their molecular weight
following treatment with endoglycosidases . The deduced amino acid sequences
of several viral isolates indicates the presence of 28-30 potential N- linked
glycosylation sites (Asn-X-Ser/Thr) within gpl60; of these, approximately
half are located with invariant regions of the polypeptide chain. The
purpose of our experiments was to determine what types of oligosaccharides
are linked to HIV/HTLV-III Env glycoproteins. Cell-free supernatants
obtained after centrif ugat ion of cultures of HIV/HTLV-III infected cells at
their peak of reverse transcriptase activity, and Env glycoproteins isolated
by micro immuno-af f inity chromatography, were subj ected to SDS-PAGE,
electroblotted onto nitrocellulose, and probed with a panel of biotinylated
lectins of well defined carbohydrate binding specificity. Lectin binding
was determined before and after exo- and endog lycos id ase treatment of virus
components. Gpl60 and gpl20 bound Con A, LCL, PSA, PHA-E and LFA. This
binding patterns suggests that ol igomannosyl , as well as nonbisected
fucosylated and sialylated biantennary oligosaccharides are present in both
glycoproteins. Binding of PHA-L was weak. Binding of PNA to gpl20 after
desialylation, and absence of binding after alkaline hydrolysis suggests the
presence of sialylated 0-1 inked Gal-GalNac sequences within this
glycoprotein. Binding of lectins to gp41 was consistently weak.
Experiments are in progress to study the possible role of gpl20
oligosaccharides in the binding of HIV/HTLV-III to the T4 receptor molecule.
WR13 Use of PHA Can InCerfere With Efficient Recovery of HIV From
Periperal Blood Mononuclear Cells.
BARBARA MICHAELIS, CM. WALKER, H. LEGG, M. WHALEN, AND J. A. LEVY, Cancer
Research Institute, University of California, School of Medicine, San
Francisco, CA.
Methods for isolation of the human immunodeficiency virus (HIV) from peri-
pheral blood mononuclear cells of HIV-seropositive individuals vary among
laboratories, but usually involve mitogenesis with phytohemagglutinin, or
addition of normal allogeneic PMC from HIV seropositive blood donors. Using
PHA as a stimulus, we can routinely recover HIV from the PMC of about 50% of
healthy HIV-seropositive subjects, and from 75-90% of those with AIDS or ARC.
We have undertaken studies to determine if PHA and allogeneic lymphocytes
function equally well in virus isolation, or if some combiatlon of the culture
methods should be used to optimize recovery of HIV. Two sister cultures
established from the PMC of 11 HIV seropositive subjects received either, (1)
medium containing PHA (3ug/ml), or (2) medium without PHA, but with 6x10
normal human PMC previously stimulated with PHA. All cultures were passed
without PHA every 3-4 days and received normal PMC after day 9 as required.
Culture fluids were assayed after day 7 for reverse transcriptase activity.
Virus was recovered from 6 of the 11 subjects. Of these, 5 released virus
only when their PMC were cocultured with normal PMC and not PHA. One subject
released virus when his PMC were cultured with either PHA or normal PMC. These
results suggest that recovery of HIV from seropositive subjects can be improved
by co-culturing the PMC with allogeneic PMC from HIV-seronegative blood donors
without the use of PHA. It is conceivable that CD4+ cells in the normal PMC
popultaion act as additional targets for virus replication, or that the pre-
sence or PHA in the culture supernatant stimulates the generation of cells
with antiviral activity. These possibilities are under investigation.
WR11 Genetic Variation of the AIDS Virus In Vitro
JOSEPH GIBBONS* , W . PARKS- * , E . PARKS** , B . HAHN* , G . SHAW* .
*University of Alabama at Birmingham, Birmingham, AL; **University of
Miami, FL
Human immunodeficiency virus (HIV, HTLV-III/LAV) isolates from different
individuals have been found to exhibit striking genetic diversity. It is
unclear , however , to what extent these sequence changes reflect variation
that has occurred in vivo as compared to in vitro. To address this question,
we compared the restriction pattern of HIV from uncultured brain tissue with
that of virus from the same brain tissue cultured in peripheral blood
lymphocytes and H9 cells. 12/12 restriction fragments generated by 4 differ-
ent endonucleases were identical in the cultured and uncultured specimens. A
second approach to assessing the relative rate of viral genetic variation in
vitro was to subject virus to repeated rounds of cell- free terminal dilution
followed by expansion in H9 cells, thus forcing multiple rounds of viral
replication and reverse transcription. Sequential terminal dilutions of
virus isolate WMJ-1 over a five month period gave rise to five virus iso-
lates, WMJ-l(TD-l) to WMJ-KTD-5). WMJ-l(TD-5) infected H9 cell DNA had an
identical HIV restriction pattern to the original parental isolate WMJ-1 for
all 6 restriction enzymes tested (Sst I, Eco RI, Hind III, Bgl II, Pst I, Pvu
II) indicating that the predominant viral species had not changed. Further-
more, 10 out of 11 full-length HIV/x phage clones derived from WMJ-l(TD-5)
were identical to the parental WMJ-1 isolate. These data demonstrate that
the striking genetic diversity observed in independent HIV (HTLV-III/LAV)
isolates results from mutations that have occurred in vivo, not j^n vitro.
Since the magnitude of the genetic changes that occur in vivo is much greater
than that observed iri vitro, it is possible that genetic variation may be
selected by host immune pressures.
WR 14 Identificacion °f HIV s
Sensitivity to Serum Ne
CECILIA CHENG-MAYER, J.M. Homsy, J
School of Medicine, San Francisco,
The Human Immunodeficiency Virus
variation, especially in the gpl20
whether this genomic heterogeneity
independent HIV serotypes , twelve
ability to neutralize infection of
panel of diverse HIV isolates. Th
United States, Dominican Republic
isolated from nerve tissues.
erotypes with Distinct Patterns of
utralization
.A. Levy, Cancer Research Institute, UCSF
California
(HIV) displays a high degree of genetic
domain of the env gene. To determine
leads to the expression of different
HIV-positive sera were tested for their
peripheral mononuclear cells (PMC) by a
e HIV used included those from the
and Africa. Some of these HIV were
Results show that the isolates can be grouped into three distinct classes:
A) those neutralized by all sera tested at high titers,
B) those neutralized by only certain sera at low titers, and
C) those neutralized by none of the sera.
No correlation was observed between the ability of patient's sera to neutra-
lize HIV infection and serum anti-env or IFA titers or severity of disease.
The data define the presence of distinct HIV serotypes and suggest that for
vaccine development, further characterization of HIV serotypes and their
use in combination may be required.
WR12 Epitope Mapping of the HIV gP120 Antigen Using Monoclonal
Antibodies and Lambda gtll Library Screening
G.R. NAKAMURA*, C. SHIMASAKI** , D. DOWBENKO*** , T.J. GREGORY**, L.A.
LASKY***, ERIC J. PATZER* , et si., Genentech, Inc., 460 Pt . San Bruno
Blvd., South San Francisco, CA , USA
Although a small number of epitopes of the HIV envelope antigen have now
been mapped, there remain several critical regions of the molecule whose
locations are unknown. In particular, epitopes which may be responsible
for interaction with the virus receptor, the CD4 antigen, have yet to be
delineated in the envelope protein. In order to begin such an analysis, a
collection of monoclonal antibodies against the gpl20 antigen has been
developed. Seven monoclonal antibodies (MAbs) from heterologous rat-mouse
and ten MAbs from mouse-mouse hybridomas were generated against a recombi-
nant form of the gpl20 glycoprotein (rgpl20) from the human immunodefi-
ciency virus strain 1 1 lb. All seven of the rat-mouse MAbs , and three of
the mouse-mouse MAbs, reacted with intact rgpl20 and a 75,000 Dalton amino
terminal proteolytic fragment by Western blot analysis. In addition, three
other mouse-mouse MAbs bound to a 55,000 Dalton proteolytic fragment
corresponding to the car boxy-terminus of rgpl20. Competition analysis of
the various MAbs has allowed them to be placed into seven different groups.
In order to map the location of the epitopes recognized by these MAbs, a
collection of small, random DNA fragments from the gpl20 gene has been
incorporated into a lambda gtll expression vector. Screening of this
library with the various MAbs , as well as with polyclonal serum from
patients, has resulted in the mapping of epitopes recognized by these MAbs
as well as by the immune system of an infected individual. The location of
these various epitopes will be presented.
WR15
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112
WEDNESDAY, JUNE 3
U/piR Genetic Analysis of cis and trans Elements Involved in the Regula-
™ ' of HTLV-III.
ERNEST F. TERWILLIGER*. CRAIG ROSEN*, JOSEPH G. SODROSKI*, and WILLIAM A. HAS-
ELTINE** . Dana-Farber Cancer Institute, Dept . of Biochemical Pharmacology, Har-
vard Medical School, and **Harvard School of Public Health, Dept. of Cancer Bio-
logy, Boston, MA.
The genomes of HTLV-III and closely related viruses are unique in their pos-
session of several novel genes not found in any other retroviruses. These in-
clude the tat and art genes, whose products play crucial roles in regulating
viral protein expression, and the sor and 3' orf genes, whose functions remain
unclear. Recently an additional novel gene has been identified in HTLV-III,
encoded within an open reading frame designated the R region - preceeding the
tat gene. Recent results will be presented from an ongoing systematic mutation-
al analysis of elements involved either cis or trans in the regulation of the
virus. Regions being investigated include the 3' orf gene, the R region, and
the art gene product.
WR19 SIV/Delta Induced SAIDS in Rhesus Monkeys: Pathogenesis of Cultured
Isolates of Rhesus and Mangabey Monkey Origin.
MICHAEL MURPHEY-CORB , G.B. BASKIN, L.N. MARTIN, E.A. WATSON, Delta Regional
Primate Research Center, Tulane University, Covington, LA. U.S.A.
As a part of a tissue transmission study, we documented the association of an
HIV-related retrovirus, SIV/Delta, with simian AIDS (SAIDS) in rhesus monkeys.
Indirect evidence suggested that the origin of SIV/Delta in the rhesus, a pri-
mate of Asian origin, was an African primate, the sooty mangabey monkey, which
may harbor this virus asymptomatically .
More recently, we have examined SIV/Delta-related pathogenesis of in vitro
propagated virus isolated from several rhesus with SAIDS and one asymptomatic
mangabey. SIV/Delta isolated from a healthy sooty mangabey monkey is as patho-
genic in rhesus monkeys as are SIV/Delta rhesus isolates. Death due to SAIDS,
evidenced by lymphocyte subset alterations, abnormal immune responsiveness, op-
portunistic infection, and lymphoma in one animal, usually occurs in infected
animals within 2-12 months post-inoculation, regardless of the source of virus.
Several rhesus isolates are pathogenic; one isolate is singularly neurovirulent.
Of 8 animals inoculated with the neurovirulent isolate, 4 have died with symp-
toms of SAIDS; in addition, all had retroviral encephalitis evidenced by numer-
ous syncytial cells in brain tissue. Long-term in vitro propagation of SIV/
Delta may result in a loss of pathogenicity. Virulence may be re-established,
however, by passage of the attenuated virus from an infected healthy rhesus
monkey to a second animal. A comparison of the genetic and antigenic composi-
tion of these isolates will provide invaluable information on viral factors re-
sponsible for pathogenesis and neurovirulence.
WR17 Hifferential Recognition of HTLV-II I/HIV Envelope Antigens is
Correlated with Clinical Outcome
TUN-HOU LEE*, R. REDFIELD**, M.-J. CHOU*, J. ALLAN*, D. BURKE**, M. ESSEX*,
et al., *Harvard School of Public Health, Boston, MA, **Walter Reed Army
Institute of Research, Washington, DC.
Two types of antigenic domains are identified on HTLV-I I I/HIV envelope
protein, gpl20. One, designated gpl20(N), requires the presence of
disulfide bonds to maintain their antigenicity, while the other, designated
gp!20{R), does not. Analysis of 135 coded serum samples from patients who
have been clinically staged by a Walter Reed staging classification system
reveals that patients with AIDS (WR6 stage) are three times less likely to
have antibody to gpl20(R) than patients with just lymphadenopathy (WR2
stage). In contrast, all 135 patients had detectable antibody to gpl20(N).
This observation raises the possibility that differential response to
different antigenic epitopes may have prognostic value and that gpl20(R)
may be more likely to elicit protective immunity than the more native
gpl20(N).
WP20 Packaging defective mutants of HTLV-III/HIV
AMANDA FISHER, C. Guo, B.R. Starcich, R.C. Gallo & F. Wong-Staal .
Laboratory of Tumor eel 1 Biology, National Cancer Institute, NIH, Bethesda
MD 20205, USA.
Although much is known about HTLV-III replication and the processing of
structural components (gag, pol and env) in infected cells, the precise mech-
anism by which genomic viral RNA is preferentially packaged into virion par-
ticles is not known. Studies in avian and murine retroviral systems have
suggested that (i) virus particle formation can occur in the absence of genomic
RNA and (ii) that sequences intervening the 5'LTR and gag gene are crucial for
virus specific packaging. To see whether analogous sequences in HTLV-III/HIV
are important in selective packaging of HTLV-III genomic RNA and hence enable
the construction of empty (non viral RNA containing) particles, we produced a
series of mutants of the biologically active molecular clone pHXB2-D( HTLV-I 1 1 g)-
These mutants were deleted of 10 to 50 base pairs in the region bordering the
5'LTR and gag. Four such clones were studied in detail and shown to generate
viral proteins and viral particles (morphologically indistinguishable from wild
type) upon transfection into cos-1 cells. In contrast to the wild type virus,
virus generated from the mutant clones was either poorly infectious (3 clones)
or resistant to transmission (1 clone) when co-cultured with lymphoid cells.
Furthermore, preliminary analysis of the virus derived from the mutants indi-
cate unusually low levels of viral RNA. These data hint that the mutants are
defective in their ability to recognise and efficiently package viral RNA. In
order to unequivocally define the status of our candidate 'packaging mutants'
we have constructed a series of cell lines which stably express high levels of
of mutant virus. A detailed analysis of these cell lines will be presented.
WR18 Approach to Development of an AIDS Vaccine Using HGP-30, a
Synthetic pl7 Peptide Analogue
ALLAN L. GOLDSTEIN*, P.H. NAYLOR*, P. SARIN**, C.J. GIBBS***, B Z00K**, S.S.
WANG**** et al. *The George Washington School of Health Sciences, Washington,
D.C., **The National Cancer Institute, Bethesda, MD., ***The National
Institute for Neurological Diseases, Bethesda, MD, ****Alpha 1 Biomedicals,
Inc. , Washington, DC.
Antisera against HGP-30 (HIV synthetic pl7 gag peptide analogue — 30 amino
acids), prepared by solid phase peptide synthesis, as well as antisera against
thymosin a (Ta ) are highly effective in neutralizing the AIDS virus in
vitro. Neutralization is defined as inhibition of viral growth in H9 infected
human cells assessed both by measurement of reverse transcriptase and viral
antigens (pl7 and p24). HGP-30 contains a region of homology with pl7 from
position 86 to 115. The HGP-30 antisera is not significantly cross-reactive
with Ta . When coupled to KLH, the antigen is highly immunogenic and effective
in generating serum antibodies to HGP-30 as well as HTLV-IIIB pl7. Used with
either alum or complete Freund 's adjuvant , the vaccine is immunogenic but not
toxic in mice, rabbits, dogs and primates. The demonstration that antibodies
to HGP-30 are neutralizing and cross-react with p 1 7 provides a new and
potentially more specific candidate for development of an AIDS vaccine. Using
HGP-30, a small synthetic peptide, as the immunogen in a vaccine against AIDS
offers the advantages of 1) ease of large-scale preparation and uniformity of
a chemically defined product, 2) safety; does not require use of killed or
attenuated virus, virus-infected cells or genetically manipulated products, 3)
overcomes the problem of genetic drift; in contrast to env proteins the pi 7
epitope identified is highly conserved. (Supported by grants and/or gifts from
the NCI (CA24974), Alpha 1 Biomedicals, Inc., and Viral Technologies, Inc.)
WP21 Comparative Sensitivity of Tests for Detection of HIV Infected
Cells. A.J. BODNER, A.J. CORRIGAN, M.M. MANAK, G. KELLER, L.L.
SIMEK AND R.C.Y. TING, Biotech Research Laboratories, Inc., Rockville, MD.
HIV infectivity assays such as virus neutralization determinations require
that sensitive methods be used for detection of infected cells so that infec-
tion can be detected as early as possible. We have developed two sensitive
tests for detection of infected cells, an immunocytochemical slide test using
APAAP methods (alkaline phosphatase anti alkaline phosphatase) and an ELISA
p24 capture assay. These two tests were compared for sensitivity with two
other methods for detecting infected cells, reverse transcriptase (RT) assays
and hybridization of P labeled core protein DNA probes with disrupted cells.
The test samples were cultures of HTLV-IIIB infected H9 cells which had been
serially diluted with H9 cells so that the cultures all contained 10 cells/ml
but various concentrations of infected cells. The cells were washed prior to
being serially diluted and were then cultured for 14 hours before being tested.
The lowest concentration of infected cells which the various tests could
detect were as follows: the APAAP slide test, 0.01%; the capture test, 0.02Z
on pelleted cells and 0,21 on supernatant; the DNA probe hybridization test,
0.15%; the RT assay, L.5Z. The APAAP slide test and the capture assay were
also comparable with each other when used over a two week period to detect
emergence of infected cells in cultures of peripheral blood lymphocytes which
had been infected with three serial 10-fold dilutions of HTLV-IIIB.
Since the capture assay is considerably less labor-intensive than the APAAP
slide test but has comparable sensitivity, the capture assay is the better
method for many types of infectivity assays. The APAAP slide test, however,
has proven to be very effective for detecting HIV antigen presence in sections
of tissues such as brain and lymph nodes.
113
WEDNESDAY, JUNE 3
WR22 Use of HaPcen Labeled DNA Probes for the Detection of HIV Sequences
in Infected Cells. M. MANAK, G. KELLER, C. CUMMING, M. BOCKELMAN
AND B. SISSON. Biotech Research Laboratories, Inc., Rockville, MD.
A hapten labeled DNA probe has been developed for the detection of HIV RNA
in infected cells. A part of the HIV genome which includes sequences coding
for the gag region of the virus were subcloned into a pBR322 vector, and the
purified plasmid DNA was chemically labeled with dinitrobenze'ne. This probe
was used to detect HIV sequences in infected H9 cells. Serial dilutions of
infected cells were mixed with uninfected cells, and the RNA from a total of
10 cells was extracted with phenol and ethanol precipitated. The RNA was
slot blotted onto nitrocellulose membranes using the slot blot apparatus of
Schleicher and Schuell. The filters were baked and hybridized with the hapten
labeled probe. Specific hybridization was visualized by reactivity with
rabbit anti-hapten antibody followed by an alkaline phosphatase conjugated goat
anti-rabbit IgG, and color development. The sensitivity of detection is 1 pg
as^tested on dilutions of plasmid DNA and was similar to that observed with
a P labeled probe and autoradiography. Virus nucleic acid sequences can be
detected in extracts of as little as 10 infected cells (10 viral genome
equivalents). For even greater sensitivity, the probe can be used to detect
viral sequences in individual infected cells by in situ hybridization. Cells
were fixed on microscope slides with 4% Paraformaldehyde and stored in 70%
ethanol until tested. Following a 3 hour hybridization, infected cells were
visualized by the double antibody system described above. Using this method,
individual infected cells can be detected in a vast excess of uninfected cells.
WR25 Localization of the Transmembrane Anchor Domain of the Envelope
Glycoprotein, gpl60, of Human Immunodeficiency Virus
PHILLIP W. BERMAN*, W. NUNES, 0. HAFFAR, Genentech, Inc., So. San Francisco,
CA, USA.
In order to understand the mechanism of HIV-1 infection, it is important to
determine which domains of the HIV envelope glycoprotein are exposed on the
surface of the virus. While there is general agreement that gp41 is an
integral membrane protein, its orientation in the membrane, and the number of
times it spans the viral envelope have yet to be determined. Hydropathic
analysis of gpl60 revealed two potential transmembrane biding domains, both
occurring in gp41 (residues 512-541, and residues 684-707). We have attempted
to identify the membrane anchor region by construction of a series of mutant
gpl60 genes with truncations or deletions occurring in the gp41 region.
Transfection of thee variants into mammalian cells demonstrated that mutations
that preserved the first hydrophobic domain in gp41 and deleted the second
hydrophobic domain encoded proteins that were secreted from the cells.. These
results demonstrate that the first hydrophobic domain of gp41 is not sufficient
for membrane biding and suggest that the carboxyterminal 174 amino acids of
gpl 60 contains the membrane anchor sequence. Although it is possible that the
two hydrophobic domains in gp41 interact to form a membrane binding domain, the
simplest model would suggest that the entire gpl60 molecule, with the exception
of the last 174 residues is exposed on the viral surface.
WR23 Incidence of Seronegativity to HIV and HTLV-I in individuals
infected with either virus.
BERNARD J. POIESZ*. C. EHRLICH*. L. PAPSIDERO**. R. MONTACNA**. S.
KWOK***. J. SNINSKY***, et.al., *SUNY Health Science Center and VA
Medical Center, Syracuse. NY, **Cellular Products, Inc., Buffalo, NY,
***Cetus Corporation, Emeryville, CA
One thousand AIDS/ARC patients and 120 adult T-cell leukemia or HTLV-I
carriers were prospectively tested for antibodies to HIV or HTLV-I, re-
spectively in an ELISA assay. One of 1000 AIDS/ARC patients (0.1%) were
seronegative for anti-HIV antibodies and 1 of 120 HTLV-I infected patients
(0.8%) were seronegative for anti-HTLV-l antibodies. Seronegativity was
confirmed by Western blot and radioimmunoprecipitation assays and was re-
peatedly negative in several samples obtained over one year's time. HIV or
HTLV-I infection was confirmed by detection of viral proteins by immuno-
peroxidase staining of infected tissue with antiviral monoclonal antibodies and
by detection of viral nucleic acids via enzmatic amplification and oligomer
restriction detection techniques. Hence, seronegativity to these 2 viruses
occurs with a finite, but real, frequency. Enzymatic in vitro gene
amplification identified both seronegative individuals and represents a
sensitive and specific method to confirm the diagnosis of HIV and HTLV-I
infection.
WP26 Serodi agnosi s of H I V-l -i nf ecti ons by an Oligopeptide
" ELISA
KARL-OTTC I HABERMEHL , B ■ ZORR , H ■ HAMPL , H . ZE ICHHAROT , P ■ W I LL I NGMANN ,
Inst. of Clin. and Exper . Vi rology , Free University of Berlin,
Hi ndenburgdamm 27, 1000 Berlin 45, Germany
The ELISA has been proven as a highly sensitive and specific method in
HlV-diaanosis. Nevertheless, unspecific reactions resulting in false
positive results occur due to impurities of the antigen preparations. This
problem can be solved in principle by using defined synthetic oligopeptides
representing well conserved epitopes from different structural proteins of
HIV-1. A number of synthetic oligopeptides (synthesized by Dr.Frenzel,
Biochrom) have been screened in different ELISAs for reactivity against
HIV-positive sera or negative controls (blood donors or patients from
routine virus-diagnostic). Four oligopeptides containing 21 aminoacids each
representing different epitopes from the proteins pl8, p24, gp41 or gpl 20
with an optimal serologic specifity were selected and combined as a mixture
in an ELISA. It could be demonstrated that with 505 blot-confirmed HIV-
positive sera a reactivity of 100 % could be obtained. 2729 out of 2735
negative sera were in this ELISA non-reactive, indicating a specificity of
99,8 %. The good specificity and sensitivity was underlined by a significant
difference between the extinctions of the non-reactives and the reactives in
so far as 97 % of the positive probes showed an extinction of > 1.95 and
99,3 % of the negatives an extinction of < 0.15.
WR24 Genetic Characterization of Biologically Different HIV-
Variants
H. RUBSAMEN-WAIGMANN*
L. BIESERT*, K. HENC0"
H. VON BRIESEN*
H.D. BREDE*
HERBERT KUHNEL*
♦Georg-Speyer-Haus, Frankfurt, FRG, **DIAGEN GmbH, Dtisseldorf, FRG
Human immunodeficiency virus (HIV) was cultured from either peripheral
blood lymphocytes (PBL) or in some cases from cerebrospinal fluid (CSF).
Cultures for virus isolation were performed from more than 180 geman
AIDS, ARC, LAS and virus exposed asymptomatic patients. These isolates
differed remarkably in their biological properties (cytopathic effect
on lymphocytes and replication rate).
In the majority of AIDS-patient with neurological symptoms well-growing
strains were obtained from PBL, whereas all but 2 isolates from CSF of
the same patients grew slow and to only low titres on PBL.
One isolate from PBL was molecularyly cloned. Restriction analysis
and nucleotide sequencing of several of the clones revealed the simultaneous
existence of at least 4 distinct HIV variants in the peripheral blood
of the patient. The amino acid sequence divergence of the variants from
LAV/HTLV III. in the env/lor region was about 10% with multiple insertions
and deletions.
While the isolate from the patient's periphery grew readyly and with
the formation of big syncytia on PBL, the virus from his CSF grew badly
and with only marginal CPE. The genetic characterization of this slowly
growing strain is in progress.
WP27 HIV antigenemia in patients with AIDS or related disorders : a study in European
and Central African populations.
F. BARIN*. A.BAILL0U*. E. PETAT*. G. GUER0IS", P. CH0UTET***, A. G0UDEAU* et
al., *lab. Virologie, CHRU Bretonneau, Tours, France, "lab. Hematologic. CHRU Trousseau,
Tours, ***Dept Medecine Interne, CHRU Bretonneau, Tours.
The presence of human immunodeficiency virus antigen (s) (HIV-Ag) was analysed in the serum
of AIDS patients, ARC patients and symptomless seropositive people using a solid-phase sandwich-
type ELISA (Abbott, Abbott Park, II.). Individuals entering the study were either French (group
I ) - or Central African residents (group 2).
GROUP I (Nb : 80) HIV Ag was detected in 48 % (10/21) of AIDS patients, 22 X (5/23) of ARC
patients, and 3 % (1/36) of symptomless seropositive individuals. HIV antigenemla was correlated
with the absence of antibody to HIV gag antigens with a competitive antibody Immunoassay
employing HIV core antigens produced by recombinant DNA technology (ENVACORE^, Abbott). Fifteen
out of 27 anti-gag negative Individuals (56 I) were HIV-Ag positive against only 1 out of
53 anti-gag positive individuals (2 I ; p<10"7). Longitudinal studies showed that HIV-Ag was
transient in primary HIV infection. On the contrary, late appearence of HIV-Ag 1n seropositive
individuals was associated with persistent antigenemla and seemed to correlate with clinical
deterioration.
GROUP 2 (Nb : 144) Only 1 out of 55 AIDS patients (2 t) was HIV Ag positive. None of 52
ARC patients and 37 symptomless seropositive Individuals presented HIV antigenemla. In contrast
with European AIDS patients, 95 I of AIDS patients (55/58) from Central Africa were positive
for antibody to HIV core antigens.
This study shows that expression of HIV-Ag in serum 1s correlated with absence or
disappearance of antibody to gag antigens.
The clinical value of HIV antigenemla that may exist for seropositive European individuals
cannot be applied to Central African seropositive populations. This observation has practical
and fundamental implications that will be discussed.
114
WEDNESDAY, JUNE 3
WR28 Expression of a Functional HIV tat-Ill Protein from a Chemically
Synthesized Gene.
E.R. HENDR1CKSON, B.Q. FERGUSON, L.S. STREHL. L.T. BACHELER, D.J. COX
AND S.R. PETTEWAY, E. I. Du Pont de Nemours. Medical Products Department,
Wilmington. DE.
The predicted 261 base pair coding sequence of HIV-IIIB tat-II I has been chemically
synthesized, cloned in E. coli and expressed in HeLa cells. The tat-Ill sequence was
fused to a translational start signal and placed under SV40 early transcriptional
control. Co-transfection of the synthetic tat-Ill gene along with a reporter gene
(chloramphenicol acetyl tranferase or (3-galactosidase) linked to an HIV LTR confirmed
that the synthetic gene product exhibits similar activity to tat-III expressed from
HIV genomic DNA in the trans-activation of the LTR. In the design of the synthetic
coding sequence, unique restriction sites that do not change the primary amino acid
sequence were introduced to facilitate assembly of the gene. These restriction sites
can be used to easily replace segments of the gene with synthetic oligonucleotides
containing any desired sequence changes (cassette mutagenesis). This approach is
being used to analyze structural changes and their effect on the function of the
tat-III gene product.
WR31 Transmission of Human Immunodeficiency Virus to
Non-hematopoietic Cells by Co-cultivation.
HIROO HOSHINO, YASUHIRO TAKEUCHI, Gunma University School of
Medicine, Maebashi, Gunma, Japan
Infection with human immunodeficiency virus (HIV) often induces
neurological disorders. We examined susceptibilities of non-
hematopoietic cell lines to HIV. HIV produced by H9/HTLV-IIIB
cells, kindly supplied by Dr. R. C. Gallo, was mainly used. NP-1 ,
NP-2, U-251 MG and HOS human cells and S+L~CCC cat cells were co-
cultivated with lethally irradiated HIV-producing Molt-4 cells.
The former three cell lines had been derived from human gliomas.
Only NP-1 cells (0.2-0.5%) became immunof luorescent on indirect
immunofluorescence assay. Sera of seropositive hemophiliacs
inhibited the transmission. U-251 MG cells were not susceptible
to HIV, although these cells expressed glial fibrillary acidic
protein which is known to be specifically detected in glial
cells. On the other hand, 1-43% of NP-1, NP-2, U-251 MG, HOS or
S+L~CCC cells became immunof luorescent after co-cultivation with
T cells doubly infected with HTLV-1 and HIV. Thus, HIV was
transmitted efficiently to non-hematopoietic cells in the pre-
sence of HTLV-1. Sera from ATL patients inhibited the trans-
mission. HIV antigen-positive NP-1 and NP-2 cells were cloned.
Each clone contained 1 or 2 copies of HIV genomes. Some clone
produced infectious HIV abundantly, while some clone produced
non-infectious HIV. Some clone contained defective HIV. The
procedures described here may be useful for elucidation of bio-
logical and pathogenic properties of HIV.
WP29 Neurological AIDS: Isolation and characterization of
noncytocidal natural variants of human immunodeficiency virus
(HIV) from AIDS patients with neurological disorders
RITA ANAND*. J. MOORE*, T. CHEUNG**, F. SIEGEL***, S. FORLENZA**** and C.
REED*. *Centers for Disease Control, Atlanta, Ga., **Coler Memorial
Hospital, Long Island, New York, ***Long Island Jewish Hospital, Long
Island, New York, ****Nassau County Medical Center, East Meadow, New York.
Heterogeneity in AIDS virus isolates has been well documented but has not
been correlated with the clinical manifestations of AIDS or with the
functional biology of the virus. The occurence of central nervous system
involvement in certain AIDS patients with minimal neurohistopathology
prompted us to isolate viruses from such patients and delineate their
cytopathic properties. Five virus isolates, termed NA1-NA5, were obtained
from four neuro-AIDS (NA) patients. The isolates were identified as HIV by
antigenic cross-reactivity and nucleic acid hybridization to HIV-specific
antibodies and DNA probes. The replication and cytopathic properties of
these isolates were studied and compared with lymphadenopathy-assoclated
virus (LAV) in vitro. All NA Isolates exhibited replication efficiency
equivalent to LAV, but four of five isolates did not kill T4 cells. The
frequency of T4-positive cells in LAV-infected cultures (normal adult
peripheral blood lymphocytes) decreased to 1.6% in 15 days, but the
frequency of T4-positive cells in uninfected cultures and in cultures
Infected with noncytocidal variants remained between 46% and 64%. These
findings provide evidence for the existence of noncytocidal natural variants
of HIV, and raise the possibility that in some AIDS patients neurologic
disorders might be caused by HIV variants that are noncytocidal to T4 cells.
WR32 HIV-related viruses in pregnant women in Gabon.
ERIC DELAPORTE*, M.C.DAZZA**, S.WAIN-HOBSON***, F.BRUN-
VEZINET**, B.LAROUZE***', A.G.SAIMOT* *• •, et al. CIRMF (Gabon)*, Laboratoire
de virologie, hopital Claude Bernard**; Unite" de Biologie Moleculaire et d1 immunologic
des retroviruses, Institut Pasteur***, IMET/INSERM U13****, Hopital Claude Bernard -
Paris - France.
During a study of vertical transmission of retroviruses in Gabon (Nov. '85 to
Nov. '86), serum samples from 750 women were collected each 3 months during and
after pregnancy. Twenty-four sera were found HIV-1 positive by Efisa (Elavia). By
HIV-1 Western blot ( WB)(LAV-Blot), one serum was negative and 2 were confirmed
as HIV-1 positive. Twenty-one sera did not fit the criteria for HIV-1 positivity but
exhibited the p25 band associated to the p55 or to another band of about 37 kD
(14 cases). The same banding pattern was found in all serial samples from each
woman. All these 21 sera were HIV-1 negative by RIPA. By LAV-2/HIV-2 Elisa all
21 sera were negative and by HIV-2 WB all presented the p26, with no antibodies
to the envelope glycoproteins.
We performed retrovirus isolation from peripheral blood lymphocytes from 2 of
these 21 women. In the two cultures a reverse transcriptase activity (RTa)was
detected at day 21 in the cell-free supernatants. The RTa persisted at the same
level (50x10 - 90x10 cpm/ml), without peak and with no obvious cytopathic effect
on the infected T-lymphocytes. No decline of the lymphocyte proliferation was
observed. The cell-free supernatants reacted with HIV-1 polyclonal antibody by an
antigen capture assay. By an indirect IF assay the cultured infected T-lymphocytes
from the 2 women reacted obviously with the sera of each patient and weakly
with human HIV-1 antibodies. No reaction was observed with HTLV-I nor HIV-2
antibodies. Southern Blot analysis showed a weak hybridization with the entire
HIV-1 genome in conditions of high stringency. In January 1987, alt these women
were healthy and their total lymphocytes count was normal.
WP30 A simPle and economical HTLV-III TEST for underdevelop
countries.
AUGUSTA K.TAKEDA;OCUNO L.; TATUTA C; OUTUKI N.K.; Salck Ind.Com.
Prods. Biol. Sao Paulo - Brasil.
Present HTLV-III tests require the use of equipment and techni-
cal skills not readily available in underdeveloped countries. In
addition the cost per test make it impossible for these countries
to establish a policy of individual testing for all blood donors.
This has resulted in the practice of blood pooling in order to re-
duce cost. To overcome these problems, PASSIVE HEMAGGLUTINATION TEST
(PHT) has been established. This test Involve the fixed red cells
sesitized with HTLV-III antigen. 25ul of sera samples of each do -
nor is mixed in 25ul of phosphate buffer saline .ISM pH 7.2 and
adding 25ul of sensitized red cells. After 15min PHT become positi-
ve if agglutination patterns can be seen, and negative when cells
do not agglutinate and form a well defined button. The specificity
and sensitivity is exactly the same compared with ELISA. In regar-
ding to reproductlvlty and stability is far better then ELISA when
it was compared with 1000 sera samples of blood donnors , suspected
and AIDS cases. All positive samples in any methods were confirmed
by WESTERN BLOT. In conclusion the PHT is very easy to be done, to
be read does not require the use of equipment or a trained techni-
cian-,and it is very fast;15min compared to 120min.The cost is only
1/20 of current methods, before adding the cost of equipment.
WR33 HIV ^utralizi"? Antibodies to a Recombinant Segment of the Virus
Envelope: Studies with Multiple Virus Variants and Neutralizing
Epitope Definition
JAMES R. RUSCHE*, D. LYNN*, R. GRIMAILA*, T. MATTHEWS**, M. ROBERT-GUROFF***,
S. PUTNEY*, et al. ,*Repligen Corporation, One Kendall Square, Building 700,
Cambridge, MA, "Department of Surgery, Duke University Medical School, Durham,
NC, ***Laboratory of Tumor Cell Biology, National Cancer Institute, National
Institute of Health, Bethesda, MD.
PB1, an E. coli produced segment from the carboxyl-terminal half of the gpl20
envelope protein, elicits antibodies that neutralize HIV infection in vitro
(Science, 234, 1392-1395, (1986)). This neutralization is HIV strain specific.
We have produced the same region from four other HIV isolates and used these as
immunogens individually and in combinations to determine the virus neutraliza-
tion patterns and to achieve an immunogen capable of eliciting broadly neutrali-
zing antibodies. In addition, we have obtained fragments of PB1 by genetic
and proteolytic means to define more precisely the epitope that elicits the
neutralizing response. These have been used as immunogens and in competition
binding experiments with neutralizing sera. Implications of the results of
these approaches for the development of an effective vaccine against AIDS will
be discussed.
115
WEDNESDAY, JUNE 3
VA/P34 Molecular Characterization of the Type D Retroviruses in Macaques
LESLEY M. HALLICK*. M.K. AXTHELM**, R.A. KARTY*, B.J. WILSON**,
S.M. SHIIGI**, AND W.P. MCNULTY**, *Oregon Health Sciences University and
**Oregon Regional Primate Research Center, Portland, OR.
A series of related, but genetically distinct type D retroviruses has been
isolated from Asian macaques suffering from simian AIDS (SAIDS) . Two serotypic
groups are recognized: SRV I, originally isolated from the California and New
England PRCs and most closely related to Mason-Pfizer monkey virus; and
SRV II, isolated from the Oregon and Washington RPRCs and associated with the
Kaposi's sarcoma-like neoplasm, retroperitoneal fibromatosis (RF) . The SRV II
strain (IIC) isolated from M. nigra with a high incidence of SAIDS/RF at the
ORPRC has been cloned in collaboration with the CAPRC , and used to screen
other macaque species at the ORPRC. Currently 5T of the rhesus colony
(M. mulatta) are virus-infected, and an additional 25% have evidence of prior
infection. The rhesus isolate (SRV IIR) Is serologically indistinguishable but
genetically distinct from SRV IIC, and is associated with a lower mortality
rate. A severe form of SAIDS has also been observed in the Japanese macaque
(M. fuscata) troop at the ORPRC. Restriction maps of isolates from affected
animals are identical to SRV IIR. In contrast to our experience with
M. mulatta, SRV IIR Infection appears to result in clinical SAIDS and death in
a high percentage of M. fuscata. Two SRV IIR isolates, one from a Japanese and
one from a rhesus macaque, exhibit a slightly altered restriction pattern.
These two variants appear to be identical to one another.
Recently, two M. mulatta imported from the People's Republic of China have
been shown to be actively infected with a new type D SRV more closely related
to SRV I than to SRV II. Investigations are underway to determine whether this
strain constitutes a third serotype.
WR37 Molecular Cloning and Nucleotide Sequence of a Highly Cytopathic
Strain of Human Immunodeficiency Virus.
BRUNO SPIRE*, V. ZACHAR**, F. BARRE-SINOUSSI*, F. GALIBERT***, J.C.CHERMANN*
and A. HAMPE***,*Institut Pasteur, Viral Oncology Unit, Paris, France,
** Institute of Virology SAV, Bratislava, Czechoslovakia, *** Hopital Saint-
Louis, laboratoire d'Hematologie Experimental, Centre Hayem, Paris, France.
A highly cytopathic variant of the human immunodeficiency virus type 1/
HI V 1/ was isolated from a zalrian patient with AIDS. When biologically tested
on MT4 cells, a striking cytopathic effect, estimated to surpass at least one
thousand times that of HIV 1 prototype was disclosed. Preliminary experiments
suggested that this variant possesses a completely different restriction en-
zyme pattern in Southern blot analysis. In order to determine the putative
genomic regions involved in observed biological features, a molecular cloning
of this isolate proviral genome was accomplished. The genomic library was pre-
pared from partially digested DNA of persistently infected CEM cell line and
established by means of EMBL 3 vector. Recombinants were obtained on succes-
sive screening employing HIV 1 probes. The nucleotide sequence and resulting
implications which will be presented might inform on the cytopathogenicity of
AIDS viruses.
WP35 Expression and Analysis of HIV gP120 Analogues Secreted from
' Saccharamyces Cerevisiae
DONALD J. DOwBENKO*, M. RENZ*, C .Y . CHEN*, R.A. HITZEMAN*. Genentech, Inc.,
So. San Francisco, CA, USA.
Yeast cells have been engineered to produce a secreted form of the HIV
envelope glycoprotein (gP120). The 500 amino-acid coding region of the gP120
envelope gene was fused to the human serum albumin signal sequence and
programmed for expression with the yeast chelatin promoter. The resulting
plasmid was transformed into a wild type yeast strain (20B-12) or into a yeast
mnn9 manno protein mutant (Tsai e_t aj_. , J. B.C., 259, p. 3805, 1984). Proteins
secreted from cells in the presence of copper were analyzed by immunoblotting
and shown to react with several HIV gP120-positive human and rabbit sera.
Secreted protein from wild type 20B-12 cells migrated as a >300 kd polypeptide
smear on low percentage gels presumably due to hyperglycosylation of the
envelope protein. However, protein from the supernatant of mnn9 cells migrated
as a diffuse band at ~130 kd. In both cell lines, the secreted envelope
glycoproteins were sensitive to N-glycanase treatment; however, only the 130 kd
mnn9 protein bound to an immunoaff inity column containing human anti-HIV IgG.
Rabbit sera directed against purified mnn9-gP130 reacted with native gP120 from
HIV infected cells.
WR38 Reactivation of Human Immunodeficiency Virus Long Terminal Repeats
by Herpesvirus Infection
J .P. MOSCA*. D. P. BEDNARIK*, N. B. K. RAJ*, W. A. HASELTINE**, G. S. HAYWARD* and
P.M. PITHA*, *The Johns Hopkins Univ. School of Medicine, Baltimore, MD,
**Dana-Farber Cancer Institute, Boston, MA
We have shown recently that the expression of chloramphenicol acetyl-
transferase (CAT) directed by human Immunodeficiency virus (HIV) long terminal
repeat (LTR) 1n stably transfected cell lines can be activated both by HSVtI
Infection (Mosca, et al., Nature 325:67-70, 1987) and 5-azacyt1d1ne treatment
(Bednarlk, et al., J. Virol., In Press). Both HSV Infection and 5-azacyt1d1ne
treatment led to an Increase in CAT activity, accumulation of CAT mRNA and an
Increase 1n CAT gene transcription, suggesting that the activation occurs at
the transcriptional level. The HSV gene product responsible for HIV LTR
activation was Identified using HSV-I ts mutants and the cloned HSV-I
1mmed1ate-early genes for IE175K, IE110K proteins and the late structural
protein Vmw65. The Inducible region within the HIV LTR was Identified using
the Bal 31 deletions 1n the 5' region of HIV LTR. When a 71 nucleotide long
fragment from HIV LTR was placed In front of a heterologous, non-1nduc1ble
gene (murine a-39/+22 CAT), the expression of a-CAT gene was Induced by HSV
infection. The HIV LTR can also be Induced by cytomegalovirus (CMV)
Infection; however, the results suggest that the activation by CMV does not
occur through the same sequences that are recognized by the HSV factors. In
addition to HSV-I Induced activation, the effect of the HIV; coded
transactivatlon TAT protein on the HIV LTR was also Investigated.
UfD*3fi Identification of gag-epitopes by a panel of MAb in a serie of HIV
Wrj0 isolates
IRENE N. WINKEL, M. TERSMETTE, P. MIEDEMA, J.G. HUISMAN
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service,
incorporating the Laboratory of Experimental and Clinical Immunology of the
University of Amsterdam, Amsterdam, The Netherlands
Immunization of Balb/c mice with TX-100 disrupted sucrose gradient purified
HIV enabled a panel of 10 monoclonals against HIV-gag products to be produced.
Characterization by immunoblotting and radioimmunoprecipitation assay using
l"I-labeled HIV-proteins together identified 8 hybridomas which were
reacting variously with gag-proteins pr55 and p24 and 2 hybridomas reacting
with pr55 and pl8 . In order to characterize the different anti-gag clones a
cross-competition RIA was developed. Purified IgG from each of the clones was
labeled with 125t and each clone allowed to compete with itself and all
other clones as radiolabels for HIV antigens bound to sepharose beads. It was
concluded that these monoclonals react with presumably 6 different
gag-epitopes. Three of these were mapped on tryptic peptides. Different
combinations of antibodies were used to detect the presence of HIV-gag
products in various isolates by a p24 capture assay. CLB-21 as catching
antibody and 125i-CLB-14 as tagging antibody appeared to be the most broadly
reactive of all antibodies. Screening of 70 HIV isolates positive in this
capture assay, two isolates failed to react with CLB-47. This was not due to a
low level of HIV expression since elevated levels of RT activity were
observed. To explain this lack of reactivity, a genetic variation or
post-translational modification of the anti-gag epitope might have occurred.
U/P39 Expression of Envelope Glycoproteins of Human Immunodeficiency
Virus by an Insect Virus Vector
SHIU-LOK HU, S. KOSOWSKI, K. SCHAAF; Oncogen and Genetic Systems Corporation;
3005 First Avenue, Seattle, WA 98121
The envelope gene of human immunodeficiency virus (HIV) has been inserted
into the genome of an insect virus vector (Autographa californica nuclear
polyhedrosis virus). Upon infection of tissue culture cells, this recombinant
virus produced a 150k immunoreactive polypeptide related to the precursor
envelope glycoprotein (gpl50) of HIV. Radioisotope labeling with H-mannose
indicated that this recombinant-made polypeptide was glycosylated. Forty-eight
hours after infection, immunoreactive proteins of molecular weights 120-130k
and 41k were also detected. By their reactivity to monoclonal antibodies,
these proteins were identified as analogs of mature envelope glycoproteins
gpllO and gp41, respectively. To demonstrate the potential usefulness of
these recombinant-made proteins in diagnostic tests for AIDS, we used infected
cell lysates as antigens in a solid-phase immunoassay to screen a panel of 48
human sera. Results of this immunoassay correctly identified all positive and
negative samples previously classified by Western blot and immunoassays based
on disrupted virions. A relatively low cutoff value (OD=0.18) and a high
signal-to-background ratio (average >9) were obtained using crude infected
cell lysate without prior purification. Studies are also in progress to
determine the immunogenic properties of the envelope glycoprotein analogs
produced by insect virus vectors.
116
WEDNESDAY, JUNE 3
U/P4Q Heterosexual Transmission Study in Infected Intravenous Drug
Abusers
J.R. ROBERTSON, CAROL A. SKIDMORE, L. ADAMS, L. McDONALD, M.M. MORRISON,
B.V. KUENSSBERG, Edinburgh Drug Addiction Study, Edinburgh, Scotland
In a cohort study of 250 intravenous drug abusers (IVDA) with a high
seroprevalence of antibody to HIV (5U of I6*t tested since September 1983)
1** couples were identified in which sexual relationship data were available
to allow heterosexual transmission studies.
Stored serum (for hepatitis testing) allowed accurate identification of
seroconversion dates and questionnaire data and the high evidence of
pregnancy (6) confirmed the absence of barrier contraception during the
study period.
The study group therefore was of 11 (92%) male and 1 (8%) female
seropositives. When tested 2 (16%) of the female partners were found
positive and the single male exposed sexually to HIV was negative.
The average length of exposure to HIV was 19.1 months in the whole group
(19.2 in the non-converters and 18. 5 months in those found to have
transmitted the infection).
If the negative status indeed indicates non infection then it seems likely
that transmission may not now take place.
The couples who had transmitted the virus were all positive at first
testing and subsequent testing in the remaining couples has revealed no new
seroconversions even in the continued absence of appropriate barrier
contraception in most cases.
The problem of early transmission followed by apparent reduced
infectiousness is similar to that seen amongst those continuing to share
infected needles and syringes in Edinburgh.
WP43 Stability of HIV Infection Prevalence Over 10 Years in a Rural
Population of Zaire.
KEVIN M. DE COCK, N. NZILAMBI , D. FORTHAL, R. RYDER, P. PIOT, J.B. MCCORMICK,
et.al Division of Viral Diseases, Centers for Disease Control, Atlanta, GA,
U.S.A.; Project SIDA, Kinshasa, Zaire; Institute of Tropical Medicine,
Antwerp, Belgium.
Five (0.8%) of 659 human serum specimens collected in the Equateur Province
of Zaire in 1976 following an epidemic of Ebola hemorrhagic fever contained
antibody to human immunodeficiency virus (HIV). Eighty-six previously
seronegative persons were traced in 1985/1986 and were found to remain
seronegative. A serosurvey in 1986 using a cluster sampling technique in the
same communities showed a prevalence of HIV antibody of 0.8% in 389 healthy
adult villagers sampled. In 136 pregnant women the seroprevalence rate was 2%
and in 283 prostitutes 11%. Patients with AIDS were observed in hospitals in
different parts of the Province. Their risk factors were increased numbers of
sexual partners and residence outside of the area. HIV infection rates have
not changed over 10 years and remain low in rural Equatorial Zaire, but risk
groups have been identified. These findings suggest that social factors
associated with urbanization are important in the rapid spread of AIDS in
Africa.
WPA1 HIV Seroconversion In Intravenous Drug Abusers : Rate and Risk Factors
"nHI ELLIE E. SCHOENBAUM*. PA SELWYN*. D HARTEL*, RS KLEIN*, K DAVENNY*,
GH FRIEDLAND*, et al, *Montefiore Med. Ctr., *Albert Einstein College of
Medicine, Bronx, NY and CDC, Atlanta, Georgia, USA.
We are studying the rate of and risk factors associated with HIV seroconver-
sion in intravenous drug abusers attending a NYC methadone program. From July 1985-
April 1986 subjects were enrolled in a prospective study of the natural history
of HIV infection. Standardized interviews eliciting demographic data, drug use,
sexual and medical histories and physical examinations were performed. Blood for
serum antibodies to HIV was obtained.
Among 498 enrolled initially, 329 (66%) were seronegative (SN) and 169 (34%)
seropositive (SP) . During 16 mos. of follow-up, 142 (98 SN and 44 SP)had repeat
HIV antibody determination. Nineteen of 98 original SN (19%) acquired HIV anti-
body after a mean 11 mos. of follow-up (range 4-16 mos.).
Interview data for the follow-up period are available for 128/142 (90%) of re-
tested subjects, (92 SN, 36 SP). In this subgroup, 77 of 92 original SNs (84%) re-
mained SN and 15 of 92 (16%) developed HIV antibody. All 36 SPs remained SP .
Among demographic variables , non-white race , but not age or gender , was associ-
ated with seroconversion. Non-whites comprised 13/15 (87%) of seroconverters and
33/77 (43%) SNs (p^.01). Of the drug variables, seroconversion was associated
with reported intravenous drug use during the follow-up period (p^.01) , mean
number of days per month using IV drugs (p.^.01), use of "speedball" (heroin and
cocaine mixed) (p<,,03), but not heroin or cocaine alone. Of those injecting
drugs , 11/15 (73%) of seroconverters reported sharing needles vs. 22/36 (61%)
of SNs (p>.05). History of sex with another intravenous drug abuser was associ-
ated with seroconversion (p<.01) . No seroconverters reported sex with prostitutes.
Male homosexual activity was reported by one seroconverter and one SN only.
These preliminary data suggest that both Intravenous drug use and sexual ac-
tivity put heterosexual intravenous drug abusers at increased risk for HIV
infection. SN intravenous drug abusers m a methadone program remain at high risk
for development of HIV antibodies (19% at mean follow-up of 11 mos.) as long as
high risk sexual and drug behavior continue .
WR44
Field Assessment of an Enzyme Immunosorbent Assay for HIV
Antigen (HIV Ag)
SALLY HOJVAT, M. LEUTHER, M. LOMBARD-CANNAN, E. M0RRISEY,
M. P0LL0WY-D0MEK, L. VALDIVIA, Abbott Laboratories, Abbott Park, IL 60064
(U.S. A)
Seven sites in N. America and Europe have assessed the reproducibility,
sensitivity and specificity of solid phase enzyme immunosorbent assay
(ELISA) to detect HIV Ag. Reproducibility was examined by multiple
testing of 4 serial dilutions (89 to 968 pg/ml ) of an HIV Ag positive
specimen. The coefficient of variability ranged from 8-16% within and
between run. The prevalence of HIV Ag and HIV antibodies, p24 and gp41 ,
as markers of HIV infection was assessed in the following groups of
individuals using specific ELISA's: 326 AIDS, 266 ARC, 436 seropositive
asymptomatic subjects, 69 hemophiliacs, 274 seronegative asymptomatic
subjects and control groups of 1460 healthy individuals and 345 patients
with diseases other than AIDS. No HIV Ag or HIV antibodies to p24 and
gp41 were detected in either control group or in seronegative
asymptomatic individuals. Antibody to gp41 was a constant marker,
present in 99 to 100% of seropositive specimens. The level of p24
antibody decreased with the severity of HIV symptoms from 81% in
asymptomatic seropositives to 61% in ARC and 45% in AIDS patients. The
prevalence of HIV Ag in seropositive subjects was 40% in AIDS, 24% in ARC
and 7% in asymptomatic subjects. In summary, HIV infected individuals,
demonstrate a direct correlation between increased antigenemia and the
severity of symptoms. This may be predictive of the clinical
complications of HIV infection, such as AIDS and ARC.
WP42 Seasonal Variation in AIDS and Opportunistic Diseases
THOMAS A. PETERMAN, R.H. BYERS, AIDS Program, Center for
Infectious Diseases, Centers for Disease Control, Atlanta, GA.
We looked for seasonal variation in the diagnosis of AIDS, and In the
diagnosis of opportunistic diseases seen in AIDS patients. Seasonal
variation in AIDS or in the initial opportunistic disease would suggest that
an agent with a seasonal variation acts as a cofactor for the development of
AIDS. Seasonal variation in subsequent opportunistic diseases could reflect
the' epidemiology of that disease in an already immunosuppressed population.
We studied the number of diagnoses per month for U.S. AIDS cases during the
72 months from January 1980 through December 1985. The upward trend in
diagnoses per month was adjusted for by linear regression, a von Hann filter
was used to smooth the curve, and Roger's test for seasonality was applied.
We observed small but statistically significant seasonality for the diagnosis
of AIDS (12% difference, peak — summer, trough — winter, p<0. 00005). For 9
initial manifestations of AIDS, we saw statistically significant seasonality
only for Pneumocystis carlnll pneumonia (14% difference, peak — summer,
trough — winter, p<0.005) and Kaposi's sarcoma (15% difference, peak — summer,
trough — winter, p<0.005). For 9 subsequent diagnoses, seasonal variation was
seen only for cytomegalovirus infection (CMV) (34% difference, peak — spring,
trough — fall, p<0.05). (Although not statistically significant, we noted a
similar distribution for CMV as the initial manifestation of AIDS.) Primary
lymphoma of the brain showed some seasonality both as the Initial and as a
subsequent diagnosis: when combined, this was a statistically significant
difference (44% difference, peak — summer, trough — spring, p<0.05). We
conclude that there is no important seasonality in the onset of AIDS, but
there may be some seasonality to CMV and primary lymphoma of the brain In
immunocompromised patients.
U/P A5 Future Invasion ol HIV into a Broader Spectrum ot Americans
""" Predicted (rom HBV Example.
DONALD P. FRANCIS'. M. ALTER"
Centers lor Disease Control. 'Berkeley, CA and "Atlanta. GA
Hepatitis B virus (HBV) has transmission patterns remarkably similar to human
immunodeficiency virus (HIV). As a result, the diseases caused by the two viruses
occur in population subgroups whose behavior or medical therapies put them at risk
of infection. HIV is a recently introduced virus which has yet to equilibrate in the
American population. We have compared the results of transmission studies of HIV
and HBV to judge the similarities of these viruses and the usefulness of HBV as a
model to predict the future of HIV disease.
Overall, the transmission of HIV and HBV are remarkably similar. A side-by-side
comparison of HBV and HIV in homosexual men found Hlv to be about 1/4 as
transmissible per exposure (Francis and Byers). Within this group the high
carrier-to-infection ratio of HIV has more than made up for this discrepancy in
terms of overall efficacy of spread Prevalence and incidence studies of
heterosexual groups exposed to infected male or female partners have shown
essentially identical rates of infection for the two viruses. For IV drug users, il is
clear that HIV can saturate the population in a manner very similar to HBV
Because of the remarkable epidemiologic similarities of HIV and HBV, we presume
that, jf nothing is done to stop lurther extension of HIV infection. HIV disease
patterns will eventually mirror HBV's. That will mean that about 1/2 the cases will
nave been infected through homosexual contact and/or IV drug use and 1/2 the cases
will have been infected by either documented or presumed heterosexual exposure.
The demography of cases, using the HBV prediction would change considerably
Whites would account for 67% of cases, blacks 24% and hispanics 8%; 67% would be
male.
117
WEDNESDAY, JUNE 3
Wn4b Predictors of Survival for AIDS Cases in San Francisco.
GEORGE F. LEHP, J.L. BARNHART, G.W. RUTHERFORD, D. WERDEGAR, Department of
Public Health, San Francisco, California.
We evaluated survival following AIDS diagnosis for 2,489 patients reported
in San Francisco between July, 1981 and September 30, 1986. Cases were
followed at six month intervals from diagnosis to death. The maximum follow-
up time was 70 months (mean = 17.8 months). Follow-up was nearly complete,
with only 2 percent of cases known to be lost to follow-up. The median sur-
vival for all cases was 11.2 months, with a three year survival rate of 13.1
percent. Median survival varied significantly (p<0.05) with: initial diagnos-
tic grouping (Kaposi's sarcoma = 17.3 months; Pneumocystis carinii pneumonia =
10.2 months; Both KS and PCP = 12.3 months; other opportunistic infections =
6.2 months); age at diagnosis {< 19 yrs. = 3.2 months; 20-29 yrs. = 12.5months;
30 - 39 yrs. = 12.0 months; 40 - 49 yrs. = 10.8 months; 50 - 59 yrs. = 8.2
months; > 60 yrs. = 5.5 months): and risk group (homosexual/bisexual male =
11.2 months; IV drug user = 6.5 months; homosexual/bisexual IV drug user =
10.6 months; all other risk groups = 7.6 months. Median survival did not vary
significantly with race, sex, or year of diagnosis. Cox proportional hazards
regression analysis indicated that initial diagnostic group, and age at diag-
nosis were significant (p<0.05) predictors of survival in a multivariate
model, while race, sex, risk category, and year of diagnosis were not. These
data suggest that length of survival is primarily determined by initial
diagnosis and age at diagnosis. Length of survival has not changed signifi-
cantly since the beginning of the epidemic.
Quarter of Diagnosis
I
II
III
IV
1984
.17
.25
.31
.27 F
1985
.15
.28
.30
.27
1986
.20
.25
.35
.20
WP49 Sea30nal Trend in flIDS Case Numbers in Seattle-King County, Washington 1984-1986.
' SHARON HOPKINS. D. Bolgiano. Seattle-King County Department of Public Health.
Seattle, Washington, USA.
Analysis of AIDS case numbers reported in King County residents by quarter-year of diagnosis
for 1984-86 revealed a consistent pattern. The table below indicates proportion of cases per
quarter by year. Quarter I is January, February, March, Quarter II is Plarch, April, Play, and so
27 Proportion
of
Cases
This seasonal variation may relate to patterns of care-seeking, changes in human activities by
season, couariability of secondary pathogens, or environmental factors which may contribute to
the development of AIDS in human immunodeficiency virus (HIV) infected persons. Recent studies
suggest that intradermal Langerhans cells may serve as a reservoir of HIV and that an
abnormality in their number or function may be involved in the pathogenesis of AIDS. As a result
of their location in skin, Langerhans cells may be influenced by sunlight. Thus, we
hypothesized a causal relationship may exsist between variability in ambient sunlight and
numbers of AIDS cases.
Analysis of local weather data supported the suspected relationship. When a log-linear model
was fit to case numbers, the effect of minutes of sunlight per quarter-year was significant
after adjusting for year of diagnosis. Our investigation should be considered preliminary, yet
suggests directions for further research.
WR47
Lymphadenopathy :
Study . DONALD I .
P. A. VOLBERDING,
Francisco, California USA
Update of a 60 Month Prospective
ABRAMS , D.H. KIRN, D.W. FEIGAL AND
San Francisco General Hospital, San
Two hundred
lymphadenopathy
involving two or
natural histor
morbidity status
47 (36%) have
patients develo
and 4 other oppo
developing AIDS
was 3.556 (+ 1.
48 months and 4 5
predicting the
thrush or hair
peripheral cyto
rate. Twenty-fo
12 months. Five
developed HIV-
analysis estimat
PGL of 73%. In
appreciated from
in therapeutic
population.
homosexual men with persistent generalized
(PGL) of greater than 6 months' duration
more extrainguinal sites were enrolled in this
y study initiated in November 1981. Current
information is available on 143 men. Of these,
progressed to AIDS diagnoses. Twenty-seven
ped Pneumocystis pneumonia, 16 Kaposi's sarcoma
rtunistic infections. The percentage of patients
after 24 months of PGL by product limit estimates
5); 1356 ( + 3.2) after 36 months; 3256 (+ 5.1) after
96 (+ 7.1) after 60 months. Significant factors
development of AIDS include shrinking adenopathy;
y leukoplakia; increased constitutional symptoms;
penias and an elevated erythrocyte sedimentation
r of the AIDS cases died with a mean survival of
additional deaths occurred in cohort members who
related non-AIDS diagnoses. A Kaplan-Meier
es an overall 5 year survival for patients with
view of the accelerating risk of developing AIDS
36 months after the onset of PGL, participation
intervention trials is warranted in this
WR50 Does prenatal human immnodeficiency virus (HIV) infection produce
infant malformations?
JOANNE EMBREE, M BRADDICK, JO NDINYA-ACHOLA, B LOW, J MURITHII, C HOFF, et al.
Univ Nairobi, Nairobi City Commission, Nairobi, Kenya; Univ Manitoba, Winni-
peg; Univ S Alaboma, Middlesex Hospital, Lodon, UK; Institute of Tropical
Medicine, Antwerp, Belgium.
A dysmorphic syndrome consisting of growth failure, microcephaly, and cra-
niofacial abnormalities has been described in children with AIDS born to drug
abusing mothers. To evaluate the frequency of anomalies associated with con-
genital HIV infection in a non-drug abusing population. Newborns enrolled in
a prospective study of perinatal transmission of HIV infection were assessed
for the presence of 67 anomalous features. To date, 27 infants born to HIV
seropositive mothers (by ELISA and western blot assays) and 19 infants of
HIV seronegative mothers have been assessed. A single feature, a long phil-
trum, has been found more frequently in infants of HIV seropositive mothers
(12/24 (46 %) vs 4/19 (21 %), p = 0.03). No difference in mean number of
anomalies (2.3 vs 2.1) nor in percentage of infants with more than 3 anomalies
(9/27 (33 %) vs 6/19 (31 %)) was seen between the two groups. Thus, no clear
dysmorphic syndrome was found which would distinguish an infant born to an
HIV seropositive mother.
WR48 Epidemiology of AIDS and HIV-lnfections in West-Germany
JOHANNA L'AGE-STEHR. C. SCHNEIDER, M.A. KOCH, National Reference Center
for AIDS-Epidemioljogy of the Federal Health Office, Nordufer 20, 1000 Ber-
lin 65, F.R.G.
Since 1982 voluntary reports on AIDS cases of West-German physicians to
the Federal Health Office are evaluated. Five cases. were reported in 1982,
39 in 1983, 90 in 1984, 243 in 1985 and 449 in 1986. Of the 860 cumulated
cases (upto Jan. 1987) 50 appeared in females; death of 405 patients was
reported; 77, b % of the cases appeared in homo- or bisexual males, 6,4 %
in hemophiliac, 6,1 % in i.v. drug abusers, 3 % in heterosexual partners of
risk groups, 1,1 % in blood transfusion recipients, 1,3 % in children of
HIVinfected mothers, in 3,8 % the risk factor is unknown. Of the female
AIDS-patients 47 % were i.v. drug abusers, 29 % had HIV-infected sexpart-
ners. The development of annual incidence rates and involvement of new
risk groups in different geographical regions (e.g. major cities) are pre-
sented and compared to the preceding epidemiological situation in USA. In-
creasing numbers of reports on patients with neurological problems associ-
ated with AIDS (e.g. AIDS dementia complex) were recieved in 1986 (about
35 % of cases diagnosed in 1986).
Seroepidemiological data on HIV-infections in various risk groups and
preliminary results of an ungoing multicentric screening study on prevalence
of HIV-infections in pregnant woman and the underlying risk factors in-
volved will be presented.
WR51
EVALUATION of an INDIRECT IMMUNOFLUORESCENCE ASSAY for HIV ANTI-
BODY DETECTION
GABY VERCAUTEREN*, G VAN GEEL*, W SCHPPERS**, G VAN DER GROEN*
and P PIOT* ; *Institute of Tropical Medicine, Antwerp, Belgium,
** Organon teknika, Turnhout, Belgium
In collaboration with Organon teknika and indirect immunofluorescence assay
kit (IFA1) for the detection of antibodies to HIV developed by IAF PRODUCTION
INC was compared with an inhouse indirect immunofluorescence assay (IFA2) and
an immunoblot assay (IBA). These tests were performed on 100 African and 95
European sera of which 58 % and 13.7 % respectively, were positive in IBA.
HIV infected H9 cells (H9) and non infected H9 were used as antigen and
control antigen in the IFA1 and the ARV4 infected HUT78 cells and non infected
HUT78 cells were used in IFA2. IFA results were read independently by three
individuals. There was a concordance of 95.4 % between the two IFA test sys-
tems. The concordance with the IBA was respectively 93.3 % for IFA1 and 92.8 %
for IFA2. The sensitivity for both IFA systems was 100 % when European sera
were tested. IFA2 was less sensitive for the African sera (91.4 %). The spe-
cificity of the IFA's was slightly better for the African than for the European
samples, respectively 95.2 % and 86.6 % for IFA1 and 100 Z and 89 % for IFA2.
No significant difference in titer was observed after parallel titration of
several sera with the two methods.
We conclude that a commercially available IFA kit can be an inexpensive
confirmatory test.
118
WEDNESDAY, JUNE 3
WP52 Projections of Cumulative Case Frequency of Acquired
Immunodeficiency Syndrome in the Bronx, New York: A Study in Small
Area Analysis Comparing Two Different Models
STEN H. VERMUND/ E. DRUCKER, Department of Epidemiology & Social Medicine/
Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY. USA
Minimum and maximum estimates of cumulative AIDS prevalence through 1991
were made for the Bronx, a borough of New York City with 1.16 million persons
and a pattern of AIDS characteristic of areas with high rates of intravenous
drug abuse (IVDA), e.g., 60% IVDA/ 20% female, 89% Black and Latin, 4.5%
children. Both models build on empirical data on reported AIDS cases. The
first was developed by M. Morgan (CDC) and is a quadratic formula with
conservative assumptions correcting for late reporting. As the proportion of
Bronx AIDS cases to all U.S. cases has not varied significantly from 4.1% in
each year from 1981 to 1986, national estimates based on the Morgan model were
multiplied by 4.1% to estimate Bronx AIDS cases through 1991, correcting for
late reporting of 1985 cases. The second model followed the method of A.D.J.
Robertson, et al . : Nature, 1987 ( in press) , using a linear regression of
logarithmically transformed prevalence data, and a 12 month doubling time
empirically derived from the best fitting straight line from recent years. The
CDC non-linear model yields a cumulative prevalence of 10900 cases of AIDS in
the Bronx through 1991, while the linear model estimates 50600 cases. The
cumulative AIDS prevalence rate in the Bronx would reach 990 cases/100000
persons to 4600/100000 by 1991 (1 per 101 persons to 1 per 22 persons). The
implications for the public health of an epidemic of this magnitude in the
Bronx community are discussed, particularly risk to sexual partners of
i nf ected persons , i ncreased ver t i cal t ransmission , and i ncreased burden of
AIDS-related illnesses.
WR55 Elevated Urinary Excretion of Modified Nucleosides in HIV Positive
Asymptomatic Women in a Methadone Maintenance Program
Wallace, J.I*,***; Borek, E**; Buschman, F.L**; Mann, J***; Solomon, S*;
Sharma, Opendra K.** *Mt . Sinai School of Medicine, N.Y.,N.Y.; **AMC Cancer
Research Center , Denver , Colorado; ***Foundation for Research on Sexually
Transmitted Diseases, N.Y.,N.Y. U.S.A.
Cancer patients and male subjects with AIDS or at risk for AIDS excrete in
their urine increased amounts of modified purines and pyrimidines. Urinary
modified nucleosides and 2-pyridone-5-carboxamide-N -ribofuranoside (PCNR)
were measured from 110 former drug users. The subjects stopped using IV
drugs between 1974 and 1985. HIV antibody was found in 46 (42%) of the
volunteers. Modified nucleosides and PCNR were quantitated by HPLC and ex-
pressed relative to urinary creatinine. The asymptomatic women positive
for HIV antibody excreted elevated levels of modified nucleosides and PCNR
compared with the women who were negative for HIV antibody. The elevated
modified nucleosides and PCNR are listed with their statistical signifi-
cance analyzed by chi square : 1-methylinosine (0. 0004) ; 1-methylguanosine
(0.002) ; 1-methyladenosine (0.003) ; N|-dimethylguanosine (0.0076) ;
N2-methylguanosine (0.017) ; pseudouridine (0.02) ; PCNR (0.089) . The
excretion of two nucleosides , N -acetyl cytidine and N -threonyladenosine
was not elevated in the women positive for HIV antibody. These results
are similar to homosexual men positive for HIV antibody. Relationship
between drug use, other viral infections and the modified nucleosides
will also be discussed.
Supported by New York State Department of Health and NIH HD20612.
U/P53 Human Immunodeficiency Virus (HIV) Infection Among Prostitutes in
Nevada*
NANCY PADIAN*, J. CARLSON**, R. BROWNING***, L. NELSON****, J. GRIMES**,
L. MARQUIS*, *U.C, Berkeley, Berkeley, CA. , **U.C, Davis, Davis, CA. ,
***Nevada Department of Prisons, ****prlvate practice, Reno, NA.
None of 535 prostitutes In three legalized Nevada brothels were infected by
HIV as compared to 23 of 370 prostitutes incarcerated in the State prison
(p<-001). To evaluate the source of infection and associated risk we examined
several factors.
Among the brothel sample, 7% shared needles during Intravenous drug use over
the last five years as compared to 100% of the inmates. 37% of the brothel
sample were aware of contact with high risk partners (bisexuals or intravenous
drug users), whereas 91% of the inmates reported contact with a high risk man
(all intravenous drug users). Detailed sexual behavior was available for a 10%
sample of the brothel prostitutes and for half of the seropositive women In the
prison. The brothel prostitutes had more male partners over the last five years
than the incarcerated women (median: 2191 and 20, respectively). All of the
women engaged in vaginal Intercourse; 30% of the brothel sample reported anal
Intercourse as compared to 44% of the incarcerated sample. None of the women
in either sample reported consistent condom use by their sexual partners for
any kind of sexual contact. We conclude that among prostitutes, needle sharing
during intravenous drug use or sexual contact with a male intravenous drug user
presents a greater risk for HIV transmission than the number of male sexual
partners.
WP56 Proposed Revision of the AIDS Case Definition.
RICHARD M. SELIK, T.J. Dondero, J.W. Curran, AIDS Program, Center
for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia, USA.
The Centers for Disease Control (CDC) is coordinating a revision of the case
definition of AIDS used for reporting in the United States. The objectives of
the revision are 1) to track more effectively the most serious morbidity
associated with human immunodeficiency virus (HIV) infection, 2) to simplify
reporting of AIDS cases, 3) to increase the sensitivity and specificity of the
case definition through greater application of HIV-antibody test results, and
4) to be consistent with current diagnostic practice. For patients with HIV
antibody, the major proposed changes are 1) inclusion of HIV encephalopathy
(dementia complex), HIV wasting syndrome, and a broader range of specific
AIDS-indicative diseases, 2) Inclusion as a separate category AIDS patients
whose indicator diseases are diagnosed presumptively (who are not currently
reportable) , and 3) elimination of the requirement of absence of other causes
of immunodeficiency. Suspected AIDS patients with a negative HIV antibody test
would be excluded for surveillance purposes unless they had Pneumocystis
carinii pneumonia or a T4 (T-helper) lymphocyte count <400/cubic mm. The
proposed revision was developed in consultation with clinical specialists and
local and state epidemiologists . Wide-scale Implementation of the revised
definition will depend on adoption at the 1987 meeting of the Conference of
State and Territorial Epidemiologists. In the last quarter of 1986, about hal
of AIDS case reports included HIV-antibody test results, of which 97% were
positive. The revised AIDS case definition should encourage greater diagnosti
application of the HIV-antibody test. The effectiveness of the revision will,
in turn, depend on how extensively the test is applied.
IA/P ^d Relationship between Recovery of HIV from Plasma and Stage of
Disease.
ROBERT W. COOMBS, A. COLLIER, B. NIK0RA, M. CHASE, G. GJERSET, L. COREY.
University of Washington, Seattle, WA
Previous studies have indicated that the lowest recovery of HIV from peri-
pheral blood lymphocytes (PBL), but the highest frequency of detecting HIV p24
antigen in serum has been from patients with advanced HIV infect ion. To
evaluate potential virologic markers for severity of HIV infections we cultured
the PBLs and plasma of 72 patients with HIV infection: 9 CDC class II, 10 CDC
class III, 53 CDC class IV patients, and 30 seronegative controls. PBLs were
separated by density centrif ugat ion . The plasma fraction was collected
separately and filtered through a .45um filter. Plasma and PBLs were inoculated
separately into PHA-st imulated lymphocyte cultures and assayed at weekly
intervals for reverse transcriptase (RT). Cultures were done without knowledge
of patient source. All 72 patients had HIV recovered from PBLs compared to 0
of 30 controls. HIV was recovered from the plasma in 22.2%, 28.6%, and 86.8%
of CDC class II, III and IV patients, respectively. (P .01 between class II
& III vs IV). The geometric mean cpm/mi of RT activity for the first and second
postive culture supernatants were: plasma — CDC-II+III (29,391/552,515) and
CDC-IV (144,465/522,257); PBLs— CDC-II+I II (124,039/751,090) and CDC-1V
(212,387/805,576). The percent of cultures that were RT positive by day 14 were
100% of CDC-II, 80% of CDC-III, and 94% of CDC-IV PBLs. For plasma these were
11%, 14%, and 68%, respectively. The frequency of isolating HIV from filtered
plasma increases with advancing stage of disease. Studies correlating progres-
sion of HIV infection with presence and titer of HIV in plasma should be
pursued .
WR57
Sexual and Other Practices and Risk of HIV Infection in a Cohort
450 Sexually Active Women in San Francisco.
JUDITH B. COHEN, L.B. HAUER, L.E. POOLE, C.B. W0FSY, Dept. of Medicine, Sai
Francisco General Hospital, University of California, San Francisco, USA
A prospective study of sexually active women at risk for HIV infection w
begun in 1985 by the Association for Women's AIDS Research and Education
(AWARE). At entry, all women met one or both of the following conditions:
l)at least one sexual relationship with a male partner known to be HIV infected
and/or bisexual and/or an IV drug user; 2)multiple sexual relationships with
male partners not in AIDS risk groups, or whose risk status is unknown. Par-
ticipants included women working in the sex industry and women who used drugs
intravenously. All women completed a detailed interview about their health,
sexual partners and practices, and other AIDS risk-related activities since
1980. The overall prevalence of HIV seropositivi ty was 5%. Crude relative
odds for HIV seropositivity were calculated for selected characteristics.
Over Last 3 Years Relative Odds p value
I.V. drug partner(s) 2.51 £- .001
Bisexual partner(s) 1.45 .469
More than 10 partners 0.70 .761
Sex during menses 2.42 4. .001
Any analsex 1.14 .881
Anal sex without condom 1.28 .788
Self I.V. drug use 4.75 <..001
These findings indicate that a relationship with an I.V. drug using or bi-
sexual male partner conveys more risk of acquisition of HIV than multiple
partner exposure. The high risk observed with sex during menses warrants
further investigation and analysis.
119
WEDNESDAY, JUNE 3
WR58 0ral Candidiasis and Progression to Initial AIDS Associated
Opportunistic Infection:
DAVID W. FEIGAL. D.I. ABRAMS, J.S- GREENSPAN, D. GREENSPAN, P. A.
VOLBERDING, H. HOLLANDER, J. ZIEGLER, M.A, CONANT, University of
California, San Francisco, CA, USA.
A clinical cohort of 1396 patients (pts) at the out-patient AIDS clinics
of the teaching hospitals at the University of California, San Francisco,
has been prospectively examined since Jan 1985. At entry, 297 study
participants had Kaposi's sarcoma (KS), 402 Pneumocystis carlnii Pneumonia,
75 both, and the remainder ARC Since dates of AIDS related opportunistic
infections and oral candidiasis are recorded the progression from oral
candidiasis, as one of the components of ARC. to AIDS can be estimated.
312 pts reported their first episode of oral candidiasis before any AIDS
associated opportunistic infection (01) or KS. 43% also had constitutional
symptoms (BSx)- night sweats, 35% fever, and 22% wt loss greater than 10 lbs
Progression to an AIDS 01 was estimated by the Kaplan-Meier method- 1 month
9% (+2%), 2 months 13% (+2%), 3 months 19% (+2%), 6 months 30% (+13%), 9
months 35% (+3%), 1 year 43% (+4Z), and 18 months 48% (+4%). BSx when
considered simultaneously with candidiasis did not significantly change the
progression times.
Candidiasis on physical examination was a common finding in cohort
participants, seen on 23% of initial examinations. Given the short time to
progression for a significant proportion of pts, this is a clinical
population that potentially demonstrate benefits of antiviral or immune
modulating agents, while at an earlier stage of HIV infection.
WR61
Surveillance for HIV-related disease that does not meet the CDC
AIDS Case Definition: Upstate New York
BENEDICT I. TRUMAN, M. W0ELFEL, D. PUTNAM, S. KAIN, D. MORSE. New York State
Department of Health, Albany, NY, USA.
Through January 1, 1987, 1329 cases of "suspect" AIDS were reported to the
New York State Department of Health from among residents of counties outside
of New York City. Of these, 804 (60.5%) met the CDC surveillance definition
of AIDS. Of the 525 non-confirmed cases, active surveillance has been com-
pleted for 317, of which 139 (44%) are seropositive (by ELISA and Western
Blot) for HIV antibody. All were hospitalized at the time of the diagnosis
suggestive of AIDS and 32 (23%) are dead. Twenty-seven (19%) were diagnosed
with secondary infections and cancers suggestive of AIDS (Group IVC1 and IVD) ,
while 12%, 3% and 12% belonged to Groups IVA, IVB and IVC2 of the CDC classif-
ication system respectively. Twenty-eight of the 29 in groups IVC and IVD
were diagnosed by the inappropriate method.
Compared to the 115 confirmed AIDS cases known to be HIV seropositive in the
Upstate registry, non-confirmed HIV seropositive cases were more likely to be
female (22% vs. 15%) or Black (36% vs. 21%) or IV drug users (45% vs. 36%).
The data suggest that females, Blacks and IV drug users are over-represented
among reported cases of HIV-related disease that do not meet the CDC case
definition for AIDS. These findings support the perception that use of the
strict CDC case-definition may distort the epidemiology of serious HIV-related
disease, especially for some subgroups.
WR59 DISEASE OUTCOME AMONG HETEROSEXUAL
S. DE WIT , P. HERMANS, D. ROTH ,
University Hospital, Brussels, Belgium).
Dur
positive
tern bio
females
practice
transfus
least a
nical an
asympt om
AIDS-Rel
During t
or sympt
de velope
(annual
stage II
( annual
after a
The
history
similar
sexuals .
AFRICANS WITH HIV/ INFECTION.
G. ZI5SIS,N.CLUMECK.(St Pierre
ing a 4-year period we surveyed in Brussels 102 HIV sera-
Central African patients (P) identified by ELISA and Wes-
t techniques. There were 49 males (mean age: 37y.) and 53
(mean age: 28y.). None of the P recognized homosexual
nor IV drug use. 9 ( 9 ?o ) had a previous history of blood
ion during the last lOy. All people were examined at at
3mo period during a mean of 16mo. According to their cli-
d immunological status, they were classified as healthy
atic (stage I) (n = 7), lymphadenopathy (stage II) ( n = 36 ) ,
ated complex (stage III) (n=38) and AIDS (stage IV) (n=21).
he study period no healthy seropositive developed signs
oms of HIV infection. 3 out of 36 P (8.3%) at stage II
d AIDS after a mean evolution of 33mo (range: 23-41)
rate of progression to AIDS of 1 . 1 ?o ) . 12 out of 38 P at
I (32 %) developed AIDS at a mean time of 7mo (range: 1-23)
rate of progression of 20.7?o). 21/36 P with AIDS died
mean evolution of 5mo (range: 1 to 7mo).
se rates of progression to AIDS suggest that the natural
of HIV infection among heterosexual African patients is
to that of American or European male homosexuals or bi-
llfpCO Perinatal Transmission of the Human Immunodeficiency Virus: A
Longitudinal Study of the Children
New York City Collaborative Study Group for Vertical Transmission of HIV,
(ELAINE J. ABRAMS, Harlem Hospital Center, New York, N.Y. Presenter)
This collaborative study aims to examine the effects of the HIV virus on
high risk women and their babies. Clinical, serologic and immunologic data
are collected prospectively on high risk women through pregnancy and one year
postpartum. The children are followed by the same parameters for two years.
Of 43 babies enrolled to date, 17 are less than 2 months of age; 15 are 2-4
months; 11 are 6-9 months. 24 babies are HIV antibody positive, 16 are nega-
tive; 3 are pending. No appreciable difference was noted in risk factors (IV
drug use, sexual partner, both) for positive and negative mothers. All antibody
positive babies have positive mothers. All antibody negative babies have nega-
tive mothers. No babies seroconverted. No significant difference was noted
in average birth weight for positive and negative babies >^ 37 weeks gestation
(positive - 2796+451, negative 3091+499, grams + S.D.) Head circumference at
birth was comparable for both groups. No notable difference was found in the
rate of preterm and SGA births. Serologic studies including IgG, IgM, IgA and
T cell subsets were not significantly different for positive and negative
babies at birth. Seven babies with positive serology are greater than six
months old. Three have developed AIDS-related complex. One child has diffuse
lymphadenopathy, recurrent candidiasis and recurrent otitis . Two are well and
one is lost to follow-up. One positive baby presented DOA at three months of
age. No other positive babies have illnesses suggestive of HIV infection.
WR60 WOMEN WITH AIDS/
ADRIANA GRIGORIL
KAPILA, M.D. University
One hundred eighty fiv
and December , 1986 have m
Group IV. Greater than 9
history of parenteral dr
enteral drug abuser(s) .
prevalence continued to
£0% and toxoplasmosis 2 .
candidiasis and lymphade
The sexual life style
small minority of bisexua
gynecological problems i
secondary amenorrhea 40%
itis 25%. There were a t
tions as Fetal wastage, e
death. Maternal morbidit
problem. In the Five yea
ber, 1985 we reported ou
represent more than doub
per i od .
The reported 185 women
women with AIDS in New
January 1 , 1987) .
The rate oF increase
and natinwide represents
A CONTIN
3. , PATRI
dicine a
an seen
:ent CDG
this pat
jse and/o
Dpportuni
3 50%,TB
th almost
ny at som
- patient
2 n . A m a j
ing multi
2S genita
af 17 ' pre
abort i ons
mortal i t
iod from
dings on
s total i
UING S
CIA KLi
d Dent
t UMDN
cr i ter
i ents
r sexu.
stic ii
30% , cr
uni vei
time
is h
or i ty
pie ov
lis 10
gnanc i
prem
cont
Decemb
53 worn
umber
M.D
New
een
oup I
1 ack
ntact
i ons
occa 1
inc i d
ng th
sexua
r pat
cyst
pers
th su
deli
to b
980 t
he 13
e pre
RAJENDRA
ark, N.J. U.S
Decemberl980
I through
with a
with par-
oF greatest
meningi t is
ence oF oral
e il lness .
1 with a
ients had
s 9%,PID 7%
istant vagin
ch comp lica-
ery and
a major
hrough Decern
2 new women
ious 5 year
this study represent 61% of the total
ersey and 9% of the total nationwide(as of
n the number of women with AIDS in Newark
major medical and social concern.
WR63 N0 HIV SEROCONVERSION AMONG MEN REFRAINING FROM ANAL-GENITAL
INTERCOURSE
ROGER DETELS, B VISSCHER, L KINGSLEY, J CHMIEL, ET AL. Multicenter AIDS
Cohort Study, NIAID, Bethesda, MD.
A cohort of 733 HIV antibody negative men in Los Angeles was followed for
18 months. HIV seroconversion demonstrated by the Genetic Systems and
Oupont ELISA tests and confirmed by Western Blot was compared among partici-
pants stratified according to reported sexual activities in the previous six
months. No seroconversions occurred among men refraining from anal-genital
intercourse.
Receptive and^ insertive: 50/522 (9.6%)
Receptive, not insertive: 2/35 (5.7%)
Insertive, not receptive: # 2/126 (1.6%)
No anal-genital intercourse: 0/50 (0%)
Over sixty percent of those refraining from anal-genital intercourse
reported one or more sexual activities with exchange of fluids including 31%
swallowing semen. Although seroconversion rates were higher for those prac-
ticing receptive but not insertive anal-genital intercourse than for vice-
versa the insertive but not receptive group had an average of twice as many
partners suggesting a lower level of transmission efficiency for insertive
anal-genital intercourse. This latter finding is consistent with reports
that vaginal transmission from female to male does occur, hut at an appar-
ently low rate of efficiency. The demonstration of litte or no transmission
from activities other than anal-genital intercourse over 18 months of
follow-up provides a rational basis for prevention of infection through
public health education. We are adding data for 24 months of follow-up from
an additional 138 seroconverters in Baltimore, Chicago and Pittsburgh.
120
WEDNESDAY, JUNE 3
WP64 MAINTAINING A STARLE LEVEL (IF CD-4 CELLS IS A FAVORABLE PROGNOSTIC
SIGN AMONG HIV POSITIVE MEN
JOHN FAHEY, R OETELS, R VISSCHER, A MUNOZ , A SAAH, V CLARK, ET AL.
Multicenter AIDS Cohort Study, NIAIO, Bethesda, MO.
A cohort of 537 HIV positive homosexual men in Los Angeles was followed
for 18 months for changes in number of CD-4 cells. Seventy-one men subse-
quently developed AIDS. The mean slope of CD-4 cells among men developing
AIDS was -.356/day (s.d. = .4?) compared to -.01/day (s.d. = .01) among
other seropositives. The distribution of slopes observed were:
Slope of CD-4
< minus .17 -.17 to + .17 > plus .17
AIDS 70% (50) 20% (14) 10% (7)
Other Seropositives 27% (127) 48% (221) 25% (117)
The mean slope of CD-4 cells was downward among men developing AIDS whose
initial levels of CD-4 cells were <200, 200-499 and >499 cells/mm3 whereas
the slopes among other seropositives demonstrated regression to the mean.
The "flat" slope in men not developing AIDS suggests that CD-4 level may not
be an appropriate surrogate for time since HIV infection. We did not follow
these men from time of infection, therefore, some of those developing AIDS
may have had a flat slope for some interval during the induction period.
Nonetheless, these observations support the hypothesis that maintaining a
stable level of CD-4 cells, even though it is at a lower level than seen
among HIV negative men is a favorable prognostic sign over at least a period
of 13 months. We will expand the data to include 1300 more HIV seropositive
men from Baltimore, Chicago and Pittsburgh.
WP67 Incidence and Significance of Persistent Generalized
Lymphadenopathy in a Large Cohort of Gay/Bisexual Men
RICHARD A. KASLOW, W.C.BLACKWELDER, J.P.PHAIR, D.LYTER, R.FOX, B. VISSCHER for
the MULTICENTER AIDS COHORT STUDY(MACS), NIH, Bethesda, MD , USA
Neither Che incidence of new lymphadenopathy nor its place in the natural
history of HIV infection is fully established. From 4 semiannual examinations
during an 18-month interval, we have documented the Incidence (Table) and
examined the prognostic significance of persistent generalized lymphadeno-
pathy (PGL) in HIV- men (Initial N=2635), seroconverters (Initial N=150),
and HIV+ men (Initial N=1625).
PGL at New PGL after entry: Cumulative
entry (%) 0-6 mo(%) 7-12 mo(%) (12 mo)
HIV(-) 3 2 13
Seroconverters 11 23 14 33
HIV(+) 30 11 9 19
PGL was more common in men when their ELISA was last negative prior to se-
roconversion (11%) than in men whose negative ELISA remained unchanged for at
least 6 months (3%)(p<0.001); early viral response could be an explanation.
Seroconverters developed PGL at 2x the rate seen in men who were HIV+ for an
unknown length of time and lOx the rate seen in those who remained HIV-.
Prior to developing new PGL, previously HIV+ men closely resembled those
without adenopathy in their mean CD4 and CD8 counts. During 12 months' fol-
low-up, in neither HIV+ men nor seroconverters was the decline in CD4 count
related to the presence of adenopathy, and PGL did not alter the risk of AIDS.
The incidence of PGL with new HIV infection is high, but its importance in
the progression to serious immunodeficiency is not apparent.
WPfiS /1re aosence or progressive loss of antibody to individual viral
proteins of HIV, predictors for development of AIDS? M. LANGE,
K.R. ONG, E.B. KLEIN, K. SHRIVER, L. GOLDSTEIN, L.Z. COOPER, St. Luke's/
Roosevelt Hospital Center, Columbia University, New York, N.Y. and Genetic
Systems, Seattle, Washington.
A low level or complete disappearance of antibody to the human immunodeficien-
cy virus has been reported by a number of investigators as a predictor of pro-
gression towards overt clinical AIDS. In order to evaluate whether this ob-
servation reflects a decreased antibody response to specific viral proteins,
western blots fWB) and radioimmunoprecipitation assays (RIP) were performed
on sera collected sequentially over a two year period from 10 AIDS patients
and 26 HIV-pos subjects with or without lymphadenopathy (PGL) progressing to-
wards overt AIDS and to ARC. Of patients with AIDS, 9 had no response to P55,
6 had no or weak (PW) response to p25 and 8 had an absent or PW to pl5/17. Of
26 HIV-pos patients at time of entry, 11 remained asynomat ic with or without
Lymphadenopathy (PGL). Only one had absent Ab to P55 whereas others had a
good AB response to all viral proteins. Of the 7 who progressed to overt AIDS
most had an absent or progressively weaker AB response to P55 and P40 on \jest-
ern blot and an absent or weak response to P40 and P18 on RIP. This abnormal
response was frequently present 1 year or more prior to the development of
overt AIDS. Using regular ELISA testing, no correlation was detected between
ELISA values and absence or presence of antibody to the above viral proteins.
Although titration was not attempted, one may assume that antibody for specific
viral proteins may be precipitated in circulating inmune complexes frequently
found in AIDS or ARC. In favor of this Hypothesis are our previously reported
findings of presence of HIV antibody in CIC purified from sera of AIDS
patients.
WPfiR AIDS-Related Kaposi's Sarcoma in New York City in 1977
UU ROBERT J. BIGGAR*, PHILIP C. NASCA**, WILLIAM S. BURNETT**
♦National Cancer Institute, Bethesda, MD; **NY State Health Dept., Albany, NY
New York City has been an epicenter of the AIDS epidemic since it was first
reported in 1981, having both the earliest and the most cases of any city in
the United States. We have shown that changes in the frequency of Kaposi's
sarcoma (KS) cases among single young men are a sensitive means of detecting
the AIDS epidemic. In this study, we reviewed the KS cases among young men
<50 years old in New York City using data collected by the New York State
Cancer Registry. Reliable data were available from 1973. Of 5 cases between
1973 and 1976 (1.25 cases per year), 4 were foreign born (including 1 from
Puerto Rico), and were known to have been married. Four were also described
as having disease of the the lower limbs compatible with classical, non-AIDS
related KS.
In 1977, both the frequency and the demographic/clinical patterns of KS
among young New York men changed. Of the 5 cases in that year, 3 were single
men, all from the United States. In 1978, another single American-born cases
occurred. In 1979, the recognized onset of the epidemic, 5 KS cases were
reported, 4 of which were single. Of the 6 cases in 1980, 4 were single; and
of the 31 cases in 1981, 28 were single. Clinically, 2 of the 6 cases in
1977/78 were recorded in unusual sites for classical KS, ear and penis; 3 were
recorded as having KS of the "skin"; and only 1 was recorded as having disease
limited to the limbs. Three of these 6 cases, all single, were from lower
Manhattan, although none of the earlier cases were. These data suggest that
the AIDS epidemic emerged in New York City in 1977.
WR66 Detection of Early HIV Seroconversion with Currently Available
Serologic Techniques
HOMAYOON FARZADEGAN*, E. Taylor*, N. Odaka*, T-H. Lee**, R. Redfield***,
B.F. Polk*, *Johns Hopkins School of Hygiene and Public Health, **Harvard
School of Public Health, and ***Walter Reed Army Institute of Research.
Early immune responses to products of env and gag genes of HIV have not been
investigated extensively in large numbers of newly infected persons. Serial
sera were collected from 45 seroconverters participating in the Baltimore
center of the Multicenter AIDS Cohort Study. Seroconversion in this high risk
group was defined as new and persistent appearance of antibody to
p24/gp41/gp>100 on immunoblot, or of antibody to p24/gpl20/gp160 by radio-
immunoprecipitation assay (RIPA) . We determined the sensitivity of seven EIA
kits, two immunoblot kits and RIPA in detecting serologic markers of HIV
infection at this early stage. The sensitivities of EIA kits were 76% to
92%; of the immunoblot kits, 82% to 96%; and of RIPA, 82%. Of interest, p24
antigen was detected in the serum of 4 of 45 seroconverters at a visit six
months prior to the visit at which presence of anti-HIV antibody was con-
f i rmed .
Seven participants had baseline sera with serologic evidence of early HIV
infection. The EIA kits were positive in 0-4 of the seven; RIPA was positive
in 3/7; and one immunoblot kit failed to detect antibody in any of the seven.
We will discuss the probable sequence of serologic events in persons newly
infected with HIV. These findings have important implications for the optimi-
zation of serologic tests for early HIV infection, especially for application
in blood banks.
WP69 Association of Plasmids and Virulence of Mycobacterium avium Complex
PATTISAPU R.J. GANGADHARAM*, V.K. PERUMAL, J.T. CRAWFORD,
J.M. BATES**, 'National Jewish Center for Immunology and Respiratory Medicine,
Denver, Colorado, "V.A. Medical Center, Little Rock, Arkansas
Organisms of Mycobacterium avium intracellutare complex (MAC) cause pulmonary
disease in humans and frequently encountered as opportunistic pathogens in Acquired
Immunodeficiency Syndrome (AIDS) patients. Our studies comparing the MAC strains
of AIDS patients with those from non-AIDS patients showed a possible relationship
with the presence of plasmids in the MAC strains. We have shown that 100% of 26
AIDS strains and only one-third of 150 non-AIDS strains possessed plasmids. To
obtain specific and direct evidence on the relationship of virulence to plasmid
content, blind comparisons were undertaken to assess the virulence and associated
parameters of MAC strain LR-25 which was shown to possess three (2 small and 1
large) plasmids and a strain derived from it, designated as LR-163, which has been
cured of the three plasmids by acriflavin treatment. Strain LR-25 consistently
caused high mortality (45%) of beige mice and CFU counts of the organisms from
spleens and lungs, while the cured variant, LR-163, showed no mortality and low CFU
counts. LR-25 is thus classified as high virulent and LR-163, low virulent.
Substantiation of the differences in virulence of this pair of strains was done by the
release of oxygen metabolites from resident and activated mouse peritoneal
macrophages. LR-25 triggered 45 and 135 n.moles of 0% and 20 and 22 n. moles of
H,02 from resident and activated macrophages; the corresponding figures for LR-
163 were 82 and 238 for O- and 38 and 58 for f^Oj. Based on our earlier finding of
an inverse correlation with virulence, these studies with oxygen metabolites
confirmed the loss of virulence when the plasmids were removed from the MAC
strain LR-25. In contrast to the association with virulence, no significant changes
with respect to drug susceptibility were noted within the two strains.
121
WEDNESDAY, JUNE 3
WP7fl Clinical and Epidemiologic Characteristics of Non- AIDS
" HIV Related Illness in NYC Hospitals
MAHY AMM CHIASSOM , M . GARCIA , E . FLEISHER , P . CREECH , A . OPPERHANN f R .
STONEBURNER, New York City Department of Health, NY, NY.
The spectrum of HIV-related disease among hospitalized persons in New York
City includes CDC defined Al AIDS and other HIV-related illnesses (suspected
AIDS) . In order to describe the clinical and epidemiologic characteristics
of this population of suspected AIDS cases, a point prevalence survey was
conducted in March of 1986 at 25 hospitals that report 66H of AIDS
morbidity .The average daily census at these hospitals for this month was 277
AIDS and 152 suspected AIDS cases. A total of 170 adult and 8 pediatric
suspected AIDS cases were identified on the day of the survey. Of these, 35
were females and 143 males; 54% black, 19% white, 27% Hispanic. The major
risk groups were; 104 (59%) IVDUs and 38 (21%) gay/bisexual men. The
proportion of IVDUs among suspected AIDS cases was significantly
greater(0R=3, p<0.01) than that among Al cases reported from these hospitals
during 1986 while the proportion of gay/bisexual men was significantly lower
(0R=4, p<0.01). Seventy-eight (44%) of the 178 cases presented with
pneumonic processes, primarily pneumonia, and 74 (42%) presented with oral
thrush. Neurologic manifestations ranging from seizures to encephalitis were
reported in 21 (12%) and CNS toxoplasmosis was suspected in 18 (10%).
Prospective follow-up of this cohort of suspected AIDS cases has identified
29 confirmed adult cases to date. The distribution of cases by risk group is
similiar to that in the original cohort. Oral candidiasis was the diagnosis
most highly associated with the development of CDC defined AIDS (0R=2,
p=0.004). These data indicate that persons infected with HIV, especially
IVDUs, are a major burden on the health care system even before they develop
confirmed AIDS .
WR73
Reactivity against p2A in confirmatory assay for anti-HIV anti-
bodies in low risk populations
KEES L. VAN PER POEL* , M. Tersmette** , P.N. Lelie**, H.W. Reesink*
* Red Cross Blood Bank Amsterdam, Amsterdam, The Netherlands
** Central Laboratory of the Netherlands Red Cross Blood Transfusion Service,
Amsterdam, The Netherlands
Among 5,000 serum samples of healthy volunteer donors used in a panel for
testing ELISA kits for anti-HIV antibodies, 9 were found with reactivity
gag
against p24 (and /or pr55) without reactivity against envelope proteins in
Immunoblot analysis (IB) of HIV. Of 6/9 donors (2 females, 4 males) 37
sequential serum samples of donations going back to January 1984 were tested
in IB and Radioimmuno-precipitation (RIPA). Upon extensive interviewing, no
risk factors for AIDS were found. Of 2/6 donors also serum samples of 2
recipients of fresh frozen plasma could be tested. Sequential serum samples of
the donors showed consistent reactivity against p24 (with pr55 in one
sample) from 1984 until July 1986 in 4/6 donors and marginal reactivity against
p24 in 2/6. RIPA was negative except for one sample (p24 ). Virus cultures
of fresh mononuclear cells remained negative in 6/6 donors during >40 days
cocultivation. Two patients receiving fresh frozen plasma of 2 donations
positive for p24 , remained negative 6 months after transfusion, as tested
by ELISA (2 kits) and IB. In Immunoblot Assays with HTLV-4 and LAV /HIV
encoded proteins , none of the donor samples showed reactivity consistent with
HTLV-4 or LAV_/HIV infection, i.e. envelope glycoproteins (P. Kanki, M. Essex,
dept. of Cancer Biology Harvard University Boston, U.S.A., Diagnostic Pasteur,
Marnes la Coquette, France). Reactivity against p24 of HIV in IB can
persist for at least 2 years without signs of HIV-infection. In low risk
populations this reactivity represents false positivity.
WP71 AIDS Surveillance in New York City
JULIETTE WALKER, A. LEKATSAS , R. O'DONNELL, N. GARCIA, P. THOMAS,
R. ST0NEBURNER. New York City Department of Health, NY, NY
AIDS Surveillance in New York City (NYC) serves as a model for
surveillance programs nationwide. As of January 1987, 8887 cases of biopsy
or culture proven opportunistic infections have been reported . The NYC AIDS
Surveillance Unit receives approximately 270 cases monthly. Surveillance is
conducted at 80 NYC hospitals and one prison infirmary. Facilities with high
AIDS morbidity are visited weekly. Epidemiologic information is collected
from personnel diagnosing and caring for patients . Cases under 13 years of
age require contact with pediatricians. Charts are reviewed for details not
obtained from physicians and nurses . Microbiology, pathology and death logs
are reviewed for AIDS-associated illnesses. Hospitals with low morbidity are
telephoned weekly. 83% of cases are reported from hospital personnel; 10%
from medical records; and 7% from death certificates including autopsies.
Validation of the surveillance system is ongoing to ensure complete and
timely reporting. Death certificates with AIDS-related morbidity are matched
to cases or investigated as new cases . A weekly census of hospital beds
utilized by AIDS patients measures the impact of the epidemic on NYC
hospitals . Special attention is given to cases which define changing disease
trends and patient characteristics. Patients denying homosexual activity and
intravenous drug use or claiming occupational exposure are extensively
investigated. Data is compiled and computerized in a system attentive to
confidentiality and accuracy. Codes are assigned and names are removed.
NYC AIDS Surveillance is committed to an accurate description of the
epidemiology of AIDS providing direction for programs in research, education
and funding .
VA/P74 Increasing Incidence of Tuberculosis in a Prison Inmate Population;
Association with HIV Infection
M. MILES BRAUN*, B.I. TRUMAN*, G. W0RMSER**, B. MAGUIRE***, R. BR0ADDUS***,
D.L. MORSE*, *New York. State Department of Health, Albany, NY, **New York
Medical College, Valhalla, NY, ***New York State Department of Correctional
Services, Albany, NY, USA.
Concurrent with the AIDS epidemic, tuberculosis incidence rates in prison in-
mates in New York State have risen 360% from 15.4 per 100,000 in 1976-78 to
70.9 per 100,000 in 1984-86 (provisional incidence of 105.5 in 1986). At the
same time, AIDS incidence in inmates increased from 8.4 per 100,000 in 1981
to 289.6 per 100,000 in 1986. To investigate the association between the
large increases in these two diseases, we reviewed data from New York Stated
AIDS and TB registries.
Over the past six years, 347 cumulative AIDS and 112 cumulative TB cases
have been reported in inmates. No geographic clustering of TB cases was noted.
Six percent of AIDS cases have had TB, and 20 percent of TB cases have had AIDS.
By year of AIDS diagnosis, the number of AIDS cases with TB has increased from
0 in 1981-82, to 7 in 1983-84, and to 15 in 1985-86.
Of the 54 TB cases reported in 1985-86, 15 (28%) had AIDS, 15 (28%) addition-
al cases were HIV seropositive, and the remainder had unknown HIV antibody
status. There were no reported seronegatives. Twenty-one (39%) of the 54 had
extrapulmonary TB, a finding often associated with HIV infection.
These findings document an increasing rate of TB in prison inmates and
strongly suggest its association with HIV infection. Standard TB control
efforts should be intensified in order to reverse this increase in TB rate.
WP72 Ris^ Factors f°r Human Immunodeficiency Virus (HIV) Infection
Among Heterosexuals in New York City. MICHAEL MARMOR.
H. SANCHEZ, K. KRASINSKI, H. COHEN, S. BARTELME, L.R. WEISS, et al . ,
New York University Medical Center, New York, NY, USA.
Patients attending the sexually transmitted disease and gynecology out-
patient clinics at Bellevue Hospital were invited to take part in a study
of HIV risk factors and seroprevalence. Male patients with histories of
intravenous (IV) drug abuse or homosexual activity were excluded from par-
ticipation. Men or women with histories of blood transfusion since 1/1/77
also were excluded. Interviews and enzyme-linked immunosorbent assays for
presence of HIV antibodies with Western blot confirmation have been com-
pleted for 76 males and 53 females. The mean number of sexual partners in
the 12 months prior to interview among males was 5.9 (min. = 0, max. = 30)
and among females was 3.3 (min. = 0, max. = 288). Three female participants
acknowledged prostitution and 10 acknowledged IV drug abuse. Sexual inter-
course with persons from AIDS risk groups was reported by 12 (16%) of the
males and 21 (40%) of the females. Male subjects reported that only 12% of
their sexual partners were protected by condoms during all sexual encoun-
ters. Women reported 100% condom use with only 2% of sexual partners. HIV
seropositivity has been detected in 2 males and 2 females without AIDS risk
factors other than heterosexual activity (equivalent to HIV infection rates
of 2.6 and 4.3 per hundred, respectively). Three of 10 female IV drug users
were HIV seropositive. These preliminary data suggest (a) that condoms are
not being used by this patient population for disease prevention, and (b)
that heterosexual spread of HIV is occurring. The study is continuing with
a goal of recruiting substantially more subjects.
WR75
HIV ELISA Results in Heterosexual Partners of Persons at High
Risk for HIV Infection. JOHN WEBER », 0. SIJIN*, A. MARCEL*,
C. LYONS*, S. LANDESMAN*. SUUY Health Science Center at Brooklyn,
Brooklyn, N.Y.
We have offered free confidential HIV counseling and testing (ELISA
and Western Blot) in conjunction with the NYC Department of Health for
a large urban population since 9/85.
Of the 430 patients that we have tested, 128 were heterosexual partners
of bisexual men or intravenous drug abusers. None of these 128
individuals used "safe sex" methods. Ninety-six were women and 32 were
men. Five of 96 women and 0/32 men had symptomatic HIV infection {AIDS,
ARC or GLA). Twenty-eight of 128 (21.9%) patients tested positive for
HIV antibody, with confirmatory Western Blots. Sixty of 96 (62.5%)
women and 11/32 (34.3%) men reported sexual contacts with known HIV
infected partners [AIDS, ARC] since 1983. Twenty-two of 60 (36.6%)
of the women and 3/11 (27.2%) men exposed to partners known to be HIV
infected were HIV antibody positive. In comparison only 1/36 (2.8%)
of the women and 2/21 (9.5%) of the men who reported heterosexual contact
with high risk partners without evidence of symptomatic HIV infection
were HIV antibody positive. While 36% (8/50) of the women whose reported
risk was with high risk husbands were HIV positive, only 5/46 (10.9%)
of the women having had sex with high risk boyfriends tested positively.
Heterosexual contact with high risk group individuals who are
symptomatic for HIV infection carries a significantly higher risk of
infection than contact with non symptomatic individuals. Women who have
had long term relationships with members of high risk groups are more
likely to be infected with HIV than those with short term relationships.
122
WEDNESDAY, JUNE 3
WP76 Clinical Course of HlV-seropositive Homosexual Men
ANN C.COLLIER1, V.L. Murphy1, P.L.Roberts1, H.H.
Handsf ield"1' * , University of Washington1 and Seattle-King Co.
Dept. of Public Health2, Seattle WA, USA.
Estimates for progression to overt AIDS among HIV-
seropositive(HIV+) homosexual men(HM) have varied from 10% to
>30%, with an apparent increasing risk over time. We report
follow-up on a cohort of 178 HIV+ HM enrolled in 1982-4. One
hundred and seventy-eight (78%) were selected for the presence
of persistent generalized lymphadenopathy (PGL) ; the rest were
asymptomatic and had no PGL. Follow-up was 3-56 mo (median 42
mo). Twenty-f ive(14%) developed AIDS, an annualized rate of
4%; the annualized rates were 5% for HIV+HM with PGL(N=22)
and 2% for HIV+HM without PGL(N=3). Using the date of
documentation of HIV seropositivity, the risk of AIDS was
higher at 4 yr than 1-3 yr, (P=0.03). Compared with the 153
HIV+HM who did not develop AIDS, the 25 who developed AIDS
had lower initial T4 cell counts (mean 285 vs 557/mm ,
P<0.001), lower T4:T8(0.38 vs 0.77, P<0. 001) , and were more
often anergic at enrollment (11/16 vs 34/127, P=0.001). There
were no differences in age, constitutional symptoms, presence
of PGL, initial hematocrit, T8 or total lymphocyte counts. In
addition, 12 subjects have developed oral candidiasis or ARC.
The risk of overt AIDS among HIV+HM appears to increase over
time; the relatively low rates in this cohort compared with
reports from San Francisco or New York may reflect a more
recent introduction of HIV into Seattle.
WP7Q Sere-prevalence of anti-HIV antibodies in Brazzaville (Congo).
WWIW3 p> MiPELE», A. IT0UA-NGAP0R0*, MICHEL ROSENHEIM**, F. YALA*,
C. BOURAMOUE*, M. GENTILINI** et al, *H6pital General, Brazzaville, Congo,
**Groupe Hospitalier Piti6-Salp§triere, Paris, Prance.
Congo is located in Central Africa, West of Zaire. The first cases of AIDS
were reported in 1983. Blood-bank screening for anti HIV antibodies is comple-
ted since July 1986. A commercial ELISA kit (ELAUIA, Diagnostic Pasteur) is
used and 4 387 blood donnors were tested between July 1986 and December 1986
among which 269 were repeatedly reactive (10,13 %) .
During November and December 1986, sera of in-patients were systematically
tested and 245 out of 654 were repeatedly reactive (37,4 %) . One hundred and
thirty five had AIDS, according to WHO clinical score for Africa. Western
blot could not be done because of lack of local facilities.
WP77 A THREE YEAR SURVEY 0F ANTIBODY RESPONSE TO HIV ANTIGENS
IN THE CENTRAL AFRICAN REPUBLIC.
D.SALAUN*. M. MERLIN**, J. P. GONZALEZ ***, F. BARRE
Central African Republic, *x0CEAC, Yaounde, Cameroon, *' * . 0RST0M
BP 983 , Bangui CAR, ****Institut Pasteur , Viral Oncology Unit. Paris,
France.
A three-year survey for HIV 1 antibodies in several population groups of
the Central African Republic was conducted between October 1984 and January
1987. This survey included 1,663 persons from randomly selected households
in Bangui, or seeking medical care in the Pasteur Institut; two groups of
377 and 930 people, aged 15-34 and one group of 320 children aged 0-14 all
randomly selected from the urban population; 830 people selected from the
rural population; 234 hospitality girls from low and middle socio-economic
status; 100 tuberculosis in-patients; 175 malnourished children along with
101 mothers; and 396 pygmies from two separate pygmy tribes. All sera were
screened using ELISA technique, then confirmed by Western Blot, and consi-
dered positive only if either GP110 or GP41 or both were present.
Results were as follows: the prevalence of anti HIV 1 antibodies in the
general population ranged between 2.1 and 4.04 in separate surveys conducted
18 months apart: an insignificant range (Chi square: 2.4). Among hospitality
girls the range was between 20.6 and 12, again separated an 18-month
interval. Anti HIV 2 antibodies were found to *.-e present both in the urban
and pygmy populations.
The striking feature of these surveys is a lack of increased incidence in
HIV 1 antibodies particularly among the prostitutes examined through a 18
month period.
U/PAfl Prospective study of the vertical transmission of HIV.
JACK LEVY, G. S0UMENK0FF, F. PUISSANT, N. CLUKECK, G. ZISSIS,
S. SPRECHER et al . , Hop Saint-Pierre, Free University Brussels,
Brabant Pasteur Institute, Brussels, Belgium.
In a ongoing study to evaluate vertical transmission of HIV, peripheral
and cord blood is obtained at delivery from pregnant women with HIV infection
and tested for HIV antibodies (Ab) and antigens (Ag) . Infants are followed up
clinically and tested at three months intervals for HIV Ab and Ag as well as
for T cells subsets. Since October 1985, 8 seropositive women have been stu-
died : 3 were IV drug abusers and 4 were of african origin ; HIV Ag were de-
tected in the peripheral blood of 4/8 at delivery. Of the 8 infants (mean
birth weight 2618 gr, range 1620-3500 gr) , 2 were born prematurely. HIV Ab
were present in cord blood from the 8 infants but Ag was detected in only
1/8. At this writing, follow up data is available for 7 infants for a mean
period of 9.5 months (range 1-16 months). None of them has clinical or im-
munological signs of HIV infection. Two infants now 15 and 16 months of age,
born to seropositive Ag negative drug abusers, have had repeated negative
tests for HIV Ag and have no more Ab detectable suggesting that HIV has not
been transmitted. The infant whose cord blood was positive for HIV Ag is now
12 months old and clinically healthy. At his 9 months follow up visit, T
cells subsets were normal, HIV Ag was present, but Ab were not detectable by
Elisa or IF ; WB was only positive for P 24 and P 53. Ag was detected at the
6 months visit of an infant whose cord blood was negative. The 3 youngest in-
fants have not yet been retested. These results indicate that, in addition to
careful clinical and serological follow up, the study of the vertical trans-
mission of HIV requires testing for the presence of HIV Ag.
WR78
A.I.D.S. SURVEY IN CAMEROON
J. P. DURAND , M. MERLIN , R. JO
NOCHE*** and all.
Centre Pasteur du Cameroun BP 1274 Yaounde.
***Ministere de la Sante Publique YAOUNDE.
GARRIGUE
WR81
O.C.E.A.C. BP 288 YAOUNDE.
Since May 1985, 25 patients affected by AIDS have been detected by Pasteur
Center of Cameroon (8 men, 17 women). 3000 serological tests were performed
during several epidemiological surveys among the cameroonian populations.
Each positive case was confirmed (RIPA Cystein or Western Blotting).
Different types of surveys were carried on:
- Household cluster sample surveys on randomly selected populations in
urban areas:
. in adults the prevalence of antibodies carriers is 0 . 6X (11/1761).
. in children under 15 the seroprevalence is OX (0/319).
- Sample surveys among out patients in Yaounde and Nkongsamba:
. 488 sera tested, none is positive
- Surveys among high risk groups:
. 358 hospitality girls have been tested, with 10 positive cases (2.8X),
3 of them being cameroonian.
- No positive sample among 40 sickle cell anemia polyt ransf used patients
followed in Yaounde.
Throughout the Cameroon Republic, AIDS prevalence among the healthy
population is therefore about 0,5X confirmed cases.
The number of false positive imrounoenzymat ic tests should be noted (72X).
Prospective Evaluation of HIV-associated Morbidity
RUEDI LUTHY. H.G. TAUBER, J. BRUHWILER, B. LEDERGERBER,
University Hospital, Zurich, Switzerland
W. SIEGENTHALER et al
The natural history of HIV-infection was studied prospectively in 142
patients (pts), who were examined at least twice during a minimum period of
6 months. Median follow-up period was 10 (range 6-37) months. The CDC
classification system for HIV-infections was used. Initial diagnoses were
Asymptomatic infection + laboratory abnormalities (II A+B) in 46 pts (32%)
persistent generalized lymphadenopathy (LAS, III A+B) in 46 pts (32%)
constitutional symptoms and minor opportunistic infections (IV A+Cj) in 32
pts (23%); and AIDS (CDC surveillance definition, IV Cj+D) in 18 pts (13%).
From group II 14 and 5 pts progressed to groups III and IV, respectively.
In contrast, only 7 pts deteriorated from III to IV (p <0.01). Within group
IV A+C2 6/32 pts (19%) developed serious opportunistic infections or tumors
(--> IV Cj+D). Overall, AIDS developed in 9/124 pts (7%) after 4-24 months,
including those 6 pts from group IV A+C2. A comparative analysis of
progression rates (Kaplan-Meier method) showed - despite similar
observation periods - that pts in group II had a significantly higher risk
(p <0. 01) for deterioration than pts in group III. 13/27 pts with AIDS
died, all of them had prior opportunistic infections (IV Cj).
Thus, 32/142 (22%) pts had evidence of progressive disease during this
limited follow-up period. We conclude that HIV-associated morbidity - even
for asymptomatic pts - is high.
123
WEDNESDAY, JUNE 3
iiipoo Update: Racial Differences between Patients with
"'•0£ Hemophilia-Associated AIDS in the United States, 1981-1986.
JEANETTE K. STEHR-GREEN, J. M. JASON, B. L. EVATT, Centers for Disease
Control (CDC), Atlanta, GA.
As of December 15, 1986, a total of 281 cases of hemophilia-associated
AIDS had been reported to CDC. These cases represent a cumulative incidence
rate of 1.6 AIDS cases per 100 persons with hemophilia. The number of AIDS
cases diagnosed annually has nearly doubled, except In 1986, during which
cases increased only 10%; however, reporting is not yet complete for that
period. Demographic characteristics of the patients diagnosed each year
have not changed significantly. The majority of patients had severe
hemophilia A (66%) and had received commercially produced clotting factors
(98%). Of the 281 patients, the proportion of blacks was significantly
lower than that of blacks in the general U.S. population (8% [22/281] vs.
12%, p=0.005). The median age for black patients was significantly lower
than that for white patients (26 years vs. 34 years, p=0.02). Significantly
more black than white patients had mild or moderately severe hemophilia
(9/19 [47%] vs. 51/216 [24%], p=0.02). Black patients were more likely than
whites to have received plasma or packed red blood cells in addition to
commercially produced concentrated clotting factors (7/17 [41%] vs. 49/203
[24%]); however, the difference was not significant. These data suggest
that AIDS is diagnosed less frequently among black hemophiliacs than white
and are consistent with a higher early mortality rate among black
hemophiliacs due to their coagulation disorder or the presence of racial
cof actors for the development of AIDS. However, population-based studies
are needed to better define these racial differences.
WR85 Serial Western Blot Analysis in the Early Diagnosis of HIV Infec-
tion
FRITZ DAGUILLARD*, P. STRICTLAND*, T. LOG*, C. LANE**, M. WELLS***, AND
D. SHEPP***, Commission of Public Health, Washington, DC, **NIH, and ***FDA,
Bethesda, MD .
Ten individuals (2 males and 8 females) presented for testing following
repeated heterosexual exposure to an HIVpositive partner. Last intercourse
had occured 6 months to several days before testing. Only 1 patient was
initially reactive by ELISA (Abbott). Western blot analysis revealed a weak
p24 band in one case (tfl) and a weak p55 band in two other cases (#2 and 3).
In each case the absorbance value of the ELISA was clearly negative. All but
one patient agreed to return for a regular follow-up which included HIV
antibody testing, viral culture and an extensive immune profile. Patient 1
did not return for evaluation before 6 months. At that time ELISA and Western
blot were strongly positive. Patients 2 and 3 were evaluated 3 months later.
In both cases bands reactive to all gag protein antigens were identified by
Western blot, while the ELISA test was still negative. Viral culture was
negative in both cases. All the other patients have remained negative by both
ELISA and Western blot when tested 1 to 4 times over a period of 3 to 15
months. In all 9 patients the immune parameters were within normal limits.
These results suggest that serial Western blot analysis which does not over-
look weak p55 and/or p24 bands is the most sensitive way to diagnose early
HIV infection.
WP83 ^ Three Year Prospective Study of Initially Asymptomatic HIV Posi-
tive Gay Men in Stockholm, Sweden.
ANDERS KARtSSON, L MORFELDT-MANSSON, 8 BO'TTIGER, G v KROGH, L MOBERG, E SAND-
STROM, et al., Venhalsan, Dept of Dermatovenereol, Sddersjukhuset, Roslags-
tulls Hospital, Dept of Immunol, The Natl Bacteriol Lab, Stockholm, Sweden.
In a health screening project in Stockholm, Sweden, consecutive asymptomatic
gay men have been enrolled and prospectively followed since Nov 1982. Frozen
coded sera from 998 men, drawn during the period Nov 1982 to Dec 1983, have
been examined for serum antibodies to Human Immunodeficiency Virus (HIV) by
ELISA. Positive reactions were confirmed by Western blotting. The seropositive
men have been followed and their clinical status three years later is presen-
ted. Repeated determination of T cell subsets were done in most men.
Results: HIV antibodies were demonstrated in 123 (12.3?0 of the 998 men. Of
the seropositive men it was possible to evaluate 116 men after a mean time of
40.6 months. Of these 116 men, 19 (16.4!S) had developed AIDS. Eleven of the
men with AIDS had died. Of the men without AIDS it was possible to clinically
evaluate 80. Of those, 8 (10. OSS) had AIDS Related Complex (ARC), 38 (1*7.5%)
had Persistent Generalized Lymphadenopathy (PGL) and 33 (41. 3%) had a minor
lymphadenopathy (ML) or were completely asymptomatic. One man (1.2?o) had died
of and one man with ML had been treated for Malignant melanoma. Of the men
diagnosed as having AIDS, 8 had Pneumocystis carinii pneumonia, 5 Kaposi's
sarcoma (KS), 2 CMV infection, 1 Candida esoephagitis, 1 Toxoplasmosis, 1
Cryptococcus meningitis and 1 both KS and Lymphoma at the time of diagnosis.
Conclusion: This study shows that the morbidity and mortality of HIV infec-
tion is high even in recently infected individuals living in a country with a
high standard of living and good health services like Sweden. T cell subsets
as prognostic markers will be discussed.
U/Pftfi Immunological Progression of HIV Infection
in Sydney Gay Men — A Generalised Linear Model
J.BURCHAM* , R.PENNY** ,G. BERRY* , B . TINDALL* * , D.COOPER**
•University of Sydney , **Centre for Immunology
(St. Vincent's Hospital) Sydney, Australia
Over a period of three years, the Sydney AIDS Prospective
Study has collected epidemiologic, clinical, serological and
immunological data, in six-monthly visits, from over 1000
homosexual men, of whom 40% are HIV ABV positive. In over 85%
of the HIV ABV positive subjects, this longitudinal study
finds the linear sequence immunological progression of the
disease to be low T4/T8 ratio, low T4%, to low T4 count, and
finally low lymphocyte count, confirming the stages found by
Zolla-Panser in a cross-sectional study. A very significant
correlation was found between this progression and the rate
of change of T4 cell count with respect to time, suggesting
that each step in the progression is determined predominantly
by T4 changes.
Each of the stages of immunological progression where
analysed in relation to clinical features which varied
from asymptomatic to LAS, ARC, and AIDS. Using logistic
regression and linear modelling tools, no correlation
was found between clinical and laboratory findings, nor
between lifestyle factors and immunological progression.
The highly variable relationship between clinical findings
and immunological changes indicate that a much more complex
branching model of the disease is needed to predict outcome.
WP84 Antibodies to HIV in Cervical and Oral Secretions of
Female Prostitutes in Zaire
DAVID W. ARCHIBALD
M. ESSEX**, J. SAUK*, J. MANN***, H.
T. QUINN****, et al., *University of Maryland Dental
Harvard School of Public Health, Boston,
FRANCIS**
School, Baltimore, MD,
MA, ***Department of Public Health, Kinshasa, Zaire, CDC, Atlanta,
GA, ****Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD.
The antibody response to HIV in cervical and oral secretions
was studied in a cohort of high risk African individuals. The
population assayed consisted of HIV seropositive and seronegative
active female prostitutes from Zaire. Oral secretions were collect
ed by rinsing the subjects' mouths with PBS followed by expectora-
tion. Cervical secretions were collected by adding a cervical
scraping to an aliquot of PBS. Secretions were assayed for anti-
bodies using a modified, IgA-enhancing radioimmunoprecipitation of
S-cysteine-labeled Molt HIV-infected cell lysates.
Seventeen of 22 cervical samples and 19 of 22 oral samples from
the seropositive individuals contained antibodies to viral anti-
gens. Antibodies to gpl60, gpl20, and p24 were consistently found.
One seropositive individual had no detectable antibodies in either
secretion. Secretory antibodies were not detected in the oral se-
cretions of 21 seronegative individuals. One of 21 cervical from
seronegative prostitutes showed a weak precipitation of gpl60 and
120. We have demonstrated that 21 of 22 serpositive women possess
viral-specific antibodies in their oral and/or genital secretions.
The presence of antibodies at mucosal surfaces may be associated
with the lower incidence of female to male transmission of AIDS.
WP87 HIV !hfection in Dialysis Centres.
U. ASSOGBA*, M. REY**, R.A. ANCELLE***, C. FOUCAULT*,
J. ROTENBOURG*, J.C. GLUCKMANN*, *Dept. nephrology, Hopital Pitig
Salpetriere, Paris, ** Dept. virology, Hopital Claude Bernard,
Paris, ***WHO Collaborating Centre on AIDS, Paris, France.
A prospective multicentre study was undertaken between February
1985 and August 1986 in 4 haemodialysis centres in the Paris area
(France) in order to assess the prevalence of HIV infection and
the risk of transmission of the virus within the centres. A four-
month follow-up was carried out in 221 patients undergoing haemo-
dialysis (HD) and in 40 staff members caring for the patients in
2 centres. 62 patients undergoing peritoneal dialysis (PD) and
126 haemodialysis patients who transited through a centre (HDT)
were screened once. A questionnaire exploring risk factors was
completed for each patient and staff member. Sera were tested for
HIV antibodies by ELISA (ELAVIA) and confirmed by Western Blot.
Of the 357 HD+HDT patients, 4 were found to be positive. Of the
221 HD patients, 1 multi-transfused haemophiliac and 1 multi-
transfused Nigerien without other risk factors were positive in
the first screening. Another patient seroconverted after trans-
fusion during the study; no other risk factors existed and the
donor has not yet been found. One of the 126 HDT patients had
received infected plasma. No staff members or PD patients were
positive. No transmission within centres, from patient-to-patient
or patient-to-staff was evidenced. Although HIV seems to be less
infectious than HBV, precautions to prevent transmission of HIV
in dialysis centres should be maintained.
124
WEDNESDAY, JUNE 3
uipoo The Impact of Presumptively Diagnosed Opportunistic Infections and
Cancers on National Reporting of AIDS
E. THOMAS STARCHER, II.,* J. K. BIEL,** R. RIVERA CASTANO,*** J.M. DAY,****
S.G. HOPKINS,***** J.W. MILLER******. *Centers for Disease Control, Departments
of Health of **New Jersey, ***Puerto Rico,****Boston, Massachusetts,
*****Was.bington, and ******Connecticut , USA
A review of death certificates in four U.S. cities suggested that at least
10% of AIDS cases do not meet the national surveillance case definition because
of the lack of biopsy or other specific confirmation of the indicative disease
and are therefore unreport able . To assess the frequency of the resulting
underreporting, health departments in five areas of the United States reviewed
medical records for all or for a random sample of patients treated during a
fixed time period who 1) had previously been considered as suspected AIDS
patients and/or 2) had discharge diagnoses consistent with the various AIDS
indicative diseasaa. Extrapolations from preliminary results in four areas
suggest that 96 AIDS cases were presumptively diagnosed during the same period
that 723 cases were definitively diagnosed, for an overall 11% rate of
presumptive diagnoses, ranging by area from 4% to 15%. Information from the
fifth area suggests the rate there may exceed 50%. Coincidentally, the studies
identified 58 (7%) previously unreported AIDS cases that meet the national
surveillance case definition, consistent with results from validation studies
elsewhere. When data analysis is completed in March, we will estimate the
impact on national AIDS surveillance of not reporting presumptively diagnosed
AIDS cases. The study will also 1) identify reasons presumptive rather than
definitive diagnostic methods are used, 2) determine which opportunistic
infections and cancers are presumptively diagnosed most often, 3) indicate
trends over time in the frequency of presumptive diagnosis, and 4) estimate the
usefulness of retrospective chart review in identifying unreported AIDS cases.
WP91 Women with the Acquired Immunodeficiency Syndrome In Miami
MARGARET A. FISCHL and GM DICKINSON. University of Miami, Miami, PI.
Miami reports the fifth highest number of cases of AIDS in the United
States, including one of the highest percentage of women with AIDS. During the
past 3 years, 111 women were diagnosed with AIDS at our medical center. Ten
were Caucasian and 101 were black, ranging in age from 20 to 57 years. Risk
factors for AIDS included intravenous drug abuse (43), heterosexual contact
with a person at risk for AIDS (8), blood transfusions (7), and 50 women of
Haitian ancestry. The number of cases and associated risks factors per year
are listed below:
Intravenous
Heterosexual
Blood
Haitian
Tears
Number
Drag use
contacts
Trans fusion
Unknown
ancestry
1983
17
4
1
1
0
11
1984
17
9
1
1
0
6
1985
31
12
3
2
1
13
1986
46
18
3
3
2
20
Ninety-eight presented with opportunistic Infections including 31 with
multiple infections, 14 with opportunistic infections and Kaposi's sarcoma,
and one each with Kaposi's sarcoma or lymphoma. The types of infections
Included: P^ carinii pneumonia (73), toxoplasma encephalitis (21), M^ avium-
complex infection (7), cytomegalovirus infect ion (10), Cryptococcosis (10),
and Cryptospor idiosis (9). Associated infection with oral thrush (63),
genita 1 herpes (32), and herpes zoster (4) were also found. Six women
presented with AIDS during pregnancy, and 18 reported a history of
miscarriage. The average length of survival after diagnosis waB 6.6 months,
ranging from 1 to 23 months. AIDS among women appears to be Increasing, is
disproportionately associated with multiple infections and has a poor outcome.
lA/PftQ CD4 + cells ' count as predictive marker of disease progression in
HIV-positive parenteral drug addicts.
MASSIMO GALLI, G. TAMBUSSI, A. CASTAGNA, A. SARACCO, M. MAILLARD, A. LAZZARIN,
et al., Clinic of Infectious Diseases, University of Milan, Italy.
CD4 + cells' count in peripheral blood is considered a valuable predictive
marker of clinical evolution in HIV infections. A clinical survey of 375 paren
teral drug addicts (PDAs) examined between 1984 and 1986 was performed. All
studied subjects (279 males, 96 females, age ranging between 18 and 33) sharing
behavioural, social and toxicomanic habits, live in Milan, where the first HIV
seroconversion in PDAs was documented in 1979. A clinical classification was
made following CDC's and Walter Reed Foundation's criteria. T cell subsets were
determined by an Ortho spectrum III cytof luorograph. Mean counts of CD4 + cells
in the overall population showed a significant decrease during the three years
of the study (from 986.5 +_642.1 in 1984 to 491.9 + 244.3 in 1986, p< 0.001).
In order to evaluate decreasing chances (below 400/mm ) of CD4 + cells in 108
already symptomatic patients, we considered as conventional starting point for
a subsequent follow-up the onset of a histologically confirmed lymphadenopathy
syndrome (LAS). Onoe diagnosis of LAS was made, CD4 + cells' chances of decrea
sing below 400/mm were 50% after 32 months. Our data confirm on the one hand
the trend to a rapid decrease of peripheral CD4 + cells in the overall popula-
tion of HIV infected PDAs, on the other hand, the relatively long average time
required by CD4 + cells to reach levels below 400/mm in symptomatic subjects,
pointing to a possible slow progression of the disease.
WR92
The Melbourne Cohort After 3 Years: Halt of Sero-conversion to
HIV and Predictors of Immune-Deficiency.
BRIAN P ■ MULHALL* , R.M. CRAPPER**. I.H. FRAZER ***, I.R. MACKAY *, The Walter
s Eliza Institute, Melbourne, Australia ** , Institute of Bone & Joint Disease,
New York, U.S.A. ***, Princess Alexandra Hospital, Brisbane, Australia.
In 1983 a cohort of 100 asymptomatic homosexual men was recruited for a
prospective study. HIV seroconversion and immune function assessments included
T Lymphocyte subsets, including helper-inducer (CD4 + 4B4) and suppressor
inducer (CD4 + 2H4+) cells, serum immunoglobulins, and capacity for recall
of delayed hypersensitivity.
The prevalence of antibody to HIV rose from 22% in 1983 to 31% (24/78) in
1985. There has been no further seroconversion in 1986, suggesting that the
spread of virus into and within this group has been halted.
We have analysed the immunologic parameters from visits 1-8 to determine
whether there are continuing group trends, single measurements are predictive,
or whether for a single individual serial measurements have better predictive
value. For T helper (Leu 3) subset numbers, correlation analysis between
visits followed by simple linear regression was not significant (p=0.15).
However, t tests for repeated measurements on same individuals was significant
in the seropositive group (t=2.18, p=0.03). Similarly, for serum immunoglobu-
lin concentrations, only the t test for repeated measurements in the sero-
positive group was significant (t=3.59, p=0.002). These results indicate that
although there are clear group trends, for a single indivual, serial and not
point-measurements are necesssary to predict immunodeficiency.
U/pOQ A Computer Model of the AIDS Epidemic
DAVID J. AHLGREN, Ph.D., ALEX STEIN; PETER LYONS;
Department of Engineering and Computer Science, Trinity College,
Hartford, CT 06106.
This model tracks the spread of AIDS through the sexually
active population, quantifies the effect of such disease carriers
as intravenous drug users, bisexuals, and hemophiliacs, predicts
infection and mortality, and evaluates the sensitivity of the
epidemic to policy and behavioral changes. These include improved
educational programs, changes in sexual habits, provision of
sterile needles to intravenous drug users, application of disease-
inhibiting drugs, implementation of testing programs, and reduction
of the likelihood of disease transmission through prophylaxis.
The model divides the sample population into three categories:
homosexuals, bisexuals, and heterosexuals. Each category includes
intravenous drug users and hemophiliacs. The transmission of
AIDS through sexual interaction, needle sharing, and blood trans-
fusions is characterized by a set of non-linear equations which
are solved using the STELLA simulation language on an Apple
Macintosh microcomputer. When quantified by United States aggregate
data from the National Centers for Disease Control, the model
predicts a peak in the AIDS-infected population in 1991 accompanied
by the devastation of the bisexual and intravenous drug using
populations, and demonstrates the relative insensi t iv i ty of
the epidemic to increased sexual frequency and to increased
number of partners.
We will show how to apply the model to a particular region by
describing a ten-year simulation of AIDS in New York City.
WR93
JOSE J.
Novel
Incuba
GONZALE
Phenomena in Epidem
tion Periods: Appli
M.G. KOCH
Karlsbo
The o
incubat
acousti
pattern
spread
order o
instanc
between
whose a
of 12 m
of only
cases
the dou
Such
extreme
ion per
may las
doublin
with nu
Genui
negativ
rg , Swed
nset of
ion peri
cs and e
of the
of the i
f the br
, a fie
1 and 5
gent (a
onths le
Z
en .
any epidemic associ
ods displays a beha
lectronics: a trans
ics Associated with Long
cation to AIDS
ID, Grimstad, Norway, VaC,
observed epidemic d
nfectious agent dur
eadth of the incuba
titious disease hav
years with a mean
virus, say) spreads
ads to an epidemic
6 months. The doubling tim
ncreases during a 5 year pe
bling time in the number of
an onset transient is very
ly long mean value and the
iod distribution imply that
t up to 7 years most of the
g time of AIDS cases is a s
merous examples for dxffere
ne drops in the rate of spr
e transients which must be
achieve a real understanding of th
ated with a
vior which
ien t appear
oes not mir
ing an init
tion period
ing an incu
incubation
with a con
starting wi
e of the ob
riod until
virus carr
important f
large varia
during an
observed i
purious eff
nt compartm
ead of HIV
taken into
e epidemic
disease having long
is well-known from
s, meaning that the
ror exactly the
ial phase of the
distribution. For
bation period
period of 3 years
s t ant doubling time
th a doubling time
served numbers of
it becomes equal to
iers ( 12 months ) .
or AIDS. Here, the
nee of the incubat-
initial stage which
ncrease in the
ect. This is shown
ents and countries,
induce again
account in order to
pattern .
125
WEDNESDAY, JUNE 3
MipQj Evidence for Heterosexual Transmission of HIV in the United Kingdom
ANDREW P. PEARSON, and N.S. GALBRAITH, Communicable Disease
Surveillance Centre, PHLS, London, UNITED KINGDOM.
Heterosexual transmission of HIV is presumed to have occurred in 18/610 (3%)
AIDS cases and in 48/3870 (1.2%) HIV antibody positive individuals reported to
CDSC between 1982 and 1986.
The 18 AIDS cases were associated, predominately, with people whose hetero-
sexual contacts or residents were abroad (14/18) . The other four cases were
'UK acquired': One case from a haemophiliac, the second case a prostitute
with American contacts, the third was an African living in England since 1963,
and the fourth was a male with multiple partners, including prostitutes, but
who had shared razors with drug users. The 48 HIV antibody positive individ-
uals most probably contracted their infection as follows: 15 from haemophil-
iacs (31%) , 8 from contacts abroad (17%) , 6 from prostitutes within Europe
(13%) , 5 from contact with IV drug abusers (10%) and four from AIDS cases or
HIV antibody positive husbands: One had a boyfriend with American contacts;
one was a wife of a bisexual man, two had a history of prosmiscuity , one with
Dutch contacts; and 5 individuals from whom the contacts are still being
sought.
Four groups make up 79% (52/66) of the reported heterosexually acquired in-
fections; the British visiting or living in Africa (19/66) , and the partners
of haemophiliacs (16/66), prostitutes and their contacts (8/66) and the
sexual partners of IV drug users (5/66) . The AIDS cases and HIV infections
occurred 1 in 1982, 4 in 1983, 3 in 1984, 16 in 1985 and 42 in 1986. The
actual number of heterosexual infections is unknown but this data is un-
equivocable. The 'heterosexual' outbreak of AIDS has started in the UK.
Surveillance and practical intervention will be discussed in the context of
these findings.
WR97 Utilization of the Highly Permissive C3 Cell Line in Rapid Serum
Neutralization Assays. W. EDWARD ROBINSON. DAVID C.
MONTEFIORI, and WILLIAM M. MITCHELL, Vanderbilt University, Nashville,
Tennessee, USA.
The HTLV-II transformed cell line C3 is highly permissive to HIV infection in vitro.
Even in the presence of low MOI (0.01-0.1), this cell line exhibits rapid expression of
viral antigens in 4-6 days with extensive cell lysis as early as 7-9 days post virus
adsorption. Utilizing the C3 cell line, a rapid neutralizing antibody screen is now
described. Demonstrated are results derived from patient sera obtained during the
course of antiviral drug therapy. Using either an increase in time to cytolysis,
reduction in reverse transcriptase assay values, or reduction in percent indirect
immunofluorescence as the criteria for neutralization of virus, it is possible to clearly
demonstrate significant differences in the anti-HIV qualities of different patient
sera. Some patients show significant neutralizing ability with either percent
fluorescent cells or reverse transcriptase levels less than thirty percent of HIV
infected control. Other patients show virtually no ability to neutralize HIV with RT
assay values or percent fluorescence eighty percent of control values. Therefore,
utilizing standard neutralizing antibody titer techniques but incorporating the C3
cell line, it is possible to completely evaluate patient serum in seven days. The
rapidity with which this cell line expresses viral antigens makes the C3 the cell line of
choice in serum testing especially when large numbers of sera must be evaluated.
WR95
HIV INFECTION AMONG FEMALE AND MALE PROSTITUTES. U.Tirelli, E.Vaccher, S.Diodato, R.
Bosio, P.De Paoli, D.Crotti et al. AIDS and Related Syndromes Study Group. Centro di
Riferimento Oncologico, Aviano, Italy.
Between September 1985 and January 1987, we carried out a prospective study in 36 female prosti-
tutes, 22 of whom were intravenous drug abusers (IVDA), and in 15 male prostitutes, 3 of whom
were IVDA, 9 transvestites and 3 homosexual men, in Pordenone and Treviso, two towns of
North-East Italy. The prostitutes were clinically examined, given laboratory tests including HIV
antibody tests (Elisa with Western Blot confirmation) and H/T8 ratios and completed a
questionnaire on their sexual behaviour. Results:
FEMALE PROSTITUTES MALE PROSTITUTES
Median age (yr)
of
Median partners / mo
Rectal intercourse
Frequency of:
HIV antibody
AIDS
Our data shows that female prostitutes who
homosexual are not at increased risk for AI0:
should be considered at risk for HIV infection.
IVDA
NON-IVOA
IVDA
N0N-IVDA
n=22)
(n=14)
(n-3)
(n=12)
24
37
26
25
2
10
1
8
70
90
NA
150
4%
7%
100%
100%
59%
0%
33%
8%
0
0S6
0%
0%
are not
IVDA and
male
prostit
utes who are not
£ while
female and
male
prostit
utes who are IVDA
WR98
V.A. PASE
E.V. KARA
parations
I vanovs ky
USSR Mosc
C3 def
interesti
ARC patie
label ed a
ve C3 mol
protein b
case its
In 20 ser
8.3 kD we
bed in th
was detec
at all.
140 kD wa
or eel 1 p
cleavage
in the de
Cleav
Relat
CHNIK
MOV**
Min
Inst
ow
icien
ng to
nts w
nti-C
ecule
ands
amoun
two
re f o
e pro
ted a
In so
s pre
rotca
of C3
velop
age of C3 Complement in the Serum of AIDS or AIDS
ed Complex (ARC) Patients
S.V. ANDREYEV*, A.M. ISCHENK0*, S.A. KETLINSKY*.
V.M. ZHDANOV**, *Institute of Highly Pure Biopre-
f Medicine and Microbiology, Leningrad, **
f Virology, Academy of Medical Sciences of
istry o
itute o
cy lead
study
ere exa
3 monoc
and i t
were de
t was a
i ntens
und . T
cess of
nd 5 se
me sera
sent
ses pro
compl e
ment pa
s to
C3 in
mi ned
1 onal
s C3a
tecte
bout
e ban
he la
C3 c
ra di
the
C3 co
duced
ment
thoge
chroni
patie
by We
a n t i b
f ragm
data
ten pe
ds , co
tter f
leavag
d not
other
mponen
d u r i n
compon
n i c i ty
cal dise
nts with
stern bl
odies (L
ent (Mr=
level o
rcents o
rrespond
ragment
e. In t
conta i n
C3a cont
t may be
g eel 1 d
ent may
of HIV
ases .
AIDS
ot an
BP Gl
9,2kD
f few
f tha
ing t
was n
wo se
C3a s
a i n i n
clef
estru
be a
i nduc
It was
.27 sera
alysis u
0) speci
). In 2
percent
t in nor
o Mr=9.2
ot previ
ra only
pec if ic
g fragme
t by the
c t i o n
new impo
ed immun
extre
of AI
sing 1
fie to
6 sera
s and
mal se
kD and
ously
this f
fragme
nt wit
virus
Enhanc
rtant
odef ic
mely
DS and
25 I
n a t i -
C3
i n one
rum.
Mr =
descri -
ragment
nts
h Mr =
and/
ed
factor
iency.
WR96 Immunological, Serological and Clinical Abnormalities in Children Born
to Promiscuous and Drug-Addicted Mothers at Risk for AIDS.
EDUARDO FERNANDEZ-CRUZ, A. FERNANDEZ, D. GURBINDO, M. GARCIA MONTES and J.M.
ZABAY. Hospital Provincial. Complutense University. Madrid. Spain.
Two different enzyme-linked immunoassays and indirect immunofluorescence or
Western blot tests were used to evaluate HIV seropositivity in 201 I.V. drug abu-
sers. In this population, 89% (71% males and 18% females) were considered to have
HIV antibodies. We studied 45 infants and children (ranging from 1 month to 6
years of age) born to drug-addicted and sexually promiscuous mothers. Thirty-six
percent were found to be HIV-positive. Furthermore, 9 of 15 children born to drug
-addict mothers (60%) and 3 of 20 born to sexually promiscuous (10%), were sero-
positive. The other 4 affected children were born to heterosexual mothers with
partners in the at-risk groups. Twenty-nine (64%) were HIV-negative children
without clinical signs, but with increased (43%) and decreased (29%) T4/T8 ratio,
reduced PWM response (50%), but normal serum levels of Igs . The other 16 were
HIV-positive, and of these 4 (24%) had asymptomatic infection and 12 (75%) were
included in group IV as clasified by CDC (2 had AIDS, 7 had ARC and the other 3
were group IV-E). In the HIV-(+) group all children showed a significant increase
of IgG as compared with HIV-(-) group (p<0.01), and there was a significant di-
fference in IgA levels between HIV-(+) group IV and HIV-(+) asymptomatic children
(p<0.05). All HIV-(+) children in group IV showed a progressive drop in T helper
cell numbers (89%) and T4/T8 ratio (100%) and decrease in blastogenic response to
PWM (100%). Children of the HIV-(+) group IV also showed infection by other viru-
ses (20% were HbsAg-(+) and 33% had antibody to hepatitis B core antigen). Of
special note is the fact that in children of the HIV-(+) group IV, 69% had been
immunized with the usual vaccines as compared with only 25% in the asymptomatic
HIV-(+) group. Further investigations are in progress to elucidate which co-fac-
tors might be involved in the evolution of AIDS in children at-risk.
WP99 Failure to Demonstrate HIV-Specific CTL in Asymptomatic
Antibody-Positive Homosexual Men,
ALISON C. MAWLE, J. A. SCHEPPLER, T.J. SPIRA, J.S. MCDOUGAL, Centers for
Disease Control, Atlanta, GA.
We have attempted to generate human immunodeficiency virus (HlV)-specific
cytotoxic T- lymphocytes (CTL) from 18 antibody-positive asymptomatic
homosexual men. This population has been shown to have elevated numbers of
cytotoxic precursor cells (Leu 2+, Leu 15"). The mean CD8+ cell number
of the group studied was 839.1346 per mm-* (normal range 192-726), with 50%
being above the normal range. Sixteen bad an inverted CD4/CD8 ratio (x=0.77)
and the mean CD4+ cell number was 6331259 per mm' (normal range
(468-1433).
PBL were cultured with live virus for 7-14 days, then assayed for killer
activity on infected autologous monocytes, infected autologous CD4+
PHA-stimulated blasts, or CD4+ PHA-stimulated blasts with virus bound to the
cell surface. In some experiments we added either IL-2 or irradiated
allogeneic PBL to the culture in an attempt to supply any factors necessary
for CTL production. We also tried to restimulate primary cultures with
irradiated HIV-infected autologous PHA-stimulated blasts. We detected no
HIV-specific CTL under any of these conditions. Cultures with infectious HIV
did not abrogate the generation of EBV-specific cytotoxic cells from normal
individuals. Since CTL specific for other human viruses, such as influenza,
EBV and CMV, are generated under similar conditions to these, we conclude that
under conditions that normally allow CTL generation in humans, HIV-specific
CTL are not detectable.
126
WEDNESDAY, JUNE 3
WP100 mce nePleted I" Vivo of "T4" Lymphocytes Do Not Die of Infection
With Ectroraella Vaccinia or Cytomegalovirus
CM. SHEARER*, M. BULLER** , A. ROSENBERG , T. MIZUOCHI*, C. S. VIA*, B.
WEATHERLY*, et al., NCI*, NIAID** , NIH, Bethesda, MD.
Many AIDS patients do not generate In vitro T cell responses to virus (self
restricted antigen, S+X) , but exhibit elevated T cell responses to HLA allo-
antlgens ( ALLO) (J. Immunol. 137:2514, 1986). Terminal AIDS patients, however,
appear to have also lost their In vitro ALLO responses. This difference raises
the possibility that the CD4~ T cell pathway responsiblle for the ALLO reac-
tivity provides some protection in AIDS patients. Murine in vitro T cell
responses to (S+X) require L3T4+ (CD4) helpers, whereas ALLO responses can be
generated by Lyt2+ (CD8) helper cells (J. Exp. Med. 162:427, 1985).
Because of this similarity in the T helper pathways of the two species, we
have tested the possibility that mice depleted in vivo of either L3T4 or of
both L3T4+ and Lyt2+ cells will be susceptibile or resistant to the murine
pathogenic viruses ectromella, vaccinia, and cytomegalovirus (CMV). Mice in
which both T cell pathways were intact generated T cell and antibody responses
to these viruses and were resistant to the infections. Mice depleted of both
L3T4 and Lyt2 cells did not generate T cell or antibody responses and died soon
after exposure to ectromelia or CMV. However, mice selectively depleted in vivo
of L3T4 cells and subsequently infected with ectromelia, vaccinia or CMV gener-
ated T cell responses, did not make antibodies, but did not die from virus
infection. Further, studies of the CMV Infected mice indicated that CMV could
be detected in the salivary glands and spleens of mice depleted of L3T4 cells
or of both L3T4+ and Lyt2+ cells, but virus was much more extensive in mice
depleted of both subsets. These in vivo studies of selective "T4" depletion
in mice raises the possibility that the elevated T4 independent pathway pro-
vides some Immune protection in the AIDS patient.
WP103 Restoration of AIDS defective Natural Killer (NK) function by OK-432
' BENJAMIN BQNAVIDA° JONATHAN D. KATZ , ARTO HADDADIAN , MICHAEL S.
gOTTLIEB*. RONALD MITSUYASU*! AND TAKASHI H0SHIN0+. From the Departments of
Microbiology and Immunology, and Medicine, UCLA School of Medicine, Los
Angeles, CA 90024 and +the Department of Immunology, Fukui Medical School,
Japan.
We have recently reported that the mechanism of depressed NK activity in
AIDS PBL is due to a defective "trigger-receptor" for target cell stimulation
and which canbe functionally restored by IL-2 (J. Immunol. 137:1157, 1986). We
have also reported that the biological response modifier OK-432 (a low viru-
lent strain of Group A Streptococcus pyogenes) , augments NK-CMC activity and
secretion of NKCF by NK cells (Cellular Immunol. 102:126, 1986). These OK-432
activation events appear to be independent of IL-2 but mimic the effects of
IFN and IL-2 activations of NK cells. The present study examines whether
OK-432, like IL-2, can also activate AIOS NK activity. PBL from patients with
AIDS/KS were treated with OK-432 for 20h, washed and tested against the NK
sensitive G8 target cells in a 4h "Cr release assay. A significant enchan-
cement of NK activity was observed which was dependent on the dose of OK-432
used. We also observed a significant enhancement of ADCC activity. These
results demonstrate that OK-432 restores AIDS NK activity presumably through
the same mechanism induced by IL-2. The mechanism of 0K432 mediated activa-
tion of AIDS NK cells will be presented. (This work was supported in part by
a grant from the AIDS Task Force, and in part by the Tumor immunology training
grant CA-09120 awarded to J.D.K.)
WP101 Further Investigation of a Suppressive Factor Associated with HIV.
B . Ho f matin, E.LANGHOFF, B0 LINOHAROT, K.ULRICH, JJ HYLOIG-NIELSEN,
A.SVEJGAARD ET AL . UNIVERSITY HOSPITAL (RIGSHOSPITALET) , COPENHAGEN, DENMARK.
We and others have earlier shown that a purified Tnton-X treated extract of
HTLV-IIIR suppress the lymphocyte transformation response of normal lymphocytes
to mitogens and antigens, whereas an extract of uninfected H9 cells do not. We
have now shown that the suppressive factor is also present in non-Tnton-X
treated virus preparation and in preparations from the MB6 cell line known not
to be mycoplasma-infected, which exclude these trivial explanations for the
ouppression. Moreover, the extract did not contain demonstrable amounts of tumor
necrosis factor or lymphotoxin indicating that it is not of cellular origin. It
suppresses all cells studied of hematopoietic origin, including the formation of
colony forming units from human bone marrow, but not fibroblasts. It has a MV of
about 70.000 on Sephadex separation. Preincubation of lymphocytes with the
extract before adding mitogen gives pronounced suppression, while addition of
extract three days after mitogen has little effect indicating that the factor
acts early. It compleately inhibits IL-2 receptor expression. It's action
cannot be blocked by addition of IL-1, IL-2, or by commercial antibodies against
p24, gp41, or gp 120, and it does not inhibit the binding of antibodies against
CD4, C08, or the IL-2 receptor. Sera from some anti-HIV positive and clinically
healthy individuals can neutralize the suppressive effect of the HIV-extract on
lymphocyte transformation. This neutralizing effect was recovered in ammonium-
precipitated immunoglobulin from the same individuals. Further investigation of
antibody preparations from these sera are currently under study. (This work was
supported by the Danish Cancer Society and the Danish Medical Council.)
WP104 Detection of Antibody Dependent Cell Mediated Cytotoxicity (ADCC)
Against Human Immunodeficiency Virus (HIV) Infected Cells.
R S. BLUMBERG, TIMOTHY J . PARADIS . K.L. HARTSHORN, M.U. VOGT, M.S. HIRSCH.
R.T. SCHOOLEY. Massachusetts General Hospital, Harvard Medical School,
Boston, MA 02114.
We studied the ability of serum from HIV seropositive or seronegative
subjects to augment killing of HIV infected H9 cells compared to
uninfected H9 cells in a 7 hour chromium release assay using peripheral
blood mononuclear cells from healthy HIV uninfected donors. HIV infected
H9 cells were more readily lysed than uninfected cells, supporting
observations by others regarding NK activity against HIV infected cells.
Much greater augmentation of killing of HIV infected H9 cells compared to
uninfected cells was observed using serum from HIV infected donors.
Target Cell
Serum n H9 H9/HIV (H9/HIV) - (H9)
None 3 58+4 66+6 8+3
HIV seonegative 21 53+1 59+2 5 ± 1
HIV seropositive 30 48+1 76+2 28+2
p<0.001
Optimal ADCC activity was exhibited at serum dilutions from 1:10 to
1:100, but were seen in some sera at dilutions of 1:10,000. ADCC was
reduced by prior absorption of HIV seropositive serum with HIV infected H9
cells or staph protein A.
This assay demonstrates the presence of antibodies in persons infected
with HIV capable of mediating ADCC in vitro. These findings may provide
further insights into the immune response to HIV, and aid in the
identification of immunogenic epitopes of HIV.
WP1D2 Serial Testing of Cell-Mediated Immunity in Haemophiliacs.
ROBERT J.G. CUTHBERT", J. TUCKER", CM. STEEL"*, J.F. PEUTHERER""* ,
CA. LUDLAM*. *Dept. of Haematology, Royal Infirmary of Edinburgh. **MRC
Clinical Population and Cytogenetics Unit, Western General Hospital, Edinburgh.
***Dept. of Bacteriology, University of Edinburgh.
Cell-mediated immunity (CMI) was assessed in 39 haemophiliacs by intradermal
response to 7 recall antigens and compared with 20 healthy male controls. A
positive response was indicated by mean diameter of induration >2mm at day
3. All control subjects were positive to 2 or more antigens and 80% responded
to 4 or more. CMI was markedly depressed in the haemophiliacs with 62%
responding to none or one antigen and only 18% responding to 4 or more.
Eighteen anti-HIV positive patients showed no significant difference in
responsiveness compared with 21 anti-HIV negative patients. However there was
an inverse relationship between annual factor VIII consumption and the number
of positive responses. Twenty-seven of the patients had been exposed to a
single batch of factor VIII contaminated with HIV; 14 developed anti-HIV
antibodies and 13 remained seronegative. Skin testing 3-9 months following
exposure to this batch showed no significant difference in responsiveness
between seropositive patients and those who remained seronegative. Ten
patients have been re-tested 2^ years after exposure. Three symptomatic
anti-HIV positive patients are now anergic (1 with AIDS, 2 with ARC) whereas
2 asymptomatic seropositive and 5 seronegative patients have maintained their
cell-mediated responses.
Depressed CMI in haemophiliacs can be correlated with factor VIII usage. In
the early period following exposure to HIV no difference in CMI exists between
seropositive and seronegative groups. An increased prevalence of anergy is
associated with symptomatic HIV infection.
WR105 Reduced Lymphocyte Cap Formation in Patients with Acquired
Immunodeficiency Syndrome (AIDS) and AIDS Related Complexes (ARC)
GEORGRANN C. BARON, L.Y.W. BOURGUIGNON, N.G. KLTMAS, M.A. FISCHL, G.B. SCOTT,
and M.A. FLETCHER, Univ. of Miami School of Medicine, Miami, FL, USA.
Isolated mononuclear cells (MNO from 16 adult and 6 children with AIDS, 1?
adults with ARC, and 12 adult controls were examined for the ability to cap
(aggregation of receptor bound fluorescein conjugated Concanavalin A (Fl-Con A)
to one pole of the cell). Cap formation was scored by enumerating fluorescent
caps on 200 MNC. Mean %Fl-Con A caps on MNC from the AIDS or ARC patients was
significantly reduced when compared to that on MNC from normal controls (27*
reduction in capping in adult AIDS patients, 53% reduction in capping in the
children with AIDS, and 30% reduction in capping in ARC patients, p=.001).
Patchy and/or punctate fluorescent patterns were observed on the surface of MNC
from the AIDS and ARC patients, while crescent shaped caps were seen on MNC
from controls. Similar abnormal patterns were present when fluorescein
conjugated mononclonal antibody to CD16 was used for capping on large granular
lymphocytes (LGL) isolated from AIDS patients, while LGL from controls formed
normal caps with anti-CD16. Normal capping was observed on MNC of 4 adult
AIDS/KS patients and ? adult ARC patients who were receiving in vivo human
lymphoblastoid interferon (Wellferon) and bovine thymic peptides
(Thymostimul in) therapy respectively. Two of the AIDS/KS were in comolete
remission. Capping of I*1C correlated with the diminished responses to Dlant
mitogens, CD4+ cells, decreased CD4/CD8 ratio, and subnormal natural killer
cell cytotoxicity (expressed on a per effector cell basis) which was observed
in these patients (p=,05). The consistent reduction in receptor capping on MNC
seen suggests lymphocyte membrane and cytoskeletal abnormalities in patients
with HIV infections which may be related to functional defects in these cells.
127
WEDNESDAY, JUNE 3
WR106 NaCural Killer Cell Activity Against HIV Infected U937 Cells in
Homosexual Men
G. RAPPOCCIOLO, P. PIAZZA, Q. CAI , P. GUPTA, D. LYTER, CHARLES RINALDO,
Multicenter AIDS Cohort Study, Univ. of Pittsburgh, Pittsburgh, PA 15261
Peripheral blood mononuclear leukocytes from homosexual men and heterosexual
controls were tested for natural killer (NK) cell activity against HIV-infect-
ed U937 cells in a Cr-release assay. HIV seropositive homosexual men were
divided based on duration of infection: group 1, documented time after sero-
conversion, 12-25 mo; group 2, estimated time of infection, 27 to 43 mo. All
group 1 and group 2 subjects were asymptomatic or had persistent lymphoadeno-
pathy at the time of study. Five non-MACS patients with overt AIDS (PCP) were
also studied.
Lysis of Uninfected and HIV Infected U937 Cells
Heterosexual
HIV-
Homosexual
Male Donors
Target
HIV-
HIV+/GRP 1
HIV+/GRP 2
HIV+/AIDS
U937
U937+HIV
392a
61%
(8/8)D
36%
41%
(12/14)
20%
34%
(6/7)
19%
24%
(6/10)
8%
7%
(1/5)
Mean Z specific lysis "Number of subjects showing greater lysis of HIV
(50:1, Effector:Target) infected than uninfected U937 cells
The results show for the first time that HIV-specific natural killer cell
activity can be detected in both HIV seronegative and HIV seropositive subjects
and Is impaired in association with longer duration of infection and presence
of AIDS. This test may be useful in evaluation of efficacy of antiviral and
immunomodulatory treatment of HIV infection.
WP10Q Immunologic Status of Patients with Chronic Progressive HIV
wr. IU3 Encephalomyelopathy (HIV-EM)
FREDERICK P. SIEGAL*, C. LOPEZ**, P. A. FITZGERALD-BOCARSLY***, J.L. ZITO*,
R. REIFE*, T.W. CHEUNG****, et al., *Long Island Jewish Medical Center, New
Hyde Park, NY, **CDC, Atlanta, GA, ***UMDNJ, Newark, NJ , ****BS Coler Hospital,
NY, NY USA.
Among a cohort of subjects across the spectrum of HIV infection, we found
k] in whom central nervous system (CNS) disease could not be explained by a
definable opportunistic infection (0l). These subjects had dementia, central
and cortical atrophy on CT/MRI scanning, myelopathy, and/or elevated CSF
protein or leukocytes. Scans did not suggest mass lesions or multifocal
l eukoencephalopathy , except terminal ly in one case who developed CNS lymphoma.
Sixteen had symptomatic CNS involvement that antedated any 01 or neoplasms
definitive for AIDS. Twenty-five others developed HIV-EM during established
AIDS. Defects in HSV-induced cellular interferon-al pha generation in vitro
and numbers of circulating helper T cells, known to be predictive of systemic
opportun i st ic i nfect i ons , were al so found to be closely associated with the
development of CNS-OI. Most subjects with HIV-EM had profound depression of
these measures of cellular immunity, but there was more heterogeneity among
the group with HIV-EM than in those with CNS-OI or systemic 01. These data
suggest that HIV does not behave as an opportunistic agent for the CNS. How-
ever, they do not exclude the possibility of a role for an early HIV-specific
immune defect in the pathogenesis of HIV-EM. Expression of HIV-EM may be as
dependent on variant viruses and other factors as on the presence of cellular
immune competence.
\MDifl7 Positive Cellular Immune Responses in Humans and
Chimpanzees Infected with the Human Immunodeficiency Virus
(HIV). JORG W. EICHBERG*, G.R. DREESMAN*, R.N. BOSWELL**,
H.J. ALTER***, J.A. LEVY****, P.W. BERMAN*****, et al.. *Southwest
Foundation for Biomedical Research, San Antonio, Texas; **Wilford
Hall, San Antonio, Texas; ***NIH, Washington, D.C.; ****University of
California, San Francisco, California; *****Genentech, San Francisco,
California.
Only a few reports have been published describing the lack of
specific cell-mediated immunity (CMI) to HIV. While this lack of CMI
is understandable in patients with advanced disease, it is surprising
in people that are only antibody positive without concomitant disease.
We have assayed in a specific CMI assay mononuclear cells from humans
that are anti-HIV positive without disease and compared them with
chimpanzees that have been infected with either HTLV-III or ARV. All
of the animals did not demonstrate any disease and have normal immune
functions. The HIV antigens used in the assays were recombinant gpl20,
gp41 and p24. All 11 chimpanzees, whether they were singly or
repeatedly infected, responded positively (blastogenic index > 3,0) at
one or several occasions to gpl20 and/or gp41 and p24. Eight of 11
anti-HIV positive humans without disease also responded to either
gpl20 and/or to gp41 and p24. To our knowledge this is the first
report demonstrating a positive specific CMI response to recombinant
HIV antigens in HIV infected humans and chimpanzees without disease.
The results also suggest that the presence, magnitude or absence of
specific CMI to HIV might determine the future outcome of HIV
Infection.
UIP1in Response to Vaccination in HIV Seropositive Subjects
Wr. IIU J.L. Rhoads, D.L. Birx, D.C. Wright, J. Brundage,
R.R. Redfleld, and D.S. Burke, Walter Reed, Washington, D.C.
The serologic and immunologic responses of 21 asymptomatic HIV seropositive
adults who were immunized with multiple polysaccharide, viral and protein
vaccines were evaluated and compared with similarly vaccinated age, sex, and
race matched HIV seronegative controls. The mean age was 24 (range 18-33)
and 20/21 were male (95%). Lymphadenopathy was present in 20/21 (95%). The
mean T4 count was 570/mnr (20% with T4 < 400/mnr), the mean T4/T8 ratio was
0.5 (80% with T4/T8 ratio < 0*8), and 5/21 (25%) were anergic to skin
tests. The number of subjects who responded to each vaccine is as follows:
Vaccine: M A4 A7 T D No response to any vaccine
HIV (N=21) 13 9 8 10 12 5
Normal (N-21) 21 15 13 9 10 0
M=Meningococcus C: response equals 4 fold bactericidal antibody titer rise.
A4,A7 = Adenovirus 4, 7; response equals 4 fold neutralization antibody
rise. T=Tetanus, D=Dlptheria; response equals 4 fold IHA titer rise.
The number of non-responders to meningococcal and adenoviral vaccines, as
well as the number of non-responders to all vaccines, in the HIV group was
significant (P < 0.05) when compared with the normals. However, the
geometric mean antibody titers of HIV infected vaccine responders did not
differ significantly from normals. HIV infected vaccine nonresponders did
not differ from HIV Infected responders In total T4, skin tests, total serum
IgG, or in vitro lymphocyte stimulation assays. These data suggest that a
subset of HIV positive asymptomatic subjects do not respond with antibody
production to newly presented antigens; however, the majority do respond and
produce functional antibody comparable to normals. At three months, no
clinically apparent adverse reactions to vaccination were noted.
WPIflft Cytotoxic Factor Secreted by Human T-Lymphotropic Virus Type III
wn,wo infected Cells
LEE RATNER*, S. P0LMAR*r N. PAUL**, AND N. RUDDLE**/ *Washington University*
St. Louis, MO, **Yale University, New Haven, CT.
The mechanisms responsible for depletion of T4 lymphocytes by human T-lym-
photropic virus type III (HTLV-III) remain to be fully characterized. To
explore the possibility that indirect effects might exist, conditioned media
from HTLV-III infected cells were tested for cytotoxic cell-derived factors.
The assay used measurements of cell proliferation of a murine fibroblast cell
line, L929, which is sensitive to the effects of tumor necrosis factors, but
non-permissive for HTLV-III replication. Significantly higher levels of
cytotoxic activity were detected in peripheral blood mononuclear cell (IBM)
cultures from HTLV-III infected individuals than from uninfected controls.
Furthermore, PBM from an uninfected individual were found to secrete this
cytotoxic activity after infection in vitro. This factor was secreted at
levels ten-fold above that of the uninfected culture, 3-7 days after infec-
tion, prior to signs of cell killing and the presence of reverse transcrip-
tase activity in the medium. Two different HTLV-I infected cell lines, Hut
102 and AIH8, were found to const i tut ively secrete the cytotoxic factor.
Upon infection with HTLV-III/ both of these cell lines manifested cell
killing, but no change in the level of the secreted cytotoxic factor. Thus,
the cytotoxic factor may not be a mediator of T4 lymphocyte depletion, but
may be released as a result of cell killing in PBM, or as a reaction to virus
replication. Oie must consider a role for this cytotoxic factor in several
aspects of HTLV-III infection in vivo, including AIDS encephalopathy and the
systemic manifestations accompanying ARC. The specific cell type synthe-
sizing this factor, its biochemical characterization, and biological signifi-
cance are being investigated.
WR111
JOHN L.
Repor
T Hel
ZIEGL
Medi ci n
We st
sarcoma
HIV ant
vi remia
Serial
from 90
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and
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acteri
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V. We
on rem
ens , a
n AIDS Patient with Persistent Normal
ducer (CD4) Lymphocyte Counts
J.M00DY, D.P.STITES, J.A.LEVY, UCSF School of
isco, CA 94143.
ear old bisexual man who has had Kaposi's
Serial virologic studies disclose persistent
immunofluorescence and immunoblot) and HIV
of peripheral blood mononuclear cells),
te counts (by Leu-3 cytof 1 uorography ) range
r cu mm, and CD4/CD8 lymphocyte subset ratios
.7, all within the normal range for our
yte responses to mitogens and natural killer
normal .
echnique, we showed that the proliferative and
solated CD4 lymphocytes to tetanus and Candida
red .
osi's sarcoma lesions appear and regress
he is otherwise completely healthy. His wife
hter are also healthy and are free of HIV
ry of AIDS is one of progressive immune im-
zed by a steady decline of CD4 lymphocytes,
t has had AIDS for three years and produces
are encouraged by the observation that his
ains relatively intact, except for anergy to
early lesion described by others.
128
WEDNESDAY, JUNE 3
WP112 " Lymphocyte-Cytotoxic Antibodies in AIDS and Related Conditions
EMILIO L. KHOURY, J.S.GREENSPAN, M.A. CONANT, R. CHAISSON,
M.R. GAROVOY, B.W. COLOMBE, University of California, San Francisco, CA.
Lymphocyte-reactive antibodies have been described in AIDS and ARC patients and
might contribute to the pathogenesis of these disorders. While most previous reports
concern presumably specific T cell-reactive autoantibodies, reactivity against normal B
lymphocytes has also been found. We investigated the prevalence, strength and speci-
ficities of B lymphocyte-cytotoxic antibodies in AIDS and ARC patients as well as in
asymptomatic individuals with +ve HIV serology, those considered at risk of HIV infection
and controls. Sera from 6 groups of male patients/controls were studied: 1) homosexuals
with AIDS and +ve HIV serology (n=I6); 2) heterosexual IV drug users with AIDS and +ve
HIV serology (n=10); 3) homosexuals with ARC and +ve HIV serology (n=10); 4)
asymptomatic homosexuals with +ve HIV serology (n=I0); 5) healthy homosexuals, -ve for
HIV serology (n=15); 6) healthy heterosexuals, -ve for HIV serology (n=6). Standard micro-
cytotoxicity assays were performed with duplicate samples on a panel of B lymphocyte-
enriched (*S0%) cells from 20 normal donors, representing all well-defined HLA-DR anti-
gens and many of the recognized HLA-A,B specificities. An average reading of "5" in the
I to 8 scoring system for the duplicates was considered a significant cytotoxic effect.
We found a progressive increase in both the prevalence of lymphocytotoxic sera and
the breadth of their reactivity in asymptomatic HIV-infected men, ARC and AIDS
patients, compared with controls. For groups (1) through (6) respectively, results were as
follows: (i) prevalence of +ve sera: 81.2%, 60%, 80%, 60%, 31.2% and 33%; (ii) average
number of reactive cells out of the 20 in the panel: 10.8, 6.6, 6.7, 5.6, 4.6, and 3.5; (iii)
average score of the +ve reactions: 7.2, 6.6, 6.7, 7.0, 5.9 and 5.5. Marked differences in
reactivity within the cell panel displayed by most positive sera suggest that allo-
reactivity may be the underlying mechanism, but no defined patterns for either class I or
II HLA specificities could be identified, and platelet absorption of 16 positive sera abol-
ished or significantly reduced the titers of their cytotoxicity on the same B lymphocytes.
lAIPIIR Immunological , Virological Correlates in the Clinical Progression of
the Acquired Immunodeficiency Syndrome
J. GEORGE BEKESI, J.I. WALLACE, P. MASON, J. P. ROBOZ , J.F. HOLLAND, Mount Sinai
School of Medicine, New York, New York.
We have been longitudinally following a cohort of 66 control, 166 prodromal
and 36 AIDS subjects for 24 months. Eight cycles of serial immunological and
virological testings have been completed. All AIDS patients and 101 of 166
(69.9%) prodromal subjects were HIV(+). All heterosexual controls and 55 of
166 (30.17.) prodromal subjects were HIV(-). The following significant clinical
changes have been observed: 14 of 55 (25.5%) of HIV(-) prodromals converted to
HIV(+) and two of these (14.37.) further developed AIDS. Twenty-nine of 111
(26.1%) HIV(+) subjects developed AIDS, of these 11 (40.7%) died of AIDS. Of
the original 36 AIDS patients 21 (58.3%) have died. Contrarwise the controls
retained unchanged clinical, virological and immunological profile. Our data
show that T ; inducer T and regulator T cell subsets are significantly ab-
normal in HTV(-) prodromal subjects and progress to complete abrogation through
AIDS and death. Lower lymphocyte function (PHA, PWM, SAC) is present in the
HIV(-) prodromals, further reduction occurs at the conversion to HIV(+). Each
further change in clinical status follows drastic reduction in T and B lympho-
cyte function. The most sensitive indicators of clinical changes are: T and
its' subsets, SAC and PWM induced blastogenesis , CMI against auto and alio
targets and clgG positive cells as well as changes of anti-pl7 and p24 anti-
bodies in the sera.
WP113 Monoclonal Antibodies Reactive to CD4 and GP120 Block HIV Induced
Fusion of Uninfected CD4+ Lymphocytes
DOROTHY B. LEWIS* , C.G. BOSWORTH* , B. YOPPE* , T. CHAbfflt, RONALD C.
KENNEDY*, 'Howard Hughes Medical Institute, "Departments of Microbiology
& Immunology and 'virology, Baylor College of Medicine, Houston, TX, and
tsouthwest Foundation of Biomedical Research, Department of virology &
Immunology, San Antonio, TX, USA.
We recently reported that mixtures of HIV infected tumor target cells (H9)
and uninfected CD4+ lymphocytes resulted in fusion and subsequent death of
both cell types (B. Yoffe et al., PNAS in press). We have used this
51Cr cytotoxicity assay to study the interaction between the CD4 mole-
cule and the GP120 envelope protein of HIV. These proteins are thought to
be responsible for the initial binding of HIV and for the development of
syncytia. We used monoclonal antibodies (mAbs) reactive to the GP120 pep-
tide 503-532 (Eur. J. Immunol. 16:1465, 1986) to block chromium release from
HIV infected cells in the presence of CD4+ uninfected lymphocytes. We
found that mAbs reactive to the Leu3a determinant but not the OKT4 determi-
nant on the CD4 molecule could prevent cytolysis. Two mAbs reactive to the
peptide 503-532 were also shown to prevent syncytia formation and cytoly-
sis. We also determined whether addition of antl-CD7, CD3, or Dr mAbs could
block cytolysis. No effect on fusion formation and cytotoxicity was
observed. These data indicate that the critical interaction involved In
syncytia formation Is between the CD4 molecule and a specific region on the
GP120 molecule. This cytotoxicity assay is a valuable tool that may allow
careful dissection of the requirements for HIV Induced cytopathology.
Supported by NIH grant AI22549.
H3/N2
WP116 The influence of HIV infection on antibody responses to influenza
vaccines KENRAD E.NELSON, H.L. Clements, P. Hiotti, S. Cohn,
N.Odaka, B.E. Polk, Johns Hopkins School of Public Health, Baltimore, MD., USA.
This study was done to evaluate the effect of HIV infection on influenza
vaccine responses. We studied HI antibody responses to A/Taiwan/86 (Hl/Nl)
and A/Mi ssissippi/85 (H3/N2) in 105 subjects 4 weeks after immunization with
monovalent and trivalent vaccines containing these antigens.
Study populations included HIV -, non - risk gp. (HIV-/NR, n = 16), HIV -
risk gp. (HIV-HR, n=22), HIV + asymptomatic/LAS (HIV +, Asym, n=29), ARC
(n=14), AIDS (n=24). The mean age of study subjects was similar in each group.
HI antibody responses (Logo) were as follows:
Hl/Nl
Diff.
5.18
3.91
3.28
2.21
1.33
Post vaccine antibody levels were significantly lower (p<.05) for HIV + Asym
than HIV - NR and were lower (p<.05) for ARC/AIDS pts than all other groups for
both Hl/Nl and H3/N2. Protective levels of Ab (£l:64) were attained to Hl/Nl by
95% HIV-, 48% HIV+ Asym and 29% of ARC/AIDS pts. and to H3/N2 by 95% HIV-,
86% HIV + Asym and 29% ARC/AIDS pts. Serum levels of p24 HIV antigen did not
increase significantly after immunization except in one subject.
Patients with HIV infections respond poorly to influenza immunization but
showed no evidence of increased HIV replication. Additional strategies, e.g.
booster doses, amantidine may be required for influenza prevention.
Gfi.
Pre
Post
HIV-, NR
2.93
8.125
HIV-, HR
4.09
8.0
HIV+, Asym
2.48
5.76
ARC
2.29
4.5
AIDS
2.88
4.21
Pre.
Post
Diff.
2.56
7.81
5.25
3.91
7.95
4.05
3.21
6.83
3.62
2.5
4.35
1.85
2.79
4.38
1.58
\A/P1"|4 Reduced Numbers and Increased Activation of Monocytes in Patients
with AIDS.
ROBERT J. PETRELLA, Y. SEI, M.M. YOKOYAMA, J.G. BEKESI, Mount Sinai School of
Medicine, New York, New York.
We analized peripheral mononuclear cells derived from 11 patients with AIDS.
12 subjects with ARC, and 10 heterosexual controls. Staining with fluorescein-
conjugated LeuM3 and phycoerythrin-conjugated HLA-DR (la) monoclonal antibodies
was carried out for immunofluorescence assay . The results indicated that in
the AIDS and ARC patients there was a uniform depletion of LeuM3+ cells, or
monocytes, of both the la- and Ia+ types. However, monocytes cultured for four
days with ConA or PHA resulted a decrease in number of Ia+ cells relative to
total monocytes . This observation corroborates previous reports of defects in
mitogen response capabilities of antigen-presenting cells. In addition, in the
fresh samples we observed an increase in the Ia-mAb binding per cell, in the
Ia+ monocyte populations of the AIDS and ARC patients relative to controls.
This increase of Ia-mAb binding is indicative of activation. These observa-
tions, then, refute the proposed notion that cells of the mononuclear phago-
cytic system in AIDS patients are deficient in la antigen expression. Rather,
they suggest that the defects in antigen-presenting function in AIDS are due to
an overall depletion of presenting cells and to impaired antigenic response.
The increased activation of the AIDS monocytes may arise as an adaptive
response by the cells to reduced numbers and to the antigenic overload Imposed
on these patients ' immune systems .
\Aipi17 Lymphocyte Phenotype and Subset Distributions in
HIV Seropositive and Seronegative Gay Men Enrolled
in the Multlcenter Aids Cohort Study (MACS).
M.J. WAXDAL*. J. Margolick**, J. Phair***, C. Rinaldo*, J.
GlorgiZ/f?, A. SaahitftO, et. al., *FAST Systems, Rockvllle, MD.,
**Johns Hopkins School of Medicine, Baltimore, MD., ***North-
western University Medical School, Chicago, IL., ^University
of Pittsburgh, Pittsburgh, PA., 99 University of California at
Los Angeles, Los Angeles, CA., 9 911 National Institute of Allergy
and Infectious Diseases, Bethesda, MD.
Bl
MACS
HIV
nega
posi
of 1
thes
colo
sero
(MAb
supp
sero
act 1
with
numb
on b
ood
par
ant i
t i ve
t Ive
ymph
e gr
pa
conv
to
re s s
conv
va t e
ABA
e r o
oth
samp
tlcl
bodl
> (2
( pe
ocy t
oups
nel .
ers 1
non-
ion
ers i
d CD
a nd
f re
CD-A
les
pant
es ,
) Se
rs is
e ph
was
Al
on ,
poly
(2HA
on ,
8 c
2HA
ce p t
for flow cytometry studies were obtained from
s In Baltimore. Based upon ELIZA results for
the men were divided into 3 groups: (1) Sero-
roconverters (within 18 months) and (3) Sero-
tant for at least 36 months). The distribution
enotypes, subsets, and activation markers in
evaluated with a 36 monoclonal antibody dual
though the CD-A population decreased upon
certain subsets increased: activated CD-A cells
morphlc antigen on HLA-DR) and inducers of
positive). The CD-8 population expanded upon
and certain subsets Increased dlsproportlonally:
ells (as In CD-A above), and cells stained singly
(many CD-8 cells stained positive for both). The
ors on the lymphocyte surface for DR and TQ-l/Leu-8
CD-8 cells also showed dramatic changes.
129
WEDNESDAY, JUNE 3
WP118 Cellular Immune Responses in HIV Infection
JANIS V. GIORGI and J.L. FAHEY, UCLA School of
Medicine, Los Angeles, CA.
Immune alterations in functional subpopulations of T-
lymphocytes have been characterized in HIV-infected individuals
using in vitro tests of T-cell function and dual-color
immunofluorescence analysis by flow cytometry. In contrast to
the popular notion that loss of the capacity of CD4 T-lymphocytes
to respond to soluble antigen is an early event after HIV
infection, we found that only 10/29 individuals who had been
infected with HIV for between 14 months and 6 years had evidence
of depression of this functional activity. By testing the
response of each person to both tetanus toxoid and Candida
albicans , it was possible to distinguish generalized non-
responsiveness to soluble antigens from a failure to respond to a
particular antigen. Three of the men who were most profoundly
deficient in the response to soluble antigen developed AIDS
within 4 months. Since men with AIDS usually were deficient in
this response, we propose that this T-cell dysfunction develops
only as a late consequence of HIV infection. Our flow cytometric
studies exclude the possibility that loss of CD4 T-lymphocyte
proliferative response to soluble antigens results from selective
loss of the Leu8-, 4B4+, 2H4-, or HB-11- subsets of CD4 cells.
We propose that in conjunction with CD4 T-lymphocyte numbers, the
lymphocyte proliferative capacity to soluble antigens is an
important variable for differential staging of HIV-infected
individuals. These findings have relevance for immune evaluation
assessment in therapeutic interventions in AIDS.
WP121 Induction of cellular receptors for Tumor Necrosis Factor by AIDS
sera.
A.S. LAP, S.E. READ, B.R.G. WILLIAMS, Hospital for Sick Children, University of
Toronto, Toronto, Canada.
Interferons (IFN) are capable of enhancing expression of cellular receptors
for tumor necrosis factor (TNF) and act synergistically with TNF in cytotoxic
and tumoricidal activities. We postulate that high levels of the unusual acid-
labile IFN in AIDS patients may induce TNF receptors and sensitize TNF respon-
sive cells in vivo. The expression of TNF receptors in tumor cells (A549, a
lung carcinoma; and Hela cells) was studied using TNF-o( (Genentech) labeled
with 1 25Iodine to high specificity by lactoperoxidase method. Saturation
binding curves were generated with "I-TNF and the binding characteristics
were analyzed to obtain receptor numbers. Serum samples from AIDS patients
with high serum levels of the acid-labile IFN and cellular 2-5A synthetase
enzymatic activities were used. Following treatment of the cells with AIDS
sera (n=5) , there was a 50 to 300% increase in TNF receptor binding as compared
to that of the controls treated with normal human serum. The extent of
induction of TNF receptor binding appeared to be dose-related depending on the
concentration of the sera used. Similar results were obtained when cells were
treated with IFN o( and Y . The induction of TNF receptors by AIDS sera can
be inhibited by neutralization of the sera with anti-IFN o( antibodies,
indicating that IFN ot is the inducing agent. The receptor induction phenomenon
can also be blocked by actinomycin D suggesting that synthesis of new TNF
receptors might be required. Thus, these studies indicate that fl( IFNs in AIDS
sera can induce TNF receptor expression, and may enhance the cytotoxic activit-
ies of TNF on susceptible cells. This may be one of the mechanisms involved in
the destruction of lymphocytes in AIDS and thus contribute to the immunopatho-
genesis of the disease.
WP11Q Amyl -Nitrite Inhalation Alters Immune Function in Normal Volunteers
r> "* ELIZABETH H. PAX, WILLIAM H. ADLER, JAMES E. NAGEL, BARBARA A.
DORSEY, AND JEROME H. JAFFE. National Institute on Drug Abuse and National
Institute on Aging, at Francis Scott Key Medical Center, Baltimore, MD 21224
Epidemiological evidence shows an association of the incidence of Kaposi's
sarcoma and nitrite use in patients with AIDS. Exposure of lymphocytes to
nitrites in vitro alters cell functions. Immune function has been examined in
nitrite abusers but not after nitrite exposure in humans under controlled
conditions. Six HIV negative, healthy male volunteers with limited previous
nitrite use, inhaled 10 doses of amyl -nitrite (0.18-0.48 ml) over 4 days(D).
The subjects were drug free for several days prior to 2 baseline tests of
immune function. Blood was drawn on D 0, I, 4, and 7 following inhalation.
In vitro immune function tests included identification of lymphocyte subsets,
natural killer cell activity, mitogenic activity to poke weed mitogen (PWM),
PHA and Con A, and polyclonal induction of IgG and IgM synthesis. The
pre-amyl -nitrite T4:T8 ratio was I. 56+0. 21 which decreased to 1.3+0.13
immediately following inhalation. By D4 the ratio was 1.59+0.23 and the
representation of T4+ cells had risen from 44.8+1 .3% to 48.6+3.3%. The T8+
cells remained constant at 36.2+3.8% and 33.3+4.5% over the same time. NK
cells (leu 7+) doubled between baseline levels and 2nd day post-inhalation
while NK cell activity showed an initial decrease then a significant increase
by D4, post-inhalation. Leu 12+ cells showed an increase from 12.6 to 17.4%
between Dl and D7 which corresponded to an increase in the mitogenic response
to PWM by D7. Furthermore, in, vitro IgG and IgM synthesis increased 519% and
301%, respectively, between Dl and D7. Results show a nitrite-induced,
non-specific immuno-stimulation which suggests that nitrites may aggravate
AIDS by enhancing HIV replication or the non-specific stimulation may mask or
interfere with specific immune responses to pathogens.
WR122
Abnormalities of Immunoregulatory Lymphocyte Subsets in HIV
Infected Subjects.
EMILIQ MANNELLA, S. COCHI, M. A. ROSCI , A. Dl LORENZO, D. FIORAVANTI, P.
ANGELONI .
National Center for Blood Transfusion-C.R. I . Rome-Italy
Department of Infectious Diseases "L. Spallanzani" . Rome-Italy
To evaluate the relationship between the infection with HIV and
immunologic abnormalities, 241 peripheral blood samples (90 positive for
anti-HIV and 151 negative) of blood donors, of politransfused patients, of
drug abusers and of subjects with ARC and AIDS were examined. The
positivity for anti-HIV was determined by commercial ELISA and confirmed by
Western Blot.
Phenotype dual color cellular analyses were performed in Flow Cytometric
on FACS 440 (BD) utilizing several combinations of monoclonal antibodies.
The preliminary results showed beyond the well known decrease of the
helper/inducer T cell and consequently the reversal Th/Ts ratio an increase
of subsets of LGL (Leu2+Leu7+) and Leu2+DR+ cells and a decrease of
Leu3+Leu8+ cells.
The in vitro proliferative responses to PHA and PWM and the cutanous
reactivity to 6 Recall Antigens (Multitest Merieux) were related with the
changes in mononuclear cell subsets.
The T colony assay showed T cell proliferation defect in seropositive
groups as to seronegative controls.
These immunological abnormalities evident in seropositive asymptomatic
subjects can occur independently of AIDS-related clinical symptoms, but they
may progress with time and were marked in subject with ARC and more marked
in AIDS.
WP120 Increased Levels in Plasma of Prostaglandin E2 (PGE2) Could Account
for the Abnormalities of Cellular Immune Functions in Drug Addicts
with HIV Infection.
EDUARDO FERNANDEZ-CRUZ, A. FERNANDEZ, C. GUTIERREZ, M. GARCIA MONTES, M. RODRI-
GUEZ and J.M. ZABAY. Hospital Provincial. Complutense University. Madrid. Spain.
Recent studies have demonstrated that PGE2 inhibit in a dose-dependent fashion
a number of immunological functions and may exert a stimulatory effect on HIV
replication in vitro. We have evaluated (over 2 years) the immunological, sero-
logical and clinical conditions of 201 I.V. heroin abusers (89% seropositivity) ,
and recently we have investigated the plasma levels of PGE2 in a group of addicts
with the various manifestations of HIV infection. Plasma concentrations of bicy-
clic PGE2 were determined by a radioimmunoassay (Radiochemical Centre, Amersham)
in 3 groups of heroin addicts: group A (n=ll) were HIV-positive, with depressed
cell-mediated immunity (CMI); group B (n=10), HIV-positive with normal CMI; and
group C (n=5), HIV-negative with normal CMI. The results showed a significant
increase in the levels of PGE2 in group A (436+62 pg/ml) as compared with group
B (158+19 pg/ml)(p<0.001), with group C (107+28 pg/ml)(p<0.01) and with 7 normal
controls (47+37 pg/ml)(p<0.001) . Group A, in which concentration of PGE2 was 10
times higher than normal basal values, showed a significant reduction (p<0.001)
in absolute numbers of T3 and T4, an inverted T4/T8 ratio, a significantly de-
pressed response to mitogens and anergy. Furthermore, in all 26 heroin abusers
studied there was a significant negative correlation between levels of PGE2 and
the following: absolute numbers of lymphocytes (r=-0 . 53,p<0 .05) and of T4 cells
(r=-0.69,p<0.01), and response to mitogens (r=-0.74,p<0.01). High levels of PGE2
also correlated with clinical deterioration. Our data suggest that PGE2 may be
one of the underlying factors leading to abnormal immunoregulation and/or faci-
litating the progression of AIDS virus infection. To confirm this hypothesis
further investigations are in progress.
WP123 Serum Interleukin 2 Receptor Levels in AIDS Patients
WILLIAM H. ADLER+, J. E. NAGEL+, B. S. BENDER+ D. KITTUR++,
R. WINCHURCrT"", J. JOHNSON1"*4 . +NIA, NIH, Baltimore, MO, ++The Johns Hopkins
Univ. School of Medicine, Baltimore, MD, +++University of Maryland, School
of Medicine, Baltimore, MD.
Activation of T cells is influenced by the binding of interleukin-2 (IL2)
to its membrane receptor (IL2R), IL2R is shed from the membrane of HTLV-1
infected cells, and serum levels of IL2R are elevated in renal transplant
patients undergoing a rejection reaction or with CMV infections. To determine
if IL2R serum levels were indicative of inflammatory, infectious or immune
responses, we measured the concentration of IL2R in the sera of normal indi-
viduals, hemodialysis patients, renal transplant patients with and without
evidence of graft rejection, burn patients, individuals with HIV antibody
but without illness, and patiens with AIDS.
Units/ml (mean ± SO)' Units/ml (mean + SD)
thermal injury 1,750 + 547
HIV+ not ill 1,361 + 828
AIDS patients 3,047 + 1,580
normals
dialysis patients
graft rejection
stable transplant
349 + 185
2,848 + 1,416
4,097 + 1,852
654 + 293
In AIDS patients there was no correlation between serum IL2R concentration
and the representation of peripheral blood CD4+ cells, but there did appear
to be a decrease in serum IL2R levels prior to death. The data demonstrates
that IL2R are released into the serum in a variety of inflammatory conditions,
and as such may offer a method for determining the degree of infection and
clinical course of an HIV+ individual. It is also possible that serum IL2R
may block the action of IL2 on T cells and contribute to the immunodeficiency
seen with HIV infections.
130
WEDNESDAY, JUNE 3
WP124 Immunological cross-reactivity between HIV gpl20 and a lympho-
monocytic activation antigen. Distribution and modulation of
the cellular protein.
ALBERTO CLIVIO, C. PARRAVICINI, F. GRASSI, A. BERETTA, G.B. ROSSI,
A.G. SICCARDI, et al. , Universita di Milano and *Istituto Superiore di
Sanita, Roma, Italia.
Monoclonal antibody M38 from a mouse immunized with HIV was shown to
react with a protein epitope of HIV gp 120 and with a cross-reacting
epitope of a cellular 80 Kd protein present on cells of the lympho-raono-
cytic lineage (see Siccardi et al., this Congress). On sections of normal
lymph nodes the antibody stains a subset of dendrite-like cells with no
correspondence to known staining patterns. Fractionation of lymph node cell
suspensions on Percoll gradients locates M38 positive cells in the low-
density monocyte fraction; only a small percentage of this fraction,
however, is stained. Peripheral blood monocytes are M38 negative and become
intensely positive in plastic adherent cultures. U937 and HL60 cells are
also negative but can be induced to express the 8o Kd protein by gamma
interferon and other activators, as demonstrated by both immunocytoche-
mistry and flow cytometry. In gamma interferon induced cultures of U937 the
appearence of the positivity is slow and involves morphologically distinct
stages, with a "late activation antigen" pattern. The involvement of the 80
Kd protein in antigen presentation is under investigation in several expe-
rimental systems.
\A/pi?7 Generation of HIV-1-Specif ic Cytotoxic T Lymphocytes in a Genetical-
ly-Defined Murine Experimental System
P. LANGLADE-DEMOYEN, F. MICHEL, F. GARCIA-PONS, S. WAIN-HOBSON and F. PLATA,
Laboratoire de Biologie et Immunologie Moleculaires des Retrovirus , Inst i tut
Pasteur, 75724 PARIS Cedex 15, FRANCE.
Cytotoxic T lymphocytes (CTL) were generated in BALB/c mice by immunization
with a clone of syngeneic 3T3 fibroblasts which expresses the env gene of HIV-1
in a stable manner following transfection of the cloned env gene. These CTL are
positive for the Thy-l and Lyt-2 surface markers, and they are specific for
HIV-1 antigens because they do not kill non-transfected 3T3 fibroblasts nor
BALB/c tumor cells induced by murine leukemia viruses. However, the same CTL
kill other mouse cells that express the HIV-1 env gene following transfection,
if the target cells share class I H-2 transplantation antigens in common with
BALB/c mice. The activity of these CTL is clearly restricted by the class I
H-2Dd antigen of BALB/c mice, since mouse L cells doubly transfected with the
H-2D<1 gene and the HIV-1 env gene were recognized and killed very efficiently.
In contrast, L cells doubly transfected with the H-2KQ* gene from BALB/c mice
and the HIV-1 env gene were poorly recognized, and low levels of killing were
detected. H-2Dd antigen consequently presents HIV-1 env antigen in an optimal
configuration. Moreover, class I transplantation antigens appear to modulate
recognition of HIV-1 env antigen by CTL in this experimental system.
The immunogenicity and antigenicity of HIV-1 products can thus be studied
under carefully controlled conditions in a murine model of cellular immunity.
WR125 HIV infection of promonocytlc U937 cells down regulates class-II
expression, diminishes accessory cell functions and Induces dif-
ferentiation-like phenotypic changes
FRANK MIEDEMA, A.J.C. PETIT, M. TERSMETTE, F.G. TERPSTRA AND R.E.Y. DE GOEDE,
Central Lab. Netherlands Red Cross Blood Transfusion Service, incorporating the
Lab. of Exp. and Clin. Immunology of the Univ. of Amsterdam, Amsterdam, The
Netherlands
Surface marker analysis and functional studies were performed with promonocy-
tlc U937 cells that had been infected with HIV and persistently produced virus
as detected by supernatant reverse transcriptase activity. Accessory-cell func-
tion of U937/HIV cells on antl-T3 Mab- and Con A- induced T-cell proliferation
was decreased to 20-60% compared to that of non-infected U937 cells. Similar ac-
cessory-cell defects were demonstrated in the monocytes of asymptomatic seropo-
sitive homosexuals, with normal CD4 T-cell numbers and ARC and AIDS patients.
The accessory-cell defect could be partially restored with r-IL-2 and monocyte
supernatants. Addition of ^ 10 TCID50 HIV did not affect T-cell proliferation
under these culture conditions. Expression of MHC class-II antigens on U937/HIV
cells was 3-10 fold decreased compared to non-infected U937 cells. HIV infec-
tion Induced expression of CD11 (C3bi receptor) and pl50/95 adhesion molecules
and induced enhanced expression of LFA-1 Q£ and y5 chains. Expression of these ad-
hesion molecules resulted in strongly enhanced PMA- induced aggregation of U937/
HIV compared to non-infected U937 cells. In addition U937/HIV cells, contrary to
U937, intensely stained for cytoplasmic non-specific esterase activity. The
phenotypic changes strikingly resemble the effects of differentiation-inducing
agents (i.e. PMA, DMSO) on the U937 phenotype. Our results suggest that mono-
cytes (APC) may be important target cells through which the immune system is
affected by HIV.
WP128 "^ne r°le °f virus and follicular dendritic cells in HIV-associated
lymphadenopathy .
PETER BIBERFELD, A. P0RWIT, G. BIBERFELD, A.B00NER, R.GALL0. Department of
Pathology, Karolinska Institute and National Bact. Lab., Stockholm, Sweden
Lab. Tumor Cell Biol., N.C.I, Bethesda, Biotech, Bethesda, USA.
Studies of HIV associated lymphadenopathy by histopathology and immunopatho-
logy showed conspicuous changes of follicular B-cell areas from a marked hyper-
plasia to complete involution. Immunohistochemistry showed a corresponding in-
crease in follicular dendritic reticulum cells (FDRC) followed by progressive
destruction of these cells during involution, concomitant with invasion of
follicles by T-cells. HIV GAG antigens were predominantly associated with FDRC
in hyperplastic follicles and diminished during involution. Virus replication
was by in situ hybridization seen predominantly in follicles, presumably
reflecting productive infection of T4 cells and/or FDRC. It was concluded that
the destruction of FDRC in HIV patients is decisive for the progressive involu-
tion and dysfunction of the B-cell compartment. The appearance of follicular in-
volution was a bad prognostic sign in follow-up studies. In vitro studies of
cultured FDRC with regard to HIV-binding and productive infection substantiate
the in vivo findings. Our studies indicate that HIV associated lymphadenopathy
represents not only a disease of T4 cells but also of follicular antigen pre-
senting cells (FDRC).
WR126 Comparative quantification of the C3b complement receptor (CR1) on
blood cells in HIV infected patients. J. H.M. Cohen^, M.H. Jouvin^,
B. Autran3, J. P. Aubry4, R. Russo2, W. Rozenbaum5. 1 : Lab. Immunol. CHU R. De-
bre, Reims. 2 : INSERM U 28 H6p. Broussais, Paris. 3 : Lab. Immunol. Cellul.
HOp. PititS SalptStriere, Paris, 4 : UNICET. Dardilly. 5 : Dpt. Path. Tropicale.
HGp. Pitie Salp^triere, Paris. FRANCE.
We have previously demonstrated the decreased expression of CR1 on red blood
cells (RBC) of HIV infected patients, which was correlated to the severity of
the HIV mediated disorders. Since the RIA employed for CR1 enumeration is deli-
cate to perform in large scale clinical applications, we have applied to the
quantification of CR1, a sensitive enhancing system for detecting low density
cell surface antigens by f low-cytometry : the super-Avidin-Biotin System CSA6S),
using the biotinylated J3D3 anti-CRl monoclonal antibody has allowed us to de-
tect less than 100 sites/cell. The quantification by flow cytometry of CR1 si-
tes on the RBC of 34 HIV positive patients and 33 negative controls was perfec-
tly correlated (r = 0,99) with the results of the conventional RIA with J3D3.
The mean numbers of CR1 sites detected by the SABS on the RBC of 17 patients
with AIDS was significantly decreased (289±163) when compared with 33 normal
controls (639*259, p<0.0025). More over, the decreased expression of CRl on
RBC was correlated to the absolute numbers of total and T4+ lymphocytes, lie ha-
ve,then, investigated the expression of CRl in neutrophils of AIDS patients.
Both the antigenic (1.84xl0~7 >umol of 125I-J3D3 precipitated from detergent so-
lubilized Neutrophils) and the functionnal expression (23 ?if6-37lC3b-Rosette
Forming Neutrophils[C3b-RFN3) were decreased in 14 AIDS patients when compared
to normal controls (3.46 x 10"' jumol l25I-J3D3 ; 65 % C3b RFN). In conclusion :
The decreased expression of the CRl on RBC and WBC is not due to the occupation
of CRl by C3b-opsonized immune complexes because of the specificity of the J3
D3 mAb and can rather be related to the T cell immune defect.
WP129 Western Blot Analysis of Serial IgG, IgM, and IgA Responses to the
Human Immunodeficiency Virus (HIV) in Recent Seroconverters
JAY EPSTEIN*, R. GREGG*. A. SAAH**, J.PHAIR**, J. FAHSY**, C. RIWALDO**, and
B. POLK**, et al.*, *FDA and **Multicenter AIDS Cohort Study Group, Bethesda,
MD.
The immunoglobulin (Ig) class-specific response of seroconverters to HIV
infection is of potential importance to the pathogenesis of AIDS and may offer
some insights regarding early detection. We used heavy chain-specific murine
monoclonal antibodies at equivalent potency to identify virus-specific IgG,
IgM and IgA present in 43 serial blood samples obtained at one (8 cases) or
two (9 cases) six month intervals from 17 healthy men at high risk for AIDS
who were part of a prospective study. Series were selected on the basis of HIV
antibody reactivity by Western blot at the first bleed using a polyclonal
anti-human IgG (H+L) reagent. Analysis was performed by conventional Western
blot techniques using a whole virus lysate antigen and a goat anti-mouse Ig
enzyme conjugate. The presence of virus-specific IgG was confirmed in all 17
volunteers. IgM was detected in 15 cases, and IgA was found in 12 cases. The
IgA response was only found in cases that showed an IgM response. The IgG
response was directed to all of the major gag, pol and env gene products
except in one case in which antibodies to pol antigens did not appear. In
contrast IgM antibodies were found to gag, pol and env proteins in 14, 12, and
9 cases respectively, and IgA responses were found in 11, 7, and 3 cases. Over
time, the intensity of the IgG responses remained the same or increased in all
cases, and antibodies to gag proteins appeared the earliest. The IgM and IgA
responses were generally weaker than the IgG responses but showed a signifi-
cant linear correlation with IgG intensity for gag and env proteins. IgM was
found to persist for at least one year in 7/7 cases in which an IgM response
could be followed. IgA reactivity rose over time in 10/12 cases. The pattern
of development of class-specific antibodies to HIV may warrant further study.
131
WEDNESDAY, JUNE 3
Hip-ion Cytomegalovirus (CMV) Induces Functional Abnormalities in Human
"n IOU Monocytes In Vitro.
Phillip P. SMITH, J.B. ALLEN, L.M. WAHL, and S.M. WAHL. Cellular Immunology
Section, LMI , NIDR, NIH, Bethesda, MD.
CMV, a DNA herpes virus, may cause immunosuppression and/or severe organ
pathology in already immunocompromised persons. Since monocytes are a likely
target of CMV, we explored monocyte-CMV interactions in vitro. Monocytes,
purified by counterflow centrifugal elutriation, were inoculated at a multi-
plicity of infection of 1.0 with a low passaged isolate of CMV. Inoculated
monocytes did not exhibit cytopathic changes or release virus. Infection was
confirmed by monocyte expression of CMV viral proteins as detected by
fluorescence activated cell sorter (FACS) analysis using monoclonal antibodies
to immediate early, early and late CMV antigens. In addition, FACS analysis
revealed that CMV-lnfected monocytes expressed interleukin 2 receptors and
increased levels of HLA-DR, which are associated with activated or different-
iated monocytes. Functionally, the infected monocytes spontaneously secreted
increased amounts of the microbicidal oxygen intermediate H„0„. In contrast,
the CMV-infected monocytes did not manifest further enhancement of phenotypic
markers or functional parameters as did the uninfected monocytes following
lipopolysaccharide stimulation in vitro. Moreover, infected monocytes did not
support mitogen-induced T lymphocyte proliferation as effectively as control
monocytes.
These data suggest that CMV infection induces suboptimal activation of
monocytes which are refractory to secondary stimuli and impaired in accessory
cell function. Thus, direct CMV infection of monocytes may contribute to the
immunosuppression in AIDS.
WP.133 Aids and Autoimmunity - Mutually Exclusive Entities?
A.M. SPONGER. L.E. ADAMS, A. FRIEDMAN-KIEN? E.V. HESS, University
of Cincinnati, Cincinnati, OH and New York University^ New York, NY.
Observation of AIDS and ARDS patients since 1981 has confirmed a striking
absence of autoimmune and connective tissue diseases (CTD) with the recent
exception of a reactive type arthritis in a very small number of patients.
This absence of the usual autoimmune serologic reactions has been well docu-
mented in our ongoing cooperative study of AIDS patients at two University
Medical Centers. To the present, 292 patients have been evaluated for auto-
immune responses. The following tests have been performed: 1) IgM rheumatoid
factor by latex and sensitized sheep cell agglutination (SSCAT) tests, the
SSCAT being performed on the latex + sera; 2) antinuclear and organ antibodies
by indirect immunofluorescence (FANA); 3) radioimmunoassays for DNAss and
RNAss (Poly A) antibodies. These patients were all capable of producing anti-
body as shown by HIV positive titers in all and antibodies to sperm/seminal
plasma in 35%. The results are:
ASSAY UCMC (% +) NYU [% +) TOTAL [%
Latex
SSCAT
FANA
5/66 (8)
0/5 (0)
5/58 (0)
28/226 (12)
0/28 (0)
0/24 (0)
33/292 (11)
0/33 (0)
0/82 (0)
Assay controls included 17 hemophiliac and 25 normal sex/age range matched
sera; only one showed a postive latex test. DNAss binding was negative; RNAss
binding was significant in some of 55 AIDS sera compared to controls
(P = <0.05). None have shown clinical evidence of an autoimmune or CTD except
for 2 with a reactive type arthritis. This data has implications for the
pathogenesis of reactive arthritis and also suggests that communication
between immunocompetent cells may be interrupted at a very specific level.
WR131 ,fPa
Natu
Human Immuned
JAMES REUBEN
Hospital
Arizona,
Indivi
killer
addition
express
helper c
the per
AIDS-rel
subjects
was a si
coexpres
AIDS/ARC
(p<0.01)
between
there wa
expressi
there wa
Leu2a+/L
defect i
that i
related
of the
individu
and
Tucs
duals
(NK)
of
the
ells
ipher
ated
for
gnif i
sing
when
Th
lymph
d
ng t
an
eu7+
n NK
pro
to in
expa
als
nsion of a subs
ral Killer Acti
eficiency Virus
, C. GSCHWIND**
Tumor Institute
on, AZ. , U.S.A.
infected with
activity whic
interleukin-2
CD8 (Leu2a) as
express the CD4
al blood lymph
complex (ARC) ,
the expressio
cant increase
the markers
compared to e
iere was no d
ocytes of cance
ecrease in the
he CD4 antigen
inverse relat
and Leu3+ on
activity may li
vided by the
fection of the
nsion of this
emains to be el
et of T Lymphocytes Capable of
vity in Individuals Infected with the
(HIV).
E.M. HERSH**. *M.D. Anderson
Houston, TX, and **University of
the HIV are defective in natural
h can be corrected in vitro by the
(IL-2). Effectors of NK activity
well as the HNK-1 (Leu7) antigens; T
antigen (Leu3). We immunophenotyped
ocytes from 27 patients with AIDS and
15 cancer patients and 18 control
n of the Leu2a, Leu7, and Leu3. There
in the percentage of lymphocytes
Leu2a and Leu7 from patients with
ither cancer patients or controls
ifference in Leu2a+/Leu7+ expression
r patients and controls. As expected,
percentage of AIDS/ARC lymphocytes
as compared to controls. Furthermore,
ionship between the expression of
cells. These data suggest that the
e in the lack of induction function
CD4 + cells. Alternatively, it may be
CD8+ cells by HIV. The significance
subset of lymphocytes in HIV infected
ucidated.
WR134 LYMPHOCYTE PROLIFERATION AND GAMMA INTERFERON PRODUCTION IN
PATIENTS WITH HIV INFECTION. ANDREA CANESSA +, V. DEL B0NO+,
M. ANSELMO+, G. ICARDI*, P. CORVARI*, A. TERRAGNA+. + I Clinica Malattie
Infettive Universita di Genova. Istituto di Igiene Universita di Genova.
The capacity of peripheral blood mononuclear cells (MMC) from patients with
HIV infection of proliferating and producing Gamma interferon (gamma IFN) in
response to the mitogen Concanavalin A (ConA) and the antigens T. gondii, C.
albicans and tetanus toxoid was evaluated. The patients were classified
according to the Walter Reed staging criteria (WR) . A control group of
healthy individuals matched for sex and age was also included. For each
patient were evaluated the number of positive responses/the total number of
mitogen and antigens tested, as well as the "cpm score" i.e. the total
cpra/the number of mitogen and antigens tested. The presence of Gamma IFN in
the culture supernatants was assayed by a commercial RIA method and
expressed in mU/ml . The mitogen-or antigen- induced proliferative response
of MNC from the 8 patients in WR2 stage (LAS), as well as the production of
GammalFN in the culture supernatants, were not significantly different from
those detected in the control group. In the patients in WR6 staging (AIDS)
the proliferative response to antigens was absent in 6/8 and the response to
ConA in 5/8. Also the mean production of Gamma IFN was significantly
impaired in comparison with that observed in LAS patients and in the control
group (P<0.01). These data which confirm previous findings in literature
suggest that the impairment of T cell function occurs in the final stages of
the evolution of HIV infection.
WR132 Antibiotics influencing PMtl- functions in HIV-AB-positives
Hoffken,G. , Renner,M., Dzwillo,G., Kramer, A. , Lode,H.
Klinikum Steglitz,D-1 Berlin 45, W. -Germany
There is an increasing number of antibiotics which have been shown
to affect neutrophil functions in healthy subjects. In HIV-positive
subjects impairments of PMN-f unctions are known. We assessed the
chemotaxis (directed migration dm:%N, index CI) and the chemilumi-
nescence (AUC . :mV.min or peak . :mV) of PMNs in 10 healthy
(33+8y) and 10 HTV-positive subjicls (33+5y). In addition, these
parameters were determined 10 h after oral intake of 1 .Og cipro-
floxacin (0.5g) and 1 .Og erythromycin (1.0g) in HIV-positive (and
healthy) subjects . Chemotaxis was performed by the under-agarose-
method,chemiluminescence was measured with a LKB-luminometer after
PMN-stimulation with AB-serum-opsonized S. aureus. No differences"
could be seen between healthy and HIV-positive subjects (dm 101 +
19 %N,CI .69 vs. .71, peak 101+47 %N). 10 h after ciprofloxacin
intake no change in the parameters could be seen in HIV-positives
(dm 102+17 %N,peak , 225+104mV vs. l99+93mV) and healthy subjects
(peak " 252mV vs. 24 5mV) TErythromycin reduced AUC (3.4+1.5 vs.
1.6+1.5mV,p O.OUand peak . (263mV vs. 183mV) in HIV-positives,
but~not in healthy subjec?sTpeak , 292mV vs. 298mV) .
These data indicate no mayor diffSrlRces in PMN- functions tested
between HIV-positives and healthy volunteers prior to antibiotic
intake. After ingestion PMNs of HIV- positive subjects seem to be
more susceptible to erythromycin- interaction than cells from
healthy volunteers, whereas ciprofloxacin doesn't reveal any in-
fluence on PMN- chemotaxis and -chemiluminescence .
WR135 Monoclonal anti-Clq binding immune complexes and hypo-
complementemia in AIDS
Robert Y. Lin, K. Candido, Metropolitan Hospital Center - NYMC,
New York, NY.
Fifteen randomly chosen AIDS patients admitted to this institu-
tion were studied for hypocomplementemia and circulating immune
complex (CIC) concentrations. CIC's were measured by employing
a monoclonal antibody with specificity for (CIC bound) Clq in
a microtiter well ELISA assay. CIC concentrations were elevated
in 7 patients (39-180 mcg/ml AHG equivalents: normal less than
34). C4 was decreased in 2 patients(8-19 mg/dl:normal 20-50),
and 6 patients had low C3(35-42 mg/dl:normal 55-120). Hypergamma-
globulinemia as assessed by serum IgG(IgG) determinations was
present in 9 patients (1840-3600 mg/dl:normal 800-1800) while one
patient had a low IgG(600 mg/dl) .
There was no statistical correlation between either IgG or
complement concentrations and CIC concentrations. However the
2 largest CIC increases were seen in 2 patients with IgG above
3000 mg/dl. Relationships between the type of infection and the
presence of CIC increases were not found.
These studies suggest that in AIDS Clq binding CIC's are common
and are not necessarily associated with hypocomplementemia which
is also common. Furthermore, artifactually elevated CIC values
from polyclonal hypergammaglobulinemia alone do not account for
these findings. The presence of CIC's and reticuloendothelial
dysfunction may play a role in the susceptibility AIDS patients
have to bacterial co-infections.
132
WEDNESDAY, JUNE 3
Neuropsychi a t r/fc
WP136 H*V SeroPrevalence among Patients Hospitalized with
Neuropsychiatric Illnesses in Kinshasa, Zaire.
BOSENGE N'GALY*, R.L. COLEBUNDERS*, M. M'PANIA**, M. MUSSA*«, H. FRAN
J.M. MANN* et al., * Projet SIDA, Kinshasa, Zaire,
Institute, University of Kinshasa. I
Numerous neurologic complications associated with HIV infection have been
described. However the importance of such complications among African HIV
infected patients is unknown.
To further define the clinical spectrum of HIV infection in Africa durj
the period April 1 to 14, 1985, an HIV seroprevalence study was performed
among patients hospitalized in a center for neuropsychiatric illnesses. Ten
(6.1%) of the 163 patients were HIV(+). This prevalence rate is similar to
that observed in the healthy adult population of Kinshasa. Patients with
the following neuro-psychiatric diagnoses were HIV(+): cerebral mass lesion
2/6 (33*), depression 3/13 (23%), psychotic delirium 2/16 f 12% ) , hysteria
1/6 (17*), unclassifiable neuro-psychiatric illness 2/19 (11*). All 3
HIV(+) patients with "depression" presented with chronic cognitive
impairement and important behavioral disturbances. In 2 of these patients
with "depression" no other HIV associated symptoms or signs were found.
Our study suggests that HIV encephalopathy in Zaire may be responsible for
only a minority of all neuropsychiatric diseases.
U/p-iOQ Peripheral Neuropathy in the Acquired Immunodeficiency
Wr. 109 Syndrome: S. M. DE LA MONTE, D. H. GABUZDA. D. D. HO, R. B.
BROWN, E. T. HEDLEY-UHYTE, M.S. HIRSCH. Massachusetts General
Hospital, Harvard Medical School, Boston, MO. USA.
A mult idiscipl inary approach to study peripheral neuropathy in
21 patients with AIDS or AIDS-related complex (ARC) disclosed 11
(52Jt) with symptomatic neuropathies with painful dysesthesias or
'numbness and paresthesias (48%), weakness (33%), or autonomic
dysfunction (10%). These deficits were confirmed by neurologic
exam in 8 of 9 tested, and electrophysiological ly using nerve
conduction, late response, and electromyographic studies in 5 of
6 tested. Electrophysiologic studies demonstrated deficits pre-
dominantly in distal peripheral nerve function due to demyelina—
tion or axonopathy. Biopsy or postmortem peripheral r^erve speci-
mens from 19 of 20 (95%) patients disclosed moderate or severe
demyel inat ion (79%), axonopathy (36%), and inflammation (37%) in
both AIDS and ARC patients. The concordance between the electro-
physiologic and histopathologic interpretations of the nature of
peripheral neuropathy was variable (0—50%) due to the low sensi-
tivity of electrophysio— log ic detection of axonopathy. Human
immunodeficiency virus (HIV) was cultured from the peripheral
nerves in 3 patients, but HIV antigen was not detected by immuno—
h istochemical staining of 8 cases. The findings demonstrate that
peripheral neuropathy in patients with AIDS or ARC is common but
frequently asymptomatic; HIV infection in nerve is implicated as
a likely pathogenetic mechanism of this syndrome.
\A/piQ7 Prognostic Significance of T4 Counts and Serum IgD Levels in a
Cohort of Haemophiliacs Seropositive for Anti-HIV.
E.J. MILLER, C.A. LEE, A. CAMPOS, M. BOFILL, G.JANOSSY, P.B.A. KERNOFF.
Departments of Haematology and Immunology, Royal Free Hospital, London, UK.
In November 1986, amongst 300 patients regularly attending the RFH
Haemophilia Centre, 106/245 (43!i) of patients with haemophilia A and 1/55 (2%)
of patients with haemophilia B were seropositive for anti-HIV. A cohort of 74
seropositive patients, whose dates of seroconversion are known by retrospective
testing of stored serum samples, -have been followed for a median period of
4.8 yrs (range 1.5 - 7 yrs). 16 (22K) of these patients have developed HIV-
related illnesses, including PGL, ARC, and pneumococcal and zoster pneumonia.
Only 3 patients, seropositive for 6.3, 4.3 and 3 yrs, respectively, have
developed full blown AIDS. Of the 17 patients in the cohort who have been
seropositive for more than 6 yrs, 6 patients (35K) currently have T4 counts
below 0.4 x 109/1, of whom one has PGL, one ARC, and one AIDS. The 11 patients
with higher T4 counts remain clinically well. Serum IgD levels were raised in
patients with PGL and ARC, but showed a marked fall with T4 counts in patients
who deteriorated clinically and developed AIDS. Serial T4 and IgD estimations
appear useful prognostic indicators in seropositive patients. The rate of
progression to AIDS seems less in haemophiliacs than in other groups at
increased risk of HIV infection, but the onset of AIDS may be delayed for at
least 6 years after seroconversion.
WR140 Effect of Corticosteroids on Immediate Survival from Pneumocystis
Carinii Pneumonia (PCP) in Patients with Acquired Immunodeficiency
Syndrome (AIDS).
A. JUBRAN, DEBBIE MATZKE, R.B. POLLARD, Division of Infectious Diseases, The
University of Texas Medical Branch, Galveston, TX.
Retrospective review revealed 42 patients with AIDS and PCP divided into 3
groups: Group I - PgOj - 60 on room air treated with antibiotics (N=17),
Group II - Pa02 1 60 on room air treated with antibiotics ( N=1 6 ) , Group III -
Pa02 1 60 on room air treated with antibiotics and corticosteroids (N=9). Com-
pared to Groups II and III, Group I had significantly fewer patients requiring
intubation, fewer ICU days, and lower A-a gradient on admission. Overall mor-
tality of Group I (12%) was significantly lower than Group II (37.5?) but not
Group III (22%). Group III had significantly longer hospitalizations and
antibiotic courses than Group I. The only difference between Group II and III
was significantly more patients in Group III (7/9) were treated with a combi-
nation of trimethaprim-sulfamethoxazole and Pentamidine compared to Group II
(3/13). Certain patients in each group had increasing A-a gradients despite
antibiotic therapy. Mortality in these sub-groups was 1/1 (Group I), 2/4
(Group II), and 1/7 (Group III). Severe PCP treated with antibiotics and
corticosteroids has an overall mortality similar to less severe disease while
severe PCP treated with an antibiotic alone had a higher mortality. Evalua-
tion of combination antibiotic therapy in severe PCP may be warranted. A
placebo controlled, double-blind prospective study on the use of corticoster-
oids in severe PCP is indicated.
WP138 Benign CMV-Mononucleosis in Non AIDS HIV-infected Patients
JEAN LOUIS VILDE, C. LEPORT, M. HARZIC, J.M. PIGN0N, F. BRICAIRE,
C. PBRR0NNE, Hospital Claude Bernard, Paris, France.
Benign cytomegalovirus mononucleosis (CMV-M) Is a well known syndrome in nor-
mal adults. The clinical and vlrologlcal features of a similar syndrome observed
in 8 non AIDS HIV-infected patients (pts) , and the relation with the course of
HIV infection were analyzed. They were 6 men (5 homosexual), one woman sexual
partner of an HIV-infected man, and one Zairlan child whose mother had AIDS.
All pts had a benign syndrome with fever (n=7) , transient splenomegaly (n=2)
or hepatomegaly (n=l) , and mononucleosis with atypical lymphocytes. Serum tran-
saminase levels were increased in 3/8 pts. Heterophile agglutinin test was
negative In 8/8 pts. All pts had either positive CMV viremla (3/7) or a 4-fold
rise of antlCMV antibodies (Ab) (6/8), or both. IgM Ab were detected In 5/7
pts. The features resolved spontaneously in all pts. At the time of CMV-M, all
the pts had HIV-Ab ; 5/8 had ARC and 3 were HIV asymptomatic.
In January 1987, 3/8 pts were in the same status of HIV Infection as at the
time of CMV-M : two ARC, one HIV asymptomatic, with a mean duration of follow-
up of 17 months since CMV-M.
AIDS developed In 5/8 pts with a mean delay of 12.4 months (range 5-19) after
CMV-M ; in January 1987, one was still alive and 4/5 AIDS pts had died, death
occurring 4.5 months (range 2-7) after the first symptoms of AIDS ; disseminated
CMV disease with extensive organ Involvement was noted in 3/4 dead pts.
These features show that a benign CMV-M without severe localization (1) may
occur In non AIDS HIV-infected pts, (2) might be a predictive factor of poor
outcome of HIV Infections as shown for high CMV Ab titer, and (3) may precede
the clinical manifestations of HIV infection, thus requiring to look for HIV Ab
In all pts with a benign CMV-M.
U/Pldl Clinical Features of Respiratory Synctial Virus Infection in Human
Im munodeficiency Virus Infected Children.
S.CHANDWANL W.BORKOWSKY, K.KRASINSKI, R.LAWRENCE, D.BEBENROTH & T.
MOORE. NYU-Bellevue Medical Ctr, New York, NY.
Respiratory syncytial virus infection may be severe in im mune compromised hosts. We
have cared for 7 HIV infected children with RSV infection, proven by RSV antigen capture
ELBA or IFA. The ages of patients were 3M,6M,7M,2 yrs,3yrs, & 4 yrs. Fever > 390C was
observed in 4/7 patients. Cough & or rhinorrhea were present in 6/7 (85.7%) patients.
Tachypnea was seen in 3/7 patients. Wheezing was noted in only 1 patient; a 3 yr old child
who was known to have recurrent wheezing episodes in the past. Pulmonary infiltrates
were seen on Roentgenographic examination of 4/7 (57%) patients. Hypoxia & respiratory
distress developed soon after admission in 2 patients. One required 0.5 Fi02 with CPAP
of 5 cm of H2O & the other 0.35 Fi02 & ventLDatory support for hypercarbia. Oxygen
requirement remained unchanged despite ribavirin aerosol therapy. On the 8th day of
hospitalization P. carinii & P.aeroginosa were detected in the tracheal lavage specimens
of one patient. On the 11th day of hospitalization, P.aeroginosa was isolated from
endotracheal secretions of the other patient and it was also isolated from the lung tissue
postmorten. Both these patients died despite appropriate antibacterialrantiviral &
antiprotozoan treatment. We treated HIV infected patients below 2 yrs with Ribavirin &
the 2 patients above 2 yrs of age were not treated. Mortality in the-1 yr age group was
50%.
The majority of our patients presented with prolonged high fever & pneumonia, instead
of bronchiolitis.
RSV may have been a contributing factor in the death of 2 patients, either directly
producing respiratory distress, or predisposing to the emergence of other pathogens.
Therefore in the HIV infected patients with RSV infection efforts should be made to
detect other pathogenic organisms.
133
WEDNESDAY, JUNE 3
WR142 Discordant Western Blot Analysis for Antibody to Human Im m unodeficiency
Virus (HIV) among Mother-Infant Pairs at Birth.
THE NEW YORK COLLABORATIVE STUDY GROUP FOR VERTICAL TRANSMISSION OF
HIV (KEITH KRASINSKI*, * N Y U-Bellevue Hospital Center, New York, NY.)
Diagnosis of HIV infection in the first year of life is confounded by passive
transplacental passage of maternal antibody. There have been 43 newborn infants
enrolled in the NYC collaborative study. Antibody to HIV, as measured by ELISA with
western blot (WB) confirmation, is present in 24/43 (56%). We compared the WB banding
patterns of serum obtained at the time of delivery for the 24 mother-infant pairs.
Discordance of WB bands was present in 7 pairs. There were 4 mothers with antibody to
pl8 whose infants did not demonstrate anti-pl8 antibody, and 3 mothers without
demonstrable antibody bo pi 8 whose infants did have antibody to pi 8. Five of the mothers
are apparently welL one (anti-pl8 pes) has rectal bleeding, and one (anti-pl8 pos) has a
history of prior Pneumocystis carinii pneumonia. Of 4 antd-pl8 negative infants 3 have
symptomatic disease possibly related bo HIV infection: 1 (age 8 months) with
lymphadenopathy, recurrent pneumonia and meningitis, 1 (age 8 months) with
lymphadenopathy, recurrent otitis media and thrush, and 1 (age 3 months) with
lymphadenopathy diarrhea and poor weight gain. One anti-pl8 negative infant is well at 4
months. Two anti-pl8 positive infants (age 5 and 7 months) are well, one other infant
without lymphadenopathy is neurologically abnormal.
These data demonstrate that de novo production of fetal antibody to pl8 occurs and can
be detected when anti-pl8 is absent from the mother. Negative anti-pl8 status in infants
could result from HIV infection depressing humoral im m unity or im mune complex
formation with antibody of maternal or fetal origin. There are 6 symptomatic children
among 24 HIV antibody positives; 4 with discordant bands and 2 with concordant matemal-
infant absence of anti-pl8; 5/6 are anti-pl8 negtive. These preliminary data also suggest
that absence of antibody to pl8 at birth could be an early indicator of progressive illness.
WP145 Detection of HIV Core Antigen in the Cerebrospinal Fluid (CSF) in
Patients within the AIDS Spectrum
I.Z. LEIDERMAN*. A.R. FLESHER**, K. SHRIVER**, B.A. SCHAEFFLER**, B.R.
ADELSBERG*, MILTON R. TAM**, *Mount Sinai School of Medicine, New York, NY
and **Genetic Systems Corporation, Seattle, WA, USA
Patients infected with HIV often develop central nervous system (CNS)
disorders including meningitis and progressive dementia. We have studied 20
patients (all HIV antibody positive) from within the AIDS spectrum, including
10 with encephalopathies, 8 with meningitis (4 cryptococcal, 4 viral), and 2
with polymyositis, for the presence of HIV p25 antigen in their CSF. To detect
antigen, an assay was developed using monoclonal anti-p25 antibody for capture
and a polyclonal antiserum directly labeled with HRP as signal. This assay
is sensitive to at least 10 pg HIV/assay using a preparation of inactivated
whole virus. The CSF samples were tested in a double blind manner. Subsequent
data analyses revealed that 10/10 patients with encephalopathies were scored
as positive using our antigen capture assay, whereas 0/10 patients with men-
ingitis or polymyositis were positive. The average OD value for the encepha-
lopathic patients was 0.128 ± 0.097 compared with an average OD value of 0.017
± 0.008 for the meningitis /polymyositis group (p 0.01). In 10 of these cases
where serum samples were also available, presence of antigen in CSF did not
correlate with the presence of antigen in serum. These data support the con-
clusion that the AIDS dementia complex is related to the presence of p25 viral
antigen in the CSF.
WP 143 Microbiologic Evaluation of AIDS Virus Associated Periodontitis.
M. Grassi. P.A. Murray, J.R. Winkler. Dept. of Stomatology, Univ. of
California, San Francisco, CA, USA.
We have recently described a periodontal disease associated with HIV infection which we
refer to as AIDS-virus associated periodontitis (AVAP). It remains unclear whether this
opportunistic infection is caused by organisms not commonly colonizing the oral cavity,
or by the indigenous flora overwhelming the compromised host. This study was
designed to investigate the microbiota associated with AVAP. Complete medical and
dental histories and full mouth radiographs were obtained on 20 patients presenting with
AVAP. Oral and periodontal examinations were done at the initial exam and every four
weeks. Subgingival plaque samples (total of 46 sites) were collected with three sterile
paper points placed to the depth of the pocket for 10 seconds. The points were
immediately transferred to 0.25 ml of reduced transport fluid without EDTA and analyzed
by culturing for selected periodontal pathogens and Candida. We also cultured
subgingival plaque and mucosal tissues for enteric organisms, Spirochetes, and motile
organisms, as well as Candida by direct microscopic evaluation. We detected Bacteroides
gingivalis. B. intermedius and Actinobacillus actinomveetemcomitans in large numbers
and Fusobacteria nucleatum was identified in over 75% of diseased sites, but the
association between these organisms and the progression of AVAP remains inconclusive.
At the most acute stages, Spirochetes and motile rods constituted greater than 50% of the
organisms observed. Also, unusual protozoans were detected in 12 sites. The
relationship of Candida to the pathogenesis of AVAP remains unclear, but is consistent
with the invasive potential of Candida in other tissues in these patients. Preliminary data
suggest that the AVAP lesion is associated with organisms typically associated with
periodontal disease overwhelming the compromised host and that Candida may play a
role in the pathogenesis of the disease. Investigations are in progress to identify any
unusual periodontal organisms or organisms not commonly found in the oral cavity.
WR146
ABSENCE OF ANTIBODIES TO HIV CORE PROTEIN CORRELATES WITH THE
DEVELOPMENT OF SYMPTOMATIC ILLNESS IN PATIENTS AT RISK TO
DEVELOP AIDS
GARY L^ NORMAN, S SU, P.S. GILL, A. LEVINE, and S. RASHEED
University of Southern California, School of Medicine, 1840 N. Soto Street,
Los Angeles , CA.
Approximately 500 sera from individuals at high risk to develop AIDS were
tested by a sensitive immunoblot (western blot) assay for antibodies to the
Human Immune Deficiency Virus (HIV). Selection of sera was based on their
positivity by the enzyme- 1 inked- imraunosor bant assay (ELISA) . Our results
demonstrated that while all sera reacted strongly with the envelope gp41
protein, reactions to the core protein (p24), varied significantly among
symptomatic patients. Comparison of the immunoblot banding patters with
clinical symptoms of these patients indicated that about 33% of patients
with AIDS-related diseases did not show any antibody reaction to the core
protein (p24) and about one third of the patients' sera showed extremely
weak reactions with the HIV-p24 antigen. These data are consistent with our
earlier reports (Rasheed et al, Virology 150:1-9, 1986) and suggest the
antibody patterns of the immunoblots may be used to monitor the wide
spectrum of disease episodes seen during the development of AIDS.
WR144
Periodontal Disease in HIV-infected Male Homosexuals. I.R. Winkler. M.
Grassi, P.A.Murray. School of Dentistry, University of California, San
Francisco, CA, USA.
Early detection of HIV infection is of great value in slowing the epidemic spread of AIDS, as well
as providing earlier treatment of opportunistic infections associated with the disease. Oral lesions,
such as hairy leukoplakia and candidiasis, are now among the first clinical signs of HIV infection.
This study presents evidence that an atypical gingivitis (ATYP) and a rapidly progressive
periodontal disease (AVAP) may serve as even earlier indicators. ATYP, is a gingivitis associated
with a generalized inflammation of the oral mucosa and does not appear to respond to
conventional therapy. AVAP is a rapidly progressive form of periodontal disease often associated
with significant pain, bleeding, and extremely rapid loss of periodontal bone. Recently, we have
observed in a number of patients, that the AVAP lesion has progressed into a potentially life
threatening noma-like lesion resulting in the sequestration of large pieces of periodontal bone.
The purpose of this study was to evaluate if these diseases have any diagnostic value of HIV
infection and their relationship to other HTV -related diseases. The patient population studied was
112 patients. Less than 25% of the patients that presented for treatment with ATYP were aware of
being sero-positive and less than 20% of these same patients had any other obvious signs or
symptoms. On the other hand, 100% of the AVAP patients were aware of being seropositive
and/or had other signs of HIV infection. Hairy leukoplakia and candidiasis were frequently
associated with AVAP, 78% and 95% respectively, but not as frequently for ATYP which was
20% and 37% respectively. Interestingly, the relationship to T4/T8 ratios was quite significant.
ATYP patients had ratios greater than 1 (p<0.001) and AVAP patients had ratios below 1
(p<0.001). Our data suggests that AVAP and ATYP are intraoral diseases related to HIV
infection and may have predictive value in identifying HIV-infected individuals. ATYP ;
'appears
to be a very early sign of HIV infection and frequently appears in the absence of other HIV
associated signs and svmtoms, AVAP appears to be associated with decreased T4/T8 ratios and
may manifest in a potentially life threatening noma-like disease. NIH Grant-R23DE07245.
WP147 Response and Survival in Patients (PTs) Treated for Presumed versus
Proven CNS Toxoplasmosis (TOXO).
J. COHN, ALEX MCMEEKING, W. COHEN, J. JACOBS, R. HOLZMAN
N.Y.U./Bellevue Medical Center, New York N.Y., U.S.A.
Twenty-eight patients with proven or suspected HIV related disease and abnormal
head CT scans were treated empirically for TOXO (E). Nine biopsy proven TOXO pta
with AIDS were also treated (B). Initial therapy included sulfadiazine,
pyramethamine and folinic acid (Rx) for at least 2 weeks. Some PTs also received
steroids or anticonvulsants. PTs who responded were continued on antimicrobials.
Among E PTs, 21 responded clinically and radiologically in 2-4 weeks (E-R), 7 did
not (E-NR). Of B PTs, 4 responded (B-R), 4 did not (B-NR), and 1 was biopsied here
and treated elsewhere. There were no significant differences in the response rates of
E and B PTs. Responders and nonresponders did not differ in the use of steroids with
initial Rx. The 4 subgroups were similar in demographics and clinical presentation.
One HIV Ab negative E-R PT and 1 E-NR pt whose CT was normal on review are
excluded from further analysis.
Survival of responders was significantly longer than nonresponders by life table
analysis (median 422 vs 67 days). Survival of E PTs was longer than B PTs (median
294 vs 90 days), but the difference was not significant. Median survival of the 20 E-
R PTs was 309 days. No deaths occurred among the 4 B-R PTs, whose median follow-
up was 365 days. Of the 6 E-NR PTs, one proved to have CNS lymphoma and 5 had
lucencies and calcifications on CT suggestive of alternative diagnoses. Four of the
responders discontinued Rx and relapsed, but improved when Rx resumed. Clindamycin
replaced sulfa in 17 PTs because of toxicity.
PTs can be treated empirically for TOXO with response rates and survival
comparable to biopsy proven cases. Empirically treated PTs without prompt responses,
or who develop new lesions on Rx, should be biopsied in search of other treatable
diseases.
134
WEDNESDAY, JUNE 3
WR148 Mer,ory Function and Motor Control in AIDS: An Evaluation of Some
Neuropsychological Measures
HANNAH AMITAI, TANIA ZAZULA, DONNA ORNITZ, RICHARD W. PRICE, JOHN J. SIPTIS,
Memorial Sloan-Kettering Cancer Center, New York, NY.
The AIDS dementia complex (ADC) has been characterized as having features
similar to "subcortical" dementia, namely apathy, psychomotor slowing,
forgetful ness , reduced mental agility and personality change. The formal
neuropsychological examination should not only provide quantitation of
relevant cognitive functions, but should also provide data that will be
useful in the eventual subclassification of patients with ADC. To these
ends, a range of neuropsychological tests of memory and motor function have
been administered in the course of 100 evaluations of over 60 AIDS patients
without evidence of focal intracranial disease (e.g., toxoplasmosis, lympho-
ma, PML) that would confound the characterization of ADC. The memory tests
included the logical memory, paired associate learning and visual reproduc-
tion subtests of the Wechsler Memory Scale, the Rey Auditory Verbal Learning
Test, and the Renton Visual Retention Test, while the motor tests included
the finger-tapping, grooved pegboard and timed gait tests. Preliminary anal-
yses indicate that different tests yielded different estimates of impairment
rates, with poor verbal memory found in 10-25% of the evaluations and poor
visual reproduction found in 25-45% of the evaluations. Similarly, motor
abnormality rates ranged from 25-50%. Although nominally assessing similar
functions, these tests also had different patterns of correlation with other
neuropsychological tests, suggesting that, for the purpose of better defining
the characteristics and natural history of ADC, detailed neuropsychological
evaluation is an important complement to briefer examinations designed for
large population studies.
UfDiRI Correlation of Specific Antibodies anti HTLV-III Proteins with the
Clinical Status. OUVIERO E. VARNIER', F.'LILLO*, G.C. SCHITO*.
A. LAZZARIN««
Genova, Italy
Bethesda, USA
The aim of
proteins of
MORONI"
"Clinic
', C. LANE"",
of Infectious
et al., "Institute of Microbiology,
Diseases, Milano, Italy, """NIAI,
this study was the analysis of the immune response to the
HTLV-III in AIDS patients to determine whether the
immunoreactivity correlates with the clinical status.
Among the 24 AIDS patients positive for antibodies to proteins coded by
both gag and env HTLV-III genes, 15 are alive. Three of the remaining 9
patients died accidently. All the last 6 AIDS dead patients had neurologic
diseases associated with the HTLV-III infection. 13 patients had antibodies
directed only against the env encoded proteins and they are all dead, with
the exception of one addict, who had an episode of PCP in September 1983.
HTLV-III related neurologic disease was present in only 1 dead patient.
Sequential serum samples of the same AIDS patient showed decreasing amounts
of anti-gag antibodies and/or their disappearance in relation to disease
progression or next to the exitus.
Progression of the disease seems to be associated with the presence of
lower levels of anti gag-protein antibodies and later on with their
disappearance. If patients survive for a relatively long period of time and
develop the full blown AIDS, their antibody profile is caracterized by an
unique reactivity for the gp41. Severe or unrecognized opportunistic
infections, neurologic diseases or unrelated complications will shorten the
survival. Moreover, clinical improvement seems to be followed up by the
recovery of the immunoreactivity for the gag-encoded antigens.
WR149 Neurological Complications of HIV Infection in the Absence of
Significant Immunodeficiency
B.J. BREW, M. PERDICES, D.A. COOPER, St. Vincent's Hospital,
Sydney, Australia.
Infection with the human immunodeficiency virus results in a wide spectrum
of neurological disorders. Whilst some of these represent opportunistic
infections or neoplasms, others likely result from direct HIV infection of
the nervous system and/or immunopathogenic processes. These neurological
syndromes include an acute meningoencephalitis related to seroconversion,
chronic meningitis, dementia, vacuolar myelopathy and peripheral neuropath-
ies. These have occurred in patients with AIDS or AlOS-related complex, as
well as in HIV seropositive individuals who are systemically well. This
report details the clinical features of 7 immunocompetent patients who devel-
oped neurological syndromes in the context of an acute febrile disorder and
HIV seroconversion. In one case, however, there was no antecedent systemic
illness. There appeared to be two phases: acute and subacute. In the acute
phase, patients developed meningoencephalitis or meningoradicul itis, usually
occurring within one to several weeks of the systemic illness. In the sub-
acute phase there was either a focal dementia alone or in combination with
optic neuritis, hemiparesis, ataxia or peripheral neuropathy. All patients
tested were found to have cognitive impairment of a similar type but of dif-
fering degree. The relationship of this to the more chronic AIDS dementia
complex is not yet clear. It is proposed that the pathogenesis of these
acute and subacute syndromes is, at least in part, immune-mediated, although
direct HIV infection of the brain likely initiates these disorders,
particularly the dementia.
WR152
and R. Aquilante , e
Center, Washington, DC,
NIH,
Center, Washington, DC and
Evaluation of the Gen-Probe Rapid Diagnostic System for the
Mycobacterium Avium Complex Using Isolates from Patients with
the Acquired Immunodeficiency Syndrome .
John F. Reiser*, E\ Witebsky A M. Hirschraann* , D. Wilkinson*, J. Brisker**'
The George Washington University Medical
Bethesda, MD. Walter Reed Army Medical
Gen-Probe Corporation, San Diego, CA.
A new 20 test product, Gen-Probe Rapid System for the Mycobacterium
avium complex, has been introduced using nucleic acid hybridization tech-
nology. Seventy-Eight isolates, identified by conventional methods, from an
equal number of patients were analyzed according to the manufacture's
specifications. The specimens included : 38 blood , 15 tissue , 2 stool, 10
Bronchial lavage , 10 bone marrow, 1 CSF, 1 urine, and 1 sputum. Of the 78
isolates, 72 were determined to be Mycobacterium avium and 5 were Mycobac-
terium intracellular . The percent hybridization for 71 of the M^ avium
isolates showed a mean of 54 percent with a range from 44-67 percent. One
M. avium isolate gave a 29 percent hybridization with the M^ avium probe and
a 9.7 percent hybridization with the M_^ intracellular probe. The M.
intracellular isolates showed a mean of 54 percent hybridization with a
range from 36-60 percent. One stool isolate gave low hybridization levels
with each probe due to bacterial contamination. For cost considerations,
isolates should be tested first with the M^ avium probe; and if negative,
followed by the M_^ intracellular probe. From our studies, 77.Qf.78 M.
avium complex isolates gave unambiguous results. The Gen-Probe test
systems shows promise as a rapid diagnostic technique. Further studies are
in progress to determine specificity and clinical relevance.
WP150 Prognostic Indicators at Presentation of Kaposi's Sarcoma-
KEN CUTLER, D.W. FEIGAL, N HEARST, PAUL VOLBERLING:
University of California, San Francisco General Hospital, San Francisco, CA,
A cohort of 162 patients with Kaposi's sarcoma (KS) treated at San Francisco
General Hospital (SFGH) was identified between November 1980 and March 1984.
Baseline history, physical exam, and laboratory variables were analyzed for
prognostic effects on survival. Follow-up in August 1986 determined date of
death for 132 patients. Twenty-six were known to be alive at least until
January 1986. 115 pts developed KS before any AIDS associated opportunistic
infection (OI). Survival was calculated from Kaplan-Meier estimates.
Patients without OI had a median survival of 672 days compared to 306 days
for those with OI before KS. Of the patients without 01 significant
prognostic variables included: oral candidiasis, sedimentation rate (ESR),
hematocrit (Hct), helper suppressor ratio (H/S), and constitutional
symptoms (BSx): fever, night sweats and weight loss greater than 10 lbs. A
dose response was noted for BSx with median survival of 1289, 657. 703, 382
days in patients with 0,l,2jand 3 BSx respectively. Median survival with and
without Candida was 649 vs 1069 days. As baseline Hct fell from >42, 38-42,
36-38, <36 median survival 1120, 848, 568, and 226 days- Similarly for ESR
<15, 15-25, 25-50, >50 median survival was 1102, 672, 527, and 422 days. For
H/S ratios <.3. .3-.7,>,7 median survival was 1102,1035,463. When Hct, or
ESR, or H/S ratios were considered simul taneously ^*ith BSx In Cox regression,
BSx were no longer statistically significant. Thus the laboratory
abnormalities were more closely linked to prognosis than clinical symptoms.
This stduy supports the collection of baseline routine laboratory studies to
estimate prognosis of newly diagnosed AIDS KS and in selecting candidates for
experimental protocols.
WR153 FETAL AIDS SYNDROME: LACK OF CORRELATION WITH MATERNAL DRUG USE.
Robert W. Marion, Andrew A. Wiznia, Kirin Shah, Arye Rubinstein;
Departments of Pediatrics, Microbiology and Immunology, Albert Einstein
College of Medicine; Bronx, New York.
The fetal AIDS syndrome (FAS) is a recognizable pattern of growth and
craniofacial dysmorphic features that occurs in HIV-infected infants and
children. Since the majority of these infants are born to women who are
intravenous drug users, it is important to distinguish the features of FAS
from those caused by fetal exposure to drugs. In an attempt to do this, 12
HlV-antibody positive children under the age of 2 1/2 years were examined
by one of us who was blinded to the mothers' history of drug use. Using
the criteria of the FAS scoring system, the subjects were divided into 3
groups: (1) severely stigmatized; (2) moderately stigmatized; (3) mildly or
not stigmatized. Seven of the subjects were offspring of confirmed maternal
drug users; of these, 3 were severely stigmatized, 3 were moderately
stigmatized and 1 fell into the not stigmatized category. Five subjects
were born to women who had become infected through heterosexual contact; 2
scored in the severely stigmatized category, 2 were judged to be moderately
stigmatized and 1 was not stigmatized. When these data were analyzed, no
differences in FAS score between the etiology groups could be identified.
Although this study population is small, these preliminary findings suggest
that FAS occurs independent of fetal drug exposure and that the features
are related to infection with HIV during the first trimester of intra-
uterine life.
135
WEDNESDAY, JUNE 3
U/P154
Multifocal Cytomegalovirus Brain Infection in AIDS: Early Detection
with Magnetic Resonance Imaging and Treatment with 9-(2-hydroxy-l-
(hydroxymethyl)ethoxymethyl) guanine .
3.C. Masdeu*, Catherine Butkus Small*, L. Weiss*, CM. Elkin*, J. Llena*, R.
Mesa-Tejadar**, *North Central Bronx-Montefiore Hospitals, Albert Einstein
College of Medicine, Bronx, N.Y., **College of Physicians and Surgeons,
Columbia University, New York, N.Y.
A 43-year-old man with AIDS had clinical evidence of multifocal
disease of the brain; however, computed tomography (CT) was negative.
Magnetic resonance imaging (MRI) revealed multifocal lesions, proven to be
caused by cytomegalovirus (CMV) by brain biopsy. CMV encephalitis was
documented by light and electron microscopy as well as by immunohistochemical
staining of the biopsy specimen. CMV viremia was confirmed by a positive urine
culture. Therapy with 9-(2-hydroxy-l-(hydroxymethyI) ethoxymethyl) guanine (BW
B759U) resulted in stabilization of the patient's clinical disease and radiographic
improvement of the multifocal lesions.
In AIDS patients, multifocal brain lesions on CT or MRI are seldom due
to CMV, but this diagnosis must be considered in the differential. MRI is
currently the procedure of choice for detecting these central nervous system
lesions. Early brain biopsy is warranted, since CMV encephalitis is a potentially
treatable infection.
WR157
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posit
gati v
e pat
257
all
in se
no s
sitiv
had a
para
t lea
onega
n is
tic p
clud
rs o
cent
(N = 2
(N=8
of
on
ive
e pa
lent
9 vs
had
r opo
igni
e pa
moeb
site
st p
tive
on
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ing 67
f risk
(215)
0), 5*
) were
their
ly one
and 33
tients
s. The
. 2899
term
siti ve
f leant
tients
iasis .
s. All
assive
women
going .
rients
WP155 Gestational Characterstics and Mode of Delivery of 98 Children
with AIDS in Mew York City.
PAULINE A. THOHAS. R. E. O'DONNELL, P. GUIGLI, C. BROWN, J. LEE, S. SCHULTZ,
New York City Department of Health, New York, NY.
It has been established that Human Immunodeficiency Virus (HIV) can be
transmitted from infected mothers to their offspring, probably in-utero, but
the possibility of intrapartum transmission has not been disproved. If it
occurs, Caesarian section (CS) delivery might be protective. We examined
birth certificate records of 98 children reported with maternally
transmitted AIDS in New York City (NYC) born between 197 7 and 1986, and all
children born in NYC during the year 1983 , to assess CS delivery rates and
other characteristics including birthweight. Of the 98, 71 (72%) had
mothers who used intravenous narcotics (IVDU) . Eleven of 62 (18%) black, 5
of 26 (19%) hispanic, and one of 10 (10%) white infants with AIDS had been
born by CS compared with 18% of 33,495 black, 20.5% of 31,083 hispanic and
25% of 32,787 white infants born in 1983. Differences were not
statistically significant. Children who subsequently developed AIDS were
more likely than the general cohort to be underweight at birth: 39% of
blacks, 38% of hispanics, and 40% of whites under 2500 grams, vs. 12% of all
black, 8% of all hispanic, and 4% of all white births. Of infants with AIDS
born to IVDU mothers, 44% were under 2500 gms vs. 33% of 843 infants with
maternal narcotics listed on the birth certificate. Further matching by
sociodemographic characteristics may lessen this difference. Prospective
studies comparing infected and uninfected pregnant women will further
elucidate the effect of HIV on fetal growth. Since the CS rate for delivery
of infants who later developed AIDS was not lower than the rate for the
general cohort, our data indicate no protection from C-section delivery.
WR158 Multimodality Evoked Potentials Studies In AIDS, S.M. VISHNUBHAKAT,
M.KAPLAN, R.BERESFORD, B.FARBER, T.FLYNN, North Shore University
Hospital, Manhasset, N.Y., U.S.A.
HIV induced central nervous system disease (CNS) has been largely studied
neuroradiologically and clinically without electrophysiologic studies which may
indicate pathology in asymptomatic areas of CNS. We studied 35 patients (18
homosexuals, 15 addicts, 2 others, 30 males, 5 females, 30 AIDS, and 5 AIDS re-
lated complex) with visual, auditory, and somatosensory evoked responses in or-
der to determine incidence, pattern, and extent of central conduction abnormal-
ities. These studies were performed using Seigen clinical averager with computer
facilities. Stimuli were delivered by pattern shift television screen for visual
evoked response (VER) , 100 decibal clicks for brainstem auditory evoked response
(BAER) , median nerve stimulation for somatosensory evoked response (SSER) . Thir-
teen patients showed abnormalities in one or two of the three modalities studiai
Five patients had VER and five had SSER abnormalities whereas 7 patients showed
abnormalities in BAER. Five patients had VEP abnormalities, 3 had bilateral, 2
had unilateral prechiasmatic delay. None had significant visual symptoms, though
visual acuity was abnormal in three. Five patients had SEP abnormalities, 3 had
peripheral delay suggesting neuropathy, and 2 had cervical delays suggesting
myelopathy affecting posterior columns. Seven patients showed BAER abnormalities
6 had delay involving pontine pathways, whereas one had peripheral delay
suggesting auditory nerve involvement. Clinical evaluation failed to reveal
significant neurologic signs indicative of the abnormality revealed by EP
studies. There was no correlation between EP abnormalities and staging of AIDS.
Eight of the thirteen patients showed presence of peripheral neuropathy in an-
other study. We conclude that approximately 367. patients with AIDS will reveal
abnormalities in multimodality evoked response study and indicate presence of
CNS pathway abnormalities in largely asymptomatic areas.
WR156 Cerebrospinal Fluid (CSF) Findings in HIV Positive Patients (pts)
without AIDS.
MARK E. APPLEMAN. S.L BREY, D.W. MARSHALL, R.N. B0SWELL, R.W. H0UK, R.E.
WINN. Wilford Hall USAF Medical Center, Lackland AFB, TX.
Lumbar punctures were done on 114 consecutive pts. without AIDS evaluated
for a positive HIV by Western blot. Fifty-seven pts. had normal CSF (grp I).
Forty-four pts (38.6%) had abnormal (abnl) CSF (grp II), defined as: protein
50 and nucleated cells (N.C.) > 7; or, protein > 60 alone; or, N.C>. 10
alone; or an elevated CSF IgG or IgG synthesis rate or the presence of
oligoclonal bands (0CB). Grp III (57 pts) included all grp II pts plus 13
other pts meeting the standard criteria for abnl CSF: protein > 45 or NC >
5. No significant differences existed between grps for age, sex, race, serum
FTA, Walter Reed classification, CD count, or CMV, toxoplasma or EBV
.-erologies. Grp III CSF findings revealed:27 pts with protein > 45 (range 22-
104); 36 pts with > 5 NC (range 0-35); mean differential 0.3% polys, 90.7%
lymphs, 9% others. Bacterial, fungal and AFB cultures were negative. Thirty-
one pts in grp II (72%) had an elevated CSF IgG, IgG synthesis rate or 0CB.
No significant neurologic abnormalities could definitely be attributed to
these CSF findings. Head CT scans on 33 pts in grp II were abnl in 3, one of
whom had an abnl MRI. This study demonstrates that significantly abnl CSF is
present in about 38% of pts with HIV infections without AIDS. Follow-up of
these pts will clarify the significance of these findings and their
relationship to HIV CNS infection.
U/PIRQ Clinical and Electrophysiological Features of Neuropathy in AIDS
"'• 'ua S. M. VISHNUBHAKAT, M. KAPLAN, H.R. BERESFORD, NSUH, Manhasset,
N. Y. , U. S. A.
Peripheral neuropathy is a known complication of AIDS. Its incidence and
electrophysiologic features have not been established fully. We studied 35
patients with sensory motor latency, amplitude, conduction velocity, and long
latency determination, and electromyography. These studies were performed using
TECA 4 machine with photographic recording for analysis of electroneurogram and
myogram. There were 18 homosexuals, 12 addicts, 3 addict wives, 1 secondary to
transfusion, and 1 with no known risk factors. Thirty-one were male and 13 were
symptomatic with predominantly peripheral symptoms of tingling and numbness in
9 and focal neuropathic symptoms in 4. One patient complained of proximal weak-
ness. Neurological evaluation confirmed features of neuropathy in 14 patients
and consisted of mild distal sensory loss in 12, and mononeuropathy in 2.
Twenty-eight patients had opportunistic infections from AIDS, and five were
classified as suffering from AIDS related complex.
Electrophysiologic Studies: Two of the 33 patient had carpal tunnel syndrome
and 3 had mononeuropathy associated with peripheral neuropathy. Eighteen
patients had symmetric peripheral sensory motor neuropathy without any evidence
of either proximal neuropathy or radiculopathy. Seven of these patients showed
mild to moderate distal sensory neuropathy and 11 had mixed distal sensory
motor neuropathy. No instance of pure motor neuropathy was seen. Three of the
18 patients showed features of axonal neuropathy, whereas 15 had mixed features
of both axonal and demyelinating type. One of the 10 patients who had normal
electroneurography revealed EMG evidence of proximal myopathy.
We conclude that careful EP studies will reveal significantly higher in-
cidence of peripheral neuropathy in AIDS and related complex than currently be-
lieved. We postulate variable etiologic factors based on the above studies.
136
WEDNESDAY, JUNE 3
WP160 Pituitary gland involvement in
pathological study.
ADRIEN G. SftlMOT, C. MARCHE, R. MAYORGA
al
P.M. GIRARD, J.L.
Hopital Claude Bernard, 75019 Paris,
VILDE, C. KATLAMA
France .
Autopsy reports in 128 cases of AIDS were examined. Fifty-
seven cases included a pathological study of the pituitary
gland. In 44 of them (77%) no lesion was found. In 13 cases
(23%) major lesions were present : 9 infections and 4 vascular
anomalies. Among the 9 infections, 5 were due to cytomegalovirus
(CMV), 2 to cryptococcus sp., 1 to toxoplasma gondii, 1 to
M. tuberculosis. Vascular anomalies were coagulation and
ischemic necrosis (2) or micro-thrombosis of the neuro-
hypophysis vessels (2).
The 5 patients with CMV had disseminated infection (^ 3
organs), conversely in 20 patients with disseminated CMV infec-
tion 15 had a normal pituitary gland. Both patients with cryp-
tococcal infection of pituitary gland also had meningeal and
disseminated crytptococcosis . Patients with tuberculosis and
toxoplasmosis of pituitary gland also had cerebral and dissemi-
nated disease. All patients had multiple opportunistic infec-
tions involving organs other than pituitary gland (> 2). Signs
and symptoms of hypophyseal dysfunction were not noted due
to the end-stage clinical status.
These findings suggest that hypophyseal function has to
be investigated carefully at an earlier stage of AIDS.
WR163 Observations following Splenectomy for HIV Associated ITP
CHRIS TSOUKAS, H. STRAWCZYNSKl, R.T. CARD, G. GROWE, J. SHUSTER,
P. GOLD. National Hemophilia Study, McGlll University, Montreal, Canada.
Immune Thrombocytopenic Purpura (ITP) Is a major hematologic abnormality
among hemophiliacs infected with the human Immunodeficiency virus (HIV).
Splenectomy is known to have a long lasting beneficial effect on resolving ITP
but lias been associated with an increased incidence of bacterial sepsis.
To determine the effect of splenectomy on the immune system of hemophiliacs,
10 splenectomlzed hemophiliacs were studied, (6 before and sequentially after
surgery for up to 5 years.) All patients had some findings directly related to
HIV infection ie. fever, fatigue, night sweats, weight loss and generalized
lymphadenopathy which resolved following splenectomy. Concurrent to this
sustained clinical improvement we noted a dramatic increase in platelets,
lymphocytes and T cells.
(10VL)
Platelets
Total Lymphocytes
Leu 2 (Suppressors)
Leu 3 (Helpers)
Leu 4 (Total T cells)
Pre-Splenectomy
(mean ± SD)
38±11
2.83+2.77
.38±.23
.43±.12
.67±.2o
Post-Splenectoray
months postoperatively
6
383*96
5.39+2.24
2.72+2.19
.93+. 3
3.29±1.53
12
323*34
5.96+1.39
2.27+1.25
1.44±.35
3.86+1.27
18
419±149
4.98+1.09
2. 11+. 86
1.24±.54
3.55±.75
One patient died suddenly 3 years after splenectomy from pneumococcal
sepsis. We conclude that splenectomy In this group Is an effective treatment
of HIV related ITP. Although It is associated with a risk of overwhelming
sepsis an overall improvement In clinical status with respect to HIV is also
noted. The importance of the sustained increase in T cells and relationship to
possible changes in immune function remain- to be determined.
WP161 — Infection: U^ual Viral Necrotic Skin Lesions
MABCO CUSINI, fi. ZER80NI, S. CAVICCHINI, E. BERTI, E. ALESSI - 1st Clinic of Derma-
tology - AIDS Screening Centre - University of Hilan - Via Pace 9 - 20122 Milan ITALY
Herpetic virus skin lesions can often have peculiar clinical aspects in AIDS patients because
of immunedef iciency: chronic perianal ulcerative Herpes simplex, maculo-papular or vescico-bullo-
us Cytomegalo-virus lesions have been described.
In September 1986, 2 young males were admitted to our department, the first suffering from con-
dylomata, the second from Kaposi's Sarcoma and Disseminated Holluscum Contagiosum. They were both
HIV infected and they had already suffered from Pneumocystis carinii pneumonia in 1986. Me were
striken by some unusual cutaneous necrotic lesions on the trunk and limbs of both patients.
The lesions were few (about 10 per patient), A-lOmm in diameter, monomorphous, not-painful,
round-shaped. The centre of the lesions was filled with a dark crust. Only some of them showed a
slightly elevated erithemato-vescicular border. At histological examination the epidermis and the
dermis were necrotic and a multilocular vescicle with some degenerating balloon cells was seen at
the border of the central necrotic area.
A herpes virus family infection was suspected and ultrastructural , cultural and iramunohistoche-
mical examinations were performed. Culture was negative but at the electron microscopy numerous
viral particles, approximately 100 nanometers in diameter, with a icosahedral nucleocapside were
seen in the higher layer of epidermis both in the nucleus and in the cytoplasm of keratinocytes.
Both patients were treated by intravenous aciclovir with only a slight and transitory improvement
of the lesions. We think that this kind of lesion could be a new expression of a herpetic virus
cutaneous disease.
WP164 Aerosol and gallium scans in HIV infected patients with normal
chest X-rays and Pneumocystis carinii pneumonia.
C. PICARD, 3. ROSSO, M. MEICNAN, C. MAYAUD, 3. REVUZ , A. S0BE1. Services
de medecine nucleaire et de pneumologie, Hop. Henri Mondor (Creteil), Hop.
Tenon (Paris), France.
In 60 HIV infected patients suspected of Pneumocystis carinii pneumonia
(PCP), we performed graded gallium scans and measurements of alveolar permea-
bility with 99mTcDTPA aerosol clearance before the bronchoalveolar lavage
(BAD. Nineteen patients had proven PCP and were non smoking and non drug
addicted. They were selected for this study. Seven of them had normal chest
X-rays. Nine had normal Pa02 (96^4.8 SD mmHg). Eleven were followed by
repeated scanning after treatment. Gallium scan is positive in 13/19 patients
and 99mTcDTPA clearance in 19/19 (5.4U1 .7%.min-1 ,p 0.001 versus control
1 . HO. 34%.min-1 ,n = 10) suggesting an increase of the permeability. Gallium
scan is positive in 3/7 patients with normal chest X-rays, two having hypoxe-
mia. By contrast 99mTcDTPA scan was always positive in these 7 patients
even when Pa02 is normal. Their mean clearance was 6.22+1 .97%. min-1 , the
lower value being 3. 2%. min-1 i.e. three times the normal. Under treatment,
7/11 patients normalized both tests. Four normalized gallium but not clearan-
ces : one died from extrapulmonary disease ; in the others, BAL demonstrated
1 )cryptococcus, 2) Pneumocystis, 3) high lymphocytosis without opportunistic
infection. Gallium scan can detect PCP when chest X-rays is normal but
failed in this study in 4/7 cases which were all detected by DTPA clearances
measurement. This test cheaper than gallium scan is highly sensitive (100%)
of PCP and normalized with recovery. Since the results are obtained in
less than an hour contrasting to 48 hours for gallium scans, this test
could be used to decide BAL in patients with suspected PCP, normal chest
X-rays or blood gases.
WR162
Seropos i
BJARNE 0
Correlation
sponse to
t ive Homo s e
.LINDHARDT*
tute ,
Dur ing
a health
well as
Further,
more fre
those wi
between
respecti
test for
and with
S erum
ves t iga t
p er sons
control s
with Th-
<500/uL
The pr
group 2)
ween gro
it seems
ted rath
function
Rigs
the
y ca
the
it
quen
thou
HIV
ve o
HIV
out
and
ed s
wi th
, 2)
cell;
and
eva 1
5%,
up 1
as
er
hosp i ta
c 1 in ic
r r ie r s
1 ymphoc
has rec
t among
t sympt
an t i gen
f the c
an t ige
immuno 1
lymphoc
ub j ec t s
Th-cel
40 wit
> <500/uL
PWM-res
ences o
group
and 4
if the
ith the
apab i 1 i
between Numb
Pokeweed M
xua 1 Ma le s
, B.HOFMAN
let, Copen
al deterio
tate to Al
yte respon
en 1 1 y been
HIV infec
oms . In o r
em ia and a
linical co
nemia i n
ogical abn
y t e s were
were s e pa
Is >500/uL
h Th-cells
and PWM-re
ponse <20%
f HIV anti
3) 13%, an
were s ta t i
presence o
viral ind
ties of th
er of T-helper (Th) Cells, Lymphocyte
itogen (PWM) and HIV Antigenemi^
WR165
N**
hage
rati
DS,
se t
obs
ted
der
bnor
nd it
60 s
orma
d ra
rate
and
>50
s pon
K.ULRIC
n , Denma
on of HI
the numb
0 m i t oge
erved th
ind i v idu
to test
mal immu
ion, we
eroposit
1 it ies .
n at the
d in 4 g
PWM-res
0/uL and
se >20%,
al s
the
n o I
*The Fibiger Insti-
nfected persons from
of T-helper cells as
frequently declines.
HIV antigenemia is
with symptoms than
possible connection
ogical parameters, ir-
d a sandwich ELISA to
homosexual males with
Progn
cl ini
J.R. BOGNER, F
Medizinische P
same occasion. The
roups, comprising 1
ponse > 20% of norm
PWM-response <20%,
and 4) 40 with Th-
genemia found were in group 1)
d group 4) 23%. The differences
stically significant (p<0.05).
f circulating HIV antigen is as
uced decay of Th-cells than wit
ese .
) 40
al
3) 40
cells
5%,
bet-
Thus,
soc ia -
h the
The ra
factors
in feet io
Beta-2-M
leukocy t
test (Mu
clinical
mean obs
regress i
di f f eren
(p=0.01)
increase
respecti
contrast
pat ients
period h
(p=0.005
unchange
So the
pred i c 1 1
persons .
te of
for th
n rema
icrog 1
es (UB
ltites
stage
erva t i
on of
ce bet
. At t
in a 1
vel y a
to th
who s
ad sig
) in t
d.
plate
ve pot
os t ic
cal co
.-D. G
olikli
deteri
e indi
in to
obul in
C) , ly
t Meri
in th
on of
their
ween
he end
1 stag
decre
e o t he
howed
ni f ica
he fir
value
urse o
0EBEL,
nik, U
ora t io
vidual
be det
(B2),
mphocy
eux)(D
e Ualt
12.4 m
WR-sta
n f ec t e
of th
es con
ase of
r not
deteri
ntly h
st exa
of 1 abo
f HIV-i
U. KR0
n i ver si
n in th
progno
ermined
immuno
tes ( L y
CH) wer
er Reed
onths 3
ge. Onl
d (UR 1
e folio
cern i ng
DCH (p
s igni f i
ora t ion
igher N
mina t io
r g I
n f e
N \U
ty
S 1 s
1
g I o
) a
p m
cl
y N
)
IN U
Np
0
can
i n
P I
n t
ory param
c t ion
ITTER, S.
of Munich
linical c
of pat ie
n 100 Pat
bul in ( Ig
nd the sc
easured a
assi ficat
showed de
p showed
nd un i n f e
p per lod
(p=0.005
001) was
t 1 y chang
the comi
a 1 ues ( p =
han those
eters in the
KELtE
Uest
ourse
nbs wi
ients
), pla
ore of
nd rel
ion (U
ter ior
a sign
cted (
a sign
and
observ
e d v a r
ng obs
0.05)
ho r
R;
Germany
and the
th HIV -
Neopterin ( Np ) ,
telets (Ptl),
the skin-
ated to the
R). After a
at ion, U%
i f icant
WR 0) persons
l f icant
Ig (p=0.025),
ed , in
iables. Those
erva t ion
and 1 ower P t 1
ema ined
let counts and Neopterin values appear to have a
ency for the individual prognosis of HIV-infected
137
WEDNESDAY, JUNE 3
WP166 Syndrome Approaches to Early and Late Outcomes in Pediatic AIDS
GWENDOLYN IK SCOTT, M.T. MASTRUCCI, S.C. HUTTO, W.P. PARKS,
Department of Pediatrics, University of Miami School of Medicine, Miami.FL
A number of distinct clinical syndromes have been identified in
longitudinal natural history studies of children with HIV infection. Of 142
cases of HIV infection in infants and children identified in South Florida
between January 1981 and December 1986, 134 (94.3%) represent perinatal
infection. The remainder acquired the infection from a blood or blood
product transfusion. Of the 134 perinatal cases the overall mortality is
35Z. In infants who meet the current CDC criteria for the diagnosis of
AIDS, overall mortality is 74%. An analysis of survival indicates that the
majority of deaths occur in the first 2 years of life and some clinical
patterns are associated with an especially poor prognosis. In our series 14
infants developed Pneumocystis carinii pneumonitis in the first 12 months
(mean 6) with an 86% overall mortality. Although the overall mortality
rate decreases significantly after age 2 there are several late outcomes of
this infection that are associated with significant morbidity and
mortality. Progressive neurologic disease has occurred in 14 children in
our series with a mean age of onset of 18 months (range 1-90) and an
overall mortality of 57%, The development of lymphoid interstitial
pneumonitis in 35 children was associated with a better prognosis. Mean age
of onset was 16 mos. (range 5-35) and overall mortality was 26%. A similar
mortality rate, 33% occurred in 6 children with nephrotic syndrome (mean
age of onset 36 mos, range 20-61) however this syndrome has significant
morbidity associated with the development of renal failure. Overall, the
prognosis for children with syndromes characterized by a
lymphoproliferative response to HIV (LIP and nephrotic syndrome) is better
than for those with syndromes (early PCP and neurologic syndrome)
associated with deficient immune responses as suggested by normal
immunoglobulins, lymphopenia and a lack of lymph node enlargement.
WR169 Polyclonal Polymorphic B-Cell Lymphoproliferative Disorder (PBLD)
In Children with AIDS
VIJAY JOSH I, S. KAUFFMAN, J. OLESKE, S. FIKRIG, E. CONNOR, T. DENNY.
Children's Hospital of New Jersey, UMD New Jersey Medical School, Newark, NJ
An unusual lymphoproliferative disorder occurring in 4 children with AIDS is
described. All patients satisfied the criteria for pediatric AIDS reported
by us (Human Pathol 1985;16:241) and had positive HTLV-III serology. Lung,
spleen, kidneys, liver GI tract and lymph nodes showed gross nodular and/or
microscopic infiltrates composed of lymphocytes, plasma cells and occasional
immunoblasts. Cell marker studies showed preponderance of B cells. Immuno-
peroxidase stains for both Kappa and Lambda chains were positive in the infil-
trates. Vessel wall invasion was seen in the spleen and kidneys. Cellular
atypia, atypical mitosis and necrosis were absent. Two of the children had
high EBV titers. We have designated this lesion as polymorphic polyclonal B
cell lymphoproliferative disorder (PBLD). It may be a borderline lesion and
not a full-fledged malignant neoplastic process. In pediatric AIDS systemic
lymphoid hyperplasia (LH) including Pulmonary LH/Lymphoid Interstitial Pneu-
monitis complex reported by us (Human Pathol, 1986;17:64l) and PBLD comprise
the spectrum of lymphoid proliferation possibly associated with EBV. The
spectrum also includes full-fledged malignant lymphoma.
\A/P1fi7 Nocardiosis in Patients with Human Immunodeficiency Virus (HIV)
Infection
ELENA YAMAGUCHI, R . B . UTTAMCHANDANI , K.RODRIGUEZ, G.M.DICKINSON, M.A.FISCHL,
University of Miami School Of Medicine, Miami, FL.
Nocardia asteroides infection has been infrequently reported in patients
with HIV infection. During a 21-month period, N. asteroides infection was docu-
mented in 10 patients with antibodies to HIV (ELISA) . There were 9 men and 1
woman aged 21-38 years (mean=33.5). Eight were intravenous drug users. Only 1
had antecedent AIDS, but 7 of 7 tested had cutaneous anergy, and 8 of 8
studied had decreased T4 lymphocytes. One had concomitant Pneumocystis carinii
pneumonia. N. asteroides infections included pneumonia in 5, pneumonia and chest
wall abscess in 1, and localized abscess of brain (1), skin (1), retroperi-
toneum (1), and mediastinum (1). Mean duration of symptoms before diagnosis
was 42 days (range=7-84) . Seven patients were treated with sulfadiazine, 2
with trimethoprim/sulfamethoxazole, and 1 with minocycline and cycloserine.
Six of 8 evaluable patients improved, but after discharge, compliance was poor
and 8 patients died with clinically active disease within 2-12 months. Autop-
sies in 3 patients disclosed persistent N. asteroides in all; 2 had concomitant
disseminated cytomegalovirus and Mycobacterium avium-intracellulare infections.
One compliant patient continues to do well 5 months after diagnosis; the other
has shown clinical recurrence 3 months after presentation due to noncompliance
with treatment.
N. asteroides is an important opportunistic pathogen in patients with HIV in-
fection and can precede or occur sumultaneously with other opportunistic infec-
tions. Specific antimicrobial therapy is associated with improvement but pro-
longed treatment appears to be necessary.
WR170
S. FIKR
Washing
Case
were re
The cas
age . A
severe
i nfecti
10 case
pneumon
documen
include
mi 1 iary
sepsi s ,
of v a r i
Centr
atrophy
pha 1 opa
1 esions
hyperpl
Other e
focal m
prol ife
AIDS
contras
chi ldho
varies
disease
progres
The
VIR
IG**,
ton, D
summar
viewed
e mix
11 Fat
thymic
ons in
s ; and
i t i s w
ted i n
d Cryp
M. tu
recur
ous st
al ner
, hydr
thy , a
i ncl u
asia o
nti tie
yocard
rati on
i s the
t to a
od pat
with t
s of i
s i o n .
Patho
GINIA
logy of
M. ANDE
Pedi
RSON*
H. LEE
.C. , S
ies an
Twe
includ
ients
atrop
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rent s
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ocepha
nd pro
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f Peye
s incl
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**, A.M
UNY Hea
d patho
nty-sev
ed 2 te
had fai
hy and
: cand
egalovi
n in ,10
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us neof
os i s an
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ystem p
ly, per
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rs pate
uded de
and gen
. MAC
lth S
logic
en co
enage
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II ha
i di as
rum,
pati
d 3 h
orman
d M
losi s
lococ
athol
i vase
i ve v
n , vi
hes, a
squam
eral i
atric AIDS
, S.L. KAU
HER*,*Pedi
cience Cen
material
mplete aut
rs and 22
to thrive,
d lymphade
is, 12 cas
9 cases .
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WP168 Malaria in African Patients with AIDS
DAVID W. ANDERSON, K. BAIRD, A. MACHER, A. NELSON, M. De VINAIEA, D. CONNOR, et
al., Registry of AIDS Pathology, AFIP .Washington, DC
Chronic malaria is endemic among adult natives of central Africa and represents a major cause
of morbidity and mortality. Acquired inrajnity to malaria, believed to be predominantly humoral,
is prevalent among the population of this area. We studied the clinical course and autopsy
findings of two black African patients who presented with malarial infections and AIDS.
Age Sex Presenting Complaints _ Habitus Exam* Hgb WBC
1. 37 years M anorexia, weight loss, cough cachectic HSM 8.8 g/dL 3650 mm--*
2. 31 years F anorexia, weight loss, malaise cachectic HSM, DIA 8.0 g/dL 4000 nro~^
* HSM = hepatosplenomegaly, DLA = diffuse lymphadenopathy
Clinical Course: Blood smears at presentation revealed malarial trophozoites in both patients
(P. falciparum in patient 2). In patient 1, malarial parasites dissappeared after antimalarial
therapy but fever and anemia persisted. the patient developed bilateral miliary pulmonary
infiltrates and died in respiratory failure 6 weeks following presentation. Patient 2 (HIV
seropositive) was treated with chloroquine and quinine but developed progressive pulmonary
insufficiency and died 9 weeks following presentation.
Autopsy Findings : Patient 1: Disseminated Histoplasma capsulatum var duboisii and multifocal
visceral Kaposi's sarcoma. Patient 2: Disseminated nocardiosis, intestinal cryptosporidiosis ,
cytanegaloviral adrenalitis, and visceral Kaposi's sarcoma. There were no malarial parasites in
any organs of either patient.
Conclusion: Despite profound immunodeficiency and associated bacterial, fungal and viral
infections in these patients, their chronic malarial infections were not overwhelming before
antimalarial therapy, and malarial parasites were not seen at autopsy. The absence of fulminant
malaria suggests that malaria may not represent an opportunistic infection in patients with AIDS.
U/PI7-J Impermeability of Condoms to HIV and Inactivation of HIV by the
Spermacide Nonoxynol-9.
SUSANNE M^ SCESNEY, N.M. GANTZ, J.L. SULLIVAN, University of Massachusetts
Medical Center, Worcester, MA, USA.
The impermeability of condoms to HIV as well as the ability of the
spermacide, nonoxynol-9 to inactivate HIV was examined. Each condom tested
received a 4ml inoculum of HIV virus (2x10^ reverse transcriptase units). The
condom was then placed over the plunger of a 50 ml disposable syringe. To
model intercourse, the plunger of the syringe was pushed up and down
forcefully 50 times into the syringe. After 50 plunges, media containing H9
cells was drawn up into the syringe, making contact with the external surface
of the condom. The cell suspension was then cultured. No virus was detected
in the H9 cells by the cytoplasmic RNA dot blot assay or by assaying cell
supernatants for reverse transcriptase activity after 12-25 days in culture.
Nonoxynol-9 was found to be cytotoxic at a dilution greater than .0005%
necessitating that the nonoxynol-9 be removed from the virus by
ultracentrifugation before inoculating of H9 cells. Nonoxynol-9 was found to
inactivate HIV at a final concentration between .05% and .005%. Nonoxynol-9
does not interfere with reverse transcriptase activity nor does it degrade the
viral RNA as indicated by dot blot. The effectiveness of nonoxynol-9 present
in a condom in inactivating HIV in the case of the damaged condom was also
tested. In 8 of 12 (66%) condoms, no virus was detectable 15 days after
inoculating H9 cells with HIV passed through a torn nonoxynol-9 containing
condom. These data suggest that condoms are impermeable to HIV and that the
spermacide nonoxynol-9 can directly inactivate HIV.
138
WEDNESDAY, JUNE 3
WP172 Changes Over Time in Anogenital Practices in a Cohort of Homosexual/
bisexual Men
JANE MCCUSKER*. A.M. STODDARD*, J.G. ZAPKA*, K.H. MAYER**, J.S. AVRUNIN*, C.S.
MORRISON*, et al., *University of Massachusetts/Amherst, Amherst, MA U.S.A.,
**Memorial Hospital and Brown University, Providence, RI, U.S.A.
Detailed information on sexual practices and HIV antibody status were
obtained at 6-month intervals in a cohort of initially asymptomatic homosexual/
bisexual men at a Boston community health center. Over 200 men have been
followed for at least 12 months. At the 12-month visit, 26% of subjects who
reported insertive anogenital contact (IAG) always used a condom, while 30%
sometimes did. The percentages for their partners' condom use in receptive
anogenital contact (RAG) were: always 32%, and sometimes 25%. Condom use
was infrequent in other practices. Condoms were used more frequently by
subjects with multiple partners. Between the initial and 12 month visits, the
percentage of subjects reporting IAG decreased from 70% to 60%, and RAG
decreased from 65% to 53%; the percentage reporting IAG who always used a
condom increased from 4% to 28%, while the percentage reporting RAG who never
had exposure to the partner's ejaculate increased from 18% to 45%. In spite
of this encouraging trend, 31% of HIV seropositive men reported unprotected
IAG with multiple partners and 16% of HIV seronegative men reported unprotected
RAG with multiple partners at 12 months. Results of sociodemographic,
attitudinal, and other determinants of unsafe anogenital contact will be
presented.
WR175 Underemphasis on Publicly-Funded Programs For Prevention of
Transmission of HIV Among Gay Men and IV Drug Users.
MEIL M. FLYNN', S. HARPER*, S. JAIN», P. HOLLAND", L. FERNANDO", V.
BAILEY7, et al.++ "Univ. of Calif. Davis, ••Sacramento Blood Center,
+Aquarian Effort, and ++AIDS Foundation, Sacramento, CA
Government responses to the AIDS crisis have been called "too little, too
late." However, with respect to preventing transmission (T) of HIV by blood
transfusion, response was vigorous and prompt. We compared resources for
prevention (P) of T by transfusion to those for P of T related to high-risk
gay and bi3exual/IV drug (G-B/IVD) activity in 1986 in an urban area of
900,000 population.
Cost of preventing transfusion-related T was $11,305/T prevented (9/80,000
units were anti-HIV +, 1.6 recipients/unit, $206,000 total cost of screen-
ing). In contrast only $87,920 was spent in programs for P of T among G-
B/IVD, a population in which we estimate that: 1) at least 600 T occurred in
1986 and 2) a future public liability for health care costs over the next 5
years of $9,375/T, or $5.8 million total was incurred. We conclude that: 1)
P of 9.3 cases of T (1.5? reduction) among G-B/IVD would justify the amount
spent in P programs for this if programs for G-B/IVD were funded at the same
rate as programs for transfusion-related T; 2) the public liability for
future medical care for G-B/IVD-related T in 1986 was much larger (66X) than
the amount spent for prevention that year.
The disparity between appropriate spending for prevention of transfusion
related T and underfunding of programs to prevent sexual and IVD-related T
must be addressed. The programs aimed at G-B/IVDU should prevent many cases
of T and be very cost-effective in view of the high cost of treating AIDS in
these groups, most of it public money.
WR173 SEXUAL BEHAVIOUR AND CONDOM USAGE BY HOMOSEXUAL MEN IN LONDON
C. SONNEX, L.C. HOWARD AND P.L. SAMARASINGHE
Department of Genito Urinary Medicine, Westminster Hospital, London, England.
This study was performed at the Department of Genito Urinary Medicine,
Westminster Hospital, London between January and March 1986. Homosexual men
practising ano-genital intercourse were asked to complete a questionnaire on
sexual behaviour and condom usage. Approximately one third of clinic attenders
practised only "safe-sex" (i.e. masturbation and body rubbing) and were excluded
from the study.
Data will be presented on 145 men and examines :-
1. The association between ano-receptive and ano-insertive sexual behaviour
preference and the presence of a regular sexual partner.
2. The number of sexual partners in the previous month and the presence or
absence of a regular sexual partner
3. Sexual behaviour preference and condom usage
4. HIV antibody status and condom usage
5. Duration of condom usage
6. Frequency of condom splitting or bursting
7. Types of lubrication used
The 28% of men who were frequent condom users were asked to try a type of sheath
promoted as being stronger than those presently available. A spermicidal gel
containing nonoxynol-9 was also given as a lubricant. Data examining their
acceptability and possible advantages will be presented.
This study is being repeated during 1987 in order to assess changes in sexual
behaviour, with particular reference to condom usage.
WP176 Non-Anonymous HIV Antibody Testing: Results in Colorado
FREDERICK C. WOLF, C. RAEVSKY, N. SPENCER, Colorado Department
of Health, Denver, CO, U.S.A.
In July, 1985, the Colorado Department of Health (CDH) implemented a
non-anonymous testing program for HIV antibody at 10 Testing Sites (HTS).
Policies included collecting patient identifiers and risk behavior
information on specially designed laboratory forms. The information is
not revealed to laboratory staff but available to epidemiologists for
analysis and followup. Confidentiality of records is protected.
Through December 1986, 10,476 tests (314.1/100,000 pop) were processed
with 13.7* positive at Denver HTS (64.9% of tests), 9.6* at HTS outside
Denver (19.1 * of tests) and 16.6* at non HTS providers (16.0* of tests).
Most volunteered for testing due to perceived risk of infection. Only
1.7* claimed symptoms of HIV disease although 42.5* of this group were
positive. Most (78.8*) tested were men with 16.1* positive compared to
2.2* positive in women. Differences in percent positive in men by sex-
preference were: heterosexual 4.1*, bisexual 16.1* and homosexual 27.3*.
Cited risk behaviors (RB) included: 18.4* denied any RB (3.4*
positive), 48.4* claimed 1 RB (14.0* positive), and 33.2* claimed
multiple RB (17.4* positive). Of those listing 2 1 RB, fewer (2.4*) of
women were positive than men (18.2*). Of those with only 1 RB, sexual
contact with homo/bisexual men was mot frequently cited by both men
(78.8*), 19.6* positive) and women (43.6*, 0.3* positive). Negatives
were less likely to return for results and prevention counseling than
positives (77.5* vs. 88.3*). Patient identifiers allows follow-up of
positives who did not return (129), as well as evaluation of the number
of persons tested (9,267), and those who seroconvert (2.1*), linkage with
AIDS reports, and efficient contact referral.
WP 174 The Need for Innovation to Halt AIDS among IV Drug Abusers (IVDA)
and Their Sexual Partners
JOHN H. RUTLEDGE, M.D., R. OONVISER, Ph.D., New Jersey State Dept. of
Health, Trenton, NJ
New Jersey's AIDS population, now 5th largest in the U.S., is unique in
that 62% of its cases are drug-related. Limiting the spread of AIDS in the
marginal IVDA population has required abandonment of traditional public
health approaches and creativity in developing a wide range of unproven
prevention modalities. In other jurisdictions, authorities have
distributed sterile needles, bleach for cleaning needles, and condoms to
IVDA.
In New Jersey innovations have included hiring ex-addict street workers,
distributing coupons for drug detoxification, and sending out mobile vans.
IVDA are far less likely than gay persons to read about health risks; the
street workers are able to warn them verbally of these risks. The coupons
have been effective in drawing addicts into detoxification programs by
gaining widespread attention and waiving initial fees. The mobile vans
constitute a proactive step by going out to places where IVDA congregate to
provide them with medical examinations, education, and AIDS counseling,
rather than waiting for them to seek out attention.
Dealing with a difficult population such as IVDA requires continuing
innovation. New Jersey is now focusing on education for the sex partners
of IVDA, seeking them out in family planning and prenatal clinics.
WR177
Prevention of HIV Infection through Sexual Behavior Change.
JOHN L. MARTIN, Columbia U. School of Public Health, NYC, NY.
Given the critical role of education and behavior change In controlling AIDS
we studied the efficacy of reductions in specific sexual behaviors as means of
preventing HIV infection. Data used in the analysis come from a prospective
cohort study of 360 NYC gay men in which HIV serologic data and detailed sexual
histories were gathered. Linear logistic regression modelling was used to pre-
dict HIV antibody status as of 1986 from seven sexual activities (kissing and
receptive/insertive anal intercourse, oral-genital sex, and oral-anal sex) mea-
sured for each of two prior annual time periods: Pre-AIDS, 1980-1981, and post-
AIDS, 1984-1985.
Frequency of receptive anal intercourse during both pre-AIDS and post-AIDS
periods were the only significant predictors of 1986 antibody status. The re-
lationships held for all levels of number of partners. The efficacy of beha-
vior change in preventing HIV infection was quantified by dividing respondents
who engaged in receptive anal intercourse during the pre-AIDS period into:
(i) those who stopped anal intercourse in the post-AIDS period, 1984-1985, and
(ii) those who did not not stop in the post-AIDS period. Of those who stopped
receptive intercourse, 22% were HIV positive as of 1986 while 48% of those who
did not stop were positive (odds ratio=3.26, 95% CI 1.70,6.22). This effect is
stronger for the most sexually active half of the sample. Among those with 15
or more partners in the pre-AIDS year, 26% who stopped receptive intercourse
were HIV positive as of 1986, while 64% of those who did not stop were positive
(odds ratio=5.02, 95% CI 2.13,11.74). These results indicate that behavior
change, specifically eliminating receptive anal intercourse, can significantly
reduce the likelihood of initial HIV infection among gay men.
139
WEDNESDAY, JUNE 3
WR178 "RAP'N Down SIDs, Drugs, and AIDS", A Community-based Approach to
AIDS Education Among Minority Adolescents
PAUL GIBSON*, F. STROUD*, L. STOLLER*, S. GROSS**, M. FULILOVE**, K. SHINE**.
•San Francisco Department of Public Health, San Francisco, CA, **Bayview Hunt-
ers Point Foundation, San Francisco, CA.
To stimulate AIDS awareness and education for minority adolescents, we pilot-
ed a cooperative community project utilizing RAP music to attract minority
teens to participate in a "RAP'N Down STDs, Drugs, and AIDS" contest. The
goals of the project were to create a fun, non-traditional approach for minor-
ity adolescents to become involved in their own learning about risk behaviors
for AIDS and other STDs, and to stimulate community involvement and support
with a highly-visible awareness campaign.
The Department of Public Health contracted with a major community organiza-
tion to coordinate the project with 5 youth-serving agencies (YSA) . Each YSA
conducted promotion and educational outreach for a neighborhood preliminary
"RAP Off", planned to coincide with the 1987 Valentine's Day and National Con-
dom week. The finalists from the 5 "RAP Offs" competed for the grand prize of
$500 on a popular television program. To win, contestants had to compose and
perform a 60-second RAP about AIDS prevention. The RAPs of the finalists were
recorded and aired as public service announcements on popular radio stations.
This project may serve as a model for innovative community-based AIDS awareness
and education campaigns for special populations in other metropolitan areas.
\A/pifl|1 I" Vitro Tests Demonstrate Condoms Containing Nonoxynol-9 Provide Effective Physical
and Chemical Barriers against Human Immunodeficiency Virus
CORNELIS A.M. RIETHEI JER* ■ J.W. KREBS**, P.M. FEORINO** and F.N. JUDSON*, ^Denver Disease Control
Service and The University of Colorado, Denver, CO, ** AIDS Program, CDC, Atlanta, GA.
In an in-vitro model 20 condoms (Ansell Inc., Dothan AL), 10 with 0.9 ml 6.6% (v/v) nonoxynol-9
(NX) and 10 without NX, were tested as barriers against human immunodeficiency virus (HIV). Each
condom was mounted on a 20 cm hollow dildo and placed in a 15 x 5 cm glass cylinder containing 10
ml of HIV-free RPMI 16M) medium. 4 ml of cell-free and cell-bound HIV medium was placed inside the
condom tip. To simulate intercourse, the dildo was pumped up and down 100 times. Samples were
taken from the media inside and outside the condom for HIV cultures. Next the condom was ruptured.
Again intercourse was simulated and samples cultured. All experiments were repeated in the reverse
fashion, i.e. with HIV medium in the cylinder and HIV-free medium inside the condom tip.
CONDOMS WITHOUT NX
CONDOMS WITH NX
HIV medium
inside
inside
inside
outside
Sample from
outside
outside
inside
outside
pre -rupture
post-rupture
pre -rupture
post- rupture
Culture positive
0/10
7/10
0/10
0/10
Cultures were tested for HIV RT activity for 6 weeks. No condom without NX leaked HIV before
rupture, but after rupture HIV could be detected in outside medium. In contrast none of the
samples taken either before or after rupture of the NX containing condoms was positive. We con-
clude that undamaged condoms provide an effective physical barrier against HIV and that 6.6 %
nonoxynol-9 diluted < 22 times after condom rupture may provide an effective chemical barrier.
WR179
A Multi-Media Campaign to Encourage Condom Utilization
CATHERINE A. HANKINS*, M. STEBEN**, B. Vigneau ***, D. Bonney ****, A.
SOHMANY**"** , H BLACK******, et al . , * Montreal Regional Sexually
Transmitted Disease Control Program, Montreal, Quebec, Canada, Community
Health Department , Verdun Hospital , Montreal , Quebec , Canada, ' Community
Health Department, Verdun Hospital, Montreal, Quebec, Canada, Community
Health Department , Montreal General Hospital , Montreal , Quebec , Canada,
Bazin, Dumas, Dupre* , Sormany, Communicateurs-Conseils , Montreal, Quebec,
Canada, ****** Publicity Kitching Advertising, Montreal, Quebec, Canada
A multi-media campaign targetting young people aged 15 to 24 years was
launched in April 1987 in the province of Quebec, CANADA. The primary message
of the campaign focussed on encouraging condom utilization to prevent
sexually transmitted diseases. On a limited budget, television, radio and
print advertising was developed to coordinate with a public relations
communications plan aimed at province wide penetration. Varied support
activities, including the distribution of pamphlets, flyers and posters, were
conducted by local health units to coincide with the campaign. Initially,
difficulties were encountered in convincing networks to carry television
advertising mentionning condoms even when presented in generic form by a
health organisation. Considerable public debate was engendered during both
the design and the implementation phases.
Pre- and post-campaign public opinion polls were conducted as one measure
of the effectiveness of the intensive phase of the campaign.
WP182 Community-Based Demonstration Project for AIDS Prevention and Risk Reduction:
Organization of a Comprehensive Prevention Program in Denver.
DAVID L. COHN*, P.J. GOURLEY*, K.R. O'REILLY**, F.N. JUDS0N*, Denver Disease Control Service
(DCS)*, Denver, CO and Centers for Disease Control (CDC)**, Atlanta, GA, U.S.A.
In 1986, DCS organized a comprehensive regional AIDS prevention program as part of a CDC-spon-
sored Conmmity-Based Demonstration Project (DP) for ADDS prevention and risk reduction. The
main purpose of the DP is to determine the most effective means for prevention of HIV trans-
mission in populations at risk, predominantly through educational programs. Educational modali-
ties include literature, posters, audio-visual aides, lectures and seminars, public service
announcements, introduction of ADDS education Into public school curricula, and skills provision
training In populations at risk. An ADDS/HIV Information Service provides educational materials
and newsletters, serves as a clearinghouse for new information, arranges seminars, has a phone
response center, and networks with other educational groups.
HTV antibody testing and counseling and serial cross-sectional seroprevalence surveys are per-
formed at an HTV testing and counseling site, STD clinic, TV drug use treatment centers, select-
ed obstetric clinics, and blood banks. Populations studied Include gay men, TV drug users, female
prostitutes, high-risk obstetric patients, heterosexuals in a STD clinic, and military recruits.
In addition, a large cohort of gay men is recruited for a prospective longitudinal study to eval-
uate different and Innovative educational modalities and to elicit extensive information about
knowledge, attitudes, and beliefs concerning ADDS and risk behaviors.
Measurements include serial seroprevalence studies; ADDS surveillance; rates of gonorrhea,
syphilis and hepatitis; and questionnaire surveys in different populations. Within the cohort,
behavioral differences between seropositive and seronegative, and seroconvertor and seronegative
subjects will be analyzed. Organization of a comprehensive ADDS prevention program requires
significant resources, long term planning, well-trained personnel, adequate laboratory and office
facilities, cooperation with diverse comiLinities and medical care providers, development of mul-
tiple education modalities, flexibility in response to changing needs, and ongoing evaluation.
WR180
DRUG USERS' ORGANIZATIONS AND ADDS PREVENTION: DIFFERENCES IN
STRUCTURE AND STRATEGY
SAMUEL R. FRIEDMAN*. W. DE JONG**, D.C. DES JARLAIS***, CD.
KAPLAN**, D. S. GOLDSMITH*, *Narcotic and Drug Research, Inc., **Erasmus
University Rotterdam, ***NY State Division of Substance Abuse Services
Organizations of homosexual men have provided services to persons with AIDS and ARC, educated gays
about risk reduction, and given gay men a voice in AIDS policy and research debates. Intravenous (IV) drug
users had less formal organization prior to the epidemic, and have been much slower to mobilize in response
to AIDS. We have conducted field research on the Dutch junJdebonden (drug users' unions) and ADAPT in
New York City. These drug users' organizations have distributed AIDS information to IV drug users both in
person and through the mass media. JunJdebonden existed before AIDS was recognized; they have reacted to
the epidemic in different ways. They have had internal conflicts over their goals and values, and external
disagreements with public health and drug treatment agencies. They had previously initiated a system for
exchanging used syringes for sterile ones, and have since taken part in the official needle exchange program,
although at times organizational instability has detracted from their ability to dispense syringes. ADAPT,
an organization of ex-IV-drug users, current IV drug users, and health professionals, was organized
specifically to deal with AIDS. It has provided training to drug treatment agency staffs, and services to
individuals with ADDS or severe ARC. ADAPT and some junkiebonden have taught individual drug users
ways to reduce the risk of exposure to HIV or of transmitting it toothers. On the basis of our observations,
it appears that organizations in which ex-users and health professionals are dominant can provide consistent
interventions which can motivate risk reduction among those drug users who are most open to change. It
also appears that organizations of hard drug users are unstable, but when they are functioning well are more
able to reach those street drug users who particularly distrust established institutions and to develop new
values among drug users that will legitimate "safe injection" procedures among persons who continue to
inject drugs.
WR183 The 800 Men SCudv: A Controlled Study Of An AIDS Prevention Program
In New York City
MICHAEL QUADLAND, U.D. SHATTLS, R. SCHUMAN, R. JACOBS
Since 1982, traditional AIDS education programs in New York City have imparted
information about the disease and its transmission. To date there has been no
systematic study of the effects of such programs on sexual attitudes or behavior.
In October of 1985, 619 gay and bisexual men participated in a controlled study
of pre- and post- test experimental design to evaluate the effects on sexual
attitudes and behavior of four different education programs. It was hypothe-
sized that a program which attempted to eroticize safer sex would be more
effective than the traditional program, that the use of explicit erotic audio-
visuals would be more effective than not, and that all three interventions in
which participants met in groups would be more effective than an information-
only, at-home control group.
It was found that: (I) there was a substantial amount of heterosexual activity
in the sample; (2) most participants had already made substantial changes In
sexual behavior, but approximately 40% were still at risk; (3) change in atti-
tudes and behavior was associated with participation in a group educational
experience; (4) changes in sexual behavior were observed in both the traditional
and eroticizing programs; and, (5) the use of explicit erotic audiovlsuals is
more effective than not In promoting safer sexual alternatives. These findings
are important in providing a rationale for a more positive approach to AIDS
prevention which includes attempts to eroticize safer sexual behavior.
140
WEDNESDAY, JUNE 3
WP184 Consequences of AIDS Antibody Testing Among Gay Men: The AIDS
Behavioral Research Project. THOMAS J. COATES, S.F. MORIN, L.
MCKUSICK, University of California, San Francisco, School of Medicine.
We followed 560 gay and bisexual men from November 1984 (before HIV antibody
testing was available) until November 1985 and November 1986 (after HIV anti-
body testing was available) to determine the consequences of such testing
on high risk sexual and drug use behavior, psychological distress, and
relationship status. In November 1984 there were no differences between groups
ultimately testing positive and negative in percent of men reporting high
risk sexual behavior. After antibody results were found out, significantly
greater percentages of those who found out that they were antibody positive
ceased practicing unprotected active and passive anal intercourse. Also, the
antibody positive group reported significantly greater stress and depression
and their relationships were more likely to break up. The results of this
study indicate that antibody testing may have positive public health outcomes.
However, even though positive antibody status was associated with reductions
in high risk behavior in those tested, it was also associated with potentially
adverse mental health consequences. We found significant increases in stress
and depression in the antibody positive group. Men in the antibody positive
group were also more likely to have their primary relationships break up and
to be celibate. More intensive study of antibody positive persons is needed
to determine the full significance of these findings particularly for long-
term mental health services.
WP187 *" MDS Education Outreach Program for Minority Corrmunities
JO ANN VALENTINE, Y. RIVERA, A. FREEMAN, C. HALEY, Dallas County
Health Department, Dallas, TX
AIDS education in minority communities must emphasize messages to reduce
fear and to increase the understanding of risk behaviors and focus on behav-
iors to reach persons who would not identify themselves to be in a risk group
but who do engage in risky behaviors. In addition, AIDS education provided
through traditional media channels has not adequately reached minorities with-
out a program that actively identifies minority communication lines and
persons of influence to deliver the messages.
The Dallas County Health Department has developed an active program of AIDS
education outreach to the black and hispanic corrmunities. The goals of the
program are to identify community leaders on health issues, enlist their sup-
port in planning an approach and provide the information in a setting that
allows attendance without being perceived as "needing" the information.
Social service organizations, community councils, minority professional
groups, ministers, health care providers and radio personalities have been
very effective in planning educational messages and in lending their support
and increasing the credibility of the messages.
Minority populations have been reached in Dallas by addressing AIDS as a risk
to sexual partners of IV drug users, persons with multiple partners and ado-
lescents. Educational outreach has been most successful in churches, schools
(after approval by parents), public housing tenants' association meetings and
English as a second language classes.
WR185 Targeted Outreach Techniques for Minority AIDS Education.
RACINE WINBORNE, B. M. Branson, J. Stein, D. Vaughan. Health
Education Resource Organization, Baltimore, MD, USA.
Disproportionate numbers of reported AIDS cases among Black Maryland res-
idents prompted the development of targeted, culturally sensitive education
efforts to improve AIDS awareness and prevention measures.
Questionnaires indicated that certain radio stations were more likely to reach
the desired population, and that print media was much less effective. A bus
poster was designed to advertise an information hotline phone number; the
large number of callers who identified this poster as their source of inform-
ation proved this to be the single most effective technique to deliver an
educational message to a large segment of the Black population in Baltimore
city. Community leaders were recruited for a Minority Task Force, and Black
church organizations were solicited to provide educational forums; church
leaders appeared in public service announcements.
Denial of the excess incidence proved to be the most significant barrier to
initiating community-based educational programs. A series of educational
presentations for tenants associations in the Baltimore City Housing Authority
served to stimulate interest, and increase receptiveness.
WR188 "fl*DS as an Industrial Issue: The Australian Experience"
MARK ANNS and ANDREW MORLET, Albion Street (AIDS) Centre, Sydney
Hospital, N.S.W., Australia.
The industrial issues surrounding the AIDS epidemic have yet to be fully
recognised in Australia. During the past two years several of Australia's
major employers have had to provide services to employees infected by HIV,
and to deal with widespread ignorance and fear. The Sydney AIDS Clinic has
been used as an outside consultant by several of Australia's major employers,
to advise on health and policy issues relating to HIV infection. This paper,
using case examples, examines the types of problems employers have
experienced: denial of a problem; absence of policies on infectious diseases;
hysterical staff reactions to fellow workers with HIV infection and
industrial, health and welfare issues relating to the identification of
infected employees. It is argued, using case examples, that industrial
problems can be minimised by a) recognising AIDS as having industrial
remif ications - both for occupational health and safety and staff welfare;
bl the development of policies related to infectious disease; c) the
provision of counsel ling/ information and in-service training; and d) the
use of outside consultants.
WP186 AIDS Antibody Testing: Who Takes the Test? STEPHEN MORIN, T.J.
COATES, W. WOODS, L. MCKUSICK, University of California,
San Francisco, School of Medicine.
This study presents data on reasons given by gay men for wanting to be tested
for antibodies to HIV. Data were gathered in 695 gay and bisexual men in
San Francisco who responded in May 1985 and 676 men who responded in November
1985, and 1986, as part of a larger ongoing longitudinal study. By November
1985 less than 31% had been tested even though anonymous and confidential test-
ing had been widely available since July, 1985. The primary motivations for
being tested were to reduce anxiety and uncertainty and to know if one was
capable of infecting others. The primary motivations for not being tested
were fears of increasing anxiety, perceptions that the test lacked meaning, and
concerns about confidentiality and the potential for discrimination. Gay men
in the sample were relatively well informed about AIDS and the meaning of the
HIV antibody test. The respondents generally recognized that a positive test
result did not necessarily mean that an Individual would go on to develop a
deadly form of AIDS. Most recognized that a negative antibody result could
mean that the body had not yet produced antibodies to the virus and that it
was possible to have the virus without antibodies. Our data suggested that
the primary reasons for wanting or not wanting to be tested were psychological
rather than medical Those who did not want to be tested believed that knowing
that one had been infected would greatly increase one's anxiety and fear.
Going through testing provokes anxiety as does living a life knowing that one
has been Infected with the AIDS virus. Community education efforts have
resolved concerns about the meaning of the test and poor test validity.
Those who did not want to be tested wanted to clear up ambiguity about past
infection and to have good information so that they would avoid infecting
Others.
WR189 Sexual Relations in Bathhouses in Los Angeles County:
Implications for AIDS Prevention Education
GARY A. RICHWALD*. A.R. KRISTAL**, G.R. KYLE*, D.E. MORISKY*,
M.M. GERBER*, *UCLA School of Public Health, Los Angeles, CA,
**Fred Hutchinson Cancer Research Center, Seattle, WA.
807 men at 7 bathhouses in Los Angeles County completed exit
interviews in July and August of 1986. 61 percent participated
in activities associated with low risk of HIV transmission, while
10% participated in passive and/or active anal intercourse
without a condom, behavior associated with the highest risk of
HIV transmission. In comparison, more of the high risk group
were under 30 (46% vs. 34%) , belonged to minority groups (41% vs.
27%), earned less than $20,000 annually (44% vs. 26%), had not
attended college (24% vs. 12%), had 5 or more male sexual
partners in the past month (46% vs. 25%) , and participated in
fellatio without a condom (60% vs. 20%) (all p<.05). Similar
proportions reported familiarity with information in the
bathhouse on AIDS (96% vs. 98%) and felt it played a role in
their understanding of AIDS prevention (84% vs. 86%) .
These data indicate that the majority of highly sexually active
men who attend bathhouses in Los Angeles County now practice low
risk sexual behaviors. However, improved programs directed
toward those young, minority, low income, less educated men who
are at highest risk of HIV transmission must be developed as soon
> possible.
141
WEDNESDAY, JUNE 3
WP190 Blood Donation Histories of Reported AIDS Patients.
E. THOMAS STARCHER, II, MC NOA, JW WARD, TJ DONDERO, Jr, JW CURRAN .
Centers for Disease Control, Atlanta, Georgia, USA
Patients meeting the national case definition for AIDS are reported to CDC
on standardized case-report forms that include a question on blood/plasma
donations since 1978. Between March 1985, when test kits to detect antibody to
HIV were licensed for screening blood, and October 31, 1986, 17,387 AIDS cases
were reported to CDC. Among the 9,143 (53%) patients who answered the blood
donation question, 394 (4%) gave histories of blood donation since 1978, but
only 25 had donated since March 1985. Of the 25 recent donors, 23 were men; of
these, 13 were bisexual, 9 were homosexual, and 1 was a heterosexual IV drug
abuser. The 2 women were heterosexual partners of high-risk individuals (a
bisexual male and an IV-drug abuser). Eighteen (72%) of the recent donors were
white; 5 (20%), black; and 2 (8%), Hispanic. When compared with all reported
AIDS patients, those answering "yes" to the blood donation question were more
likely to be white and bisexual. Since intensive screening of blood donors
began in the spring of 1985, some members of high-risk groups continue to
donate blood or blood products. Although still important for preventing
transfusion-associated AIDS, blood donations by high-risk individuals suggests
an even larger problem in the broader effort to prevent the spread of AIDS:
persons who do not perceive themselves at high risk and therefore ineligible
for donating blood may also not perceive the need to engage in risk-reduction
behaviors. Since our data pertain only to reported AIDS cases and do not
include the larger pool of HIV-infected persons without overt AIDS, the risk
awareness problem may be considerably greater.
WR193
Virus Edu
Wl+houi
prevent Jc
ep I dem I c.
to reach
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educat 1 or
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what klnc
(2) wheth
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Al I res
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about HIV
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*VEY S. BART
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all po
and Resear
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mission. 60
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WR191 A Modified System of Contract Tracing for HIV Seropositives
MICHAEL L. REKART, Division of STD Control, British Columbia Mini-
stry of Health, Vancouver, B.C., Canada
Control strategies for sexually transmitted diseases (STD's) must be appro-
priate, effective and acceptable. Both formal contact tracing, where a public
health worker notifies named sexual partners, and simplified contact tracing,
where the index patient does the notification, are well accepted methods of
STD control. A simplified system is usually used for AIDS patients and HIV
seropositives. A formal system of naming contacts to an interviewer would be
unacceptable and counter-productive in HIV infections.
There may be contacts, however, whom the seropositive patient wishes to be
notified but will not himself notify because of inability, fear or embarass-
ment. Public health officials should make themselves available to locate such
contacts. This is especially important since such contacts may include
persons who have no suspicion of HIV exposure, for example, female sexual
partners of unacknowledged bisexuals.
In British Columbia, HIV seropositives are requested to anonymously submit
to STD control authorities identifying information on contacts they themselves
will not notify. These sexual partners exposed to HIV are then located through
the traditional public health infra-structure, notified of the exposure and
offered information, counselling, antibody testing and support. This system
has found acceptance and support from all groups involved in AIDS and early
results are encouraging.
WP1Q4 Changing the Public Debate on AIDS: A Need for a Communal or
' Societal Approach to The Problem. SHELDON H. LANDESMAN*, M.D.
SUNY Health Science Center at Brooklyn*, Brooklyn, N.Y.
In the absence of effective medical therapy, control of the AIDS epidemic
requires the dissemination and acceptance of complex and controversial
educational messages . The nature of the public debate has undermined our
ability to delivery effective education to the public. Examples include
( 1 ) discussions of anal -genital intercourse as dangerous (as opposed to
any intercourse with an infected person being dangerous ) , ( 2 ) comments
about AIDS not being a threat to the "general population" (as if the 1.5
million infected persons are not the "general population" ) . Statements
such as these stimulate the public ' s perception that AIDS is "their" (gay
and drug users ) problem, not "our" problem and heighten the public • s
sense that "they" , the infected , may give the disease to "us" , the healthy .
It is only by emphasizing the communal nature of the AIDS threat and seeking
from all members of society an increased measure of trust and sacrifice
can the public debate on AIDS result in positive steps directed towards
decreasing transmission.
In the absence of a communal or societal view of the epidemic, the public
debate will become increasingly rancorous as uninfected populations begin
to feel more threatened. The result will be increasingly oppressive social
legislation (mandatory reporting or testing, quarantine, etc. ) put ' in
place as "quick fix" solutions that are usually counterproductive to the
aim of slowing transmission . Examples of such processes are already
visible-six states have mandatory reporting of HIV seropositivity (an
obvious disincentive for testing ) . A societally centered public debate
is essential to avoid an acrimonious and adversarial public fight over
how best to control the AIDS epidemic.
U/D1QO The National Condom Awarenes
wr. WL Survey of Knowledge of AIDS,
Behavior Among College Adole
RALPH J. DICLEMENTE, PhD and
University of California, School of M
Epidemiology and International Health
The National Condom Awareness Proje
underway, is a survey assessing colle
knowledge , attitudes and misconceptio
condoms and type and frequency of sex
Approximately 2,000 college undergr
major universities geographically-dis
States are participating in the proje
anonymous self-report questionnaire d
information about knowledge of AIDS:
and misconceptions , knowledge of othe
diseases, attitudes regarding perceiv
use of condoms, decision-making proce
risk of engaging in high-risk sexual
frequency of sexual practices. Data
describing geographic , ethnic/racial
well as the interrelationships be twee
perceived risk of HIV infection, type
use of condoms . The NCAP can be usef u
information on this population as wel
development and implementation of pub
based AIDS risk-reduction education p
s Project: A National
Use of Condoms and Sexual
scents
KATHERINE FORREST, MD, MPH
edicine, Department of
San Francisco, CA 94143
ct (NCAP), presently
ge-age adolescents '
ns about AIDS , use of
ual practices .
aduates matriculating at 18
tributed in the United
ct . Students complete an
esigned to elicit
transmission , prevention
r sexually transmitted
ed risk of HIV infection,
sses which influence the
behaviors and type and
will be presented
and gender differences as
n knowledge of AIDS,
of sexual practices and
1 in providing baseline
1 as in the planning,
lie health and college-
rograms for adolescents .
WP195 Lessons of History: What Really Works in Reducing STD Rates?
CHARLES F. CLARK, M.D. , AUSTIN C. KUHN, MSW, SHAPE Hospital,
Casteau, Belgium, EDMUND C. TRAMONT, M.D., Walter Reed Army Institute of
Research, Washington DC.
With the realization that the HIV epidemic heralds a catastrophe for
American society, scientific and social organizations have called for massive
educational efforts costing hundreds of millions of dollars. What can we
learn from past experience about the effectiveness of such programs?
Because the introduction of sulfonamides and penicillin in the early 1940s
so effectively treated gonorrhea and syphilis as to eliminate Venereal
Disease treatment as a medical specialty r the experience of controlling
sexually transmitted diseases by social engineering has been lost.
A massive unitary US Army program to educate and protect soldiers from
sexually transmitted diseases was implemented in 1911.
The effects of this massive program may be seen in the statistics for STD
in American troops stationed in the Panama Canal Zone from 1911 to 1922.
1911-118 1913-197 1915-137 1917-124 1919- 83 1921-154
1912- 69 1914-136 1916-116 1918- 67 1920-139 1922-144
The drop in 1912 reflects confusion over the beginning of the program. The
sharp drop in 1918 and 1919 reflects the takeover of the cities of the Zone
by military authorities as decreed by Treaty during the time of declared war
in Europe with the authorities immediately and vigorously suppressing
prostitution. The standardized education, inspection, distraction, and
punishment campaign had no perceptible effect whereas the suppression of
prostitution had a clear and dramatic effect, but even then the rate was
halved, not brought to zero.
142
WEDNESDAY, JUNE 3
WP196 Inter- and Intra- Personal Factors in the Recruitment and Retention
of Research Subjects For an AIDS Intervention Research Study
SALLY DODDS*, M.A. FLETCHER**, P. Cf HEARN**, P. COLE*, P. CARALIS**, et al.,
♦Health Crisis Network, **University of Miami, Miami, FL.
University AIDS researchers and staff and volunteers of a community AIDS
service organization have collaborated to design and implement a multi-year
study on the effects of stress, psychosocial variables and exercise on the
health and immunologic status of gay men at risk for AIDS. More importantly,
the study will evaluate the efficacy of exercise and stress reduction
techniques as buffers of possible adverse effects of stress on health and
immune function. Observation and subject reporting of the initial three
groups of subjects (N=25), have revealed several inter/intrapersonal factors
that have implications for the success of this type of research project with
this population. Some of these factors are: that subjects move through
several psychological phases including engagement, affiliation, committment
and termination; that voluntary participation in the study requires that high
risk men accept the realities of their risk factors, confront the anxiety
related to disclosure of HIV status and immune function, develop group
identity with other subjects, commit to attendance at frequent study-related
appointments, and integrate new patterns of stress reduction and exercise
into their lives; that substantial staff support has been necessary to
adequately obtain informed consent, provide crisis counseling after
disclosure of HIV positivity, encourage discussion of feelings related to
behavior change, and; that subjects themselves serve to perpetuate the study
by becoming spokespersons, exercise trainers and recruiters. (Supported by
grant No. 1 P50MH42455-01 from NIMH).
WP199 Patterns of Distress Following HIV Antibody Test Notification.
ROBERT STEMPEL*, J. MOULTON**, T. KELLY*, D. OSMOND*, A.R. MOSS*,
*University of California, San Francisco, **Langley-Porter Neuropsychiatric
Institute, San Francisco, CA. , USA.
The psychological impact of informing at-risk individuals of their HIV
antibody test results is assessed in a group of 108 gay men from San
Francisco, 66 of whom elected to be notified of their results. Of those
notified, 44 were seropositive and 24 were seronegative. We compare self-
report measures of psychological distress and potential psychosocial media-
tors prior to receipt of results, and again two weeks and three months
following their notification session.
We found a small, but significant, (p<0.03) increase on the Beck Hopeless-
ness Scale, but no significant increase in several other measures of distress
following notification of seropositives. We found a significantly higher
perceived risk of developing AIDS at baseline (p<0.01), among both seroposi-
tives electing to know their results than among subjects who elected not to
know. This difference persisted at three months post-notification even among
those notified of a negative serostatus.
This lack of substantially increased distress following notification of
seropositives may be explained by the subjects participation in a prospective
epidemiological study which has returned clinical and immunological
information to participants, and by participants' expectation of their
serostatus (96% of seropositives correctly anticipated their serostatus).
Our group may resemble many at-risk populations in having long considered
themselves to be seropositive, and so at decreased risk of severe adverse
psychological reactions to antibody test results.
WP197 "AIDS Community Outreach for Intravenous Drug Users" Harvey W.
Feldman, Ph.D. & Patrick Biernacki, Ph.D. YES Project, 1779
Haight St., San Francisco, CA 94117.
In May 1986, a community health education/outreach program was created in
San Francisco to stop the spread of AIDS among intravenous drug users
(IVDUs). Currently, the program employs eight workers who provide AIDS
education, counseling and referral to drug users in those areas of the city
that contain the highest concentrations of IVDUs. This paper describes and
analyzes the major stages undergone since the program's inception and
addresses problems encountered. The analysis will help other communities to
develop similar outreach efforts.
The program developed in the following stages: 1) Formation of the overall
strategy guiding the program effort toward the major goal of stopping the
spread of AIDS among IVDUs; 2) Ethnographic studies of target areas to map
out & analyze the needle-using scenes and drug-using practices; 3) Recruit-
ment & training of an outreach staff component; 4) Successful entree into
the target community; 5) Development & distribution of health promotion
materials, condoms and small bottles of bleach; 6) Use of indigenous field
assistants, who are natural leaders, to help promote safe health practices;
7) Utilization and management of the media to promote the project's goals;
8) Evaluation and reassessment of project plan and ensuring compliance with
health messages, & 9) Entry into new IVDU scenes, when and how to move
beyond the original target groups.
An administrative project evaluation indicates that, contrary to popular
wisdom, IVDUs will change their behavior, especially in relation to sani-
tizing their shooting paraphernalia.
WR200 Tne Unique Counselling Interventions Required for Intravenous Drug
Abusers (IVDAs) with AIDS/ARC and their Families
Catherine Lyons, M. Cossaboom, V. Graham, E. Honey, S. Landesman, Kings
County Hospital Center, AIDS Team, Brooklyn, NY.
The psychosocial and economic realities surrounding people infected with HXV
who are IVDAs, or sexual partners of IVDAs warrant particular counselling
interventions. The population is predominantly poor, black, and hispanic for
whom the diagnosis of AIDS compounds pre-existing social and economic
stressors, as well as the effects of long term chronic drug abuse.
Systems must be set up to provide an interdisciplinary approach m a coor-
dinated and integrated manner from diagnosis to death. Entire families become
the clients - be they parents and babies who are all sick with AIDS/ARC or in-
fected with HIV or be they adult siblings who used IV drugs together and are
now being cared for by other family members.
Counselling interventions are directed at the emotional and social impact, of
an AIDS/ARC diagnosis in conjunction with the unique pre-existing psychosocial
variables in this population. Some of these include: l)that day-to-day
survival issues are frequently the primary psychosocial concern, 2) the sense
of alienation and expandability already experienced that is compounded by the
diagnosis, 3) the feelings of low self esteem absorbed from society's view of
the associated high risk behaviors this diagnosis may reinforce, 4) that drug
abusers may have severed relations with family and become particularly
isolated .
For health care providers to provide compassionate care, as well as in order
to disseminate proper information regarding transmission of HIV to IVDAs and
their sexual partners, systems must be established that address the particular
needs of this population.
WR198 Patients with Kaposi's sarcoma who opt for alternative therapy:
immune and psychological measures.
ELINOR M.LEVY*, M.COTTRELL** L.H.KUSHI***,and P.H.BLACK*,*Boston University
School of Medicine, Boston, MA,* Fashion Institute of Technology, NY, ***University
of Minnesota, Minneapol is, MN.
Twenty four men who have chosen a holistic approach to their diagnosis of
Kaposi's sarcoma have been studied sequentially. They are all following a
macrobiotic regimen. The median survival for the 8 men who have died is 19 months
(range 5-46 months). None of the surviving members of the cohort have required
hospitalization. One has required local radiation. Four are alive 3 or more years
after diagnosis. Contrary to what might be expected, the number of lymphocytes in
the group has increased with time over the first 3 years after diagnosis
(r=0.474,p=0.006). The number of T4 cells increased over the first 2 years after
diagnosis (r=0.458,p 0.03). The percentage of T8 cells was unchanged (r=-
0.06,p=0.69). A subset of approximately 1/3 of these patients have filled out
psychological questionnaires, including the Beck Depression Inventory (BOI) and
the McNair's Profile of Moods Survey (POMS). Preliminary data suggests these men
are generally less depressed (median BDI score 10, range 1-28), less anxious
(median POMS Tension score 4, range 3-6),and feel more energetic (median POMS
Vigor score 23, range 8-32) than has been reported for other cohorts of men with
AIDS. The psychological profile associated with this group is hypothesized to
have a beneficial effect on the clinical course of their disease.
WP201 A Longitudinal Study of Distress and Coping
In Men with AIDS and AIDS Related Complex
Lvdia Temoshok. D.M. Sweet, J.M. Moulton, J. Zieh
University of California School of Medicine San Francisco
The problems associated with AIDS spectrum disorders transcend the medical
dimension of the disease. In a 5-year study, we are documenting the psychosocial
impact of events that occur along the disease continuum. Fifty gay or bisexual
men with AIDS, recruited from San Francisco General Hospital, were administered a
battery of standard self-report measures of distress and coping 2-8 weeks after
diagnosis, and then 4, 7, and 15 months later. Fifty-three men wit ARC were
administered the same battery at the same intervals except the 4-month follow-up.
Surprisingly, the number of self-reported AIDS-related "hard" or "soft" symptoms
were only correlated with two measures of distress at the initial assessment for
men with AIDS, and were not associated with distress at any follow-up point. At
the initial assessment point, men with ARC reported — unexpectedly — highex levels
of anxiety, confusion, depression-dejection, fatigue-inertia, tension, and anger-
hostility than men with AIDS. Seven months later, however, these group
differerences had diminished. Men with AIDS were significantly more confused at
the initial assessment than at 4-month follow-up, and were significantly less
anxious 7 months later. Men with ARC were significantly moxe. anxious 7 months
later than initially, but also significantly less hopeless. The psychological coping
style of "Hardiness" was significantly negatively correlated with all scales of
distress and mood at initial assessent for men with ARC. In a multiple regresison
analysis, less Hardiness was the best predictor of overall distess. Hardiness played
less of a role, however, in affecting distress for men with AIDS, or for men with
ARC at follow-up assessments. Data for the 15-month follow-up will be presented,
as well as implications for psychosocial interventions.
143
WEDNESDAY, JUNE 3
WR202 Tne Importance of Supportive Interventions for Caregiving Family/
Friends during the AIDS Crisis.
SANDRA JACOBY KLEIN*, W. FLETCHER.* *
*private practice, Encino,CA;AIDS Project Los Angeles;UCLA Division of Cancer
Control, Los Angeles, CA. **AIDS Project Los Angeles, Veterans Administration
htdical Center West Los Angeles, CA, USA.
Long term institutional care for AIDS or ARC patients is often unavailable
in many communities. After periods of hospitalization the burden of continu-
ing care may fall upon the patient's family and/or friends. These caregivers
have become an important resource in the overburdened AIDS treatment network.
Consequently it is vital that they be given the support and training necessary
to enable them to persevere despite overwhelming obstacles.
As Co-therapists of ongoing grief recovery groups over the past three years,
we have observed surviving family members and friends as they related diffi-
culties encountered relative to their unmet needs during the period preceding
the patients's death. Many in this already high-risk population found them-
selves without adequate social, legal, financial or emotional supports;
knowledge of available community assistance programs; or nursing skills to
care for the patient at home. They were neither able to communicate with
health care professionals nor understand and cope with changes in their re-
lationships. They tended to experience more depression, fatigue, guilt, anger,
helplessness and illness both before and during the mourning period than did
survivors who felt that their needs were met.
We offer a program of education and supportive interventions that could free
these caregivers to continue a level of essential care by reducing immobiliz-
ing stresses. This ancillary support network for health professionals and
persons with AIDS/ARC will then be maintained.
UjponR Nurse Recruitment and Screening of Patients for AIDS Research
nr.tuu Protocols
MARGARET MEGILL, B. HERPIN, B. BAIRD, National Institutes of Health, Bethesda,
MD~! As the number of AIDS cases and the number of investigational drug
studies have increased, an efficient yet individualized screening process for
matching patients to particular protocols is required. In order to focus and
expedite patient recruitment efforts, protocol-specific checklists were
formatted by the nurses and used in their telephone communication concerning
760 referrals. Among the elements found to be most valuable were relevant
patient history (Kaposi's sarcoma, type of opportunistic infections, current
symptoms), hemoglobin, and T4 numbers. A cut-off of 200-400 T4 cells was found
to be helpful in distinguishing patients with a high risk of developing an
opportunistic infection during study. Following initial telephone selection,
277 patients were scheduled for a screening visit to NIH, limited to HIV
culture of blood, an immune profile, CBC/diff, SMAC chest x-ray, and a brief
nursing interview. Obtaining a chest x-ray at this early point in screening
helped identify patients with unsuspected abnormalities who were not
appropriate candidates for research but who required routine medical
follow-up. Utilizing personal computers and the NIH DEC-10 system, a
computerized data retrieval network was established into which results from
either the clinical pathology laboratory or the various research laboratories
were entered as generated. Once data collection was complete, the patient was
reviewed by the research nurses and the senior investigator, a decision made
as to protocol eligibility, and the patient and the referring physician
notified. Only then were history and physical scheduled for suitable research
candidates, of whom approximately 83 of 107 were found to be protocol
eligible. Thus, preliminary phone and blood screening evaluation may greatly
enhance the efficiency of screening patients for research protocols.
WR203 Providing Psychological Support to Children with AIDS
LEWIS KATOFF, Ph.D., Gay Men's Health Crisis, New York City, USA
There have been approximately 400 children with AIDS reported to U.S. Centers for Disease
Control, and estimates of over 3,000 unreported or undiagnosed cases. A large percentage of
these children, 80% of whom are the offspring of IV drug abusers, are in the New York metropolitan
area. Limited social and educational services, as well as a lack of advocacy for children with
AIDS is conrnon. In December of 1985, the Gay Men's Health Crisis began a volunteer program
serving children with AIDS and their families. All direct services are provided by volunteers,
in hospital or at home. The "Buddies" provide social and developmental stimulation for children,
while "Crisis Intervention Workers" are focused on emotional support for parents and caregivers,
child advocacy ,referrals to social services and entitlement programs. So far, we have worked
with 25 children, between 12 months and seven years of age. Problems of these children and
families, as well as services provided will be reported.
WR206 Dilemmas of an AIDS Residence Program: the Legal, Ethical and
Psychosocial Issues Integral to a Program and its Residents
ELLEN COUSINEAU, RN,.MHS, Director, Shanti Residence Program, 890 Hayes,
San Francisco, CA
Now existing in many parts of the United States and Europe, housing pro-
grams for people with AIDS are a vital community resource. By coupling stable,
low-cost housing with advocacy services, AIDS residence programs enable PWAs
to remain as independent as possible, in a supportive home-environment.
Such programs do not always run smoothly. In spite of — or perhaps because
of — proceeding "with the best of intentions," AIDS residence programs are
forced to continually re-evaluate the ways they operate.
What flexibility is needed in interpretting program policies? How does a
program carefully screen applicants without discriminating against the dis-
ease itself? What must a program know about tenant rights and probate? How
sick is "too sick" to live independently? How does a program avoid inter-
agency combat-zones?
This paper provides case studies demonstrating ways in which Shanti Resi-
dence Program has, since 1983, dealt with these and other issues. It hopes
to increase sensitivity and problem-solving capabilities of persons who inter-
act with — or hope to form — AIDS residence programs.
WR204 fostering and adoption of infants at risk of HIV
infection
K Skinner, J Mok, RP Brettle, Lothian Region Social Work
Department and City Hospital, Edinburgh, Scotland.
To date we have cared for 25 babies at risk of acquiring HIV
from 24 mothers. Three mothers acquired the HIV infection by
heterosexual contact the rest via intravenous drug misuse although
only 9/21 are currently abusing. Eight out of 24 were single
parent families and there were immediate demands for adoption or
foster care.
Thirty four foster families offering places to babies were
approached and following interviews 3 offered to care immediately
for a high risk baby. Twenty seminars followed, initially
conducted by a social worker and physician and latterly by a
social worker resulted in 12 further families being identified for
these infants. To augment all family placements, a pool of 20
specially prepared nursery nurses are available to cover family
illness. Short term emergency care was provided by an Infectious
Disease Unit but to date no at risk, or high risk child has
required long term hospital or residential care in Edinburgh.
The likelihood of children returning home diminishes with the
length of time in care and plans are being made for the future of
the fostered children. The local authority's commitment to giving
children as normal a life as possible in securing foster and
adoptive families has been aided by well prepared, flexible
families who care for children with a range of special needs. The
general method is now being adopted by other local authorities
faced with similar potential problems.
WR207 view From Wltnin " Coping With Isolated Thrombocytopenic Purpura
Inge B. Corless*
D. Abrams**, E. Biglieri**, M. Dodd**
♦University of North Carolina, Chapel Hill
"University of California, San Francisco
The significance of how individuals perceive themselves and their illness and
the effect on recovery has too often been given inadequate attention. This
paper reports the results of the interview data and the drawings of eight
homosexual males with Isolated Thrombocytompenic Purpura who participated in
research on the impact of a psychophysiological intervention on psychological,
physiological and immunological parameters. At the study's onset an interview
was conducted in which questions of the meaning of the illness, its timing,
previous approaches to coping with crisis, life changes which they desired to
make, and factors considered important for maintaining their present level of
functioning were asked. In subsequent interviews discussion focussed on
coping, and changing perceptions of life and Its meaning. Interview responses
were compared with adults with acute leukemia undergoing induction chemotherapy.
The latter although mentioning their own resources emphasized the help to be
provided by doctors, nurses and chemotherapy. The men with Isolated
Thrombocytopenic Purpura noted their own inner resources. This was
substantiated by the cancer Locus of Control Scale. The homosexual males as
compared with three other groups were higher on Internal scores and lower on
those for Chance and particularly, Powerful Others. Changes in self
perception over time were indicated 1n drawings in which participants depicted
themselves, their illness, mood changes and approach to life.
144
WEDNESDAY, JUNE 3
UippnO Evaluation of an Educational Program to Help Perinatal Nursing
Staff Provide Care to HIV Infected Patients
KATHERINE M. NELSON, R. FAHRNER, J.B. COHEN, Dept . of Staff Development and
Research, San Francisco General Hospital, San Francisco, CA , USA.
The increased incidence of perinatal HIV infection has had significant impact
on nursing care practices in Labor and Delivery and the Nursery. Nursing staff
education and support are necessary to circumvent exaggerated fears of AIDS.
At SFGH an educational and support program has been developed to facilitate
high-level nursing care standards as well as appropriate multidisciplinary
patient management .
Program methods were: I) a baseline survey of knowledge and attitudes about
AIDS prior to the intervention program; 2) a multistage intervention program
extending over a 4 month period, and 3) a post-intervention evaluation exam-
ining knowledge, attitude, and behavior changes. Intervention programs were
for all nursing staff in Nursery and Labor and Delivery (N=45). Strategies in-
cluded open staff meetings, didactic programs, onsite reinforcement, and
implementation of perinatal HIV infection control guidelines.
Results : Changes observed included increased knowledge about HIV transmission
and infection control. Staff also demonstrated increased sensitivity to more
appropriate discharge teaching and made increased numbers of referrals for
follow-up. Some nurses increased their skills in providing patient education
about prevention of HIV transmission. Attitude changes were less predictable
and more complex. Changes tended to proceed through several stages, but most
staff reported reduced fear and more confidence in caring for HIV infected
patients .
WR211
Service Characteristics of U.S. Public and Teaching
Hospitals with AIDS Patients
D.P. ANDRULIS, Ph.D.*, VIRGINIA S. BEERS, H.P.A.*. J. BENTLEY, Ph.D**, L . GAGE*,
^National Association of Public Hospitals, Washington, DC, USA, ^Council of
Teaching Hospitals, Washington, DC, USA.
A 1985 AIDS survey of 450 major U.S. public and teaching hospitals conducted
by the National Association of Public Hospitals and the Council of Teaching Hos-
pitals has yielded responses from 223/450 institutions. These hospitals, which
treated almost 5,000 patients in the calendar year, were asked to identify the
presence or absence of the following services to AIDS patients: separate AIDS
unit; specifically designed system to monitor or track patients on an out-
patient basis; a formal suicide watch program, training protocols for
AIDS staff in hospitals ; education programs for non AIDS staff; formal
linkages with various community groups representing high risk populations (homo-
sexuals, minorities, drug users, hemophiliacs, women at risk).
Responses were analyzed according to four major institutional characteristics:
hospital size, location, ownership and number of AIDS patients served. Findings
describe similarities and differences among the institutions with regard to
tendency for hospitals to establish AIDS units, the extent and type of hospitals
able to coordinate and integrate inpatient and outpatient care, the emphasis on
formal suicide prevention approaches, the extensiveness and sophistication of
AIDS training programs, and the extent to which hospitals coordinate AIDS treat-
ment with the key community groups.
WP209 Nursin8 Staff Knowledge, Attitudes and Self-Reported Behavior with
Respect to Patients with AIDS.
MARY ALICE O'DOWD, N ADACHI, AM RAZIN, RS KLEIN. North Central Bronx Hospital,
Monteflore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
AIDS has evoked considerable fear and anxiety in the general public and among
health care workers. A study of the attitudes, knowledge, and self-reported be-
havior with respect to AIDS of a group of 135 nurses and student nurses, 126 of
whom worked in a large municipal hospital In NY City with an average daily cen-
sus of 14 patients with AIDS or ARC, was done. A questionnaire was administered
between 9/12/85 and 11/5/85. Confidentiality was ensured. Demographic data
were obtained and subjects were asked to rate on a 5 point Likert scale 115
statements. All statements were ordered randomly and both positive and negative
phrasing were used. Sixty-six statements dealt with knowledge, attitude and
self-reported behavior in relation to AIDS and AIDS patients. For comparison,
16 of the statements were repeated with respect to three other diseases, which
shared with AIDS the possibility of transmissibility (tuberculosis), of patient
behavior in causality (emphysema) , or both (hepatitis) .
This initial survey found that while these nurses shared the fear and anxiety
of the general public about AIDS, (57% worried about hospital transmission of
HIV and 44% worried about the risk to themselves of opportunistic infection) ,
they were able to make distinctions as to the risks to themselves and other
patients, based on current knowledge about the four diseases surveyed, for 12
out of 16 disease comparison questions (p<.05). Although AIDS patients were
blamed for their illness by 7-37% of the nurses, most nurses (72-87%) demon-
strated a consistent attitude of compassion. Risk group was not a factor. This
study instrument appears to be a valid means of assessing staff knowledge and
attitudes towards patients with AIDS.
WP212 Comprehensive Case Management
Utilizing Hospice Concepts: A Statewide Program
LYNNE CR7AWFORD, New Mexico AIDS Services, Inc., Albuquerque, New Mexico, USA
New Mexico AIDS Services is the only AIDS service organization in New Mexico
and offers case management services for all persons with AIDS/ARC in this rural
state. Case management is based on the Hospice concepts of: a wholistic view of
client needs, an interdisciplinary team approach to meet those needs and the
promotion of quality of life. We utilize trained volunteers and existing com-
munity resources to reduce hospital in-patient days and therefore the cost of
patient care by increasing in-home and out-patient support.
The case manager's role includes acting as: a client advocate; an educator-
resource person to medical professionals; and a coordinator of support services.
Another important element of a case management program is counseling of PWAs in
regard to: living wills, power of attorney, medical guardianship, right to
refuse treatment, informed consent and confidentiality.
The development and delivery of a comprehensive case management program in-
volves establishing liaisons with existing services that provide in-patient
acute and long term care; homecare and hospice nursing; delivery of meals and
homemaker services; transportation, social service counseling for disability
income and financial support. These liaisons optimize out-patient support and
promote the education of community resource persons. To assure services to
clients who live in rural areas the case manager must identify and educate
health care professionals and appropriate resources in those areas by offering
inservices, guidance and support.
The case management services are offered in adjunct with an emotional support
and counseling program and are available on a 24 hour a day basis.
WR210
EPSTEIN
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GE_IIL*-S. LANDERS*. A. BARRY*. G. LAMB"
epartment of Health and Hospitals.
Research. Harvard School of Public
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U/D01Q Enhancing the Coping Skills of Families of Children with AIDS
nr'£-l° MARY TASKER, P. EVANS, M. BOLAND, J. KERESZTES, E. CONNOR, J. OLESKE
Children's Hospital of New Jersey & UMD-New Jersey Medical School, Newark, NJ
The AIDS program at Children's Hospital of NJ is a multidisciplinary, multi-
service program that utilizes a chronic illness model in providing care to
children andsupport services to their families. In 46/50 families with a
child with perinatally acquired infection, diagnosis in the child resulted in
identification of a primary caretaker (30/50) and sibling (7/50) with HIV
infection. Initial response to the diagnosis included prolonged (longer than
3 months) denial in 12/50. In 6/12 denial interfered with acceptance of
services for the child. Development of symptoms in the parent was associated
with improved utilization of services for the child. Primary caretakers
identified a need for asisstance in the following areas: access to entitlements
(welfare, medicaid, WIC) 31/50, transportation 27/50, housing 16/50, school
entry 9/50, decision making related to medical care 30/50, assistance with
family problems unrelated to AIDS 30/50, medical care and service for the
parent 12/50. When provided with the opportunity for ongoing therapy, 1/10
parents followed through on the referral. The social worker's role is to
assist the caretakers to define their own needs realizing that the perceived
need may be for concrete services rather than counseling and psychological
support. Social work interventions are directed towards linking families with
services and helping families adapt to chronic illness.
s of this study ind
sons with AIDS is d
come important as t
with few AIDS cases
icate the inpatient cost of
eclining. Clarification of this
he epidemic spreads into areas of
to date.
145
WEDNESDAY, JUNE 3
WP214 A Hospice's Response to the AIDS Dilemma
ROSEMARY J. HURZELER, R.N., M.P.H., H.A., DIANNE RAWSON, R.N., M.S.
The Connecticut Hospice, Inc., Branford, CT.
The Connecticut Hospice, Inc., the first hospice in America and, the only
teaching hospice to offer ACCME credits through its Institute training pro-
grams, examined in Dec, 1983 the question of whether the current criteria for
admission to Hospice inpatient and home care settings allowed for the admis-
sion of patients with AIDS. On April 11, 1984 the Medical Board voted that
such criteria did fit. Between April, 1984 and July, 1985 a series of steps
were undertaken to implement this decision including: multiple inservices for
paid and volunteer staff and families on infection control aspects and psycho-
social issues involving the State, user-friendly hospitals, Shanti Project in
San Francisco; the administration of Hepatitus B vaccine to all patient care-
givers. The first person with a diagnosis of AIDS was accepted in July, 1985.
Since then Hospice, inpatient and home care, has seen many patients (12 case
reviews) with a diagnosis of AIDS with various causes of onset and has worked
extensively on psychosocial issues with those patients, families and signifi-
cant others. As this Hospice is a statewide facility and these patients have
come from all over the State, there has not been a time when it has not ac-
cepted a referral (AIDS). In recognition that there has been several patients
who have been inappropriately institutionalized in acute care settings who are
neither eligible for hospice inpatient and do not have a home, this led
Hospice to undertake a hospice home for the homeless.
WP917 Mycobacterium Avium Complex Isolated from the Lung Only, Does it
" Disseminate? TIMOTHY P. MESS. San Francisco General Hospital,
San Francisco, U.S.A.
In December 1986 a retrospective review was conducted to investigate for
dissemination of Mycobacterium avium complex (MAC) in AIDS patients who had
culture proven MAC from the lung only. From January 1982 to October 1986, 107
patients had MAC cultured from the lung at SF General Hospital (SFGH) . 22 of
these patients had negative blood cultures for AFB at the time of their posi-
tive lung isolate. 16 of these 22 had follow-up AFB blood cultures of >1
month to investigate for dissemination and in 5/16 (31.3%), these cultures were
positive for MAC. The last negative blood culture was at 21-224 days (median
100 days). The first positive blood culture was at 24-280 days (median 171
days). All 5 patients had significant diarrhea preceeding their MAC blood
isolate. 2 had Cryptosporidium, 1 had CMV colitis and the other 2 had uptake of
gallium in their colon. (Stool AFB's are not available at SFGH.) Only 1 pa-
tient had an abnormal CXR suggestive of pulmonary MAC disease (hilar adeno-
pathy). 2 of these 5 patients received anti-tuberculosis (anti-TB) medications
for 2 and 5 weeks prior to their dissemination. The 11 patients without evi-
dence of dissemination had follow-up with negative AFB blood cultures of 31-
442 days (median 112 days). 6 of these 11 patients received anti-TB meds
(range; 2-8 months, median; 6 months). Only 2/11 complained of diarrhea and
none had known intestinal pathogens. Only 1 patient had an abnormal CXR
suggestive of pulmonary MAC disease (cavitary lesions) which improved with
anti-TB meds. In these 11 patients 7 had 10 repeat sputums for AFB. 2 of 3
patients treated with anti-TB meds had a positive repeat sputum culture for MAC.
Overall, 6/10 repeat sputum samples were negative for any AFB. Dissemination
of MAC is associated with diarrhea. Use of anti-TB meds is of uncertain value.
WR215 Prospective HIV Serologic Survey of Employees in a Canadian Teaching
Hospital
NORBERT GILMORE, S-L TAN, J C MCDONALD, S JOTHY, N CHERRY, M 0 'SHAUGHNESSY, P
GILL. Division of Clinical Immunology and Department of Pathology, Royal
Victoria Hospital; School of Occupational Health, McGill University, Montreal;
and Laboratory Centre for Disease Control, Ottawa, Canada.
1,496 employees at a 780 bed teaching hospital in Montreal have been enrolled
in a prospective survey for evidence of HIV infection beginning June 1985.
Work-related exposure to HIV and hepatitis B are being assessed by 6 monthly
questionnaires and blood tests. During this study, 56 cases of AIDS have been
diagnosed, resulting in 106 hospitalizations. The cohort includes 344 men,
employed 3.5 years t 3.8 (SD), and 893 women, employed 2.6 years ± 2.3, and 259
new employees (53 men and 206 women), working less than one month. The cohort
consists of 275 administrative personnel without patient contact (18.4% of the
entire cohort); 322 support and maintenance personnel with variable patient
contact (21.5%); 93 physicians (6.2%); 614 nurses (41.0%); and 192 laboratory
technicians (12.8%). Sera were assayed for HIV antibodies by ELISA assay; the
nspecificity of repeatedly reactive sera was verified by Western blotting and
an immunoblot assay, using cloned gpl60.
Sera from 10 employees were repeatedly reactive on HIV-ELISA testing: 4
subjects were initially reactive (2 male and 2 female) and 6 were initially
negative but found to be reactive 6 months later (4 female and 2 male). Only
one male with a history of sexual exposure to HIV was seropositive by Western
blotting and gpl60 immunoblotting.
This study has failed to identify occupational risk for HIV infection,
associated with hospital work, and confirms the very low prevalence of HIV
seropositivity in urban non-risk populations in Canada.
WR218 Use of HPA~23 in Patients with AIDS: Observed Toxicity During
an Eight Week Trial.
george f. Mckinley, a. englard, k. ong, m. lange, e.b. klein, m.h. grieco,
St. Luke's/Roosevelt Hospital, Columbia University, New York, N.Y. 10019.
As part of a multi-center phase I trial, the experimental antiviral agent
HPA-23 (Heteropolyanion-23, or antimonio-tungstate ) was given to 16 patients
with CDC-AIDS (10 with Pneumocystis carinii pneumonia, 4 with cutaneous or
oral Kaposi's sarcoma, one with both PCP and KS, and one with Candida
esophagitis). Protocol required five daily intravenous injections per week,
and lasted eight weeks. Four dosing levels were used (0.25, 0.5, 1, or 2 mg/
kg/day) with four patients assigned to each level. Four patients did not
complete protocol because of intercurrent illness (one had rapidly
progressive KS and three required conventional antibiotic therapy).
The only immediate toxic reaction occurred upon extravasation of drug, on
at least one occasion in each subject, and was characterized by rapid onset
of pain followed by erythema and swelling around the injection site. Symptoms
persisted for 3 to 5 days after extravascular injection, but there were no
long term sequelae. Subjective side effects included a slight metallic taste
noted by several patients and nausea and loss of appetite. The most
consistent toxic effect was a decrease in platelet count which occurred in
all twelve patients who completed protocol. Platelet counts (xlOOO): week 1:
193 + 14 SEM, week 5: 124 + 13 week 9: 97 + 16. Marked leukopenia ( < 2000)
occurred in a few patients, but did not persist on continuation of HPA-23.
Renal function remained unimpaired. Moderate elevation of transaminases did
occur in the group receiving the highest dose. Overall, HPA was well
tolerated in this group of 16 patients with AIDS.
WP216 Evaluation of the antiviral activity and tolerance of
HPA23 in 38 patients with HIV related disorders.
DANIEL VITTECOQ*,B.AUTRAN*. B. ROUQUETTE**, JC. CHERMANN**, R. WOERLE***.
*St Louis Hospital, **Insti tut Pasteur. Paris, ***Rhone Poulenc, Lyon,
Fiance.
22 AIDS (12 KS,7 01,3 KS/OI) and 16 preAIDS patients staged accor
ding to the Walter Reed classification (3 WR5.4 WR4, 1 WR3.8 WR2)
entered a HPA23 protocol: 2 IV injections per day (3mg/kg/day)
during 14 days. 48 treatments were provided. 7 patients had a thrombo
penia<150 000 before treatment. After treatment 15 patients had a
reversible thrombopenia<100 OOO ( 5<50 000 ).
Reverse transcriptase activity was studied by culture and cocultu
re of the blood and CSF before treatment. Viremia was studied in 17
cases after HPA. Coculture was taken into account only when culture
was negative. On blood cultures, viral inhibition was defined as a
decrease of at least 400 OOO cpm or a delay 10 days of the reverse
transcriptase peak, failure as an increase of the activity and
stability as no significant modification. Considering viral activity
in the blood, among 6 patients with positive CSF culture before
treatment, we noticed 2failures,2 inhibitions, 2 stabi lities. Among
the others, we noticed 2 failures, 7 inhibitions and 2 stabilities.
This study confirms that a short HPA23 treatment appears to inhibit
viral replication in blood, and side effects are not limiting
factors. We suggest to carry on this study with higher dosages and
shorter courses which could be repeated every 2 months.
Topical Acyclovir for Treatment of Hairy Leukoplakia
University of California Medical
WR219
MARCUS A. CONANT, B. NEWLIN, M. ILLEMAN,
Center, San Francisco, CA.
This is a double-blind placebo-controlled crossover study to test effective-
ness of 5% Acyclovir ointment in controlling lesions or oral "hairy" leuko-
plakia (HL) in a group of immunosuppressed volunteers infected with HIV.
HL was described by Greenspan, Greenspan, and Conant in 1985, and is charac-
terized as a white, adherent, often filliform oral lesion found mainly on
lateral tongue borders with characteristic histologic appearance showing fine
keratin projections, koilocytosis of prickle cells, and little subepithelia
inflammatory cell infiltration. There is evidence of Epstein-Barr virus
in the epithelial cells. HL has been observed only in immunosuppressed
individuals, a >,reat nany of whom are homosexual males, seropositive for HIV
antibody, it is highly associated with progression to AIDS in these individ-
uals. Treatment of lesions of in, is useful in relieving patient anxiety
and removing lesions which might be confused with oral candidiasis.
Twenty subjects with clinically diagnosed HL applied ointment to lesions
5 times a day for 4 weeks (2 weeks ACV ointment, 2 weeks polyethylene
glycol base placebo) . Nystatin suppositories were dissolved orally twice
daily during the month of treatment and Candida cultures were done both
before and at the completion of the study to eliminate confusion of HL with
oral Candida. Clinical evaluations, including photographs of the lesions,
were done weekly. A beneficial effect of study medication ointment has
been observed in some patients, suggesting that topical ACV may be effective
in suppressing Epstein-Barr viral replication in these lesions.
146
WEDNESDAY, JUNE 3
WP220 Treatment of Pulmonary Kaposi's Sarcoma with a Combination of
Adriamycin, Vincristine, and Bleomycin*
Craig E. Metroka. St. Luke's/Rooaevelt Hospital Center, New York, New York.
Pulmonary Kaposi's sarcoma (KS) in AIDS is a late manifestation usually
diagnosed in patients with extensive cutaneoue disease. In one series the
median survival after diagnosis was 1.5 months. Between 7/85 and 1/87, 12
patients with extensive pulmonary KS were seen. Patients ranged in age from 23
to 61 years (mean, 38 years). 2 had received prior chemotherapy. There were
5 patients with B-symptoms and 2 patients with a prior opportunistic infection.
All patients had exteneive cutaneous and endobronchial involvement with KS,
pulmonary symptoms, and negative gallium scans. Other problems included
hemoptysis in 4 and serosanguineous pleural effusions in 2. The chemotherapy
regimen consisted of Adriamycin 50 mg IV on day 1, Vincristine 2 mg IV on days
1, 8, and 15, and Bleomycin 15U IV days 1 and 15 of a 28 day cycle. All
patients received dapsone 25 mg po qid as prophylaxis for PCP. 6 patients
initially received a reduced dose of Adriamycin because of leukopenia. None
had a measureable response and the mean survival was 1.5 months. In contrast,
all 6 patients who received the full dosage achieved greater than 75% clearing
of their pulmonary infiltrates, resolution of their pulmonary symptoms, and had
a mean survival of 10 months (range 7 to 12). 4 of these patients required a
reduction in the dose of Adriamycin after 3 to 7 cycles because of leukopenia.
Progressive pulmonary KS appeared within 3 months in these patients. To date,
10 patients have died, 9 of pulmonary KS and 1 of sepsis. No patients developed
an opportunistic infection. Toxicity included mild myelosuppression, moderate
alopecia, and mild nausea and vomiting in all patients. Our results indicate
that this regimen is effective and well tolerated in the subset of patients who
have adequate bone marrow reserve.
UIDOOO Improvement In HTLV-III/LAV-Associated Dementia and Neuropathy
Associated with Administration of 3' -Azido-2 ' , 3' -Dideoxy thymidine
ROBERT YARCHOAN*. G. BERG**, M. FISCHL***, M. DALAKAS****, C.E. MYERS*, S.
BRODER*, et al., *NCI, **NIH CC, and ****NINCDS, Bethesda, MD, and ***U. of
Miami, FL.
Neurological manifestations of HTLV-III/LAV infection are increasingly being
recognized as an important clinical problem and, as has been shown by Drs. Shaw,
Gallo, and coworkers, the brain is a major site of replication of HTLV-III/LAV.
Based on these findings, we have administered 3 ' -azido-2 ' ,3' -dideoxythymidine
(AZT) to 7 patients with HTLV-III/LAV-associated neurological disease: 4 with
dementia, 2 with peripheral neuropathy, 1 with both dementia and peripheral
neuropathy, and 1 with a T10 paraplegia. Levels of AZT In the cerebral spinal
fluid 4 hrs after a dose were 55% of simultaneous plasma levels. By 3 to 8
weeks after being started on AZT, each of the 6 patients with dementia and/or
peripheral neuropathy had improvement in neurological dysfunction as assessed
by examination, neuropsychometric testing, and/or nerve conduction studies. In
particular, patients with dementia had substantial improvement in Trailmaklng,
Weschler memory, and pegboard tests. The patient with T10 paraplegia, however,
did not improve. One patient whose dementia improved was studied by positron
emission tomography (PET). At the start of therapy, he had a heterogeneous
pattern of glucose metabolism with relative decreases in the posterior temporal,
occipital and thalamic regions; a repeat PET scan after 13 weeks had become
more normal. In 2 of the patients the improvement seen was transient, and they
expired from pneumonia after 6 to 8 months of therapy; the other 4 patients who
improved continue to do well after 2 to 16 months of therapy. These results
suggest that certain HTLV-III/LAV-associated neurological abnormalities are
reversible following the administration of anti-retrovlral chemotherapy and
they provide a rationale for a larger study in patients with this disorder.
WR221 Major Opportunistic Infections in AIDS Patients after More than
Eight Weeks of Azidothymidine (AZT) Therapy.
DENNIS M- CAUSEY. J.M. LEEDOM, and P.N. Heseltine. Los Angeles County/Univer-
sity of Southern California Medical Center. Los Angeles, CA USA
This report examines the frequency, types, and outcomes of AIDS-def ining
opportunistic infections (OI's) in patients treated with AZT for more than 8
weeks. Twenty-two patients with previous Pneumocystis Carinii pneumonia (PCP)
were enrolled in our study. Nineteen of the 22 completed more than 8 weeks of
AZT therapy. Eleven patients were treated with 250 rog every 4 hours for 10-12
weeks and then 200 mg every 4 hours thereafter. The other 8 patients were
treated with 200 mg every 4 hours. AZT was discontinued or reduced to 100 mg
every 4 hours if patients developed granulocyte counts of <750 or platelet
counts <50,000.
Eight of 19 patients (42%) developed recurrences of PCP. These infections
were documented between weeks 10-24 after starting AZT. Host of these
recurrences were mild as measured by febrile days, arterial oxygen tension,
and length of hospital stay; two of five tested had negative lung gallium
scans. However, fatal complications developed in 2 of the recurrent PCP
patients, one from respiratory failure due to PCP and another due to severe
Candida esophagitis, aspiration pneumonia, and lung abscess. Two patients
developed cryptococcal meningitis at weeks 12 and 20; one died. One patient,
at week 24, developed peri-rectal herpes simplex ulcerations which persisted >
1 month despite concurrent acyclovir therapy. In summary, 12 out of 19
patients (63%) developed major OI's after week 8 of AZT therapy. Three of
these OI's were fatal. While AZT therapy may decrease the incidence of OI's
initially, such OI's continue to occur and can result in fatality.
WR224 Longterm Treatment of Severe AIDS and ARC Patients with Oral
Ribavirin: A Pilot Study
CLYDE S. CRUMP ACKER, G. BUBLEY, J. LOFTUS, S. HUSSEY, Beth Israel Hospital,
Harvard Medical School, Boston, MA, U.S.A.
A Phase I Study of oral Ribavirin (RBV) for 8 weeks (Dec-June 1985-86) in
10 AIDS and 5 ARC patients showed suppression of HIV in blood, enhanced
lymphoprolif erat ive response to lectins and fewer opportunistic infections
on RBV. On stopping drug, HIV was again detected in blood (Crurapacker et
al., Proc. 2nd Int. Conf. on AIDS, Paris, 1986, p. 34). To determine if
prolonged use of RBV would enhance survival, 5 AIDS patients and 3 ARC
patients who had survived the 8 week trial of oral RBV were enrolled in a
study of continuous RBV at 600 mg/day in July 1986. AIDS patients had PCP
as their initial opportunistic infection, had T4 cells less than 100/mra
(mean^O/mm-* ) and none had KS at start of Rx. From July-Feb 1987, no
patient has had recurrent PCP, and 6 of 8 are surviving. (In a comparable
untreated group of 10 AIDS patients followed at BIH, 7 developed recurrent
PCP in a mean time of 6.5 months.) Two AIDS patients died after 4 months on
RBV with progressive AIDS encephalopathy, but no other infections were
found. In 8 patients, 4 AIDS associated events occurred: 3 episodes of CMV
retinitis (2 In 1 patient) 1 episode of Candida esophagitis and 1 new KS
lesion. In 3 ARC patients, one developed CMV retinitis to progress to AIDS.
In the AIDS patients, initial clearing of HIV with RBV and enhanced lympho-
prolif erative response to lectins was associated with prolonged survival.
Mean survival time from initial diagnosis of AIDS with PCP is 18.5 months
(as of 2-1-87) in the 5 AIDS patients on prolonged RBV. RBV is well
tolerated as 4 patients have required no transfusions and 4 have required 2
units of packed RBV/per month to maintain HCT-30. This pilot study of
prolonged oral RBV in severe AIDS patients shows that RBV is well tolerated,
associated with prolonged survival and fewer opportunistic infections.
WP.222 Blood Levels of Pentamidine in AIDS Patients (Pts) Receiving Monthly
Prophylaxis
SJ REHM*. C KARAFFA-MYLES*. JE CONTE, JR**, *Cleveland Clinic Foundation,
Cleveland, OH, **UCSF, San Francisco, CA.
Pneumocystis carinii pneumonitis (PCP) recurs in 20 to 70% of AIDS pts; most
are unable to tolerate prolonged oral TMP/SMX prophylaxis. Pentamidine prophy-
laxis is appealing because of its prolonged tissue half-life, but the pharmaco-
kinetics in pts receiving intermittent doses is not known. Preliminary studies
indicate a decrease in PCP recurrences with monthly pentamidine prophylaxis.
Eight pts receiving monthly intravenous infusions of pentamidine at a dose
of 4 mg/kg were studied. All had received previous pentamidine therapy for
PCP (avg. total 3338 mg), and all had at least one dose of prophylactic pen-
tamidine (avg. 5.6 doses) before blood levels were determined. The average
cumulative prophylactic dose was 1526 mg. An HPLC assay with a sensitivity
limit of 2.29 ng/ml was used to determine peak and trough pentamidine blood
levels. Levels were performed 2 or 3 times for each pt.
In 6 of 8 pts trough blood levels were consistently detected; one pt never
had detectable trough levels and another had intermittently detectable levels.
Peak blood levels averaged 949 ng/ml (range 130-2612 ng/ml). The presence of
detectable trough levels and the magnitude of the peaks did not correlate with
the cumulative dose. Two of the 8 pts had recurrent PCP; one had discontinued
pentamidine prophylaxis when AZT treatment was initiated, and one other was
terminally ill with disseminated MAI infection and Kaposi's sarcoma.
Detectable blood levels of pentamidine are present for at least one month
after a 4 mg/kg intravenous dose in AIDS pts who have received previous
therapy with pentamidine. Further studies of the pharmacokinetics of inter-
mittently administered pentamidine are in progress.
WP225 Transplantation of Thymic Tissue to Reconstitute the Immune System
of Patients with AIDS
JOHN M. DWYER*. CC. WOOD**, G.J. McNAMARA**, B. KINDER**,
♦Department of Medicine, Prince Henry/Prince of Wales Hospitals, Randwick,
N.S.W. Australia. "Division of Clinical Immunology, Yale University School of
Medicine, New Haven, CT. U.S.A.
Thymic epithelial fragments were transplanted into 15 patients in an advanced
stage of the acquired immune deficiency syndrome (AIDS). One patient was given
interleukin 2 in addition to thymic tissue. We demonstrated the following :
( 1 ) Thymic epithelial fragments cultured before transplantation to remove T
cells survived for months after transplantation in 8 of 15 patients and seemed
to be responsible for a partial, selective, but transient repopulation of the
circulating T cell pool. (2) The absolute number of T8 cells, but not T4 cells,
increased three to four weeks after the procedure in eight of the fifteen
subjects. (3) This increase in T8 cells was associated with clinical improve-
ment and increased T cell responsiveness in vitro in some cases. In one case
a severe bilateral retinitis thought to be due to cytomegalovirus (CMV) cleared
spontaneously, a development unique in our experience with patients with AIDS.
Improved control of tuberculous infections was noted in two cases. The clearance
of resistant Pneumocystis carinii pneumonia and a cessation of previously intra-
ctable diarrhoea in two patients coincided with engraftment. (4) Thymic tissue
transplantation as a single therapeutic manoeuvre is unlikely to reconstitute
the immune system of patients with AIDS, but the potential of the approach,
used in combination with agents that block replication of human T cell lymphc—
tropic virus type III deserves further study.
147
WEDNESDAY, JUNE 3
\JUp??fi Evaluation of HIV Antibody Reactivity in Blood Donors with Atypical
"u Western Blot Patterns
NANCY L. DOCK*, H.V. LAMBERSON*, T.A. O'BRIEN**, S.R. PETTEWAY**,
S. ALEXANDER***, B.J. POIESZ****, *American Red Cross Blood Services, Syracuse,
NY, USA, **E.I. duPont de Nemours & Co., Wilmington, DE, USA, ***Biotech
Research Laboratories, Inc., Rockville, MD, USA, ****SUNY Health Science
Center, Syracuse, NY, USA.
Blood donors reactive for HIV antibody by ELISA who showed atypical patterns
on Western blot (WB) representing several patterns of core protein reactivity
(pl5/pl7, pl5/pl7 and p55, p24, p24 and p55, pl5/pl7 and p24) were followed for
2-10 months. Characterization of these antibodies was performed by 1) use of
recombinant HIV proteins and synthetic peptides, 2) determination of cross-
reactivity to HTLV-I, HTLV-II, HTLV-IV, 3) assessment of immune status and
potentially interfering auto-antibodies. All but two donors maintained the
same HIV core protein antibody reactivity throughout the follow-up period; one
showed a diminished pattern; the other became fully antibody positive.
Eighteen of 20 donor sera showed clear core reactivity with GAG-55 HIV recom-
binant protein. Ten of 19 donors' samples demonstrated cross-reactivity to
HTLV-IV; three of these 10, in addition, cross-reacted with HTLV-I. Immune
status of all donors was normal, but rheumatoid factor was detected in 2 of 20.
Thus our evidence so far strongly suggests that the atypical WB reactivity
observed is directed against retroviral core proteins. As part of this study,
donors were questioned during the follow-up visits. On interview, three donors
reported possible risk factors for HIV infection that were not acknowledged at
the time of donation. Based on these results, we conclude further study of
donors with this "atypical" reactivity is warranted. As an interim measure
blood identified by screening tests which detect antibodies reactive with core
proteins should not be transfused.
IMMUNOMOPULATION with BESTATIN in a Double-Blind Controlled Trial
WR229
u/ith HIV-positive Homosexual Men.
MERETE HBRDING; I .C.BygbjerrfjP.C.Gatzsche", K.Bergt L.Dalh Christensen* V.Eaber*
et al"*Department of Infectious Diseases, Rigshospitalet*; Institute of Medical
Microbiolog*^, The State Serum Institute , Copenhagen, Denmark.
Bestatin has previously been used to stimulate the cell mediated immune re-
sponse in immunodepressed cancer patients. In this study u/e investigated the
effect on immunological, haematological and biochemical variables in HIV-posi-
tive homosexual men. q
22 subjects u/ith PWM £5o?o of normal and/or T-helper cell count ^0,6 lo /l,
but without any opportunistic infections aocording to the CDC definition of
AIDS were treated u/ith bestatin capsules 6o mg daily or placebo for 4 u/eeks.
The immunomodulating effects were evaluated by lymphocyte transformation
tests, T-cell subsets, natural killer cell activity, in vitro alpha-interferon
production, ohange in HIV antigen titre and basophil histamine liberation.
Values were measured before treatment and 4 weeks and lo weeks later.
Full results will be presented at the conference.
WP227 "jOW Dose Naltrexone in the Treatment of AIDS
Bernard Bihari, F. Drury, V. Ragone, G. Ottomanelli, E. Buixnovici-
KLein, M. Orbe, W. Foeste, J. Thomas, R. Kirk
Thirty-nine patients, 38 with CDC defined AIDS and 1 with ARC were treated
with 1.75 mg. qhs of naltrexone, an oral opiate antagonist, in a double blind
placebo controlled study. The naltrexone group showed a significant drop in
pathologically elevated levels of serum alpha interferon compared with the
placebo patients (p<.01). The double blind phase was ended at 3 months, and
placebo patients were given naltrexone. Of 39 patients on naltrexone, 23
showed a marked decline in alpha IFN levels (from means of 144 i.u. to 11 i.u.)
over a 12-month period. Sixteen patients showed sustained alpha IFN elevation.
Accordingly, a patient classification of responder vs nonresponder was estab-
lished. During the course of the study, the 23 responders experienced signif-
icantly less O.I's than the 16 nonresponders (p<£.01). There were 8 O.I.'s
in the responder category and 19 O.I.'s in the nonresponder category. Of the
8 O.I.'s in the responders, 4 were mild episodes of P.C.P. Three of these 4
episodes occurred before the patient's alpha IFN level had decreased from the
admission level. All of the other 23 O.I.'s in both groups were life threat-
ening and in fact, 17 were fatal. In addition to the significantly higher
rate of 0.1. . occurrences in the nonresponder group, there was also a signif-
icantly higher death rate. As of December 17, 1986 there were 13 deaths (8121)
in the group of 16 nonresponders and 4 deaths (17%) in the group of 23
responders (p<L.01). No side effects were noted.
Minoon Gastrointestinal (GI) Non-Hodgkin ' s Lymphoma (NHL) in Patients (pts)
" at Risk for Acquired Immunodeficiency Syndrome (AIDS)
MARGARET DUGAN, C. ODAJNYK, D. KNOWLES, B. RAPHAEL, J. WERNZ, Rita and Stanley
H. Kaplan Cancer Center, New York University Medical Center, New York, NY.
At our institution 89 cases of diffuse aggressive NHL occurred in AIDS-risk
pts since 1981. Of these, 15 male pts (14 homosexual, 1 IVDA) were diagnosed
(dx) with GI NHL. Pathologic type was diffuse large cell, immunoblastic plasma-
cytoid (6) and diffuse large cell noncleaved (9) or by Rappaport classification
diffuse histiocytic lymphoma (15) . Concurrent CMV was evident in 2 biopsies and
Kaposi's sarcoma (KS) in one other. Median age was 37 years (31-45). 5 pts (33%)
had prior AIDS (3 opportunistic infection (OI), 2 KS) and 10 pts (67%) had NHL
as their initial manifestation of AIDS. Of the latter 10, 5/5 were (+) for HIV
antibody. Of the 5 not tested, 2 had prior ARC and 3 were only known to be in
an AIDS-risk group. 4 pts (27%) had a concurrent 01 at dx of NHL. Sites of pri-
mary disease were stomach (3), small bowel (6), large bowel (1), rectum (2) and
perirectal mass (3). Median LDH at dx was 303 (164-1521). Clinical staging
showed: Stage 1-8 pts. Stage II - 2 pts, Stage III - 2 pts and Stage IV - 3
pts. 12/15 had B symptoms. Treatment (rx) of pts has varied including surgery
and combination chemotherapy (3), combination chemotherapy alone (8), surgery
alone (1) or radiation therapy (1) . Median survival is 16 weeks (w) with 8 pts
dead, 6 alive (7,8,16,17,18,27 w) and 1 lost to follow up. Because of the indi-
vidualized nature of rx regimens employed, no overall conclusion can be drawn
regarding response to rx. In conclusion, GI NHL occurs in a subset of AIDS-risk
pts as their initial dx of AIDS presenting as local regional disease. NHL should
be considered in AIDS-risk pts with abdominal/rectal symptoms or GI ulcers even
with documented 01 or viral GI infection. Despite its early stage at presenta-
tion, this subset of extranodal NHL has a poor prognosis and warrants aggres-
sive rx.
WP228 Response to therapy in 50 patients with HIV-related thrombocyto-
penic purpura.
Eric OKSENHENDLER", P. BIERLING", L-J . COUDERC*, P-M. GIRARD*** , M.
SELIGMANN*, J-P. CLAUVEL*. *: Hopital Saint-Louis, ** : HSpital Henri Mondor.
»»»: Hopital Claude Bernard, PARIS, FRANCE.
Fifty adults (43 males and 7 females) with serum antibodies to HIV were
treated because of profound chronic thrombocytopenia with clinical bleeding
in all but two cases. These patients included 25 intravenous drug addicts, 22
homosexual men, 2 transfused patients and 1 hemophiliac. None had full blown
AIDS ; 20 had persistent generalized lymphadenopathy and 5 splenomegaly.
Mean (+ SE) platelet count was 14+2.10 /l (range 2 to 48). Thirty of 40
tested patients had elevated platelet-bound IgG levels and 11 of 23 had
antiplatelet serum antibodies. Lymphocyte count was below 1 500/mm in 28
patients and T4 cell count below 400/ mm in 20 of 46 patients.
Prednisone (1 mg/Kg/day for at least 1 month) was given to 31 patients. A
response occured in 19 cases with platelet count > 100.10 A in 9 and
J> 50.10 /l in 10 oth* s ; 6 patients sustained their response off steroids.
Three of 21 patients esponded to danazol therapy (600 mg/day for 6 weeks).
Fifteen of 21 patients receiving high dose intravenous IgG (0.4 g/Kg/day for
5 days) responded and 6 of them could be maintained upon repeated boosters.
Nine patients received anti-Rhesus immunoglobulin infusions (1 000 /jg/day for
2 days of anti-D IgG in 7 Rh+ patients or anti-c IgG in 2 Rh- patients. A
partial response occured in 6. Splenectomy was performed in 20 patients and
was successful in 16. In our experience, it was the best treatment for
patients with severe and symptomatic thrombocytopenia. During a mean follow-
up of 16 months (range 4 to 46) one patient developed AIDS (15 months after
the diagnosis of thrombocytopenia).
WP.231
Oral Ganciclovir: Human Pharmacokinetics and Tolerance
Mark A . Jacobson* , P deMiranda**, D.M. Cederberg**, E C
Brodie , J Mills , UCSF School of Medicine and S.F. General Hospital, San
Francisco, CA. f Burroughs Wellcome Co., Research Triangle Park, NC.
Ganciclovir (DHPG, BW759U) is a nucleoside analog which inhibits herpes
viruses in vitro, and which has been effective in treating severe
cytomegalovirus (CMV) infection in immunocompromised patients. To date, the
drug has been administered only intravenously. As most patients with AIDS
and severe CMV disease have required lifelong daily suppressive ganciclovir
(GCV) therapy to control disease progression, oral therapy would appear to
have practical advantages . We studied the pharmacokinetics of orally
administered GCV in 4 patients with AIDS and CMV retinitis. Repeated oral
GCV doses (10-20 mg/kg every 6 hours) were well-tolerated. With a 10 mg/kg
dose given every 6 hours, mean steady-state peak (Cmax) and trough (Cmin)
plasma levels were 2.01 uM and 0.87 uM, and the AUO was 33.6 uM.hr. With
a 20 mg/kg dose given every 6 hours, mean Cmax and Cmin were 2.96 uM and
1.05 uM, and the AUO was 47 uM.hr. Based on urinary excretion and blood
levels, calculated absorption was 4.5X of the 10 rag/kg q 6 hour dose and
3.0% of the 20 mg/kg q 6 hour dose.
The low blood levels achieved make it unlikely that oral GCV therapy will
be effective for acute treatment of CMV infections. However, with the 20
mg/kg dose, the mean Cmax exceeded the ED of most clinical CMV isolates,
and the mean Cmin level was 5 times higher than that typically obtained with
daily intravenous GCV maintenance therapy. Despite its limited
bioavailability, orally administered GCV should be studied to determine
whether it will be useful for long term suppressive anti-CMV maintenance
therapy in AIDS patients with severe CMV disease.
148
WEDNESDAY, JUNE 3
WP232 ^e effi-cacy °f stress management in reducing high risk
behavior and improving immune function in HIV antibody
positive men.
THOMAS J. COATES and LEON MCKUSICK, University of California, San
Francisco, School of Medicine
This study was conducted to test the hypothesis that stress mana-
gement training for HIV antibody positive men would result in
(1) lower stress and depression, (2) decreased high risk sexual
behavior, and (3) improved immune function. Sixty gay men, who
were positive for antibodies to HIV but otherwise healthy except
for lymphadenopathy , were randomized to treatment of wait-listed
control groups. Treatment Ss were given an 6-week stress manage-
ment program which included training in the relaxation response,
strategies for coping with being antibody positive, strategies
for coping with relationships, strategies for coping with common
stressors, and motivation for health habit change. Dependent
measures included scales to assess stress and depression, reports
of sexual behavior during the month prior to assessment, WBC ,
T-Helper and T-Suppressor enumeration, and measures of immune
function(NK Activity, Lymphocyte Response to Mitogens, Lymphocyte
proliferation to antigen) . The stress management intervention was
effective on several dimensions. We found no differences between
treatment groups at baseline. At posttest, the treatment group
reported significantly less stress and depression than control
Ss. Treatment Ss also reported significantly lower rates of
sexual behavior capable of transmitting HIV. We also found
significantly Mgher levels of NK activity and response to mitogen
in the treatment Ss .
IMP?^ Summary of a Statewide Program to Identify Blood Donors Infected
"r,WJ with Human Immunodeficiency Virus (HIV): Minnesota, USA.
KRISTINE L. MACDONALD*, S.J. SCHLETTY*, R.J. BOWMAN**, H.F. POLESKY***,
R.N. DAN I LA*, M.T. OSTERHOLM*. *Minnesota Department of Health, Minneapolis,
MN, **American Red Cross Blood Services, St. Paul, MN, and ***Memorial Blood
Center, Minneapolis, MN, USA.
HIV antibody screening (with Western blot confirmation) of blood donors
began in March 1985 in Minnesota. Follow-up of infected donors can provide
useful public health information. We report here the results of a statewide
program sponsored by the MN Dept. of Health to identify HIV-infected donors.
Approximately 400,000 donors have been screened in Minnesota for HIV antibody.
To date, 15 state residents who have antibody to HIV have been identified.
14 are male and 1 is female. The mean age is 30 years (range, 20 to 39).
36 patients in Minnesota received blood from previous donations from these
donors; 3 of 15 recipients without other risk factors (20%) were determined
to be HIV antibody positive (14 others are known dead and 7 have not been
contacted). To date, interviews have been completed for 12 donors (all
male). Risk factors were identified for 11: 10 are homosexual or bisexual,
and 1 had sex with a female prostitute. For homosexual or bisexual men,
the mean number of male sexual partners since 1977 is 20 (range 1 to 50).
When asked why they had donated blood, 8 indicated that they did not perceive
they were at risk for acquiring HIV infection, 2 felt peer pressure to donate
blood and 1 wanted to know his HIV antibody status. Our results indicate
that most HIV antibody positive blood donors in our state have known risk
factors for acquiring infection and that lack of (or denial of) perceived
risk is the major reason that persons in high-risk groups continue to donate
blood.
WP233 Inactivation of the Human Immunodeficiency Virus by Neutral
Buffered Formalin and Quaternary Ammonium Compounds.
LINDA S. MARTIN, S.L. LOSKOSKI, W.W. BOND, Centers for Disease Control,
Atlanta, GA.
Because persons working in pathology laboratories have expressed
concern about the survival of the human immunodeficiency virus (HIV) in
tissues fixed with 10% neutral buffered formalin (NBF), we evaluated tbis
reagent's effect on HIV survival. HIV preparations (LAV prototype strain)
with ID-50 titers _> 10^ were rendered undetectable in the ID-50 assay
by treatment with 1% (1% NBF = 0.37-0.4% formaldehyde) or greater NBF. We
also tested effects of quaternary ammonium coumpounds (quats) on virus
viability. The three quats tested — a double quat , a twin-chain quat and a
single chain quat — either alone or in combination constitute virtually
all commercial products marketed in the United States. In our test system
all quats were capable of inactivating HIV (effective concentrations
ranged from 500 to 1000 ppm) further demonstrating HIV's sensitivity to a
spectrum of disinfectant chemicals.
WP236 Confirmation of Antibodies to HIV Prior to Donor Notification of
Test Results: The New York Blood Center Approach. C. BIANCO,
B. HOSEIN, A. WALDMAN, J. VALINSKY, V. MALAVADE, and J. PINDYCK, The New York
Blood Center, New York, N.Y. 10021.
Despite improvements in the specificity and sensitivity of ELISA screening
assays for antibodies to HIV, high frequency of false positives warrants
performance of additional assays prior to donor notification. The most
accepted is the Western blot (WB) , a research test without uniform criteria
for interpretation which in some instances produces uninterpretable results.
We have found strong positive correlation between WB positivity and
absorbance in the ELISA assay for two commercially available tests. WB
positivity is low at low ELISA absorbance ranges and approaches 100% at
high ranges. However, some samples are WB positive in the low range, and
others are negative in the bigh range. To address these inconsistencies we
used additional assays such as the indirect immunofluorescence (IFA) and
ELISA based on different antigenic preparations.
Analysis of results generated a decision tree for confirmatory assays:
(a) WB negative in the low absorbance range or positive in the high
absorbance range is accepted as a true result; (b) all other samples are
subjected to additional confirmatory assays.
The majority of the individuals found to be antibody positive returned
for test repeat, notification and counselling. Results indicated that the
initial decision was correct in all cases. Studies of helper and suppressor
T cells showed that 60% of these individuals had ratios below one,
suggesting alterations of immune function.
WR234 Development of a Simple Clinical Method to Screen for AIDS Virus
1n Blood Donors 1n Underdeveloped Countries.
J ALLEN MCCUTCHAN, M. KLAUBER, C. KENNEDY, S. KLAUBER, P. SPECHKO, D.
JAC0BS0N, et al., University of California, San Diego, San Diego, CA.
A low-cost clinical method for determining AIDS virus (HIV) positive blood
donors 1s needed to control the spread of AIDS via blood transfusions 1n
underdeveloped countries. In many areas of the world cost precludes the use
of antibody screening tests. Using a San Diego population of 159 healthy gay
men of whom half were HIV antibody positive, three simple clinical tests were
used 1n a logistic model to detect seropositive men: hematocrit, number of
enlarged (>1 cm) cervical lymph nodes and number of non-1ngu1nal regional
sites with enlarged lymph nodes.
This 3- factor model yielded a test with 91% sensitivity and 62% specificity.
Addition of more expensive or more complicated predictors made only slight
Improvement 1n test performance. A simpler model which excluded hematocrit
and utilized only the examination of lymph nodes maintained sensitivity (90%),
but was less specific (42%) and thus, would exclude more uninfected donors.
Even at the high seroprevalence (18%) currently reported 1n blood donors
from some African cities (Lancet 1986;11 :1113), the predictive value of a
negative test for the 3-factor model 1s 97% and for the 2-factor model 1s 95%.
Deployment of these tests requires that they first be validated 1n the popu-
lation 1n which they are to be used because sensitivity and specificity of
the test may differ between populations and observers. We conclude that a
simple, low-cost clinical exam may provide a means to screen blood where
cost precludes use of currently available antibody tests.
WP237 Looking Forward: The Challenge of Lookback
S.SAMSON*. M.BUSCH*, J. GARNER*, D.DEITCH*, J.WARD**, H. PERKINS*;
*Irwin Manorial Blood Dank, San Francisco, CA; **CDC, Atlanta, GA.
The vast majority of high-risk donors self-excluded prior to anti-HIV test
licensure, and thus are not presenting to blood banks and triggering lookback.
This is evidenced by extrapolation from the progressively declining seropre-
valence rate over the first two years of the testing (0.3% to O.03*), and our
experience with an expanded lookback effort. As of January, 1987, prospective
screening has identified 32 HIV-positive donors with prior donation histories,
which has resulted in notification of only 200 potentially exposed recipients.
Our broader program has been triggered by two additional events: active
identification of reported AIDS patients with a history of donation, and active
investigation of reported transfusion-transmitted HIV infections. Of 139 AIDS
patients who donated blood at Irwin Memorial Blood Bank since 1977, only 10X
were reported as such by local health departments; the remainder were identi-
fied by active cross-referencing of AIDS case listings with donor records.
These 139 AIDS patients donated blood to ca. 950 people (53/106 tested reci-
pients are HIV+), 28 HIV+ high-risk donors found while investigating 50 TAA
cases has led to notification of an additional 322 potentially infected reci-
pients thus far. Recipient testing of each group showed that 50" of traced
recipients were infected. Although our broader lookback efforts result in
7 fold greater notification over standard programs, it is unlikely that even
this program is tracking the majority of exposed recipients.
149
WEDNESDAY, JUNE 3
WR238 CLINICAL OUTCOME OF HIV INFECTION IN HAEMOPHILIA
UNI. DEBT OF MEDICINE GLASGOW ROYAL INF SCOTLAND.
RAJ AN MADHOK J A GRACIE GDO LOWE CD FORBES
The outcome of HIV infection in Haemophilia is not clear. One US study
showed a 13X 3 yr. incid. of AIDS (SCIENCE 231992-5). No similar studies are
available from elsewhere. We report on the clinical immunological outcome
of 23 HIV antibody positive haemophiliacs followed since seroconversion mean
:49.5 mths range 24-66. One patient is lost to follow up but is known to be
alive .
No patient has developed AIDS but 1 Pts. has had recurrent bacterial
infections. 1 pts. oral Candida. Specific manifestations of HIV infection
include thrombocytropenia in 1 pts. episodic lymphadenopathy in 3 pts.
The total lymphocyte cnt fell over 3 yrs. All pts. had a T4 lymphopenia
median 423 range 321-734. The T4 cnt in early seroconverters ( >_ 50 raths . )
was no different from late seroconverters but in individual pts. th T 4 cnt
fell significantly (p<_ 0.05 prd WX test). The results of this cohort
confirm the previous finding of a lower risk of AIDS in haemophilia.
(SCIENCE 231 992-5) relative to other risk groups. Factors other than time
may influence the decline in T4 cell numbers.
WR241
HIV Positivity: The Psychosocial Impact of Donor Notification
DEBORAH K. DOUGLAS*, H. HARPER*, F. POLK**, American Red Cross,
Chesapeake Region, and Johns Hopkins Hospital**.
We began to notify and counsel donors with confirmed positive HIV antibody
results in July 1985. In our experience, although the majority of donors from
whom a reliable history could be obtained readily admitted to being in a known
risk group for HIV infection, 24% denied any history of exposure to HIV. 43%
of confirmed positive female donors and 18% of males were thus classified as
risk "unknown . "
All counseled HIV positive donors are invited to participate in a prospective
natural history study of HIV infection in blood donors. As part of this study,
we administer the Center of Epidemiologic Studies Depression Scale (CES-D
Scale). This scale is a self-administered questionnaire designed to detect
both the presence and the degree of depression in study participants.
Questions address both affective and physical symptoms. Overall scores range
from 0 to 60, with a score of greater than or equal to 16 indicative of
clinical depression.
CES-D data is presented for the first 48 HIV positive donor subjects, as
performed within two months of notification of their serologic results. 38
successfully completed all questions, and 45% had scores _>_ 16. Donors who
acknowledged risk activity of HIV infection had higher scores (mean = 21)
than donors who acknowledged no risk (mean = 13) (p < 0.1).
We conclude that broad denial mechanisms exist in donors who deny risk for
HIV infection. These mechanisms are intact not only when they donate blood but
also when they are confronted with evidence of infection. Such denial will
complicate donor notification, counseling and recommendations for behavior
modification to prevent further transmission of HIV in this population.
WR239 Immunological Alterations Unrelated to HIV Infection in Transfused
Children with Sickle Cell Disease
NAOMI L.C. LUBAN*. A.E. WILLIAMS**, M. SULLIVAN**, G. REAMAN*, Children's
Hospital National Medical Center and **Jerome H. Holland Laboratory, American
Red Cross, Washington, D.C. and Rockville, MD. USA
Immunological abnormalities similar to those seen in AIDS have been reported
in adults and children with sickle cell disease (SCD) receiving chronic RBC
transfusion. The extent to which these abnormalities develop in the absence of
HIV infection is unknown. We have performed longitudinal serological and
immunological evaluations of 20 transfused children with homozygous SCD from
1983 to 1986 to determine the frequency of immunological alterations over time.
Seven children (2-16 years) receiving sporadic transfusion (STX), and 13
children (9-16 years) receiving chronic transfusion (CTX) were studied.
The mean numbers of transfusions received prior to the first assessment of
the STX and CTX groups were 5.9 and 90.7 respectively. The second assessment
was done from 25 to 44 months following the first. The groups received a mean
of 4.5 and 79.7 transfusions respectively during the study interval.
No correlation was observed in either group between the transfusion load and
0KT3, 0KT4, or 0KT8 numbers, 0KT4/0KT8 ratio, and serum levels of total Ig or
beta-2 microglobulin. Four of the 13 STX children experienced absolute 0KT4
reductions of greater than 85% over the study interval. Three of the seven CTX
patients experienced absolute T4 reductions of greater than 50%. All other
children remained normal. One CTX patient with a 51% reduction in T4 count
seroconverted to HIV. All other patients were HIV-EIA negative, although four
demonstrated reactivity to HIV/p24 by Western blot. Our data suggest that no
consistent immunological abnormalities are produced by large numbers of RBC
transfusions over time, but that T4 lymphopenia not directly attributable to
HIV may occur, in. selected children .
WR242 Diagnosis of HIV Exposure With a Competitive Enzyme Immunoassay
(CIA) for Antibody to the Transmembrane Envelope Glycoprotein
(gp41) of Human T-Lymphotropic Virus, Type III (HTLV-III).
J. SCOTT WEBBER, G. J. DAWSON, J. C. HUNT, R. G. ALLEN, E. CHAN, R. H.
DECKER, et al., Abbott Laboratories, North Chicago, IL.
Conventional ELISA techniques have proven extremely useful 1n removing HIV
infectious units from the blood supply. We have developed a specific and
sensitive two-step competitive immunoassay (CIA) that utilizes a recombinant
DNA derived full length p41 protein and a monoclonal antibody to detect
antibodies to the transmembrane envelope glycoprotein (gp41). To show the
reliability of anti-gp41 as an indicator of HTLV-III (HIV) exposure, we
tested sera from patients with acquired immunodeficiency syndrome (AIDS),
AIDS related complex (ARC), asymptomatic patients, and blood donors that
were identified as seropositive by conventional screening ELISA and by
Western blot. All samples tested were reactive using the recombinant p41
based CIA. To quantitatively compare sensitivity between Western blot and
CIA, serial 2-fold dilutions of eleven patient sera (5 AIDS, 3 ARC, 3
asymptomatic) were tested. The CIA proved to be three to six 2-fold
dilutions more sensitive than Western blot when scoring for gp41. In
addition, early antibody response to HIV in seroconversions was detected by
the CIA in samples nonreactive or weakly reactive with conventional
screening tests and/or Western blot. These data Indicate that antibody to
gp41 is a highly reliable and consistent marker for HIV exposure throughout
all stages of the disease.
WP240 THE EFFECTS 0N THE DONOR BASE OF A NATIONWIDE SCREENING PROGRAM
FOR THE PREVENTION OF TRANSFUSION ASSOCIATED HIV INFECTION
J.B. Derrick, S. Mankikar, M.G. Davey, Canadian Red Cross Blood Services,
National Headquarters, TORONTO, CANADA
Maintaining an inventory of the safest possible blood and components while
maintaining an adequate donor base has been a continuing challenge ever since
the possibility of transmission of AIDS by blood was recognized. Through the
implementation of nationwide, standardized donor and donation screening
procedures the Canadian Red Cross has, however, been able to essentially
eliminate the threat of HIV infection through transfusion with no significant
impact on the donor base. Donor screening includes obligatory reading of an
information pamphlet, individual interviews with options to exclude use of
possibly infectious units, laboratory testing of donations by enzyme immuno-
assay (EIA) , discard of repeatably EIA reactive donations, and confirmatory
testing by Western blot (WB) . Donors are forewarned that a positive test
means that they will be permanently deferred from donating, that they should
consult their doctor and that, where required by law, their anti-HIV status
will be reported to regional health authorities. Nevertheless, donations
during the first year of anti-HIV testing increased over the preceding year
by 2%. The incidence of repeatably reactive donations was 0.3% and some
95.6% of these could not be confirmed by WB. A follow-up study of those who
return to donate is underway. Preliminary analysis of 377 returnees shows
47.5% tested EIA-/WB-, 34% remained EIA+/WB-, 18% tested WB indeterminate and
0.5% had seroconverted to EIA*7WB+. A policy for notification of donors
who consistently test EIA+ and/or WB indeterminate is under development.
The data and findings outlined above will be updated on the basis of 1% years
experience at the time of presentation.
WP243 H0W SAFE WAS <AND IS' BL00D TRANSFUSION IN SYDNEY, AUSTRALIA.
ARCHER GT, BOLTON W, COOK LA, COULITS T, KENRICK KG, LEARMONT J.
New South Wales Red Cross Blood Transfusion Service, Sydney, Australia.
72 cases of post-transfusion HIV infection in patients other than
haemophiliacs have been reported and or traced by the Blood Transfusion
Service in Sydney to the end of January 1987. 20 of these patients have
developed AIDS (18 deaths), 14 have lymphadenopathy, the remainder have no
symptoms. HIV infection has resulted from transfusion of whole blood, red
cells, platelets and plasma. Follow-up studies have shown an extremely high
risk of HIV transmission from all donations made subsequent to implication
of that donor in a known case.
The number of donors who have been proven anti-HIV positive in look-back
studies to date stands at 27; 18 of them have been responsible for
transmission of the virus in 32 cases.
The risk of HIV infection increased progressively from 1 to 85,000 per unit
transfused in 1980 to 1 in 4,000 in 1984. No case has been reported in
patients transfused since routine screening for HIV antibodies commenced In
Australia on 1 May 1985.
150
WEDNESDAY, JUNE 3
WR244 Comparative Detection of anti-HIV in a Seroconverting Blood Donor
RICHARD T. SCHUMACHER* , G.E. TEGTMEIER**, D. THOMAS***, *Boston Bio-
medica, Inc., Mansfield, MA, **Cortmunity Blood Center of Greater Kansas City,
Kansas City, MO, ***Electro-Nucleonics, Inc., Columbia, MD
Plasma drawn from a male homosexual at weeks 0, 9, 12, 15, 17, 18, 19, 20,
and 23 (1981) was tested (1987) for anti-HIV by seven FDA licensed ELISA proce-
dures, an unlicensed ELISA (Abbott: Envacor), Western Blot (WB) , and IFA, as
well as for HIV antigens by an experimental antigen-capture assay (Electro-
Nucleonics) , and for antibodies to H-9 cellular antigens.
One licensed ELISA procedure (Organon Teknika: Bio-EnzaBead fflLV III) de-
tected anti-HIV at 12 weeks; the other six first detected anti-HIV at week 15.
Signal to cutoff (s/co) ratios consistently increased following initial reac-
tivity. With Envacor, anti-gp41/160 was detected at 12 weeks; anti-p24/55 at
week 18. By WB, anti-p24 first appeared at week 15, followed by anti-gp41 at
week 18; anti-p31 was never detected. With IFA, the 15 week and subsequent
specimens were reactive. Antigen-capture assay detected HIV antigens at week 12
only; antibodies to H-9 antigens were never detected.
These data suggest 1) in anti-HIV seroconversion, HIV antigens are tran-
siently serologically detectable, suggesting the presence of infectious virus,
2) anti-HIV can be detected by sensitive ELISA concomitantly with the first de-
tection of HIV antigens, obviating the need for HIV antigen tests in current
blood bank screening, 3) repeatably positive ELISA reactions with IFA/WB nega-
tive or WB p24 positive only results may represent early seroconversion; thus,
follow-up studies are essential, 4) in sequential samples, consistently in-
creasing s/co ELISA ratios, positive IFA results, and the emergence of anti-
bodies to additional HIV antigens in WB are indicative of seroconversion, thus
confirming infection, 5) current ELISA procedures have end-point sensitivities
equal to IFA and WB, except Bio-EnzaBead which appears slightly more sensitive.
WR247 Studies of Normal Donor Specimens Causing Various Reactivity Patterns
in Sensitive Western Blot Assays.
PETER L. TAN, J. W. D. KAY, and D. MUNJAL, Organon Teknika Corporation,
Durham, NC.
Western blot (Wb) has become a valuable technique for demonstrating the anti-
body fingerprint of a particular serum to the antigens of HIV. However, as
has been recognized, there are many Western blot assays being used currently
with variations in virus preparations, blotting techniques, reagents and in-
cubation conditions, visualization techniques and standards for acceptability.
Recent attempts to use a very sensitive Western blot test to evaluate speci-
mens from the clinical evaluation of the improved Bio-EnzaBead HTLV-III ELISA
test system indicated that there were normal donor specimens having a variety
of reactive bands, primarily in the pl7, p24, p53 and p66 regions. However,
periodically there was some reactivity in the gp41 area, but the banding was
more restricted and not the characteristically diffuse zone, and repeated runs
of the same specimen would not yield reproducible detection of bands in the
gp41 region. Two specimens that appeared to have this type of nonreproducible
gp41 reactivity were analyzed with a sensitive IFA technique used by the San
Francisco Department of Public Health (J. Wilber); both were nonreactive even
at a 1:3 dilution. Adsorption of the sera with a T-cell line followed by
Western blot showed elimination of reactivity; the major reproducible band
seen is to the p24 region, and this was completely eliminated. These results
would caution that the use of very sensitive Western blot tests for evaluation
of normal donor specimens may require multiple blot tests and/or possible
adsorptions in order to indicate significant reactivity in Western blot.
WR245 Importance of T Cell Subset Determinations in Heavily Treated, Se-
vere Hemophiliacs
SHELBY L. DIETRICH*. D.C. BOONE**, J.W. PARKER**, *Hemophilia Treat-
ment Center, Orthopaedic Hospital, Los Angeles, CA, **USC School of Medicine,
Los Angeles, CA.
A retrospective study was undertaken to determine correlation between T cell
changes and clinical outcome of patients with severe A or B hemophilia. 186 pa-
tients were followed from 1983 through 1986 with serial determinations of lympho-
cyte subsets and white cell and platelet counts. The patients were arbitrarily
assigned to two groups based on T4 cell counts: 46 with less than 400 T4 cells
(Croup 1) and 140 with more than 400 T4 cells (Croup 2). Median follow-up
times were 17 months for both groups. In Croup 1, 10 (22%) developed AIDS,
13 (28%) developed ARC, and 46 (50%) remained asymptomatic. In Croup 2, 9
(6%) developed AIDS, 11 (8%) developed ARC, and 120 (86%) remained asympto-
matic. When data from the AIDS patients were separated from the groupings,
median T-lymphocyte values were:
NonAIDS AIDS p
i-400 T4 Cells
^400 T4 Cells
Initial T4 297 693 322 0.01
Final T4 224 562 143 0.01
The relatively unchanging course of Croup 1 subjects may indicate either a
long incubation period prior to clinical disease or a relatively high resistance
to clinical infection. Subjects who had relatively stable values tended to remain
asymptomatic. The T cell counts of the AIDS subjects were characterized by
a marked progressive decline. Therefore, serial declines in T cell subsets may
be an early indicator of clinical disease.
WP248 TRACING OF SEROPOSITIVE BLOOD DONORS TO ASSESS THE PRESENCE OF
RISK FACTORS
G. IPPOLITO*, P. ANGELONI**, E. MANNELLA**, CA. PERUCCI* *Latium Region
Epidemiologic Unit, National Center for Blood Transfusion- Italian Red
Cross; -Rome, Italy
Starting from 1983 National Health Services and blood bank associations made
recommendation that members of risk group for AIDS should refrain from blood
donation, to reduce the risk of infection associated to the administration
of infected blood. Nevertheless after the availability of screening tests
for anti HIV antibodies, person at increased risk for AIDS started to donate
blood to have a ascertain their immunologic status versus HIV infection. In
Latium Region screening of blood unit for anti HIV antibodies is mandatory
starting from 1985. Prevalence of seroposit ivity , Western blot confirmed is
.0006. To evaluate the risk factors of seropositive blood donors and
compliance to the self-exclusion programmes all seropositive subjects from
National Transfusion Center of Italian Red Cross were contacted. From March
1985, 89113 blood donors have been tested. 228 were repeatable seropositive
to screening tests and 53 confirmed by WB. 42 out of 53 seropositive have
been traced. Of These 5 (11. 9%) were intravenous drug addicts (IVDA), 21
(50%) IVDA in the past, 6 (14. 3%) partners of a IVDA, 1 (2.41) homosexual
and IVDA, 3 (7.1%) homosexuals, 3 (7.1%) promiscuous heterosexuals, 2 (4.8%)
not Known risk factors. This result evidences that the alternative sites
availability, free of charge in Italy, for anti HIV testing and predonation
appeals to refrain from donating plasma and/or blood are not effective in
dissuading subjects at risk. Mass campaigns and more extensive pre-donation
counselling and medical examinations are needed to avoid the risk increase
of transfusion associated infections.
WP246 Evaluation Of HIV Antigens Obtained From Commercial Sources By The
Western Blot Technique
RONALD C. FITZGERALD, L. A. MOTLEY, J. A. ROKOVICH, K. C. PALLIS, D. GOLDSTEIN,
G. B. LAMOTTE , Bio-Rad Laboratories, Clinical Division, 1000 Alfred Nobel
Drive, Hercules, CA 94547.
HIV antigen preparations consisting of disrupted virus particles are avail-
able from several commercial sources and have been used as antigens for de-
tection of antibodies. In order to evaluate the relative concentrations of
the viral proteins and purity of these preparations, the HIV proteins were
separated by the Western Blot technique. The relative amounts of viral and
non-viral prbtein were determined by' protein staining and analyzed by reflect-
ive densitometry. Immunoreactivity to a panel of patient sera was measured by
enzyme immunoassay of the WB strips. With many of the commetcial HIV antigen
preparations, the majority of the proteins did not migrate at positions cor-
responding to immunoreactive viral-specific proteins and glycoproteins. Large
amounts of protein were found at 70,000 Daltons and/or less than 18,000
Daltons. With some preparations, these contaminants reacted with ELISA nega-
tive sera samples to give faint bands. With some preparations a weak non-
viral band was also noted at a position corresponding to the viral major cap-
sid protein p24. These contaminants could confuse interpretation of HIV
negative sera. The amount of protein migrating at particular band position
did not necessarily reflect the potential immunoreactivity. This was most
evident for high and low molecular weight regions. The highly immunogenic
gpl60/gpl20 were often barely detectable or non-existent in some preparations
by immunoreactivity. These studies emphasize the importance of careful eval-
uation of the purity and immunoreactivity of each commercial HIV antigen by
WB analysis for diagnostic and analytical purposes.
WP249 Prospective follow-up of transfusion-associated acute HIV infection
JI_ESTEBAN,J GENESCA.JM HERNANDEZ, L MASSUET, JWK SHIH.HJ ALTER, et al
Hospital Vail d'Hebron, Barcelona, Spain and Dept .Transf. Medicine, National Insti-
tutes of Health, Bethesda.MD.
To identify recipients during the acute phase of TA HIV infection, 4,725 donor
samples, collected in Barcelona during the 2 months prior to routine screening,
were tested for anti-HIV by EIA.Of the 4 units positive by EIA and WB, only 3
had been transfused to 4 recipients .Of these, 2 were dead at the time of identi-
fication,! could never be contacted and 1 has been prospectively followed since
posttransfusion week 4. This recipient, a 54-year old woman who received 1 posi-
tive unit of PRCs during breast cancer surgery, is currently undergoing weekly-
plasma and lymphocyte-pheresis. Results on initial evaluation of HIV-antibody ,
HIV-antigen (using commercial kits) and T-cell subsets are shown in the table.
WEEKS POSTTRANSFUSION
•I
5
6
~
S
9
11
12
HIV-Ab EIA
1:2*
1:2
1:2
1:1
1:1
1:1
1:2
1:8
HIV-Ab WB pl60
+
+/-
+/-
-
-
-
+
++
p41
-
-
-
-
-
-
+/-
+
p24
-
-
-
*/-
+
+ +
+ ++
++ +
HIV-Ag EIA
T4 (cells/mm )
+
-
-
-
-
-
-
-
ND
ND
NA
213
850
452
926
983
T8
ND
ND
NA
1,175
1,006
964
1,109
T4/T8
ND
ND
NA
0.07
0.7
C.4
0.8
ND:Not done; NA:cells not available; *end-point dilution
No clinical symptoms or physical abnormalities have been detected during follow
up. Attempts to recover the virus from cryopreserved lymphocytes and plasma, cha-
racterization of early morphological and functional changes in PBLs and search
for neutralizing antibody in sequential samples are currently under way.
151
WEDNESDAY, JUNE 3
WR250 Anti-HIV igM Screening in High-Risk Subjects
G. BEDARIDA*, P. CROCCHIOLO*. GIUSEPPE CAMBIE'*, F. D'A-
GOSTINO*, I. ARCIDIACONO*, M. PASQUALI**, et al. , *Ospedale Maggie—
re, Lodi, Italy, **Istituto dei Tumori, Milan, Italy.
Most of the tests developed for the screening of HIV antibodies
are aimed at HIV-IgG, only a few at HIV-IgM detection, while com-
petition tests theoretically should be able to evidence both clas-
ses of immunoglobulins. Sixty-five parenteral drug-addicts (PDAs)
and 123 poly transfused subjects, all resulting HIV-IgG negative by
different commercially available tests, were investigated for the
presence of HIV-IgM also by a modified ELISA method which we deve-
loped to make it more specific and sensitive for IgMs (Tech IgM
HTLV III, Technogenetics, Torino, Italy). According to this 5 out
of 65 HIV-IgG negative PDAs (7.7"/) were found HIV-IgM (WB-IgM con-
firmed) positive; IgM positivity was also evidenced in 3 polytrans
fused, HIV-IgG negative subjects. IgM-IgG switch was shown in 4
out of 5 PDAs 1 to 38 weeks (mean 19 weeks) after the first IgM-po
sitive result. In the 3 HIV-IgM positive polytransfused subjects,
for each of whom an HIV-positive donor was traced, IgM appeared ap-
proximately 12 weeks after transfusion and, in 2 of them, IgM-IgG
switch occurred after another 8 weeks. In all subjects examined,
HIV-IgM, representing the earliest sign of infection, were detected
by our test (WB-IgM confirmed) at least some weeks before this
could be done by other methods, including competition tests.
152
THURSDAY, JUNE 4
Plenary Session V
Virology — Related Viruses
TU -1 -1 The Human Immunodeficiency Viruses: 1987.
Luc MontaRnier, Institut Pasteur, Paris, France.
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
TH.2.1 Nucleotide Sequence Analysis of the West-African AIDS Virus, HIV-2.
M. GUYADER', P. SONIGOZ, M. EMERMAN', F. CLAVEL', L. MONTAGNIERl, and
MARC AL1ZON1. 1 : U. d'Oncologie Virale, and 2 : UREG, Institut Pasteur, Paris,
France.
A novel retrovirus, the human immune deficiency virus type 2 (HIV-2, previously
named LAV-2), was isolated from patients with AIDS and related conditions originating
from West Africa (Guinea Bissau, Senegal, Gambia, Ivory Coast ...). This virus is related
to HIV-1, the causative agent of AIDS in Central and East Africa, as well as the USA
and Europe, by its morphology and by its tropism and in vitro cytopathic effect on CD4
(T4) positive cell lines and lymphocytes, but differs from it by lack of hybridization of
the genomes and absence of antigenical cross-reactivity of the envelope glycoproteins.
The complete proviral DNA from one HIV-2 isolate (ROD) was cloned, and used to
confirm the distant relationship of HIV-1 and 2, this latter being more closely related to
a simian retrovirus termed STLV-3 or SIV. Polymorphism is observed by restriction
mapping of HIV-2 isolates.
We have sequenced the complete HIV-2rod genome and observed an overall genetic
organization similar to HIV-1. However, the HIV-2 genome is longer (9.6 kb. against 9.2
kb.), mainly because of large insertions in the LTR. The proteins of HIV-1 and 2 are
highly divergent, the degree of conservation ranging from 50 % (for gag and pol) to less
than 30 % of the aminoacids for the large env glycoprotein, F and Q proteins.
Homologous domains in env will be very useful to delineate domains involved in
functions common to HIV-1 and 2, such as cell fusion and T<f binding.
TH.1.2 Human and Simian T Lymphotropic Retroviruses: Serologic
Identification and Vaccine Development.
M. ESSEX*, P. KANKI*. R. MARLINK*, S. M'BOUP**, F. BARIN***, F.
DENIS****, et al., *Harvard School of Public Health, Boston, MA,
"Dakar University, Dakar, SENEGAL, ***Univ. Bretonneau, Tours, FRANCE,
****Univ. Dupuytren, Limoges, FRANCE.
Retroviruses related to HIV have been detected in subhuman primates
where up to half of the wild-caught African green monkeys have
serologic evidence of exposure to such viruses, designated STLV-3.
Following natural exposure monkeys rarely, if ever, develop disease.
Using seroepidemiological approaches, healthy people in West Africa
were found to be exposed to viruses that are closely related to STLV-3,
and designated HTLV-4, LAV-2, HIV-2, SBL-6669, or West African
retroviruses (WAR). In some instances such viruses are found in
individuals with AIDS-like illnesses. However, seroepidemiological
studies did not reveal an association between antibody positivity and
disease development.
Infection rates vary widely for different geographical locations in
West Africa, but Central Africa seems free from exposure to this virus.
HTLV-4 type viruses are transmitted primarily by sexual contact as
illustrated by elevated infection rates in female prostitutes. Yet
infected prostitutes generally remain healthy and free of lympha-
denopathy. Understanding why infection with STLV-3 or HTLV-4 does not
pose a high risk for AIDS should be important to determine how to
generate immunity in people exposed to HIV.
TU O 2 Conservat
' VANESSA H
VIGLIANTT AND JAME
Harvard School of
Type 3 Simian
biologic character
as a receptor, syn
similar ultrastruc
transcriptase, maj
proteins of simila
from African Green
virtue of weak nuc
acid sequence anal
and STLV-3 share a
sequences of the e
55% homology in re
env gene, and anal
dues in HIV. This
possess a similar
found to be unique
(tat and art) are
STLV-3 likely util
et al ) . A high de
sequence was also
is unknown, and in
has yet been ident
play an important
ion of genome organiz
IRSCH, NORBERT RIEDEL
S_ I_5. MULLINS Departm
Public Health, Boston
T-lymphotropic virus
istics with HIV, util
cytia formation in T4
tural morphology, Mg+
or gag-, env-, pol-
r size and immunologi
monkeys was recently
leic acid cross-react
ysis of the 3' 4.2 kb
similar genome struc
nvelope gene of STLV
gions identified as c
ogous positioning of
indicates that these
backbone structure.
to HIV and shown to
preserved in STLV-3,
ize similar regulator
gree of conservation
noted within the 3'-
the "R" open reading
ified. This strongly
role in the life cycl
ation between HIV and STLV-3
HARDY KORNFELD, GREGORY
ent of Cancer Biology,
MA 02115
(STLV-3) shares many
ization of the T4 molecule
-lymphocytes in vitro,
2 dependent reverse
and 3 ' orf -encoded viral
c cross-reactivity. STLV-3
molecularly cloned by
ivity with HIV. Nucleic
of STLV-3 reveals that HIV
ture . Predicted amino acid
3 and HIV share up to 50-
onstant domains of the HIV
all of 18 cysteine resi-
divergent proteins likely
Coding regions previously
encode regulatory functions
indicating that HIV and
y mechanisms (see Viglianti
of predicted protein
rf region, whose function
frame for which no protein
suggests that both genes
e of each virus.
TH.1.3 HIV infection in the central nervous system
LENNART WETTERBERG, ANDERS SONNERBORG, the Karolinska Institute, Stockholm,
Sweden.
The central nervous system (CNS) effects of human immunodeficiency virus
(HIV) has recently been acknowledged. CNS involvement may be monitored using
psychological testing, computer tomography and magnetic resonance (MR) imaging
technique. By combining the MR unit with an imaging enhancing technique
reconstruction of different brain regions can be made and treatment effects
may be followed by measuring the relaxation times T 1 and T 2.
New treatments using short peptides such as the octapeptide, peptide T are of
interest since clinical testing indicate that it appears non-toxic and may have
potential benefit. The working hypothesis is that peptide T, D-Ala-Ser-Thr-Thr-
Thr-Asn-Tyr-Thr, inhibits HIV-infection by blocking the binding of the viral
envelope to the CD4-receptor. Peptide T is a segment of the envelope glyco-
protein (gp-1.20) of the HIV.
Neuropathological findings in the brains of patients with AIDS are common and
suggest that HIV might induce irreversible damage. There is however a dis-
crepancy between the degree of cerebral atrophy and the severity of the CNS
symptoms. The new results using reconstructed MR images in patients treated
with peptide T suggest that the CNS involvement is at least partly reversible.
The methods to test neuropsychiatric dysfunction caused by HIV will be
summarized as well as objective measures to follow the presence of HIV in the
cerebrospinal fluid.
By mimicking the action of peptides, viral proteins could exert hormonal
effects throughout the body, including the CNS, and thus may have a role in
the etiology of the progressive dementia of patients with AIDS.
TH.2.3
Molecular characterization of HTLV-4
B. HAHN*, S. ARYA**, P. KUMAR*, M. TAYLOR*, L. KONG*. S. LEE*,
F. WONG-STAAL**, R. GALLO** , G. SHAW*. *University of Alabama at Birming-
ham, Birmingham, AL; -'"''Laboratory of Tumor Cell Biology, NCI, NIH. ,
Bethesda, MD.
A novel human retrovirus, termed HTLV-4, has recently been isolated from
West African individuals at high risk for sexually transmissible diseases .
This newly discovered virus is related to HTLV-3/LAV in its tropism for 0KT4
lymphocytes, the antigenicity of its core proteins, and its in vitro growth
characteristics but is clearly distinct from the AIDS virus in its
ultrastructure, the size and antigenicity of its envelope proteins, and its
apparent clinical sequelae. The existence of these two viruses -- both
tropic for OKT4 -positive cells yet possessing major differences in protein
structure and biologic activity -- provides a unique opportunity to study
the molecular biology and structure-function relationships of both
HTLV-3/LAV and HTLV-4. We have molecularly cloned the full-length provirus
along with unique flanking cellular sequences from two isolates of HTLV-4
and have prepared subclones for transfection and for nucleot ide sequence
analysis. Comparisons between HTLV-4 and HTLV-III/LAV reveal underlying
similarties in gene organization (env, 3'orf, and LTR) although overall
nucleotide sequence homology is in the range of only 402. Interestingly, a
peptide sequence from the 3' terminus of the HTLV-III/LAV envelope implicat-
ed in its cytopathicity is conserved (12 out of 14 amino acids) in HTLV-4.
Structure-function relationships especially concerning the envelope
glycoprotein between HTLV-4 and HTLV-III/LAV will be discussed.
153
THURSDAY, JUNE 4
TU O A Molecular Cloning and DNA Sequencing Analysis of LAV-2 (Lymphadeno-
pathy Associated Virus Type 2)
BRUNO STARCICH, J. F. ZAGURY, S. JOSEPHS, F. WONG-STAAL and R. C. GALLO,
Laboratory of Tumor Cell Biology, National Cancer Institute, NIH, Bethesda MD.
A new subgroup of primate retroviruses serologically related to the human
AIDS agent, HTLV-III(HIV) has been recently identified. This includes the
simian T-lymphotropic virus type III (STLV-HI) , isolated from African green
monkeys , and three human retroviruses, HTLV-IV, LAV-2 , SBL6669, from patients
of West African origin. These viral agents share similar morphology, recognize
the same receptor, (OKT-4) but show different pathogenetic potential. In vitro
all but HTLV-IV are able to kill their target cells. In vivo, in their natural
hosts, only LAV-2 and SBL6669 appear to be associated with an immunodeficiency
syndrome . In order to better define the genetic relationship between this new
subgroup of pathogenic viruses and the HTLV-III(HIV) subgroup and to gain
insights into their cytopathic mechanism, we have undertaken the cloning and
sequencing analysis of an LAV-2 isolate. The virus was isolated from an AIDS
patient originally from Senegal seropositive for LAV-2 antibodies. A permis-
sive cell line, H9, was infected with the viral isolate. The genomic DNA was
extracted, partially digested with the restriction enzyme Mbol and used to
construct a lambda phage library. The library was screened using a cDNA probe
homologous to the 3' LTR region of LAV-2 genome. Ten positive clones were
detected and characterized by restriction mapping. The results show an overall
divergence in restriction sites in comparison to HTLV-III(HIV) restriction
map. To further investigate the structure of the LAV-2 genome , we have
sequenced the entire genome of the integrated form of LAV-2 using the Sanger
dideoxy technique . The results of this analysis will be presented.
Health Care — Patient Care, Attitudes,
Knowledge, and Risks
TH 3 1 Helping Young People Face Death: Resuscitation Status and
in First Episode Pneumocystis Carinii Pneumonia (PCP)
RITA FAHRNER,M.J. CLEMENT, A. KLINE, J.B. COHEN, San Francisco Genera
San Francisco, CA, USA.
Since the onset of the AIDS epidemic in 1981, ICU use for a group o
with a uniformly fatal disease has been frequently questioned. Addres
issue, all first episode PCP admissions at San Francisco General Hosp
reviewed for the last six months of 1986 (N=Il5), and DNR choice, ICU
outcome (death or discharge) were noted.
Outcome
1 Hospital,
f patients
sing this
ital were
use, and
DNR Status
No. Patients ICU Admit Discharge or Death
Full code
10
0
10
0
DNR
55
0
42
13
Code, then DNR
4
4
1
3
Code status not addressed
46
0
46
0
This pattern of ICU use reflects the added knowledge on the part of the house
staff, attending physicians, and patients of the poor prognosis of patients
with AIDS requiring ICU admission. With this knowledge, less than 10% of
patients chose to be on full code status.
Patients should be given the early opportunity to discuss their resuscitation
status, and counseled regarding the poor prognosis for PCP patients who require
intubation. A mult idiscipl inary approach to the patient's choice, using medical,
nursing, and counseling resources, allows the patient and family to best under-
stand the implications of their decision. This decision will become more
complex as potentially effective ant iretroviral therapy for AIDS becomes avail-
able. Therefore, we will be monitoring patterns of choice during January -June
1987.
TH 2 5 Characterization of a Pathogenic Lentivirus From Cattle Which is
Structurally, Immunologically, and Genetically Related to the Human
Immunodeficiency Virus (HIV)
MATTHEW A. GONDA*. M.J. BRAUN*, S.G. CARTER*, T.A. KOST*, L.O. ARTHUR*, and
M.J. VAN DER MAATEN**, *Program Resources, Inc., NCI-FCRF, Frederick, MD,
**NADC, USDA, Ames, Iowa.
An infectious retrovirus was previously isolated from leukocytes of a cow
with persistent lymphocytosis, lymphadenopathy, CNS lesions, progressive weak-
ness, and emaciation (Van Der Maaten et al., J. Natl. Cancer Inst. 49:1649,
1972). In vitro the virus replicates and induces syncytia in cells derived
from various embryonic bovine tissues, including brain. By electron micro-
scopy, the virus morphologically resembles HIV and other pathogenic lenti-
viruses. This virus, designated BIV (bovine immunodeficiency-like virus),
possesses a major protein band of 26 kD (p26) and several smaller and larger
virus-specific protein bands by SDS-PAGE. A rabbit antiserum to BIV reacts
strongly in immunofluorescence assays to HIV-infected cells and on Western
blots with p26 and p24, the major core proteins of BIV and HIV, respectively,
but not those of visna or caprine arthritis encephalitis viruses. A competi-
tive radioimmunoassay using the rabbit anti-BIV serum and lz5I-labeled HIV p24
was developed. Consistent with the Western blotting data, disrupted BIV and
STLV-III competed equally well with HIV p24 in this assay, whereas other
lentiviruses competed poorly or not at all. Molecular clones of BIV proviruses
have been isolated from a \ library constructed from genomic DNA of BIV-
infected cells using a cDNA probe made from BIV viral RNA. These clones
hybridize with pol gene probes made from HIV and visna virus. DNA sequence
analysis of the 5' pol gene region of BIV has enabled us to construct a phylo-
genetic tree elucidating the relationship of BIV to other lentiviruses.
TH 3 2 Housestaff Attitudes Towards The Acquired Immunodeficiency Syndrome.
' ' MOLLY COOKE*, B. KOENIG, University of California, San Francisco,
San Francisco, CA.
Care of AIDS patients elicits strong emotional and psychological responses
in providers. In September 1983, we surveyed medical houseoff icers (HO) at
UCSF, addressing estimation of risk to health care workers (HCW's), anxiety
elicited in HO's and satisfaction in the care of AIDS patients. 68% of res-
pondents felt HCW's were at risk of acquiring AIDS. Men and women HO's
differed significantly in their estimation of risk: 84% of men versus 48% of
women agreed HCW's were at risk (p=0.004). Sense of risk affected precautions
followed with significantly more men reporting mask use and glove wearing.
>80% of medical housestaff were at least mildly anxious about taking care of
AIDS patients and estimated that 20% were "very anxious". 97% reported worry-
ing about getting AIDS at least on occasion. 35% reported worrying about giv-
ing AIDS to a family member, 20% reported dreams or nightmares about AIDS and
18% reported symptoms which they felt were suspicious of AIDS. Men were more
likely to report their preoccupation, dreams and nightmares and rated their
anxiety significantly higher than did the women respondents (p=0.03). House-
staff chose the midpoint of a 4 point Likert scale when asked to express satis-
faction. Increased contact with AIDS patients predicted a less negative res-
ponse with 68% of HO's who had cared for <10 patients disliking AIDS care com-
pared to 35% who had cared for >10 (p=0.02). To a large extent these responses
are gender dependent. HO's have responded to this lethal epidemic with exper-
tise and compassion but need more assistance in handling the stress induced by
assuming their professional responsibility.
TH 2 6 Immune Selection of Antigenic Variants of Equine Infectious Anemia
Virus May Occur Through Elimination of Infected Cells Rather Than
Through Neutralization of Cell Free Virions
SUSAN CARPENTER, LEONARD EVANS and BRUCE CHESEBRO, LPVD , N1AID, NIH, Rocky
Mountain Laboratories, Hamilton, MT
The morphological, genetic, and serological relatedness between equine infec-
tious anemic virus (EIAV) and human immunodeficiency virus (HIV) has increased
interest in understanding the role of variation of EIAV in viral persistence
and the host response to infection. EIAV was Isolated from peripheral blood
leukocytes collected during two, early, febrile periods of an experimentally
infected horse. These isolates, referred to as MA-1 and MA-4, were shown to be
genetic and antigenic variants by RNase T. -resistant oligonucleotide finger-
print analyses and membrane immunofluorescence of infected cells. The finding
that variant-specific epitopes of EIAV were expressed on the surface of infect-
ed cells indicated that immune selection of viral variants might occur through
immunologlcally-mediated destruction of EIAV-infected cells. Furthermore,
antibody to variant-specific cell surface antigens was detectable prior to the
development of virus neutralizing antibody. This suggested that neutralization
of cell-free virions may not be important in the selection of EIAV variants.
Biochemical identification of viral proteins expressing variant-specific
antigens was assayed by radioimmunopreclpitation (RIP) using detergent lysates
of EIAV-infected cells. Early immune serum, specific for MA-1 by membrane
immunofluorescence, was found to be broadly reactive by RIP. This apparent
paradox Indicated that EIA viral antigens exposed in detergent lysates were
highly cross-reactive, whereas viral antigens exposed on the surface of live
cells were strain-specific. These data caution against the use of immunoassays
which rely on detergent treatment of antigens in looking for strain-specific
antibody with potential biological importance In variant selection.
TH 3 3 Concerns of Medical and Pediatric House Officers about Acquiring AIDS
from their Patients
R. NATHAN LINK*. ANAT R. FETNGOLD**. MITCHELL H. CHARAP*. KATHY FREEMAN**. STEVEN
SHEL0V***, *New York University School of Medicine. "Montefiore Medical Center,
"•Albert Einstein College of Medicine: New York, NY, USA.
To assess the degree of house officers' concerns about acquiring AIDS from their
patients, we surveyed medical and pediatric residents in four New York residency
programs with large AIDS patient populations. During the study period. 2/1/86-
5/1/86, multiple choice questionnaires were distributed to all house officers present
at the study sites (outpatient clinics) and were completed anonymously. Of 263
questionnaires distributed, 258 (98*) were returned. Thirty-six percent of medical
and 17* of pediatric house officers reported needlestick exposures to blood of
AIDS patients. Forty-eight percent of medical and 30* of pediatric house officers
reported a moderate to major concern about acquiring AIDS from their patients.
Thirty percent of all respondents believed concern about AIDS increased the stress
of their residency moderately to extremely.
Multivariate analysis demonstrated that a greater concern about personal risk was
independently associated with an increased number of AIDS patients treated (p=0.01),
the year of residency training (greater concern in earlier years. p=0.002), and the
type of residency program (greater concern In medical than pediatric house officers,
p=0.0003). A history of needlestick exposure was not significantly associated with
increased concern (p=0.4). Thirty percent of all respondents Indicated they would
want to know their current HTV serology status. Ninety-three percent of respondents
believed concern about acquiring AIDS did not adversely affect their care of
patients; however, 25* stated that they would not continue to care for AIDS patients
if given a choice. The results demonstrate a considerable degree of concern about
acquiring AIDS among house officers caring for AIDS patients and suggest the need
for housestaff training programs to formally address these concerns.
154
THURSDAY, JUNE 4
Clinical Studies — Opportunistic Infections
TH 3 4 AIDS Train the Trainer Program for Health Care Providers: California
Nurses Association's Innovative Approach
HELEN SCHIETINGER*, Z.A. FITZHUCH*, P.K. MCCARTHY*, C. MORRISON**, California
Nurses Association, San Francisco, CA, **AIDS Health Services Project, San
Francisco, CA.
Many health care providers' still harbor fears and misunderstandings about
AIDS that negatively affect the delivery of patient care. In order to resolve
these fears and misunderstandings, the California Nurses Association, working
with the AIDS Project Los Angeles and the San Francisco AIDS Foundation, devel-
oped, implemented, and evaluated an innovative AIDS "train the trainer" pro-
gram. The program was designed to replace didactic lectures with more effective
methods to meet the needs of adult learners. By April 1987, 27 two-day train-
ings were conducted throughout California to certify 750 key health care pro-
viders in both adult learning principles and AIDS content. Creative teaching
strategies such as guided fantasy, role play, and simulation were utilized to
encourage group interaction and the analysis of sensitive issues underlying the
fear of AIDS. By May 1, the 750 certified AIDS educators had each conducted
instructional programs for groups of 25 or more health care providers, includ-
ing direct care providers, support services personnel, and administrators. A
total of 18,750 people were educated in these secondary trainings. Summative
evaluation of the primary trainings indicates that this model is effective for
increasing trainers' competence and confidence related to teaching about AIDS
and HIV infection. Summative evaluation of the secondary trainings is still in
process.
TH 4 1 Preliminary Results of a Phase I-II Trial of
Trimetrexate Therapy for Pneumocystis Pneumonia In AIDS
Patients
CARMEN J. ALLEGRA*, B. CHABNER* , C. TUAZON** , H. C. LANE*, D.
ARAKAKI*, H. MASUR*, et al . , *National Institutes of Health,
Bethesda, MD , **George Washington University, Washington, D.C.
Trimetrexate ( TMTX) , a potent Inhibitor of dihydrofolate
reductase, has been shown in laboratory studies to have potential
advantage over conventional agents for therapy of Pneumo cy s t is
carinii pneumonia (PCP). In this trial, AIDS patients wit!
histologically proven PCP (first or subsequent episode) wer
treated with TMTX (.30 rag/M QL> xZl days; plus leucovorln (.LV
(20 mg/M2 Q6h x 23 days) ± Sulfadiazine (S) (1.0 g Q6h x
days). Pharmacokinetics of TMTX were highly predictable with a
1/2 of 9 hours. Toxicity possibly related to TMTX was minima
consisting of purpuric rash (1/42 patients), mi
granulocytopenia (5/42 patients) and thrombocytopenia (8/
patients), plus mild t ransaminas emia (8/42 patients). Cytopeni
were easily managed by dose adjustments of TMTX or LVN. Comple
responses were seen in 9/13 previously untreated patients w
received S + TMTX/LVN; 9/14 previously untreated patients w
received TMTX/LVN without S; 9/13 patients who fail
conventional therapy and received TMTX/LVN without S. Relaps
within 1 month were seen in 5 patients. Results of this tri
indicate that TMTX ± S is an effective and well tolerated thera
for PCP, the relative merits of which need to be compared
conventional agents in a larger controlled trial.
TH 1 S Low Occupational Risk of HIV Infection for Dental Professionals (DP) .
ROBERT S. KLEIN*, J PHELAN* , GH FRIEDLAND*. K FREEMAN*, C SCHABLE**,
N STEIGBIGEL*, ET. AL. *Montefiore Medical Center, Albert Einstein College of
Medicine, Bronx, NY, and **Centers for Disease Control, Atlanta, GA, USA.
In Oct. 1985 we began a study of the prevalence of serum antibodies (Abs) to
HIV In DP recruited via a mailing and at professional meetings. Subjects com-
pleted questionnaires on demographics, type, duration and location of practice,
AIDS high risk behavior, precautions used in treating patients (pts) , and types
of pts treated. HIV Abs were assayed by EIA, with Western blot confirmation of
positives. Homosexual men and parenteral drug abusers were excluded.
Of 1009 subjects, 919(91%) were dentists, 90 hygienists; 807(80%) were male.
Major types of dental practice were restorative(52%) and oral surgery(5%) . 324
DPs(32%) practiced In the New York City area, 43(4%) in Miami, and 20(2%) in
Houston, Los Angeles, or San Francisco. 116/988 respondents (12%) had treated
known AIDS pts (median 2, range 1-78), 708/983(72%) members of AIDS risk groups.
At time of screening 313/977(32%) used gloves at all times, 579(59%) for selec-
ted pts or procedures, 85(9%) never. Eye protection was used by 581/899(65%)
always, 238(27%) sometimes, 80(9%) never. 531/936(57%) had increased use of
precautions since 1983, 83% at least partly due to concerns about AIDS. 895/987
(91%) reported accidental parenteral puncture wounds by instruments; median
number per subject over the preceeding 5 years was 10(range 1-1000). 568/1002
respondents (57%) had not received hepatitis B vaccine; of these, 122/546
tested (22%) had Abs to hepatitis B surface antigen.
None of the 1009 subjects had Abs to HIV confirmed by Western blot.
Therefore, DP appear to be at very low risk of occupational acquisition of
HIV infection (95% C.I., 0 to .003), even though recommended precautions are
not always used and accidental parenteral puncture wounds are frequent.
Routine use of recommended precautions should make any risk even more remote.
TH 4 2 Studies on Successful Eflornithine Treatment of Pneumocystis Carinii
Pneumonia (PCP) in AIDS Patients Failing Conventional Therapy
B.D.McLees, J. L.R. Barlow, R.J.Kuzma, D.C .Baringtang , P. J. Schechter ,
A.Sjoerdsma, Merrell Dow Research Institute, Cincinnati, Ohio.
Eflornithine (E; DL-a-dif luoromethylorni thine) is an irreversible inhibitor
of ornithine decarboxylase with activity against several protozoan species re-
lated to Pneumocystis carinii (PC). This antiprotozoan activity, plus dramatic
therapeutic results in a few patients, led to compassionate E use by 189 inves-
tigators treating 345 AIDS patients with proven PCP. The patients, entered be-
cause of treatment failure and/or intolerance to trimethoprim-sulfamethoxazole
(TMP-SMX) and/or pentamidine (P), had no therapeutic alternatives and little or
no chance for survival . The recommended E dose was 100 mg/kg I.V. q6h for 14
days followed by 4-6 weeks oral therapy at 75 mg/kg q6h. Efficacy was measured
by survival to hospital discharge and clinical response evaluated from changes
in arterial blood gases , chest X-ray, defervescence and followup lung biopsy.
Survival for patients receiving >4 days of E therapy (266/345) was 10/101 (10%)
in patients receiving mechanical ventilation (MV) at study entry and 109/165
(66%) for spontaneously breathing (SB) patients at study entry. Survival for
subjects receiving M4 days E treatment ( 160/345) was 10/43 (23%) for MV
patients and 91/117 (78%) for SB patients. Clinical responses were higher:
27/43 (63%) MV patients completing >14 days therapy and 102/117 (87%) SB
patients had positive responses. Followup examinations showed clearing of PC
in 30/74 (40%) patients; the relationship between the disappearance of the
cysts and survival was significant (p <«05). E was generally well tolerated
with thrombocytopenia (48%) , diarrhea (20%) and leukopenia (16%) reported as
the most frequent adverse events. The survival, clinical response and clearing
of PC in patients with little/no expected survival demonstrate E effectiveness
comparable to first line treatment with TMP/SMX and P.
TH ^ fi Prevalence of Unsuspected Human Immunodeficiency Virus In Critically
111 Emergency Patients
JAMES L. BAKER*, G. Kelen*, K. Sivertson*, T. Quinn**, *Department of Emergen-
cy Medicine, The Johns Hopkins Hospital, Baltimore, MD, **Laboratory of Immun-
oregulation, National Institute of Allergy and Infectious Disease, Bethesda, MD
Implementation of recommended guidelines for prevention of transmission of
the human immunodeficiency virus (HIV) to health care workers is not uniform,
and in part is based on a lack of recognition of the extent of asymptomatic
HIV infection in this country. In order to reinforce the need for appropriate
infectious disease precautions, we tested for HIV antibody seropositivity in
203 critically ill patients presenting to an urban emergency department, none
of whom had a previous diagnosis of HIV infection.
We found that 6 (3%) of the total were seropositive by both enzyme-linked
immunoassay (EUSA) and Western Blot, and that these 6 represented 16% of the
37 patients between 25 and 34 years of age. All seropositive patients were
victims of trauma, and of 10 gunshot wound victims between the ages of 25 and
34, 3 (30%) were seropositive .
None of the seropositive patients had been suspected of being infected, all
were actively bleeding, and all required multiple invasive procedures , includ-
ing by paramedics in the field and by physician staff in the emergency depart-
ment .
These results reinforce the necessity of infection control precautions, whe-
ther or not previous suspicion of HIV infection exists.
TU A Q Cyclosporin A may induce deterioration in patients with AIDS.
" ' ANNE PHILLIPS*, M. FANNING, P. HALLORAN, R. COATES, M. KLEIN,
S. READ, et al., University of Toronto, Toronto, Canada M5G 2C4.
The pathogenesis of AIDS remains unclear but it may be in part an Immune-cyto-
penia. The lack of efficacy of other therapies and the proven benefit of
Cyclosporin A (CyA) for many patients with immune cytopenias as well as favour-
able reports from French investigators prompted this study In the belief that
CyA might ameliorate some of the immunoregulatory disturbances involved in AIDS.
Eight stable AIDS patients were treated for a mean duration of 49 days with
biologically active doses of CyA. Clinical, hematologic, immunologic, renal
and hepatic functions were followed at least weekly before, during and after
administering CyA.
The white count, lymphocyte count, hemoglobin, platelet count, total T cells,
T4 and T8 cells fell significantly during treatment. HIV-1 was cultured more
frequently during treatment. The white blood count, platelet count, total T
cells and T8 cells reached pre-treatment values after therapy was withdrawn.
Hemoglobin remained significantly lower than prior to treatment and T4 cells
rose towards pre-treatment values but did not reach statistically significant
levels.
Severe toxic symptoms, not characteristic of CyA therapy in other patients,
affecting functional capacity were experienced by all 8 patients and necessit-
ated discontinuation of the drug in 6. The symptoms included nausea, vomiting,
anorexia, fatigue, pain and extreme swelling and increased number and size of
Kaposi ' s lesions.
CyA does not improve, and may worsen the symptoms and laboratory findings in
AIDS.
155
THURSDAY, JUNE 4
TH.4.4
Cytomegalovirus and Adenovirus Infections: Response to DHPG.
*A.S. TYMS, 'D.L. TAYLOR, *J.M. DAVIS, **D. TAYLOR-ROBINSON, •••A.J. PINCHING,
•D.J. JEFFRIES, et al *Virology Department, •••Immunology Department,
St Mary's Hospital Medical School, London W2, ••Clinical Research Centre,
Harrow, UK.
Infections with human cytomegalovirus (CMV) show marked sensitivity to
treatment with DHPG in vitro and this drug has proven clinical efficacy
against disease in AIDS patients. We now have evidence that infections with
adenoviruses also respond to treatment with DHPG, which maybe important in the
clinical management of opportunist infections in AIDS patients. Patients
suffering pneumonitis, retinitis or colitis were treated with DHPG on the
basis of virological, histological or clinical evidence that CMV was the
aetiological agent. During these investigations, repeated isolations of CMV
and/or adenovirus was made and viruses were characterized by restriction
analysis of viral DNA after comparison with prototype strains. Plaque-
reduction assay showed the sensitivity of adenovirus isolates (ED50 7 to 10 uM)
to DHPG was about 10-fold lower than values recorded for CMV, but within the
range of concentrations achieved during treatment (peak levels 46 - 56 uM 15
minutes post-infusion 500 mg/kg bd). Sensitivity of adenovirus isolates in
cell culture was confirmed by studies using high multiplicity of infections.
The clinical, virological and molecular aspects of the study will be
illustrated by comparison of three AIDS patients all treated with DHPG from
whom 1) only CMV, 2) only adenoviruses, 3) both viruses were isolated.
Prevention/Public Health — Drug Users and
Other High Risk Groups
TH.5.1 Hi9n Rate of HTLV-III/HIV Exposure in IVDA's from a Snail-Sized City and the
Failure of Specialized Methadone Maintenance to Prevent Further Drug Use
RICHARD G. MARLINK*, B. FOSS**, R. SWIFT***, W. DAVIS**, M. ESSEX****, J. GROOPMAN*, et
al., *New England Deaconess Hospital, Boston, MA, **New Bedford Center for Human
Services, New Bedford, MA, ***Brown University, Providence, RI, ****Harvard School of
Public Health, Boston, MA.
To investigate the seropreval ence to HTLV-III/HIV and HTLV-I in a non-metropolitan
area in New England, we conducted a voluntary screening program in New Bedford, MA,
from April 1986 to December 1986 at the only drug treatment center serving this pre-
dominantly Caucasian community of 100,000. Of greater than 300 clients, 114 chose to be
screened in our program. 27 clients (24%) were found to be seropositive for
HTLV-III/HIV and none were found to be seropositive for HTLV-I.
All seropositive clients were given individual, long-term counseling and medical
follow-up in addition to the opportunity to receive "methadone maintenance", instead of
simply short-term drug detoxification with methadone. Positions in the otherwise full
methadone maintenance program were still offered to all seropositive clients. Even with
additional counseling, medical care, and priority for entrance and continuation on
methadone maintenance, 67% (18/27) returned to I.V. drug use as determined by urine
drug screens, personal histories and drop-out rates in the 6 months since initiating
this specialized methadone maintenance program. This is compared to 7% (10/134) for the
entire established methadone maintenance program over the same period, and to 24%
(6/25) for a group of seronegative clients, and to 8% (2/25) for a group of "never
tested" clients who were matched by age, sex, employment status, and drug usage at the
beginning of the 6 month folow-up of the seropositive cohort.
The high rate of seropositivity to HTLV-III/HIV in this smaller sized community and
the lack of compliance to a novel attempt at curbing continued I.V. drug use among
seropositivies makes the call for new programs geared to prevention of viral trans-
mission in this population all the more urgent and difficult.
TU A c Successful Therapy of Cytomegalovirus (CMV) Infections in Patients
(pts) with Acquired Immunodeficiency Syndrome (AIDS) with Gan-
ciclovir (DHPG)
DOUGLAS T. DIETERICH, F. LAFLEUR, A. CHACHOUA, C. WORRELL, Kaplan Cancer
Center, New York University Medical Center, New York, NY
Since January 1985, 122 pts with AIDS and severe CMV infection were treated
with DHPG. 118 were male, 4 were female. 117 males were homosexual, 1 male and
1 female had transfusion related AIDS, 3 females were sex partners of IV drug
users. The mean age was 38 years. 25 had Kaposi's sarcoma, 70 had PCP and 36
had both. Diagnosis of CMV was made on positive tissue biopsy, a positive urine
culture or positive fundoscopic exam. Responses were measured clinically and
virologically by objective criteria including endoscopy. Sites of CMV were:
colon and rectum 51 (42%), retina and CNS 46 (38%), esophagus, stomach and
small bowel 14 (11.5%), lung 9 (7%) and liver 2 (1.5%). DHPG was administered
at a dose of 5 mg/kg IV BID for 14 days. On relapse pts were retreated and
placed on maintenance (M) of 6 mg/kg daily. Clinically, 88 of the 122 improved
(72%), 8 stabilized (6.5%) and 22 worsened (18%), 4 were not evaluable (3.2%).
107 pts survived for more than 4 weeks. Overall median probability of survival
was 19 weeks with a median follow up of 16.6 weeks. 59 (48%) pts became
culture negative, 16 (13%) did not change. 47 (39%) were not evaluable. Revers-
ible leukopenia < 2,000 occurred in 6/122 and skin rashes in 4/122. 62 pts
received M with DHPG. Probability of survival of pts on M was 33 wks compared
to 18 wks on no M p < 0.001. In PCP pts, probability of survival from date of
PCP was 45 wks on M, compared to 35 wks for pts not on M p < 0,001 (controlled
for PCP prophylaxis) . We conclude that Ganciclovir (DHPG) is effective in the
treatment of CMV in AIDS pts. A high proportion of pts will relapse, M treat-
ment may be associated with an increased probability of survival.
TH 5 2 A Coupon Program: AIDS Education and Drug Treatment
' ' JOYCE JACKSON, L. ROTKIEWICZ, N.J. State Dept. of Health (NJSDH),
East Orange, NJ.
In New Jersey, IV addicts comprise the majority of AIDS cases, but under
10% are currently enrolled in a drug treatment modality. Imposition of
patient fees in 1981 resulted in a loss particularly of black males. This
paper describes an effort by the NJSDH beginning in September 1986 to
induce addicts into treatment and to provide AIDS education to reduce the
rate of HIV transmission.
Serially numbered coupons, redeemable for a free outpatient
detoxification, were distributed in inner-city neighborhoods by previously
established ex-addict AIDS outreach workers. Eligible recipients were IV
drug abusers who had not sought treatment in at least one year. Programs
were reimbursed under contract for collecting demographic data on coupon
bearers, providing heroin detoxification and priority for extended
treatment, providing one hour of AIDS education with pre- and post-testing,
and maintaining a file matching coupon numbers with patient names.
By January 15, 1987, of 607 coupons distributed, 76% had already been
redeemed. Coupon redeemers were 76% black and 81% male. Fifty-four
percent had ages between 26 and 35 and 40% were over 35; 41% had no
previous treatment attempts and 44% had 1-3 attempts. AIDS education had
been provided and pre- and post-tests administered to over 90% of
redeemers. The program appears successful in meeting its goals.
111. 4.0 A Clinical Trial of Recombinant Alpha Interferon in Patients
with AIDS
G.H. FRIEDLAND1, S.H. LANDESMAN2, C.S. CRUMPACKER3, M.S. HIRSCH4, H.H.
HANDSFIELD3, D.J. PIZZUTI6, et. al., JMontefiore Medical Center, Bronx, NY, 2SUNY
Health Science Center, Brooklyn, NY, 3Beth Israel Hospital, Boston, MA, ^Massachusetts
General Hospital, Boston, MA, '^Harborview Medical Center, Seattle, WA, ^Hoffmann
La-Roche, Clinical Research and Development, Nutley, NJ.
We report the results of a randomized, double-blind, placebo-controlled trial of
recombinant interferon-alpha-2A (Roferon®-A) in unselected AIDS patients without
Kaposi's sarcoma. Sixty-seven patients were enrolled and received 1 of 3 regimens:
placebo or 3 or 3fi million units of Roferon®-A 3 times weekly IM for 12 weeks. The
3 groups were comparable in number of patients, age, gender, risk behavior, clinical
measures of HIV infection, and initial T4/T8 ratios. Thirteen patients received less
than 4 weeks of therapy, 54 patients were thereby available for efficacy analysis.
There were no significant differences in survival or rate of opportunistic infection
during or after treatment in the 3 groups. A significant decrease in T8 cells occurred
in the 3 million unit group but no significant differences in T4, total lymphocytes or
T4/T8 ratio occurred. There were no significant differences in adverse drug reactions
including those in central nervous and GI systems, or laboratory findings among the
3 groups. Six patients required reduction in dose because of side effects, 4 in the 3
million and 2 in the 36 million group. Seven patients dropped out due to adverse
reactions, 2 in the 3 million group, 4 in the 36 million group, and 1 in the placebo.
The preliminary analysis of this study did not demonstrate effectiveness of Roferon®-A
in the treatment of unselected AIDS patients without Kaposi's sarcoma. However,
the drug was acceptably tolerated and might have a role in therapy of AIDS patients
in combination with other agents.
TU c O Evidence of Reduced AIDS-associated Risk Behavior in
Homosexual/Bisexual Men but Not in Heterosexuals or IV Drug
Users in 4 Widely Dispersed U.S. Counties.
MIRIAM J. ALTER*, D. FRANCIS** and the CDC Sentinel County study group
Centers for Disease Control, Atlanta, GA and Berkeley, CA
Since hepatitis B virus and human immunodeficiency virus have remarkably
similar transfusion patterns, epidemiologic changes in one should mirror
epidemiologic changes in the other. We have used changing epidemiologic
patterns of hepatitis B in 4 U.S. counties, 1 each in Florida, Alabama,
Colorado and Washington as an indicator of the effectiveness of AIDS
prevention measures (presumably individual behavior changes). In these 4
counties there was, for the first time, a dramatic change in hepatitis B
cases associated with homosexual behavior (201 of all cases in 1985 versus
9% in 1986). In contrast there was a relative and absolute increase in the
number of IV drug-related cases (161 vs. 27X) and documented heterosexual-
intercourse-related cases (121 vs. 18%). Racially there was little change
(approximately 2/3 white and 1/4 black) but there was a 101 increase in
female cases (33X in 1985, 431 in 1986).
From these data it can be inferred that the AIDS-prevention message has
been heard and acted upon by a considerable number of homosexually active
men across the United States, but similar behavior change is not yet
apparent among either heterosexual men and women or IV drug users.
156
THURSDAY, JUNE 4
Roundtable Discussion
TH 5 4 Use of Condoms for che Control of AIDS: A Cross-Section Study in
Rikai District, Uganda.
A.M.T. LWEGABA, Project Mgr., Uganda AIDS Programme, Kampala.
AIDS, locally known as "SLIM" has been known in Uganda since late 1982, and
then described as an obscure wasting disease. It was not until late 1984 that
the disease became associated with AIDS, as proven by serologic tests. The
areas most greatly affected are Rakai and Masaka Districts. The incidence
rate in Rakai was 0.12% in 1986. Amongst preventive measures instituted was
the distribution of condoms primed by a health education campaign. By August
1985, 20,000 were distributed.
Recommendations of the Regional Conference on AIDS in Africa (Brazzaville:
November 1986) include studies of attitudes on condom usage and methods to
increase availability, distribution and use of condoms. A study has been
initiated in the Rakai District to determine attitudes and use of condums
among randomly-selected cohort of sexually-active adults. Market places are
good venues for cross-sectional selection in rural Uganda and comprise the
study sites. Mature, experienced health professionals administer standardized
interview forms and record responses to questions regarding subject's biodata,
knowledge and use of condoms, and knowledge and affect on sexual behavior of
AIDS. Interview records are serially numbered and names deleted to ensure
confidentiality. Data will be analyzed categorically, subjected to
significance test, and presented in tables and graphs.
TH.6
Developing Community Based Service Organizations
Panel Organized By: Paul Kawata
National AIDS Network
Washington, D. C .
Tim Wolfred, San Francisco AIDS Foundation, San Francisco, California
Richard Dunne, Gay Men's Health Crisis, New York, New York
Judith Peabody, Gay Men's Health Crisis, New York, New York
Epidemiology — Perinatal Transmission and
AIDS
TH 5 5 Effect of an AIDS education program on increasing condom use in a
cohort of Nairobi prostitutes
ELISABETH N NGUGI, FA PLUMMER, DW CAMERON, M B0SIRE, JO NDINYA-ACH0LA et al.
Kenya Medical Research Institute; Univ Nairobi; Ministry of Health, Nairobi,
Kenya; Univ Manitoba, Winnipeg.
In order to control sexual transmission of HIV, modification of sexual be-
haviour through education must be achieved. We have been studying cohort of
Nairobi prostitutes for 24 months who are at high risk of HIV infection (over
80 % positive) and pose a substantial risk to their clients. Beginning in
November 1985 we provided education on AIDS to this cohort of 596 women.
Several different methods of education - public meetings, individual counsel-
ling on the basis of HIV results and general health education - were employed.
In June 1986 distribution of condoms through the clinic began. In October
1986 we began surveying the frequency of condom use in the cohort. 126 women
who were newly recruited served as controls. Some condom use was reported by
8 % of women prior to the education program vs. 90 % of the most intensively
educated group (Grp I), 85 % of the less intensively educated group (Grp II)
and 73 % of the control gropu (Grp III). In Grp I and II no condom use was
reported by 5/61 women who received counselling vs 10/33 women who did not
receive counselling (p^.05). HIV antibody status did not influence frequen-
cy of condom use. Condom use was more frequently client initiated in the
control group. We have witnessed a remarkable increase in condom use as a
result of the program. Although more intensive education resulted in incre-
mental increases in condom use, minimal education with provision of condoms
was the most important step.
TU "7 ^ National Trends in Perinatally Acquired AIDS, United States.
' * MARGARET J. 0XT0BY*, M.ROGERS*, P.THOMAS**, S.MANOFF*, K.WINTER*,
R.BYERS*, *Centers for Disease Control, Atlanta, GA; **NYC Dept of Health, NY
As of January 19, 1987, 423 children under 13 years of age with AIDS have
been reported to CDC; the number of cases is currently doubling every 13
months. Perinatally acquired cases (PA) continue to predominate, accounting
for 338 (80%) of cases; 24 (6%) are hemophiliacs, 50 (12%) are children
infected through transfused blood, and 11 (J%) have incomplete risk histories;
no case acquired through household, school or daycare contact has been
reported. Notably, the geographic distribution of children with PA is changing.
The proportion of cases outside the high-risk areas of New York, New Jersey
and Florida has increased from 21% of cases diagnosed through 1984 to 37% of
cases diagnosed in 1985-1986 (p=0.002). This trend is consistent with the trend
among women with AIDS, which shows an increase from 23% to 32% in cases
reported outside these high-risk areas. The risk factors of mothers of children
with PA are also changing; the proportion of mothers infected through hetero-
sexual contact has increased from 34% of PA cases diagnosed through 1 984 to
44% of cases diagnosed in 1985-1986 (p=0.01); nearly all other mothers are
IV drug abusers . PA continues to affect mostly blacks (64% of cases) and
His panics (25% ) , with cumulative incidences in these respective populations
29 and 18 times the rate among whites. Although older children with AIDS are
being increasingly recognized, the median age at diagnosis has remained con-
stant at 6 months, reflecting increasing ser op re valence rates in child bearing
women. Compared to children older than 1 year of age when diagnosed, children
diagnosed under 1 year of age are more likely to have Pneumocystis carinii
pneumonia as an initial opportunistic infection (71% vs 36%), and have a poorer
prognosis (median survival time after diagnosis of 4 months vs 22 months).
TH.5.6 Drug Use and Sexual Behavior Change in a Cohort of Homosexual Men
DAVID G. OSTfOJ, M. VAN RADEN, L. KINGSLEY, R. FOX, J. DUDLEY, R.A. KASLOW,
and the Multicenter AIDS Cohort Study (MACS).
We have examined the association between the use of recreational drugs
(marijuana, cocaine, volatile nitrites, amphetamines, sedatives, hallucinogens
and opiates) and sexual behavior in a cohort of 5,000 homosexual/bisexual men
residing in Chicago, Baltimore /Washington, D.C., Los Angeles and Pittsburgh.
At both baseline and six month follow-up evaluations, men using recreational
drugs were significantly more likely to be engaging in sexual practices be-
lieved capable of transmitting HIV infection. These associations were
strongest when drug use with sexual activity was examined and were independent
of the number of sexual partners. Furthermore, when changes in sexual behavior
were examined, men who had been using recreational drugs were significantly
less likely to have reduced their level of unsafe sexual behavior than men not
using drugs (relative risks ranging from 1.2 to 2.2 for each drug examined).
These findings provide a possible explanation for the observation of a higher
prevalence of HIV antibody positivity in MACS participants using recreational
drugs and suggest intervention strategies for controlling the sexual spread
of HIV infection.
TH 7 2 Perinatal Transmision of HIV in Intravenous Drug Abusers (IVDAs)
PETER A SELWYN*. EE SCHOENBAUM*. AR FEING0LD*, M MAYERS*, K DAVENNY*
M ROGERS** et al. , Montefiore Med. Ctr., /Albert Einstein College of Medicine,
Bronx, NY, **CDC, Atlanta, GA, USA.
To determine the rate and outcome of perinatal transmission of HIV to infants
we are prospectively studying pregnant IVDAs and their offspring. Women in a NYC
methadone program (MMTP) receive prenatal care and HIV serum antibody (Ab) test-
ing. Infants are examined at birth and at 3 month intervals, and monitored for
growth and development and signs of illness. Cord and peripheral blood are test-
ed serially for HIV Ab and cells stored for HIV culture.
Since 9/85, we have studied 16 infants of 15 seropositive (SP) mothers and 30
infants of 29 seronegatives (SN) . Mothers did not differ by age or obstetrical
complications. 14/15 (93%) SPs were non-white vs. 18/29 (62%) SNs (p<.05). In-
fants did not differ in frequency of intrapartum fetal distress, APGARs , gesta-
tional age, or neonatal complications. Mean birthweight was 2860g for SPs, 2830g
for SNs. Of 12 infants of SP mothers tested, all had HIV Ab in cord or neonatal
specimens; none of 17 infants of SNs had HIV Ab at birth or thereafter. No in-
fant has AIDS to date. One SN died from sudden Infant death syndrome. 12 in-
fants of SP mothers had HIV Ab tests £4 weeks of age (mean of 27 wks. at last
follow-up); 6 remain SP (50%), 6 became SN (50%). Those becoming SN had mean age
at first negative Ab test of 34 wks. (range 12- 55). 1/6 infants SP at last test was
healthy, 5 had either: failure- to- thrive (FTT)(3) , developmental delay (3) , lymphad-
enopathy in > 2 sites (LA) (3) , persistent oral thrush ( 1) , or multiple bacterial in-
fections(BIs) . 5/6 infants becoming SN were well; 1 had FTT, LA and Bis . 2/17 infants
of SN mothers (mean age 30 wks.) had LA(1) or BIs(l).
Results show that maternal HIV Ab was not associated with adverse peri-or neo-
natal infant outcome. Preliminary data showed that 6/12 (50%) of infants of SP
mothers became SN within 1 year; 5/6 of these infants remained healthy . The rate
of HIV transmissionmay be<60%. 5/6 (83%) infants retaining HIV Ab had possible
HIV related disease. Similar clinical findings in 1/6 infants who became SN
suggest that HIV Ab testing may be < 100% sensitive for HIV infection in infants.
157
THURSDAY, JUNE 4
TU "7 O Human Immune Deficiency Virus in Pregnant Women and their
Offspring
ANNE WILLOUGHBY*. H. MENDEZ**, H. MINKOFF**, S. HOLMAN**, J. GOEDERT**,
S. LANDESMAN**, et al., *National Institutes of Health, Bethesda, MD,
**SUNY Health Sciences Center, Brooklyn, NY.
The effect of HIV on pregnancy, the rate of perinatal transmission, and a
description of perinatally acquired HIV infection are important aspects of
the natural history of HIV. We are studying the perinatal transmission of
HIV on drug using (DU) and Haitian (H) populations. Pregnant women are
identified in the prenatal clinics. Demographic, sexual, drug use, and
medical histories are obtained. Evaluations (clinical and laboratory) are
performed in the mothers pre- and post-partum and in the infants at regular
intervals. As of January 15, 1987, 89 women have been enrolled. Sixty-five
infants have been born, 44 to DU mothers and 21 to H mothers [27 (42%) to
seropositive (SP) mothers and 38 (58%) to seronegative (SN)]. The SP and SN
women from the DU and H cohorts have been compared on the basis of
background factors and with regard to obstetrical, perinatal, and
post-partum outcome. The infants have been compared with regard to birth
weight, gestational age, and perinatal problems. The mean duration of the
pediatric follow up is 5.5 months (range 0-12 months). Two infants have
AIDS, three have persistent hepatosplenomegaly and lymphadenopathy, and
four have persistently palpable lymph nodes in multiple anatomical sites.
Data will be presented on the expansion and continued follow up of these
groups.
TH 7 6 Perinatal HIV Transmission in Two African Hospitals.
NZILA NZILAMBI", R.W. RYDER*, F. BEHETS**, H. FRANCIS*,
E. PAYENDE*, A. NELSON*, J.M. MANN* et al. ,*Projet SIDA, Kinshasa, Zaire,**
Ngaliema Hospital, Kinshasa.
Twenty four hundred of a target population of 7000 women have been
enrolled in a longitudinal congenital HIV transmission study; 13S (5.64)
were HIV(+). Age, parity matched, pregnant control women have also been
selected. Lymphocyte cell typing, HIV cultures (antenatal maternal and cord
blood) and maternal examinations and cultures for other sexually transmitted
diseases have been obtained.
Seventeen (45.94) of 37 infants born to HIV(+) mothers had HIV IgM
antibodies (Western blot). Women delivering infected children had a
significantly lower mean T-Helper/T-Suppressor ratio (Th/Ts) [ratio of .55]
than infected women delivering non-infected infants(Th/Ts=.99), or
non- infected control women [Th/Ts=3.53]. The Th/Ts ratio in cord blood of
infected infants (Th/Ts=2.7) was no different than the ratio in noninfected
infants (Th/Ts=2.3). Three (174) of 18 placentas of infected women but none
of 23 placentas of non- infected women showed unusual perivascular
calcifications. Twenty (394) of 51 HIV(+) mothers reported having lost at
least one infant prior to their current pregnancy compared to 9 (164) of 55
HIV(-) mothers (p=.01).
Congenital transmission of HIV infection is not rare in Africa. A low
maternal antenatal Th/Ts ratio is associated with congenital HIV infection.
HIV(+) pregnant women in an advanced stage of their disease are more likely
to infect their children in utero.
Clinical Management — Infections I
TH 7 4 PROSPECTIVE STUDY ON NEWBORNS OF HIV SEROPOSITIVE WOMEN.
" " S ■ BLANCHE , C. ROUZIOUX, F. VEBER, F. LE DEIST, M.J. MAYAUX, C.
GRISCELLI. PARIS, FRANCE.
The exact incidence of mat erno- foetal transmission of HIV as well as the
natural history infection in infants is not yet well known. We have conducted
a prospective study on newborn of HIV seropositive mothers in Paris area
since September 1985- To date, 158 children are enrolled with a mediam rate
of increase of 3 children per week. These children were clinically examined
monthly during the first 18 months. The presence of IgG HIV antibody by
Western Blot and viral antigen (p25, Abbott Lab) were evaluated at birth,
9 months , 18 months or earlier if symptoms occuiTed. Immunological inves-
tigation were performed simultaneously. HIV infection of infants was proven
by persistance of positive IgG HIV antibody after one year of age and/or
occuaence of clinical or immunological symptoms . The analysis of the first
34 observations have shown that 14 infants .are infected and 20 are free
of HIV (infection rate ^ 40 %) . Only one out '158 newborn had HIV-associated
clinical manifestation at birth. The mean age of the first symptoms was
6 months ± 2. Normal number of CD4 + and CD8 + T lymphocytes were found
at birth except in the symptomatic child. Our preliminary results show that
the procedure used for the detection of HIV antigen p25 is not as useful
as expected for an early diagnosis of virus infection since only 4/48 cord
blood samples were found positive.
TH ft 1 Treatment of Cytomegalovirus Retinitis with Trisodium
Phosphonoformate (Foscarnet)
SHARON L. WALMSLEY, E.CHEW, M.M. FANNING, S.E. READ, H. VELLEND, I.E. SALIT,
et al,, Dept. of Medicine, University of Toronto, Ontario, Canada.
Cytomegalovirus (CMV) is a frequent cause of retinitis and a leading cause
of blindness in patients with the Acquired Immunodeficiency Syndrome (AIDS).
Ten immunocompromised men (9 with a diagnosis of AIDS and 1 with angio-
immunoblastic lymphadenopathy with dysgammaglobulinemia (AILD)) with CMV
retinitis were treated with a new anti-viral agent, trisodium phosphonoformate
hexahydrate (Foscarnet) . This compound has potent in vitro anti-viral activity
against the entire Herpes group.
On therapy, all 10 patients had improvement or stabilization of their eye
disease, and in 5 patients (50%) the retinitis resolved completely. The drug
was well tolerated in most patients but minor adverse effects were frequent.
Four patients experienced a rise in serum creatinine necessitating discontinu-
ation of the drug. Confounding medications and infections contributed to this
rise. No patient developed neutropenia on the drug. Recurrence of CMV retini-
tis occurred in 6 of 8 (75%) surviving patients, usually within one month of
stopping therapy. One patient died 22 weeks after Foscarnet was discontinued
without a recurrence. In 3 patients, the retinitis responded to subsequent
courses of Foscarnet. One patient stabilized during an intermittent maintenance
course of therapy.
We conclude that Foscarnet is an effective agent for the treatment of CMV
retinitis and appears to be less toxic than previously described agents. The
need for continuous intravenous infusion is its major drawback. Further eval-
uation is necessary to determine whether prolonged remissions can be achieved
with intermittent maintenance therapy.
TU "7 C Congenital transmission of HIV in Nairobi, Kenya
m',,U MICHAEL BRADDICK, JK KREISS, T QUINN, JO NDINYA-ACHOLA, G VERCAU-
TEREN, FA PLUMMER et al. U of Nairobi, Kenya, The Middlesex Hospi-
tal, London, U of Washington, Seattle, National Institutes of Health, Bethesda
Md , U of Manitoba, Winnipeg, Institute of Tropical Medicine, Antwerp.
Transmission of HIV from mother to child is a major public health problem.
To determine the risk of congenital transmission of HIV, we screened the sera
of 2265 women in labour at the Pumwani Maternity Hospital, Nairobi, Kenya for
HIV Ab. 62 women were seropositive for HIV Ab by ELISA and WB assays (HIV +) *
124 seronegative mothers and their newborns served as a control group. Mater-
nal age, marital status, parity, and prior stillbirths and miscarriages were
similar in cases and controls, but HIV + mothers were more likely to have had
previous infant deaths (15/90 livebirths vs 15/213, p^.02). Infants of HIV+
and HIV- mothers were similarin birthweight, gestational age, and Apgar scores
but infants of HIV+ mothers had a higher prevalence of palpable lymph nodes
at birth (24/50 vs 22/103, p^.001).
Sera from cord blood of infants of HIV+ mothers were analyzed for HIV IgG
and IgM Ab. All 53 sera tested were positive for HIV IgG Ab by ELISA and WB
and 9/53 (17 %) were positive for IgM Ab by WB. Three correlates of infant
IgM Ab were identified; a history of prior infant deaths (7/21 vs 8/67,
p ^.03), incurrent maternal infection during pregnancy (4/6 vs 6/39, p^ .02)
and maternal lymphadenopathy (6/6 vs 23/37, p<^ .08). If HIV IgM Ab in cord
blood accurately reflects in utero infection, these results suggest that con-
genital transmission of HIV occurs in only 17 % of affected pregnancies. Cord
blood lymphocyte cultures, serial IgG and IgM Ab assays, and clinical follow
up will determine if cord blood IgM Ab is an accurate marker of in utero HIV
infection.
TH A 2 Detection of Cytomegalovirus -Immediate Early Antigens in
Blood Leucocytes as a Marker for Activity of Cytomegalo-
virus Infections in AIDS.
HERMAN G. SPRENGER*tJ. WEITS* , W . V . d. BI J* , R . TORENSMA* , J . SCHIRM**,
T.H. THE*, et al.,*University Hospital, Groningen, **Public Health
Laboratory, Groningen, The Netherlands.
Eight patients with AIDS were longitudinally studied on 57 occa-
sions by detection of Cytomegalovirus (CMV)-immediate early anti-
gens (IEA) in peripheral blood leucocytes. CMV-IEA detection was
done by direct staining of leucocyte preparations in an immuno-
peroxidase assay, using monoclonal antibodies against the major
CMV immediate early proteins. Simultaneously viral cultures of the
blood buffy coat were done. CMV-IEA positive leucocytes, mainly
neutrophils, characterized by a nuclear staining, were found in
38 of the 57 samples (67%). Twenty four of 57 blood cultures were
positive for CMV (42%):23 (96%) were in the 38 CMV-IEA positive
samples (61% ) .
The CMV-IEA assay was semiquantif ied in negative, low, inter-
mediate and high levels of positive cells. Buffy coat cultures
were only once positive at a negative CMV-IEA level (1/19), often
(12/26) positive at low levels and nearly always positive at in-
termediate and high levels (11/12). Clinically disseminated CMV-
disease correlated only with intermediate and high levels of posi-
tive cells and responded to antiviral therapy (DHPG), resulting
in negative CMV-IEA tests and buffy coat cultures.
Conclusion: the CMV-IEA test seems to be a measure of CMV-vi-
raemia in AIDS patients and might help in therapy decision making.
The test can be performed in 3 hours.
158
THURSDAY, JUNE 4
TH.8.3 "9m
alovirus Colitis: can it be caused by Adenovirus?
JACQUELINE PARKIN, STANLEY TYMS, ADRIAN ROBERTS, ROBERT BURNELL,
DONALD JEFFRIES, ANTHONY PINCHING. St. Mary's Hospital Medical School, London.
Although commonly isolated from patients with AIDS adenovirus has previously
been considered to be non-pathogenic. We suggest that this virus may be the
cause of colitis indistinguishable clinically and histologically from cytomeg-
alovirus disease.
The evidence is as follows: we have shown that isolation of adenovirus from
any site is more common in patients with colitis than in those with disease at
other organ sites, and adenovirus isolation rates from rectal biopsies/swabs
in such patients are very high; although co-infection with CMV is common we
have documented 2 cases of colitis where adenovirus was the only relevant
pathogen isolated from any site at any time during the illness; histology of
rectal biopsies from these patients has shown inclusion bodies "typical" of
CMV. However culture of the same sample revealed adenovirus only, and electron
microscopy of the inclusions demonstrated localised virus particles of -70nm
in size (adenovirus characteristically being 65-80nm) which are unlikely to be
CMV (-lOOnm) ; the patients described have shown clinical and viralogical
response to DHPG (an anti-CMV agent to which adenovirus is also sensitive at
the normal therapeutic levels of 46-56uM achieved in both these patients,
personal communication S.Tyms); clinical relapse was associated with recurr-
ence of the adenovirus infection. Immunohistology and in-situ hybridisation
studies of inclusion bodies in colitis are in progress and will confirm
whether this is a common condition in AIDS patients .
TH 8 6 Intrathecal Production of Antibodies Against T\ gondii in
Patients with Toxoplasmic Encephalitis and AIDS.
I. POTASMAN***, L. RESNICK*. B. J. LUFT**, JACK S. REMINGTON***, *Mount
Sinai Medical Center, Miami Beach, Florida, **State University of New York,
Stony Brook, New York, and ***Research Institute, Palo Alto Medical Founda-
tion, and Stanford University School of Medicine, Palo Alto, California.
Toxoplasma encephalitis (TE) has been recognized as a major cause of
central nervous system (CNS) infection in patients with the acquired
immunodeficiency syndrome (AIDS). The definitive diagnosis is difficult
and sometimes requires the use of surgical procedures. Because of this we
attempted to demonstrate local production, in the CNS, of antibodies to T.
gondii and to determine the usefulness of these antibodies for the diagno-
sis of TE. We examined 22 patients with AIDS and TE and 12 patients with
AIDS and non-toxoplasmic encephalitis. Antibodies to T. gondii were deter-
mined by using the DS IgM ELISA and the Dye Test (DT). Paired serum and
cerebro spinal fluid (CSF) from each patient were used to determine intra-
thecal synthesis of antibodies. DT titers in serum and CSF as well as the
total concentrations of IgG in these body fluids were used to determine
production of specific IgG to T. gondii in the brain.
All patients had serum IgG but not IgM antibodies to T^ gondii. Intra-
thecal synthesis of IgG was significantly higher in all patients studied.
Local production of antibodies to T\ gondii was noted in 10 of 13 patients
with TE but only in 1 of 7 patients of the control group.
Our results suggest that demonstration of local production of T^ gondii
antibodies in the CNS may be useful for the diagnosis of TE in the appro-
priate clinical setting.
Immunology — HTV-Specific Antibodies
TH 8 4 Zoster-associated Meningitis in HIV-infected Individuals
HARRY HOLLANDER, C PETERSEN, R JACOBS, UCSF School of Medicine, San
Francisco, CA, USA
Over an 18 month period, 7 patients in a cohort of approximately 150 HIV in-
fected individuals developed dermatomal Herpes zoster. Of these 7, 5 had the
onset of severe headache and fever within 4 days of the appearance of cutaneous
lesions. Three subjects had previously been diagnosed with AIDS, while 2 had
other HIV-related illnesses. Examination revealed meningismus in 4 patients
and normal cognitive function and neurological examination in all 5. CSF ab-
normalities were consistently seen, with leukocyte counts of 14-128/mm and
protein of 89-256mg/dl (nml<50). Varicella-zoster (VZ) was recovered from CSF
in 2 subjects. HIV was recovered from cell-free CSF of 1 of 2 individuals in
whom isolation was attempted, including 1 man who also had VZ in CSF. All 5
patients began to resolve their illness and CSF abnormalities within 3 days of
beginning high dose intravenous acyclovir.
One possible explanation of these observations is that dermatomal VZ triggers
HIV-associated meningitis. However, the apparent clinical response to acyclo-
vir and recovery of VZ directly from CSF in several cases suggest an etiologic
role for this virus. The degree of clinical illness and height of pleocytosis
differentiate this illness from the mild pleocytosis sometimes seen with derma-
tomal zoster. The high frequency of this complication in our patients and the
absence of encephalitis differentiate this entity from neurological complica-
tions of VZ in other immunocompromised patients. Thus, HIV infection appears
to predispose to this specific complication of VZ. This potentially treatable
form of meningitis should be considered when HIV-infected individuals present
with headache and a vesicular exanthem.
In. 9.1 HTLV-III(HIV) Synthetic Peptides: Generation of Murine Monoclonal
Antibodies (MAb) and Analysis of Human Antibody Responses. Paul Durda*. B.
Leece*, H. Rabin*, S. Petteway*, K. Krohn**, A. Ranki**, F. Wong-Staal**,
and R. Gallo**. *E. I. du Pont de Nemours and Co., N. Billerica, MA, and
Wilmington, DE, **NCI/NIH, Bethesda, MD
Antibodies (Abs) to specific regions of viral proteins will have utility
in mapping functional domains of such proteins. Furthermore, such Ab
reagents can be used to probe for the presence of intact or degraded viral
antigens. We have used synthetic peptides conjugated to immunogenic carrier
proteins to develop MAbs to HTLV-III(HIV) . MAb 2549 is specific for HTLV-3B
envelope gp 120 (amino acids (aa's) 482-493, MRDNWRSELYKY). In
Western blots (WB) it reacts with gpl60/120 and with two other components of
Mr-40.5 and 43.5Kd from disrupted purified virus. Comparable extracts of
noninfected H9 cells were unreactive. MAb 2549 specifically stained H9
cells infected with the RF or 3B strains of HTLV-III in indirect
immunofluorescence assays, but did not inhibit HTLV-3B virus replication in
neutralization assays.
ELISA analyses were performed on various synthetic peptides or peptide
carrier conjugates using twenty human sera from apparently well blood donors
positive for antibody to HTLV-3B by WB and by ELISA with viral lysates (Du
Pont). Nine of these 20 positive sera were reactive with gpl20 by WB. None
of these reacted with peptide aa's 482-493, 474-487, and 488-502 in ELISA,
but 8 of these 9 positive sera reacted with a proximal c-terminal gpl20
peptide (aa's 503-518,).
These results show that synthetic peptides will aid in the mapping of
human antibody responses to HTLV-III (HIV) antigens and that MAbs to specific
viral protein regions make excellent controls for WB analyses.
TH.8.5 Disseminated Ecthymatous Varicella Zoster in AIDS
Ian Gilson'
*Uni ver
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Wisconsin
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, P.G.Jones*,M.A.Conant**,O.L.Laskin***,
.Milwaukee Clinical Campus, Milwaukee, WI,
ia.San Francisco, CA,***Cornell University
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nsible for
TH 9 2 Immunodominant Epitopes of HIV Envelope Glycoproteins.
JOHN F. KROWKA*. D.P. STITES*, B. SINGH+, V. MAIN0*. K. STEIHER0,
H. HOLLANDER*, et al . *University of California, San Francisco, University of
Alberta, Edmonton, *Becton Dickinson, Mountain View, CA and the "Chiron
Corporation, Emeryville, CA, USA.
A computer program was used to predict the epitopes of HIV envelope glyco-
proteins which are highly immunogenic. Both hydrophi 1 ici ty and interactions
between amino acids were used to calculate which regions of the folded native
proteins are exposed on their outer surfaces for immune recognition by anti-
bodies or T cells. Nine major immunodominant regions were identified. Compari-
son of amino acid sequences among HIV isolates revealed that 5 of these regions
contain epitopes which are conserved. Peptides constituting highly conserved
epitopes were synthesized and purifed by reverse-phase HPLC. Serum antibodies
from some HIV-seroposi ti ve men but not from any HIV-seronegative men which
recognize these peptides were demonstrated by ELISA, providing evidence of
the antigenicity of these peptides. Antibody reactivity to these peptides
in asymptomatic individuals and ARC, LAS, or AIDS patients was compared. The
specific immunogenicity of these peptides was demonstrated by ELISA analysis
of sera from peptide-immunized rabbits. Studies of the anti-viral effects
of anti-peptide antibodies and the ability of these peptides to inhibit anti-
CD4 monoclonal antibody binding are in progress.
159
THURSDAY, JUNE 4
TH.9.3 A Synthetic Peptide Derived from the Viral gp41 Protein of HIV is
Highly Immunoreactive with Sera from Patients Infected with HIV
MARJA-LIISA HUHTALAl , A. NKRVANEN1 , M. K0RK0LAINEN1 , S. KONTIO' , P. PARTANENl,
A. VAHERI^, AND J. SUNI2, 1|_absystems Research Laboratories, Pulttitie 8,
SF-00880 Helsinki, 2Department of Virology, University of Helsinki,
Haartmaninkatu 3, SF-00290 Helsinki.
A model for the transmembrane orientation of gp41 protein of HIV was pro-
posed based on our computer analysis (LSAP). According to this model there
are three transmembrane regions in gp41. Between two transmembrane sequences
there is a loop on the surface of the virus membrane. This loop region is
highly conserved between different HIV strains. To verify this model several
peptides were synthesized from the loop region and transmembrane regions and
polyclonal antibodies raised against these peptides. Peptides were tested in
EIA with HIV-infected patients sera. None of the selected peptides from
transmembrane regions were immunoreactive with sera from HIV-infected pati-
ents, whereas one of the selected peptides from the loop region (14 amino
acids in length) was highly immunoreactive. All 50 serum samples tested,
which were positive in both commercially available whole virus HIV-EIA and
Western blot analysis, reacted with this peptide, indicating that this loop
region is highly immunogenic. The specificity of this peptide to distinguish
between positive and negative serum samples (1000 tested) was high (99,7 %).
According to our preliminary results this peptide do not react with HIV-2/
LAV2 positive sera.
TH 9 6 A comParison °* the interaction of HIV-1 and LAV-2 with the CD4
antigen.
QUENTIN J. SATTENTAU*, P.C.L. Beverley**, F.A
Klatzman***
Halabi***, J. Montagnier**** ,
♦Academic Department of G.U. Medicine, Mid-
J-C. Gluckman***, D.
dlesex Hospital Medical School, London, U.K. **ICRF Human Tumour Immunology
Group, University College, London, U.K. ***Laboratoire d' Immunologic, Groupe
Hospitaller Pitie-Salpetriere, Paris, France. ****Institut Pasteur, Paris.
LAV-2 is a retrovirus isolated from individuals with an AIDS-like disease in
West Africa. It is related to HIV-1 morphologically but these viruses have
very little or no serological cross-reactivity in the envelope glycoprotein
when tested with sera from infected patients. The CD4 antigen is an important
part of the receptor for both HIV-1 and LAV-2, and the virus-receptor interact-
ion can be blocked by monoclonal antibodies (Mabs) to different epitopes of
CD4. We show here that the same or very similar CD4 Mabs which specifically
inhibit the formation of syncytia between cell lines infected with various
isolates of HIV-1 and CD4 bearing target cells, also inhibit in this assay
with LAV-2. Similar results have also been obtained in an infectivity assay,
in which HIV-1 or LAV-2 containing supernatant are used to infect CD4 bearing
peripheral lymphocytes which have been pre-incubated with CD4 Mabs at varying
concentrations. Reverse transcriptase (RT) values are then determined at var-
ious times after infection. Preliminary data from these experiments suggest
that LAV-2 may bind with a higher affinity than HIV-1 to CD4. The inference
from these results is that the binding site on these viruses is conserved, and
since there is negligable serological cross-reactivity between antisera to
these viruses, we conclude that the binding site is: a) not accessible to the
immune system; b) non- immunogenic , or; c) a forbidden specificity. The impli-
cations for the preparation of a vaccine will be discussed.
Blood and Blood Products — Transfusion
Associated AIDS and Hemophilia
TH 9 4 Antisera to Leu 3a with anti-idiotypic activity react with gpllO/
130 of HIV-1 and LAV-2
QUENTIN J. SATTENTAU*, J.N. Weber**, R.A. Weiss **, P.C.L. Beverley***. ♦Acad-
emic Dept. G.U. Medicine, Middlesex Hospital Medical School, London, U.K.
** Institute of Cancer Research, Chester Beatty Laboratories, London, U.K.
***ICRF Human Tumour Immunology Group, University College, London, U.K.
The CD4 antigen is an essential part of the receptor for the human immunode-
ficiency viruses HIV-1 and LAV-2 (HIV-2) and binds directly to the envelope
glycoprotein. Although there is virtually no cross-reactivity between these
viruses when tested with sera from infected patients, both can be inhibited
from interacting with CD4 by monoclonal antibodies (Mabs) to the same or very
similar epitopes of CD4 . Mabs to 2 distinct epitopes of CD4 were used to imm-
unise mice to raise anti-idiotypic (anti-id) reagents which might react with
the surface glycoproteins of these viruses. Antisera from 2 mice to one CD4
Mab (MT151) had strong anti-id activity as demonstrated by binding to the id-
iotype (id), but did not react with HIV by immunofluorescence, radio immuno-
precipitation (RIPA) or a neutralisation assay. Antisera to Leu 3a, however,
had strong anti-id activity, specifically stained the HIV infected cell line
CEM, reacted with the gpllO of HIV-1 isolates CBL1 and RF and gpl30 of LAV-2
by RIPA, and blocked syncytium formation between a CD4 bearing cell line and a
HIV producing line. The antisera to Leu 3a strongly inhibited binding of lab-
elled Leu 3a to CD4, but did not react at all with CD4 in competition studies
or immunof luorescent staining. The antisera were unable to bind to a Mab
(0KT4) directed to a different epitope of CD4, implying a private specificity.
In conclusion, we have produced antisera with strong anti-id activity specific
for Leu 3a. These react specifically with a conserved region of the surface
glycoprotein of divergent isolates of HIV-1 and LAV-2ji and identify a potential
neutralisation site on these molecules.
TH 10 1 Transfusion-Associated AIDS in the United States
THOMAS A. PETERMAN*, S.D. HOLMBERG* , K-J Lui** , *AIDS
Program, Center for Infectious Diseases, Division of Injury Epidemiology
and Control, Center" for Environmental Health, CDC, Atlanta, GA.
We evaluated reported cases of transfusion-associated (TA) AIDS to
characterize the natural history of HIV infection, estimate the magnitude of
the epidemic, and monitor the effectiveness of HIV antibody screening. As of
January 15, 1987, 570 TA-AIDS cases had been reported to CDC from 40 states.
Males outnumber females by about 2:1 in every age group except 21 to
40-year-olds, for whom the ratio is 1:1. The mean incubation period is
shorter for children aged < 13 years (mean 24 months) than for adults (36
months, p<0.001), but it is too early to detect cases with incubation periods
> 9 years. Mathematical modeling had estimated the mean incubation period
for adults will be 5 years, but current data suggest it will be longer.
Because of the long incubation period, the incidence of TA-AIDS continues to
increase in all age groups. No TA-AIDS cases have been reported in
recipients of blood screened for HIV antibody whereas 10 TA-AIDS patients
reported receiving their transfusions In the first 4 months of 1985. We
estimate that 10,000 persons in the United States have TA HIV infections.
Our study of families of adults with TA-AIDS found 38% had steady sexual
partners, and transmission had occurred to 16% of the females and 8% of the
males. If these estimates are generalized to all Infected persons, 3,800
infected persons may be involved In sexual relationships, and 450 may have
already transmitted infection. For 10 reported AIDS patients, the only risk
for Infection appears to be perinatal or sexual contact with an infected
transfusion recipient. Secondary transmission from previously infected
recipients may now be occurring more often than transmission by transfusion.
TH 9 5 internal Image Anti-idiotypes Representative of Homobodies
Mimic the CD4 Molecule and Bind Human Immunodeficiency Virus.
RONALD C. KENNEDY, E.-M. ZHOU, G.R. DREESMAN AND T.C. CHANH.
Dept. of Virology and Immunology, Southwest Foundation for Biomedical
Research, San Antonio, TX 78284.
Internal image or related epitope anti-idiotypic antibodies (anti-Id)
that mimic specific ligands and bind receptors have been referred to as
homobodies. A monoclonal anti-Id was generated against Leu-3A, a mouse
monoclonal antibody (MoAb) specific for the CD4 molecule on human T-helper
/inducer lymphocytes. The anti-Id demonstrates CD4 mimicry indicative of a
homobody based on the following properties: (i) it reacted with Leu-3a and
not a panel of irrelevant mouse MoAbs; (11) it partially inhibited the
staining of CD4+ T-cells by Leu-3a; (iii) it detected a common idiotype
present on other CD4 MoAb which block HIV infection in_ vitro; (iv) it
stained HIV infected, but not uninfected T-cells and; (v) it bound a
recombinant gpl60 peptide and reacted with a molecule of Mr 110-120 KD
protein in Western blot. The anti-Id also partially neutralized HIV
infection _in_ vitro. Baboons (Papio Cynocephalus Anubis) were immunized with
0K.T4A. An anti-Id response was produced that bound HIV in commercial
ELISA's and recombinant gpl60 in a solid phase immunoassay. In addition,
the baboon anti-Id reacted with an HIV infected T-cell line and its binding
inhibited the Immunofluorescence staining of CD4+ T-cells by Leu 3a and
0KT4A suggesting the anti-Id recognized the antibody combining site of the
anti-CD4 MoAbs. The possibility that the baboon anti-Id may possess in
vitro neutralizing is currently being examined. These results support
further studies of the use of idotypes and anti-idiotypes as a potential
vaccine candidates for HIV.
TH 10 2 The Transfusion Safety Study
" ' JAMES W. MOSLEY*, THE TRANSFUSION SAFETY STUDY GROUP* **,
*USC
School of Medicine, Los Angeles, CA, **other participating institutions.
The Transfusion Safety Study (TSS) is a multifaceted, cooperative evaluation
of factors influencing risk of transfusion- transmit ted HIV infection, and in-
teractions associated with progression. Subject groups include: (1) Persons in
the 4 highest prevalence areas of the United States who donated blood in Sep-
tember, 1984, through January, 1985, just prior to routine donor screening; (2)
recipients of components from anti-HIV(+) and (-) donors; (3) patients with
congenital clotting disorders (CCD) receiving concentrates and components; (4)
patients with congenital anemias (CA) receiving large numbers of transfusions;
(5) untransfused subjects with CCD or CA; and (6) household contacts of treat-
ed subjects having CCD or CA.
Findings to date include: (1) The estimated prevalence of anti-HIV positiv-
ity among donors was 10 to 20 per 10,000 at the time of the survey; (2) homo-
sexual contact was overwhelmingly the most important risk factor among donors;
(3) 89% of recipients of anti-HIV(+) components have become anti-HIV(+); (4)
there is a large difference in anti-HIV positivity associated with Factor VIII
and Factor IX concentrates (78 vs 44%); (5) only 20% of CCD subjects treated
just with components are anti-HIV (+); (6) only 6% of heavily transfused CA sub-
jects are anti-HIV(+), and these cases are confined to high prevalence areas;
(7) 17% and 0% of sexual and non-sexual household contacts of anti-HIV(+) CCD
and CA have become seropositive; (8) no seroconversion of any subject has been
observed on follow-up. (Supported by Contracts No. NO1-HB-4-7002 and N01-HB-
4-7003 of the National Heart, Lung, and Blood Institute.)
160
THURSDAY, JUNE 4
TH 10 3 Clinical Observations on HIV Seropositive Hemophiliacs after 4 1/2
Years of Followup and Efficacy of Heat-treated Products.
MARION A^ KOERPER, J. A. LEVY, University of California San Francisco, San
Francisco, CA.
Individuals with hemophilia represent one of the four major groups at risk
for developing acquired immunodeficiency syndrome (AIDS) because of their use
of blood products. The majority of hemophiliacs seroconverted to human
immunodeficiency virus (HIV) by late 1982. We have been prospectively
following a group of 84 hemophiliacs since July 1982. All were healthy and
asymptomatic at that time. Our results show the following:
HIV Positive
HIV Negative
Factor
Total
Asymptomatic AIDS
ARC
Total
VIII
IX
45
10
36 4
9 0
5
1
14
15
Of the factor VIII patients, 11% have developed AIDS and died during the
past 4 1/2 years, and 9% have developed ARC. Of the factor IX patients, 10%
have developed AIDS and died; none have symptoms of ARC. In 1984, all of the
seronegative patients were switched to factor VIII and IX concentrates that
had been heated at 60 or 68 for 72-77 hours, and all have remained
seronegative and asymptomatic for 2 1/2 years. These patients have received
1000 - 100,000 units of the concentrates. These results indicate that in 4
1/2 years 11% of seropositive hemophiliac patients have developed AIDS and 7%,
ARC. These results also document the efficacy of heat-treatment at 60 or 68
for 72-77 hours in eliminating HIV from factor VIII and IX concentrates.
TH 1fl fi Incidence of H^V-1 and HIV-2 antibodies in hemophiliacs
L.G. GURTLER ( w. SCHRAMM**, i. WEIGEL**, J. EBERLE*, F.
DEINHARDT ,Max von Pettenkofer Institute, Klinikum Innenstadt, University of
Munich, Federal Republic of Germany
The presence of antibodies to HIV-1 (anti-HIV-1) in a group of hemophiliacs
has been monitored since the autumn of 1984. Increasing numbers of HIV-1
infected patients were observed in the years 1981 to 1986 from 0 to 51% (85
patients of 166 positive for anti-HIV-1). Most infections occured between
1982 and 1984 and only 5 seroconversions were observed since 1985. Only heat
or chemically inactivated clotting factor preparation were used for
substitution of the patients since the spring of 1985. Two of the five
seroconversions in 1985/86 may have been due to a factor VIII preparation
inactivated by heat in the dry state and this preparation is no longer used.
The other 3 seroconversions possibly were caused by an occasional use of an
non inactivated preparation in the beginning of the change to inactivated
clotting factor preparations. 38 of the anti-HIV-1 positive sera were tested
also for the presence of anti-HIV-2 by an ELISA prepared in our own
laboratory , immunofluorescence and immunoblot. HIV-2 ( LAV-2 ) for these tests
was kindly provided by L. Montagnier . Antibodies specific for HIV-2 antigens
were not detected , but crossreactions were observed between anti-HIV-1 with
HIV-2 antigens particularly epitopes on HIV-2-p27.
The data inidicate that the use of adequately inactivated clotting factors
can prevent infection of hemophilia patients by this route and that HIV-2 was
not present in the clotting factor preparations used for the substitution of
this group of patients.
Health Care — Issues in Health Care Delivery
TH.10.4 No Anti-HIV Seroconversion after Replacement Therapy with Pasteur-
ized F VIII Concentrate. A Study of 151 Patients with Hemophilia A
or von Willebrand's Disease.
KLAUS SCHIMPF*. H.H. BRACKMANN, W. KREUZ, B. KRAUS, F. HASCHKE, W. SCHRAMM et
al . *Rehabilitation Hospital and Hemophilia Center Heidelberg, Rehabilitation
Foundation, Federal Republic of Germany
Transmission of hepatitis viruses and HIV has proven to be a risk of repla-
cement therapy in hemophilia. As regards F VIII products a concentrate (Hemate
HS or P) in which viruses are inactivated by heat-treatment over 10 hours at
60° C in aqueous solution is available since 1979. Our clinical studies have
shown that this product does not transmit HBV and HNANBV. As the product was
manufactured by 80% from US plasma it was necessary to prove that it also does
not transmit HIV. As it is, for ethical reasons, not possible to treat a con-
trol group with non-virus-inactivated F VIII, non-transmission of HIV can only
be proven if anti-HIV seroconversion does not occur in larger groups of pa-
tients treated exclusively with this virus-inactivated product. We collected
data from 151 patients treated with Hemate HS (P) who had never before re-
ceived blood or blood products. Therapy was started between Feb. 1979 and Jan.
1986 (median July 7, 1983). The median length of observation till the last
anti-HIV testing was 24 (3 - 83) months, the median total dosage was 17,000
(500 - 2,155,375) IU of F VIII, the median patient age was 6 (0,5 - 68) years.
In none of these patients anti-HIV seroconversion (ELISA test) was observed.
According to the rule of three, the upper 95% confidence limit for a random
sample of 60 cases with zero events would be 3/60 or St. For greater numbers
of n cases, as in our study, the range of confidence narrows increasingly. The
period of observation of this study is hitherto the longest.
TLj -M -| Comprehensive outpatient-based healthcare reduces inpatient stay for
persons with AIDS or ARC: the Los Angeles County Model.
PETER N.R. HESELTINE. J.M. LEEDOH, M. HEDDERHAN , M. RIPPER, F. SATTLER. Los
Angeles County - University of Southern California Medical Center, Los
Angeles, CA, USA.
Patients with HIV infection have complex health-care needs. Several problems
are perceived with hospital inpatient based programs: care for multiple AIDS
diagnoses may be dispersed, acute-care services are used for convalescence,
procedures require repeated admissions. We have previously reported the cycle
of new symptoms, procedure-oriented diagnosis and treatment is more frequent
for persons with AIDS than other chronic illnesses and results in an average
of 2.3 Inpatient admlssions/patient/year . As the number of HIV Infected
persons seeking medical attention increases, alternatives to inpatient care
are needed. We examined the effect of an outpatient-based program on the use
of acute-care inpatient resources by persons with AIDS or ARC. Each new
patient was assigned a physician supervised, primary care nurse and social
worker outpatient team (PCT) which coordinated all clinic visits. Physician
specialists varied with time based on the patient's AIDS diagnoses. Over two
years of study, a strong inverse correlation was noted between the number of
monthly outpatient visits and Inpatient length of stay (LOS). Reasons for
admissions when regular clinic visits were not planned or available Included
diagnostic tests, hydration, drug infusions and psychosocial support.
Reduction of LOS was associated with significant reduction in charges/patient
served. This study supports the hypothesis that an outpatient-based PCT case-
management strategy reduces LOS and charges for persons with AIDS/ARC and may
prove to be more flexible In meeting increased demand and patient
satisfaction.
TH.10.5 Antibodies to HIV in Israeli Hemophiliacs: Prognostic Significance
of Serological Profile
SHLOMIT ORGAD*. G. MAL0NE**, R. ZAIZ0V***, U. MARTINIWITZ*. E. GAZIT*, M.
ESSEX**, *Sheba Medical Center, ISRAEL, **Harvard School of Public Health,
Boston, MA, ***Beilinson Medical Center, ISRAEL.
We studied 66 Israeli hemophiliacs for antibodies to HIV on blood samples
collected between 1978 to 1985. By May 1985, 2 had AIDS, 2 had ARC, 4 had
lymphadenopathy , and 58 were asymptomatic. Antibodies to HIV were detected in
40 (60.6%) patients. Presence of HIV antibodies was significantly associated
with receipt of non-heat-treated commercial factor VIII concentrates
(NHT.Fac.VIII) between 1980 to 1983. 84.44% of patients treated with
NHT.Fac.VIII developed antibodies, compared to 25% treated with cryoprecipi-
tates and fresh plasma only. All 40 seropositive patients had antibodies to
viral env gene encoded gpl20/gpl60 antigens. Twenty-four (60.0%) also had
antibodies to viral gag gene encoded p24 and/or p55 antigens. While antibodies
to gpl20/160 persisted during the follow-up time, a loss of antibodies to
P24/55 was observed in 25% of seropositive patients from whom multiple samples
were available. Gpl20/160 positive p24/55 negative hemophiliacs had
significantly lower absolute T-helper cell counts and reversed Th.Ts ratios
compared to gpl20/160, p24/55 seropositive patients. Four of 16 (25.0%)
asymptomatic gpl20/160 positive p24/55 negative patients developed overt
disease within 15 months of the last blood collection. The data suggest that
antibodies to gpl20/160 are of important diagnostic value while loss of
antibodies to p24/p55 may be of prognostic value.
TH 11 2 HosPital- Utilization Patterns and Charges for the Care of Inner
City AIDS Patients: By Risk Group, Sex & Race/Ethnicity
ERNEST DRUCKER, P. MCMASTER, A. WEIN, J. BLOOM, T. DAVIS, M.H. ALDERMAN,
et.al., Department of Epidemiology & Social Medicine, Montefiore Medical
Center/Albert Einstein College of Medicine, Bronx, NY, USA
The hospital records for 39 AIDS patients who received all of their
inpatient care at Montefiore between August 1981 and June 1986, were examined
to determine patterns of utilization (length of stay (LOS) and number of
admissions); charges (room, board and ancillary services): and the
relationship of these to patient characteristics. Sixty percent of the
patients had a history of intravenous drug abuse (IVDA); 40% were women; 30%
were Black; 44% Hispanic; 25% White. Overall, these patients had a mean
survival time of 7.75 months after diagnosis (range 3 days to 42 months), and
averaged 3.2 admissions (1-18) of 17.6 days (11-186) each. The mean total LOS
was 56.3 days, with total charges $41,484 per patient (329,143 room & board;
$12,341 ancillary services). IVDA's did not differ from non-IVDA's in number
of admissions, LOS or charges. Women had fewer hospital admissions (2.4 vs.
3.8); shorter per patient total LOS (44.4 vs. 64.7 days); and, accordingly,
lower total charges ($33,514 vs. $46,038). These differences (n.3.) were
attributable to those 19 patients diagnosed prior to July 1984 when women had
a significantly shorter interval between diagnosis and death than men (3.7 vs.
14.2 months, p= .001). Black patients had a shorter total LOS than Whites and
Hispanics (38.3 vs. 66.1 days, n.s.), and this trend held when stratified for
sex and risk group. These findings show total hospital LOS and costs to be
considerably higher than a recent comparable lifetime cost study of primarily
homosexual patients in San Francisco (Scitovsky, et.al., JAMA, 1986).
161
THURSDAY, JUNE 4
TH 11 3 Medica]L Care Costs of Children with HIV Infecti
JAMES D. HEGARTY,E. ABRAMS M.D..V.E. HUTCHINSON
M. HEACARTY M.D., Department of Pediatrics, Harlem Hospita
We have examined the costs of medical care for infants d
infection at Harlem Hospital (N = 33). From a careful rev
a total utilization of medical resources was determined
value. The cost value was determined independently from c
records and standardized to Medicare reimbursement figures
The costs of caring for these infants range form $250 to $
wide range reflects the variation in resource utilization
matic infants (Ab+) versus infants with ARC or AIDS.
What is common to all of these infants are lengthy hospi
of the current absence of viable placement alternatives to
Once admitted, these infants may never leave the hospital
need. The mean length-of-stay for nine of the unplaced i
will exceed one year in April 1987. Our study demonstrate
cost of care for several infants has already exceeded $300
one year of hospitalization.
A recent study reported that the lifetime cost of AIDS i
on in Harlem
M.D. ,S. NICHOLAS M.D.
1, New York, NY.
iagnosed with HIV
iew of patient charts,
d assigned a cost
ha rge -based billing
whenever possible .
700 per day. This
exhibited by a symp to-
tal stays as a result
the home or hospital,
regardless of medical
fants was 280 days and
s that the individual
,000 after more than
n adult patients
days for a cumulative
ply contrast with our
findings for the medical costs accrued by pediatric HIV infected patients at
e children in our
(vol. 256, no. 22)
averages $733 per day. over a total hospitalization of 37. 6
mean cost of $25, 571. These data for adult patients shar
Harlem Hospital. The potential. expense of caring for thes
city hospitals is enormous . [ Scitovsky , A. et_ . ajL . JAMA
December 12, 1986. ]
TH 11 6 hospice Care of Intravenous Drug Abuser AIDS Patients in a Skilled
Nursing Faci 1 i ty.
W BULK IN/ L MCNALLY, G MCOJIRE, L BROWN, GH FRIEDLAND. Beth Abraham Hospital,
Monte fiore Medical Center/Albert Einstein Coll. of Med., Bx., N.Y., USA.
Thirty two percent of AIDS patients in NYC are intravenous drug abusers (IVDA).
Hospice care for AIDS patients in NYC has been limited and there is no previous
experience with IVDAs with terminal illness in this setting. We report on the
initial experience in hospice care for a predominately IVDA AIDS population at a
Skilled Nursing Facility (SNF) with a Certified Hospice Program delivering home care
and inpatient care.
To familiarize staff with AIDS issues, a staged educational program preceded
patient admission. Between Feb. 1986 and Jan. 1987, 80 patients were referred and 30
were accepted. Of these 22 were male, 8 female. 20 were IVDA, 7 homosexual men, 2
sex partners of IVDA, 1 unknown. Mean age 35, all 30 had AIDS dementia complex.
Total days of hospice care 867, mean length of stay 30 days (range 1-280). 88% days
spent in inpatient hospice care, only 12% in home hospice care. Mean daily inpatient
census, 4.
Based on daily rate of $758 for acute hospital care and $346 for hospice care,
estimated savings in decreased costs for 12 months, $357,204. Compared to other
hospice patients, unanticipated problems included: (1) inability to provide home
hospice care because of inadequate or absent housing and IVDA related social
disruption, (2) continuing drug abuse, (3) increased nursing, medication,
psychosocial needs, (4) difficult interactions with funeral directors. Continuing
fear of transmission among staff was not a major problem.
Hospice care of AIDS patients in a SNF is feasible, humane and cost effective.
However, problems of IVDA require special attention and program modifications, if
hospice care is to be provided for this population.
Roundtable Discussions
TH 11 4 MDS Medical Day Care for Intravenous Drug Abusers
GLORIA RODRIGUEZ, J. JACKSON, N.J. State Department of Health,
East Orange, N.J. AIDS Contnunity Support Unit
New Jersey presently ranks fifth nationally in the number of confirmed AIDS
cases. As of Dec. 1, 1986, this number had risen to 1,709 with an overall
mortality rate of 61%. Of special significance is that 52% of the total num-
ber of cases are intravenous drug abusers. Presently, chronic long term care
facilities and extensive home health care are not available. Consequently many
AIDS/ARC patients must remain hospitalized at considerable cost. Comprehensive
cost-effective specialized services must be created and made accessible in order
to meet the multiple needs of the AIDS/ARC patient. The AIDS/ARC Medical Day
Care Program addresses the needs of recipients of the N.J. Medicaid Program
who could benefit from a health service alternative to institutionalization.
AIDS Medical Day Care is a program of medically supervised, health related
services in an ambulatory structured drug treatment program setting to persons
who do not require 24 hours in-patient institutional care and yet, due to their
physical and/or mental impairment, need supportive health maintenance and re-
storative services. Services provided include medical, nursing, social, trans-
portation, personal care, dietary, recreational, rehabilitative, drug counsel-
ing and dental. The structured drug treatment setting meets their needs, helps
reduce transmission, provides a cost effective, humane mode of health care and
enables IVDA AIDS patients to remain in the community.
TH.12
People. Living with AIDS: Personal Perspectives
Panel Organized By: Stephen Beck
National Association of People with AIDS
Washington, D.C.
Panel Moderator: Frederick Garnett
National Association of People with AIDS
Washington, D.C.
People of Color with AIDS
IV Drug Users with AIDS
Women with AIDS
Canadian PWAs
European PWAs
Caribbean PWAs
TH 11 5 A Hospital-based Volunteer Program Utilizing Methadone Patients and
Others to Provide Support for Inner-city AIDS Patients
LEA TENNERIELLO, M. CALLAN, L. GORDON, J. LEVINE, B. POUST, E. DRUCKER,
Hontefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA
We report the initial six-months of a hospital-based Volunteer Program
designed to serve a patient population of predominantly minority backgrounds,
low socioeconomic status, and minimal personal support systems: 56% are
intravenous drug abusers; 10% are heterosexual partners; and 35% are gay men.
The volunteer population mirrors the composition of this patient group and 50%
are patients in our Methadone Program. As of February 1987, 20 volunteers had
completed a 2-day training program and attend weekly volunteer support groups
with professional supervision of their individual work. Volunteers have
provided over 1000 hours of service to over 30 different patients and have
organized large Thanksgiving and Christmas celebrations for hospitalized
patients. The Project's successes include: the establishment of a positive
working coalition of volunteers from diverse backgrounds; the use of Methadone
patients (often stereotyped, discounted and self-disparaging) to help the AIDS
community while increasing their own self-worth; the creation of a strong
source of group support and breavement consolation for survivors of deceased
patients. Program difficulties include: recruitment and selection of
appropriate volunteers from a population which includes many multi-problem,
poorly functioning persons; the need for safeguards against destructive
experiences for patients and volunteers; adaptation of the training program
and supervision to the needs of the volunteers and the hospital; and securing
adequate funding for the project. The paper describes in detail the process of
screening, training, on-going support and supervision of volunteers and
discusses plans for future expansion.
TH.13
Prevention of Perinatal Transmission of HIV Infection
Panel Moderator: James Allen
Centers for Disease Control
Atlanta, Georgia
Jeffrey P. Davis, Wisconsin Department of Health and Social Services,
Madison, Wisconsin
Howard Minkoff, Downstate Medical Center, SUNY, Brooklyn, New York
Janet Mitchell, Beth Israel Hospital, Boston, Massachusetts
James Oleske, St. Michael's Medical Center, Newark, New Jersey
Gwendlyn B. Scott, University of Miami School of Medicine, Miami, Florida
Pauline A. Thomas, New York City Department of Health, New York, New York
162
THURSDAY, JUNE 4
TH.14
AIDS Education for the General Public
Panel Moderator: Paul Kawata
National AIDS Network
Washington, D. C.
Hillary Pickles, Department of Health and Social Security, London, England
Walter Dowdle, Centers for Disease Control, Atlanta, Georgia
Jan-Olog Morfeldt, National Bacteriological Laboratory, Stockholm, Sweden
Carol Sussman, American Red Cross, Washington, D.C.
TH.17
Current Issues in Drug Abuse and AIDS
Panel Organized By: Peter Bridge
Department of Health and Human Services
Bethesda, Maryland
Panel Chairman: Roy Pickens
NIDA
Bethesda, Maryland
John Newmeyer, University of California, San Francisco, San Francisco,
California
Don Des Jarlais, New York State Division of Substance Abuse Services,
New York, New York
Jerome Jaf fe, NIDA, ARC, Baltimore, Maryland
George Bigelow, Johns Hopkins University, Baltimore, Maryland
Poster Session
TH.15
AIDS in the Developing World (Social/Economic)
Panel Moderators: Bradshaw Langmaid
Agency for International Development
Washington, D.C.
Lair G.M. Rodrigues
National AIDS Program
Brasilia, Brazil
Oleh Wolowyna, Research Triangle Institute, Research Triangle Park,
North Carolina
Dr. Benjamin Were, Kenya Medical Research Institute, Nairobi, Kenya
Charles Meyers, Harvard Institute for International Development, Cambridge,
Massachusetts
Michael Micklin, Florida State University, Tallahassee, Florida
V. Ramalingaswami, Harvard School of Public Health, Cambridge, Massachusetts
THP1 Select Lectins Inactivate HIV In Vitro. W. EDWARD ROBINSON, DAVID
C. MONTEFIORI AND WILLIAM M. MITCHELL, Vanderbilt University,
Nashville, Tennessee, USA.
To evaluate the potential role of oligosaccharides in the attachment of HIV to the
T4 receptor, we examined the effect of several lectins on viral infectivity. Lectins
tested were BS-II, lentil, wheat germ agglutinin (WGA), hairy vetch, red marine
algae, phytohemagglutinin-P (PHA), concanavalin-A (Con-A), and succinyl
concanavalin-A (sCon-A). We found that at 500 nM concentrations Con-A and sCon-
A preincubated with virus completely inhibited virus expression in target C3 cells as
determined by indirect immunofluorescence (IIF) and reverse transcriptase assay
(RT). Lentil and PHA greatly diminished viral infectivity (IIF and RT <20% of control)
while WGA only slightly inhibited the virus (RT and IIF <60% of control). BS-II, hairy
vetch, and red marine algae failed to inactivate the virus at all (RT and IIF >80% of
control). We further found that monovalent sCon-A can prevent HIV infection of
target cells significantly at a concentration of 400 nM. Since there is no relationship
between lectin size and degree of inhibition of HIV infectibility, the observed
antiviral activity appears to be related to lectin oligosaccharide specificity rather
than simple, non-specific stearic hindrance. Thus, these findings indicate that the
oligosaccharide side chains of the HIV envelope proteins may be involved in the
attachment of the virus to the T4 receptor of T-helper lymphocytes and that
modulation of HIV oligosaccharides may be a useful target for the development of
chemical anti-HIV agents.
TH.16
Hemophilia: Where Should the Preventive Effort Be Placed?
Panel Moderator: Peter Levine
Worcester Memorial Hospital and
University of Massachusetts Medical School and
New England Area Comprehensive Medical Center
Worcester, Massachusetts
Peggy Heine, The National Hemophilia Foundation, New York, New York
Jean-Pierre Allain, Abbott Laboratories, Abbott Park, Illinois
Piero M. Mannucci, University of Milan Hemophilia Center, Milan, Italy
THR2 A RaPi" and Convenient Detection of HIV by in situ Hybridiza-
tion Using Non-Isotopical ly-Label led Probes
KEVIN S. BYRON. SUSANNE M. SCESNEY, JOHN L. SULLIVAN and ROBERT H. SINGER*,
U. Mass. Medical School, Pediatrics and Anatomy*, Worcester, MA 01605
We have developed an i_n situ hybridization methodology for rapid detec-
tion of HIV in infected cells using H9 or CEM cells as models. Cells were
probed with a biotinylated DNA HIV probe followed by streptavidin and then
biotinylated alkaline phosphatase (ABAP). An intense colorimetric reaction
is generated in HIV-infected cells which can be easily distinguished at cell
dilutions of 1 X 10-5. When compared with isotopic probes, it was deter-
mined that the sensitivity of non-isotopic detection was comparable. Using
both isotopic and non-isotopic probes we have detected HIV-infected cells in
peripheral blood lymphocyte cultures within ten days of stimulation with
PHA. S35-labelled probe was more sensitive for low levels of infection,
however, for routine viral isolation procedures the ABAP technique was sev-
eral orders of magnitude more sensitive than reverse transcriptase assays or
RNA dot blot hybridization. We are currently studying splenic mononuclear
cells (obtained from an HIV-infected individual splenectomized for ITP) for
direct visualization of HIV-infected cells using both detection systems. In
addition to HIV detection in patient samples, we have used the ABAP techni-
que to develop an HIV neutralization assay. This assay can be easily quan-
titated with stringent end-point titration of serum neutralizing antibody to
HIV. These studies Indicate that non-isotopic in situ hybridization for de-
tection of HIV is a convenient and rapid method for clinical and research
laboratory investigation of HIV infection. Supported by NIH Contract
N01-HB-67022
163
THURSDAY, JUNE 4
THP3 Presence of Human B-Lymphotropic Virus (HBLV) Antibody in Sera from
Infected AIDS Patients
DHARAM V. ABLASHI*. Z. SALAHUDDIN*, M. KAPLAN**, F. IMAM*, C. CAIN*, and
R. GALLO*, *National Cancer Institute, Bethesda, MO, ** North Shore University
Hospital Long Island, NY
We recently described the isolation of a novel herpesvirus (HBLV) from
patients with lymphoprol iferate disorders as well as from 2 patients with
HTLV-I II-related diseases. One hundred and twenty sera obtained from AIDS
patients, 33 with lymphoma and 46 with Kaposi's Sarcoma (KS), were tested
for antibody to HBLV by indirect immunofluorescence assay (IFA). Out of 120
sera from HTLV-I II-related diseases, 31 contained IgG antibody to HBLV by IFA
(25.8%). In addition to 220 sera from normal healthy individuals tested
previously (4 contained HBLV antibody) for HBLV antibody, 80 additional normal
sera were included in the present study. Among the 80 healthy donors, 6 sera
were positive to HBLV (7.5%). Out of the 13 (39.3%) HBLV antibody-positive
8-cell lymphomas sera, 4 exhibited strong IFA positivity to HBLV (1:40
dilutions), whereas the remainder of the positive sera were reactive at 1:20
dilution. Also, sera (32.6%) from KS patients were found to contain HBLV
antibody. These results are consistent with the role of HBLV in lymphopro-
1 iterative disorders and/or diseases of the immune system, but much more
information is needed to draw any conclusions.
THR6 In vltro Mutagenesis of the HIV (HTLV III/LAV) Genome
ANDREW DAYTON*, JOSEPH POTZ* , BRUCE WALKER*, TATYANA DORFMAN*, and
WILLIAM A. HASELTINE**.*Dana-Farber Cancer Institute, Dept. of Biochemical
Pharmacology, Harvard Medical School, and **Harvard School of Public Health,
Dept. of Cancer Biology, Boston, MA.
We have introduced a series of mutations into the HIV genome by random linker
insertion mutagenesis. Our early work has concentrated on the effects of mu-
tations in the integrase region of the genome, just 3' to the reverse trans-
criptase gene.
Cloned genomes with integrase mutations transiently synthesize a complement
of viral proteins normal except for the lack of the integrase protein. These
DNAs also transiently produce reverse-transcriptase-containing particles which
are, however, defective for replication. Preliminary data suggests that these
particles may be defective at a point past the formation of proviral DNA sub-
sequent to infection. The results legitimize the integrase gene product as a
potential therapeutic target.
JHP4 Immunological Detection of HIV-infected Peripheral Blood
Lymphocytes
RUDOLF O.F. KUNZE and M.A. KOCH, Robert Koch-Institut des Bundesgesundheits-
arates, 100 Berlin 65, F.R.G.
Virus antigen expressing cells can be detected by the APAAP-technique
using a cocktail of murine monoclonal antibodies against viral pi 5, p24 and
gpl20. In freshly isolated peripheral blood mononuclear cells (PMC) from
HIV infected persons only an occasional cell in 5000 will exhibit typical
staining. If such cells are cultured for 3 days in the presence of PHA (1
ug/ml) HIV antigen positive cells are demonstrable regularly with a
frequency of 1:1000 to 1:100. From the results of kinetic studies of in
vitro HIV infected PMC it can be excluded that the HIV infected cells
observed result from infection during in vitro cultivation, i.e. either the
majority of cells expressing antigens after stimulation, produce without
stimulation antigen below level of detection or are latently infected.
Number of CD4+ positive cells were determined for the same samples. On the
assumption that only CD4+ cells express viral antigens 1-10% of these cells
are infected in the patients investigated. This suggests that number of
virus bearing PMC is far greater than hitherto assumed. No correlation
between number of infected cells and stage of disease was observed.
THR7 Clinical, Hematological, and Immunological Evaluation of Individuals Exposed
to Human T-Lymphotropic Virus Type IV (HTLV-IV)
RICHARD G. MARLINK*,. D. RICARD**, S. M'BOUP**, P. KANKI*, J.L. R0MET-LEM0NNE*. M.
ESSEX, et al., *Harvard School of Public Health, Boston, MA, "University of Dakar,
Dakar, SENEGAL.
We studied various epidemiological and clinical parameters in over 300 prostitutes
from Dakar, Senegal. Of this cohort, 7% were found to be seropositive for exposure to
HTLV-IV as compared to a seropositive rate for the general population in Dakar of
ial.5%. All prostitutes were evaluated in a clinic which serves the medical needs of
this population. Follow-up has been for greater than 18 months and the seropositive
prostitutes have remained without significant lymphadenopathy, without a history of
chronic fevers, diarrhea, pruritis, or weight loss, and without significant differences
in cutaneous anergy when compared to prostitutes seronegative to HTLV-IV. The estimated
number of lifetime sexual contacts was comparatively increased in the seropositive
prostitutes, but serology to sexually transmitted diseases and/or endemic diseases
including HTLV-I was not significantly correlated with HTLV-IV seropositivity.
Significant elevations of polyclonal IgG levels (p=.0001) and of absolute T8 lympho-
cyte counts (p=.04) were found among the HTLV-IV seropositive prostitutes when compared
to seronegative prostitutes and to surgical controls from Dakar. Notably, both total T
cell counts and absolute T4 cell counts showed an inverse correlation to age greater
than 40 years in all 3 populations, regardless of serologic status. Other significant
findings were the presence of immune complexes in at greater levels in sera of sero-
positive prostitutes, as well as elevated levels of B„-microglobulin.
We conclude (1) that HTLV-IV is a sexually transmitted virus, (2) that certain
immunologic parameters are' consistent with a persistent viral infection, and (3) that
the absence of abnormal clinical findings in this cohort over time is markedly distinct
from similar cohorts exposed to HTLV-II I/HIV in Central Africa and may represent
reduced pathogenicity of HTLV-IV compared to HTLV-II I/HIV.
THR5 MOLECULAR CLONING AND BIOLOGICAL ACTIVITY OF HUMAN T-
LYMPHOTROPIC VIRUS TYPE-4 . Hardy Kornfeld, Norbert Riedel,
Gregory Viglianti, Vanessa Hirsch and James I. Mull ins.
Department of Cancer Biology, Harvard School of Public Health, Boston, MA
02115, USA.
Using raolecularly-cloned DNA of simian T-cell lymphotropic virus from an
African Green monkey (STLV-3AGM) as probe, we examined the genetic
relationship between individual isolates of STLV-3AGM, STLV-3 derived from
macaques from the New England Primate Research Center, and HTLV-4. The
consensus restriction site maps for all of these isolates differed at no
more than 3/34 sites examined. Strong homology, but distinct restriction
site patterns were detected in cell lines infected with STLV-3 from a sooty
mangabey from the California Primate Research Center and a macaque isolate
from the Delta Primate Research Center, possibly infected from a sooty
mangabey.
Molecular clones of HTLV-4 were obtained and shown to encode
transmissable virus which induced formation of giant multi-nucleated cells
in HUT-78, but with minimal cytolysis. Infection could be blocked by pre-
treating cells with anti-CD4 antibodies indicating that HTLV-4 likely
employs the same receptor as HIV. Comparison of the STLV-3/HTLV-4 consensus
with that of the LAV-2/HIV-2 reveals some restriction site conservation and
sequence homology in the LTR considerably stronger than either sequence
shares with HIV.
THP8 Anti-HIV Activity of 2' ,3'-Dideoxycytidine and the Unsaturated
Derivative (2' ,3'-Dideoxy 2' ,3'dehydrocytidine) Compared to 3'
Azidothymidine (AZT) .
ELAINE KINNEY-THOMAS*, TAI-SHUN LIN**, WILLIAM H. PRUSOFF**, and ISMAIL
GHAZZOULI# *Genetic Systems Corp., Seattle, WA; **Yale University School of
Medicine, Pharmacology Dept., New Haven CT; #Bristol-Myers Co., Virology
Dept., Syracuse, NY
Anti-HIV activities of 2',3'-dideoxy 2' ,3'-dehydrocytidine(ddd-C) ;
2',3'-dideoxycytidine(dd-C), and 3' azidothymidine(AZT) were compared in an
infectivity assay which employs the LAV isolate of HIV to infect CEM cells.
Virus production was monitored 15 days after infection by an EIA which uses a
monoclonal antibody to capture viral core antigen (p25) and a polyclonal
antiserum congugated to HRP as signal.
The three compounds, when added 24 hours prior to infection at a concen-
tration of 1 ijK, inhibited production of detectable viral antigen when the
virus inoculum was 50 TCID 50. When the inoculum was 500 TCID-50, viral
antigen production in the presence of 0.5//M and l,uM AZT was 66% and 23%,
respectively, of virus control antigen levels. In contrast, ddd-C at
concentrations of 0.5/oM and l^tfl showed complete inhibition of viral antigen
production. To determine the effect of these compounds after virus infection,
an experiment was performed, allowing the virus to adsorb to the cells 45
minutes prior to the addition of the drugs. The results show that both dd-C
and ddd-C at a concentration of 1//M inhibited viral antigen production
completely, even when the virus inoculum was 500 TCID-50, while antigen
production in the presence of 1//M AZT was 100% of virus control levels. This
indicates that both dd-C and ddd-C are more effective inhibitors of HIV
antigen production than AZT in both formats of this in vitro infectivity assay
system.
Other compounds have been tested, and results will be discussed.
164
THURSDAY, JUNE 4
THP9 Detection of HIV antigen and specific antibodies to HIV core and
envelope proteins in sera of patients with HIV infection.
YUNZHSN CAP*, S. H0JVAT+, P. VALENTINE*, J. P. ALLAIN+, P. RUBINSTEIN**, A.
FRIEDMAN-KIEN*. et al., *NYU Medical Center, New York, NY, +Abbott Labs,
Chicago, IL, **New York Blood- Center, New York, NY.
We have tested clinically well characterized populations for 3 markers of
HIV infection; HIV antigen (HIV Ag), p24, and gp41 antibodies (Ab) to HIV.
Of 56? patients, 251 were from populations diagnosed as AIDS with
opportunistic infections (AIDS-OI), AIDS with Kaposi's sarcoma (AID3-KS) and
ARC. 176 specimens were from high-risk asymptomatic individuals and 136
from control subjects or patients with non-AIDS related disease. None of
the 136 control individuals that we tested were reactive for either HIV Ag,
or HIV antibodies to p24 and gp41.
Of the 427 HIV seropositive individuals, 99 to 100^ were reactive for gp41
Ab to HIV. In contrast, we found that the seroprevalence of p24 Ab to HIV
varied from 23 to 83% and appeared to be inversely associated with the
severity of clinical symptoms. When specimens were analyzed for the
presence of HIV Ag, we observed that in seropositive individuals, the
prevalence rate for this marker was lowest (l.4#) in asymptomatic
individuals and highest (50$) in the AIDS-OI diagnosed group. Also, 240
cases with AIDS-KS, 01, ARC and high-risk asymptomatic individuals group
were analyzed for T4 cell number and T4/T8 ratio; only one (2.0$) HIV Ag
positive case showed a T4 cell number > 400 and a normal T4/T8 ratio.
These studies appear to demonstrate a direct correlation between the
presence of HIV Ag and the severity of HIV infection illnesses. In one
individual, HIV Ag was the only marker present, suggesting to us that in
similar cases, the detection of HIV Ag may be the sole evidence for a
biological diagnosis of HIV infection with current diagnostic procedures.
THR12 Murine Retrovirus Model Systems for Evaluating Antiviral Agents:
Efficacy of AZT and ddC In vitro and In vivo.
JOHN A. BILELLO*,**, E. TRACEY*, B. BENJERS", R. YETTER",**,
P.M. HOFFMAN","*, Research Service VA Medical Center and University of
Maryland Baltimore, MD.
Two murine retroviral systems have been used to evaluate the efficacy of
AZT and ddC. LP-BM5 MuLV induces a lymphoprol if erative/ immunosuppressive
disease in adult C57BL/6 mice which has a number of similarities to human
AIDS. Cas-Br-M MuLV induces a spongiform encephalopathy in NFS/N mice. In
vitro studies have indicated that both AZT and ddC protect murine cells from
infection with LP-BM5 and Cas-Br-M and inhibit the cell to cell spread of
virus . ddC was effective at 50 to 100-fold higher concentrations than
reported for human cells infected with HIV. Neither AZT nor ddC reduced
virus release from murine cells chronically infected with MuLV. Preliminary
experiments indicate ddC was ineffective in: (a) protecting C57B1/6 from de
novo infection with LP-BM5 (b) reducing virus load in infected mice (c)
stimulating the immune response. In fact ddC appeared to depress the CTL
response. AZT prevents the dissemination of Cas-Br-M MuLV and the
development of neuronal degeneration in NFS/N when administered prior to or
at the time of infection. Maternal transfer studies demonstrated that AZT-
treated mothers transfer protective levels of AZT to their offspring.
Newborn mice of AZT treated mothers challenged with lO^PFU ic, had no
detectible virus in their spleens or brains 3 and 8 weeks after AZT
treatment. These results suggest that AZT treatment of an infected mother
may inhibit viremia and protect newborns from MuLV infection.
THP10 Activity of dideoxynucleosides against HTLV-III/LAV in vitro
in different human cells.
CARLO F. PERNO*, R. YARCH0AN*, G. T0SAT0**, D. C00NEY***, H. MITSUYA*, and
S. BR0DER*, *Clinical Oncology Program and ***Developmental Therapeutics
Program, NCI, and **Bureau 6f Biologies, FDA, Bethesda, MD.
Several dideoxynucleosides have been shown to have potent activity against
HTLV-III/LAV ^n_ vitro in T cells. It has recently been shown that macrophages
and Epscein-Barr virus (EBV)-inf ected B cells may be infected by HTLV-III/LAV;
macrophages may be particularly Important clinically. Dideoxynucleosides must
undergo anabolic phosphorylation and the enzymes that mediate this may vary from
cell to cell. We have examined the ability of several dideoxynucleosides to pro-
tect two macrophage lines (THP-1 and U-937) and two EBV-infected B cell lines
(VDS0 and HER) against infection with 3000 virions/cell of HTLV-III/LAV. Cultu-
re supernatants were examined for reverse transcriptase (RT) and HTLV-III/LAV
p24 antigen. 2 ' ,3' -dideoxyadenosine (ddA) completely protected both VDS0 and HER
even at 5 to 10 uM. An IL-2 dependent T cell line derived from the same donor as
HER, as well as the T cell lines ATH8 and H9, were also protected at concentra-
tions down to 5 to 10 uM of ddA. Proliferation of these B and T cell lines was
not affected at concentrations up to 50 uM. Thus, ddA is effective at protecting
both EBV-transformed B cells and T cells. THP-1 and U-937 were completely pro-
tected against infection with HTLV-III by 0.2 uM of 2 ' ,3'-dideoxycytidine (ddC) ,
while proliferation was not affected. THP-1 was also completely protected by
3'-azido-3'-deoxythymidine (AZT) at concentrations down to 0.5 uM, while U-937
was only 85% protected at a concentration of 10 uM. Studies of the phosphoryla-
tion of dideoxynucleosides In these lines are ongoing at present. These results
indicate that while there may be some differences among these different human
cell types, dideoxynucleosides can protect EBV-infected B cells and macrophage
lines as well as T cells against infection by HTLV-III/LAV.
THP13 Phosphonoformic acid (Foscarnet) treatment and the effect on Human
Immunodeficiency Virus (HIV) isolation
BIRGITTA ASJO*, L. M0RFELDT~MA\NS0N**,S . BERGDAHL**, J. ALBERT*, L. VRANG*, E.M.
FENYO*, *Department of Virology, Karolinska Institute, Stockholm, Sweden,
**Department of Infectious Diseases, Roslagstull Hospital, Karolinska Institute,
Stockholm, Sweden.
Phosphonoformic acid (Foscarnet) is an efficient reverse transcriptase (RT)
inhibitor in vitro and it has been shown to effectively inhibit HIV infection
of H9 cells in tissue culture. The strong inhibitory effect on RT in addition
to a low toxicity and little side effects make Foscarnet an attractive drug
for treatment of HIV infected individuals. In the present study Foscarnet was
given to 8 homosexual males with persistent generalized lymphadenopathy (PGL)
or AIDS related complex (ARC) as a continous intravenous infusion at a dose of
0.1 4—0 . 1 6 mg/min/kg body weight/24 hours for 13-21 days. Virus isolations were
initiated from peripheral blood mononuclear cells (PBMC) before treatment, the
last day of treatment and at varying times after treatment. The results show
that continous intravenous administration of Foscarnet reduced the frequency of
positive HIV isolations from 13/14 (93%) before treatment to 18/34 (53%) after
treatment. Foscarnet had no effect on the frequency of virus isolations in
patients with advanced disease. PBMC cultures from these patients regularly
yielded virus both before and after treatment. In contrast, PBMC cultures from
patients with PGL were virus negative up to 8 weeks after treatment. No diffe-
rence in sensitivity to Foscarnet was noted between different HIV isolates.
THP11 Cytopathlc Effects of the Human Immunodeficiency Virus do not
Correlate Necessarily with Cell Fusion.
MOHAN SOMASUNPARAN and H.L.ROBINSON, Worcester Foundation for Experimental
Biology, Shrewsbury, MA, USA.
To study the role of syncytium formation in the cytopathlc effects of HIV
infections on TU+ lymphoid cells, we followed the infection of an
established laboratory stook of HIV, HTLV III, as well as a recent patient
isolate, HIV(UMA-CB), on H9 cells, CEM cells, and peripheral blood lymphocyte
(PBL) cultures. Virus spread and the onset of cytopathlc effects were similar
in each of the HIV-infected cultures. Unexpectedly, HIV-induced syncytia were
not observed except in infected H9 cells with the peak occurence of syncytia
preceding peak cytopathlc effects in these cells. Mixing experiments and flow
cytometry were used to determine whether cell-specif io expression of HIV
envelope glycoproteins or density of the TM receptor determined
susceptibility to HIV-induced fusion. The results of these experiments
indicate that (i) actively infected cells that both do and do not undergo
fusion express HIV envelope antigens which can initiate cell fusion, (ii)
HIV-infected cells initiate syncytium formation more efficiently with
uninfected than infected cells (presumably due to viral envelope
glycoproteins interfering with the expression of T*l antigen in infected
cells), and (iii) the apparent surface density of TU on a TH+ lymphoid cell
does not determine susceptibility to HIV-induoed fusion. On the basis of
these results it seems likely to us that the primary cause of T-cell loss in
HIV-infected patients will not be the result of HIV-induced cell fusions and
that T-cell lines which undergo HIV-induced cell fusion are not appropriate
model systems for the study of the loss of TU+ cells in HIV-induced AIDS.
THR14
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165
THURSDAY, JUNE 4
THP15 HTLV-IV, LAV-2, SBL6669 and STLV-III Possess Transactivator Gene
SURESH K. ARYA, BARBARA BEAVER, BARBARA ENSOLI, FLOSSIE WONG-STAAL,
ROBERT C. GALLO, et al.. Laboratory of Tumor Cell Biology, National Cancer
Institute, NIH, Bethesda, MD.
HTLV-III/LAV/HIV is the etiological agent of AIDS. It possesses a novel gene,
termed tat, which is essential for its replication and as such but indirectly
may play a role in its pathogenicity. Recently, new viruses antigenically
related to HTLV-III and even more closely to ST3LV-III have been isolated from
individuals from some West African countries. These include HTLV-IV, LAV-2
and SBL6669, isolated respectively from a lymphocytes of a healthy female
prostitute, an AIDS patient, and an individual with lymphadenopathy . Some of
these viruses cause immune deficiency whereas others may not. To test if the
new viruses possess a tat gene, we linked their cloned 3'-LTRs to the bacterio-
logical CAT gene. By DNA mediated transfection assays using virus-infected
cells as the source of tat function and CAT gene as the test gene, we find that
all three new viruses HTLV-IV, LAV-2 and SBL6669 as well as STLV-III possess a
functional tat gene, irrespective of their pathogenic potential in vivo. Such
structural and functional studies further suggest that (i) HTLV-IV, LAV-2 and
STLV-III 3'-LTRs are structurally and functionally related, (ii) their trans-
activator genes are also structurally and/or functionally homologous, (iii)
their 3'-LTRs and transactivator genes are related to HTLV-III LTR and trans-
activator gene and (iv) their LTRs and transactivator genes are more related
among themselves than to HTLV-III.
THR18 Comparison of 6 ELISA Assays for Detection of HIV antibody in
African Sera
LUBAKI NDONGALA*,J. ROWLAND**, H. FRANCIS*, M.P. DUMA, M. KASALI*,T.C. QUINN**
et al., * Project SIDA, Kinshasa, Zaire, **NIAID, Johns Hopkins Univ.,
Baltimore, MD.
African sera has been documented to cause many spurious results on
ELISA assays because of immune complexes, auto-antibodies and many other
immunologic reactions caused by continous exposure to endemic diseases.
To systematically evaluate which tests are most effected by these conditions,
we tested the Oreganon Teknika, Wellcome, Genetics Systems, Abbott, Electro-
Nucleonics and Dupont ELISA assays on 300 well characterized patient sera
collected at the Mama Yemo Hospital in Kinshasa, Zaire. Forty-four percent
of the sera were HIV positive by western blot. The Oreganon Tecknika test
was 99% sensitive and 98% specific in detecting HIV cases. The Wellcome
test was 97% sensitive and 100% specific, the Genetics Systems assay 98%
sensitive and 99% specific, The Dupont test 98% sensitive and 85% specific,
the Abbott test was 100% sensitive and 72% specific and the Electo-Nucleonics
test was 98% sensitive and 92% specific. The Wellcome test had the highest
positive predictive value of 100%, Oreganon's was 98%, ENI's was 95%,
Genetics Systems was 99%, Abbott's was 89% and Dupont's was 82%. Fifteen
patients that were positive by the Dupont ELISA were asymptomatic, HIV
antigen negative (Abbott), IgM negative (Dupont western blot) but p24
positive on IgG western blot. The results of the Dupont assay may represent
either cross reactivity with other retrovirus infections or be false positive
reactions. Almost all of the ELISA assays were able to detect true HIV
infections however, in the African setting, the Wellcome test was the most
rapid, (2 hours vs 4-6 for the others) and the easiest to use.
I tin ID Antibody Reactions to Human B Cell Lymphotropic
Virus (HBLV) in my Infection.
HARK H.KAPLAN, B.Farber, M.H.Dosik*, J.Kochen, S.Katz,
V. Vinceguerra. Cornell University Medical College, North Shore
University Hospital, Manhasset N.Y.
We studied sera from patients with HIV infection for antibody
to HBLV. Clarified, heat inactivated sera were reacted with
phytohemagglutinin stimulated cord blood lymphocytes infected
4-5 days with HBLV (acetone fixed) . Antibody was determined
using fluorescene tagged goat antihuman antibody. Sera were
screened for 3-4+ activity at a dilution of 1:40. 19/39 sera
from patients with opportunistic infection (01), 6/12 Kaposi's
sera, 40/76 lymphadenopathy sera and 2/5 lymphoma sera were
reactive with over 1/2 having titers of >1:160. In pts without
HIV infection ,29/42 Hodgkins disease, 10/14 Acute lymphoblastic
leukemia ,12/20 non Hodgkins lymphoma, 25/41 Crohn's
disease, 6/18 normal donors and 2/5 EBV negative sera reacted to
HBLV often with titers greater than 1:160. Some 4+ sera showed
reactivity to uninfected PHA stimulated CBLs and to nuclear
antigen (ANA) . Radio-immuno-precipitation antibody assay using
35 [S] methionine labeled virus and uninfected control CBLs
revealed that reactive sera produced 2 bands at 96-110, OOOmw and
at 62-66, OOOmw. The disease produced by this virus and its role
in HIV infection and other disorders still remains unclear. This
virus is however widely distributed in man as are other better
known herpes viruses.
THR19 Evaluation of a Latex Agglutination Assay Using Recombinant Envelope
Polypeptides for Detection of Antibody to HIV
THOMAS C. QUINN*, H. FRANCIS***, R. KLINE**, M.P. DUMA***, M. SENSION**
C. RIGGIN****, et al., *NIAID, Bethesda, MD, **Johns Hopkins Univ, Baltimore,
MD, ***Project SIDA, Kinshasa, Zaire, ****Cambridge BioScience, Hopkinton,
MA.
Screening of blood donors for antibody to HIV is not feasible in most developing
countries due to the lack of blood banking facilities and equipment, including
refrigeration and ELISA readers. The cost of HIV ELISA kits and microplate ELISA
readers is frequently prohibitive and technical support is often limited. Consequently,
unscreened blood transfusions remain one of the major modes of HIV transmission in
developing countries, such as in Central Africa where 5 to 15% of blood donors are
seropositive to HIV. We therefore evaluated a rapid latex agglutination slide test
for the detection of HIV antibodies in order to facilitate routine screening of blood
transfusions in these areas. A recombinant HIV envelope antigen expressed in E_.
coli was attached to 0.5 microns latex beads, and mixed with 2.5 ul of patient sera
diluted 1:10. Sera from 2,000 patients residing in Zaire, Kenya, Haiti, and Trinidad
were evaluated by the latex agglutination slide test, ELISA (Organon-Teknika) and
Western blot analysis (Dupont). Overall 6t% of the sera were positive by repeat
ELISA and Western blot. On a single determination for each sample the latex
agglutination slide test was found to have a sensitivity of 99.1%, specificity of
99.4%, and positive predictive value of 99.5% compared to Western blot. The test
was found to be simple, rapid (less than 2 minutes per test), and more specific than a
single ELISA. Use of this assay will allow for the immediate implementation of
blood bank screening for HIV in developing areas of the world where standard screening
procedures are impractical or are not available.
THP17 Human Immunodeficiency Virus (HIV) Encodes an Alternate gag
Precursor Protein of 41 kDa.
SUNDAPARAJAN VENKATESAN*, ERIK P. LILLEHOJ*, ROBERT J. MERVIS*, HARDY CHAN**,
MIKE RAUM***. *Laboratory of Molecular Microbiology, ***Laboratory of
Immunoregulation , NIAID, NIH, Bethesda, MD 20892; and **Syntex Corporation,
Palo Alto, CA.
During actue HIV infection, two gag specific polypeptides of 55 and 41 kDa
were shown to be rapidly labeled in an almost equimolar manner under pulse-
chase conditions. Both of them were processed in an identical manner to
mature gag polypeptides. p55 and p41 were readily expressed in a variety of
non-lymphoid primate cell lines transfected with subgenomic proviral DNAs
containing only the gag ORF under the control of HIV LTR, thus eliminating the
possibility the p41 resulted from viral protease mediated processing of
p55. p55 and p41 were metabolically labeled and purified from either
persistently infected cells carrying a defective copy of proviral DNA or
lymphocytes infected with virus prepared by transfection with cloned proviral
DNA. Attempts at direct N-terminal sequencing of either protein failed,
presumably due to blocked N-terminus. Comparative tryptic peptide mapping
revealed that p41 peptide constituted a subset of p55. Four peptides unique
to p55 were selected for automated N-terminal sequencing. Preliminary
sequencing localized two such peptides to the N-terminal domain (residues
28-30 and 109-112) of the gag ORF. Although the exact N-terminus of p41
was not deduced, the wieght of the evidence suggested that p4I resulted from
an alternate initiation at the MET codon at position 142 of the gag ORF.
Functional role(s) of the p41 protein are being evaluated using
mutagenized proviral DNAs incapable of expressing this protein.
THR20 Humoral an<' Cellular Immune Response to Recombinant HIV Glycoprotein,
gP120, in Rodents and Primates.
PHILLIP W. BERMAN*. T. GREGORY*, J. EICHBERG**, J. GR00PMAN***, R. WEISS****,
L. LASKY*, et al_. , Genentech, Inc., So. San Francisco, CA, **Southwest
Foundation, San Antonio, TX,***New England Deaconess Hospital, Boston, MA, USA,
****Chester Beatty Laboratories, London, U.K.
A mammalian cell line has been developed that produces useful quantities of
the major envelope glycoprotein, gPl 20, of Human Immunodeficiency Virus. The
recombinant protein, r-gP120, is fully glycosylated and able to bind to CD4
(T4) antigen with high affinity. Rodents and primates immunized with r-gP120
incorporated in an adjuvant suitable for human usage (alum hydroxide) formed
antibodies that reacted with native HIV glycoproteins gP160 and gPl 20 in
Western Blot and radioimmunoprecipitation assays. Sera obtained from guinea
pigs, rabbits, baboons, and chimpanzees contained antibodies that were able to
neutralize viral infectivity in a variety of in vitro neutralization assays
including: inhibition of reverse transcriptase, and VSV pseudotype assays.
Chimpanzees immunized with r-gP120 developed a cellular immune response as
measured by the ability of peripheral blood lymphocytes to proliferate in vitro
in response to purified immunogen. Antibodies from several species were able
to inhibit the binding r-gP120 to cell surface CD4 (T4) antigen in an in vitro
binding assay. Finally, antibodies raised against r-gP120 from the HTLT 1 1 lb
isolate were able to neutralize, albeit at a somewhat lower titer, a number of
diverse HIV-1 isolates including those obtained from Europe, Africa, and the
United States. Sera from rodents and primates gave somewhat different patterns
of cross neutralization, thus it appears that host factors may be important in
determining the degree of protection that can be provided by a monovalent
vaccine. These studies provide support for further consideration of r-gP120 as
a„vaccine, against; AIDS.
166
THURSDAY, JUNE 4
THP21 Comparative Neuropathology of SIV and HIV Brain Infection.
LEON G. EPSTEIN*, L.R. SHARER*, E.-S. CHO*, H. MURPHEY-CORB**, G.B.
BASKIN**, *UMD-New Jersey Medical School, Newark, NJ, **Delta Regional
Primate Research Center, Covington, LA.
A strain of simian immunodeficiency virus (SIV/Delta, or STLV-III),
originally isolated from a lymphoma from a rhesus monkey (Macaca mulatta),
regularly produces immune deficiency and encephalitis when inoculated into
juvenile rhesus monkeys. Brains from 5 infected monkeys were compared with
those of 18 children who died with human immunodeficiency virus (HIV)
infection and progressive encephalopahthy. A hallmark of the simian disorder
is disseminated, multinucleated, syncytial cells occuring in liver, gastro-
intestinal tract, lymph nodes, spleen, and brain. Multinucleated giant cells
in brain contain SIV particles on ultrastructural examination and are
remarkably similar to those seen in the central nervous system of humans
infected with the related retrovirus, HIV. In monkeys, these cells were
predominantly perivascular, occurred in both gray and white matter and were
often associated with foci of necrosis and karyorrhexis. Basal ganglia and
deeper structures were frequently involved, as was the cerebral cortex;
brainstem lesions were infrequent. In children with HIV encephalitis, such
cells were often perivascular, but in some instances the cells bore no
obvious relation to vessels. Diffuse white matter changes (pallor,
astrocytosis) were only rarely observed with SIV but were common in children.
One monkey had multinucleated cells in a leptomeningeal infiltrate.
Complicating simian infections included simian cytomegalovirus and
adenovirus. SIV infection in monkeys sufficiently mimics the human disease to
warrant investigation of such pathogenetic features as penetration of virus
into brain and syncytial cell formation.
THR24 HIV-2 infection in a couple of french homosexual men.
G. BRUCKER*, F. BRUN-VEZINET**, MICHEL ROSENHEIM*, M.A. REY**,
C. KATLAMA**, H. GENTIUM*, *Groupe Hospitalier Pitid-Salpetnere, Paris,
France, **H6pital Claude Bernard, Paris, France.
HIV-2 (Human Immunodeficiency Virus type 2) is a retrovirus isolated from
AIDS patients from West Africa. Cross reactivity with HIV-1 is restricted to
core proteins.
We have identified anti HIV-2 antibodies in two french homosexual men who
never travelled to West Africa. One patient has AIDS (Kaposi's sarcoma) and
the second, who is his sexual partner, is asymptomatic. In both cases, ELISA
for anti HIV-1 antibodies was negative, Western blot only showed p 25 and p 34
in patient one, p 18 and p 25 in patient two. Those reactions, using HIV-2
antigens, were reactive ; Western blot demonstrated, in both patients, anti-
bodies to p 26, p 16, p 55, gp 130-105, p 68, p 41, p 30-33. HIV-2 uas isola-
ted from the two patients peripheral blood lymphocytes.
Since Kaposi sarcoma was diagnosed in 1985 it could be speculated that
HIV-2 infection occured in patient 1 at least two years before. This suggests
that, now, HIV-2 infection could be spreading in homosexual french community.
The negativity of the sera by HIV-1 ELISA has been already reported. Thus,
in patients with AIDS or AIDS related complex, HIV-2 infection must be sus-
pected when HIV-1 antibodies are lacking.
A blood-bank screening test using both HIV-1 and HIV-2 antigens is now
required.
THR22 Identification of Functional Regions in the HIV Reverse Transcrip-
tase by Site-Directed Mutagenesis
BRENDAN. A. LARDER, D. J .M.PURIFOY, K.L.POWELL and 6. DARBY, The Wellcome Research
Laboratories, Beckenham, Kent, U.K.
We are currently studying the reverse transcriptase (RT) of HIV expressed in
E.col i , with the aim of identifying those regions and specific amino acid
residues involved in the catalytic activity of the enzyme. Initially, a large
DNA fragment comprising most of the HIV pol gene, including the protease and
RT sequences, was sub-cloned into an M13 expression vector which contains the
strong inducible "tac" promoter. Infection of E.col i with this recombinant
bacteriophage (mpRT1) resulted in significant levels of RT activity being
induced. Through a series of manipulations, including ol igonucleotide-
directed deletion mutagenesis, the protease and endonuclease sequences flan-
king the RT coding region have been removed, giving a construct (mpRT4) which
expresses large amounts of the native enzyme. The RT expressed by mpRT4
exhibits similar properties to the "authentic" enzyme found in HIV-infected
cells, including sensitivity to PFA and AZT-TP, and apparent Mr (~66 kDa).
A number of regions of the RT which share homology with other polymerases
have been probed by site-directed mutagenesis and using this approach, we have
identified two small areas of the RT polypeptide which are likely to be
involved in enzyme function, one of these being centred around two Asp resi-
dues (positions 185 and 186). It is hoped that studies of this nature will
provide information about the interaction of HIV RT with its substrates and
may facilitate the more rational design of chemotherapeutic agents.
THR25 Comparative Quantitative Investigations on HIV-1 -neutra-
lizing Antibodies with Respect to different Epitopes
BERND ZORR.K.O.HABERMEHL, Inst. of Clin. and Exper . Vi rol ogy , Free
Uni ver si ty of Berlin, Hi ndenburgdamm 27, 1000 Berlin 45, Germany
Quantitative determination of HIV-neutralizing antibodies is a pre-
requisite for developing vaccines. Using a sensitive plaque reduction assay
50 sera of HIV-1-infected patients showed a linear correlation between H I V-
specific antibodies on the one hand and neutralizing antibodies on the
other. Since all of the examined sera without exception showed this corre-
lation one can conclude that in spite of the genetic variability of HIV-1
the majority of the neutralizing epitopes seems to be conserved. This in-
dicates that similar as in Hepatitis B the total amount of (ELISA-deter-
mined) HIV-1-antibodies gives an information about the magnitude of the
humoral immune status of the patient. - Further investigations concerning
single epitopes on different structural proteins have been performed using
synthetic oligopeptides. One neutralizing epitope located on p 18 showed a
significant concentration-dependent correlation between ELISA-reactivity
(based on an oligopeptide according to this epitope) and the neutralizing
activity. Since 100 % of the patients sera (n=30) showed this behaviour one
may conclude that this epitope has a high genetic stability. Similar results
could be obtained with an epitope from gp 41 whereas another epitope on gp
41 showed no genetic stability. The capability of the epitopes to induce
neutralizing antibodies was confirmed by an antiserum obtained from sheep
immunized against the corresponding oligopeptide (the synthesis of the
oligopeptide and the immunization was performed by Or.Frenzel, Biochrom).
THR23
CELL SPECIFICITY OF HTLV-IV AND LAV-2 PROMOTERS
BARBARA ENSOLI
ROBERT C
Institute, NIH
SURESH K. ARYA, BARBARA BEAVER, FLOSSIE WONG-STAAL AND
GALLO, Laboratory of Tumor Cell Biology, National Cancer
Bethesda, MD.
Human T-lyraphotropic viruses (HTLVs) display preferential specificity tor
CD4+ lymphocytes. This characteristic is partly due to the specificity of
the virus-cellular receptor interaction but could also be influenced by
other cellular factors and their interaction with viral promoters. We
recently tested the ability of the HTLV-IV promoter to function in a variety
of cell types. We linked the HTLV-IV 3 ' -LTR to the bacterial CAT gene and
measured the expression of the CAT gene to assess viral promoter function by
DNA-mediated transfection assay. The HTLV-IV LTR-CAT DNA was transfected
into human H9 and Jurkat lymphocytes, human HOS , rhabdomiosarcoma and glial
cells, and hamster CHO cells. The results showed that HTLV-IV promoter
functions in all cell types tested and it appeared to function more
efficiently in monkey COS cells. This suggests that the HTLV-IV LTR per se
lacks tissue specificity in its function as a promoter. Similar
observations have been reported previously for HTLV-I and HTLV-III.
THR26 Expression in E. coli. Purification, and Analysis of Full Length HIV gag
Antigen
D. TRIBE. B.FERGUSON. D. REED. D. MCCABE.and S.R. PETTEWAY. E. I.DuPontde
Nemours. Medical Products Department. Wilmington. DE.
The full length, non-fused H1V-11IB gag gene product has been expressed at high
level in E. colj. E. coM-expressed gag was obtained as a soluble protein and
purified by cation exchange chromatography. Competition binding experiments indicate
that all the immunoblol delectable gag-specific epitopes recognized by several AIDS
patient sera are presented by full length E. coM-expressed gag. Thus, this protein
will clearly be a sensitive reagent for the detection of gag-specific antibodies in
human sera.
An high-tiler antiserum specific for full length E. coli-expressed HIV gag was used
to detect gag-derived proteins by Western blot in a licensed preparation of purified
virus. In addition to p55, p24. and p 1 7. minor gag-derived proteins were detected at
approximately 130 and 41 kDa. We note that this gag-specific reactivity in a Western
blot could be falsely interpreted as HIV eny reactivity (gpl60/l20 and gn4l). In
addition. HIV gag-specific antisera are being used to examine cross-immunoreactivily
between gag proteins from different viruses.
167
THURSDAY, JUNE 4
THR27 Hlv tat/LTR-mediated Expression of Heterologous Genes: Derivation of
Stable Cell Lines
L. T. BACHELER. L. L. STREHL, B. Q. FERGUSON AND S. R. PETTEWAY. JR.,
E.I. Du Pont de Nemours, Medical Products Department, Wilmington. DE.
Stable cell lines carrying a functional HIV ]at gene, a reporter gene linked to the
HIV LTR. or combinations of these genes, have been isolated following DNA
co-transfection of appropriate plasmid constructions and pSV2-neo as a selectable
marker into HeLa cells. Clones constitutively expressing a functional tat gene
product (under SV40 early transcriptional control) were identified by the ability of
such clones to express a high level of chloramphenicol acetyl transferase (CAT)
shortly after transfection with a HIV LTR-CAT plasmid. Clones carrying HIV LTR-CAT
or HIV LTR-g-galactosidase plasmids in an activatable form express low or
undetectable levels of the reporter gene protein, but are readily activated to high
level expression by the introduction of a HIV jat-expiessing plasmid. Clones
expressing high levels of (3-galactosidase under combined HIV tat/LTR control have
been isolated, but no stable lines expressing high levels of CAT activity under HIV
]at/LTR control could be derived. This observation suggests that high level
expression of the CAT gene product is lethal for HeLa cells. Similar experiments
using human IL-2 as a reporter gene are in progress. Our results demonstrate the
derivation of stable cell lines containing heterologous genes under tight HIV tat/LTR
control. Such cell lines should be useful for further studies of the mechanism of
tat function, and for high level expression of heterologous genes in HeLa cells.
THR30 Immunoperoxidase Localization of Human and Simian Immunodeficiency
Antigens 1n Surgical Pathology and Autopsy Specimens. JERROLD M.
WARD*, T.J. O'LEARY**, R.H. RHODES***, R.E. BENVENISTE*, G.B. BASklN****,
and C.C. TSAI*****, et al., *Nat1onal Cancer Institute, Frederick, MD; "Food
and Drug Administration, Bethesda, MD; ***Univers1ty of Southern California,
Los Angeles, CA; ****Delta Regional Primate Research Center, Covington, LA,
and *****Reg1onal Primate Research Center, Seattle, WA.
Surgical lymph nodes from 23 AIDS patients, fixed 1n B-5, and selected
autopsy specimens from 39 AIDS cases, fixed in formalin, were stained by the
ABC immunocytochemical technique using polyclonal and monoclonal antisera to
localize HIV (also known as HTLV-III/LAV) antigens Including core protein
p24. Biopsy specimens with follicular hyperplasia had immunoreactlve viral
antigens in follicular dendritic cells, rare immature B lymphocytes and
extracellular spaces of follicles, sinus macrophages and postcapillary venule
endothelium, while atrophied nodes were usually not immunoreactive. In 2/8
cases of Kaposi's sarcoma, histiocytic cells or vascular endothelium was
immunostained in lymph nodes with metastatic tumors. A small proportion of
multinucleated giant cells and mononuclear macrophages were immunoreactive in
8 of 15 brains with such cellular infiltrates including 3 cases of Progres-
sive Multifocal Leukoencephalopathy and in vascular endothelium of one case.
Monkeys, Macaca mulatta or Macaca fascicularis, inoculated with Simian Immu-
nodeficiency Viruses (SIV Ill/Delta or MnlV [WPRC-1]) had viral antigens in
macrophages, reticular cells and giant cells in sections of formalin fixed
tissues with lymph node follicular hyperplasia, lymph node and splenic giant
cell histiocytosis, and in retroviral encephalitis.
THP28 Rapid Direct Detection of HIV in Lymphocytes of Seropositive, Asymptomatic
Persons by Selective DNA Amplification.
C.Y. 01)*, S. MITCHELL*, P.M. FBORKO*, S. KHOX+, J.J. SNTNSKr1", and G. SCHDCHETMAN*. *AIDS
Program, Centers for Disease Control, Atlanta, GA 30333. "^Department of Diagnostic Research,
Cetus Corporation, Emeryville, CA 94608.
Confirmation of current infection with HIV requires virus isolation by cocultivation of
patients' lymphocytes with PHA-stimilated lymphocytes from normal individuals. This requires
up to 3 weeks with virus only being isolated from a portion of seropositive individuals. We
have used a modified form of a DNA amplification technique to rapidly detect HTV sequences in
chromosomal DNA isolated directly from patients' lymphocytes without prior cultivation. Two
oligomer primers of 20 nucleotides each and an oligomer probe of 40 nucleotides from the highly
conserved amino terminus of gp41 were used. HTV sequences from patients ' lymphocyte DNA were
amplified using DNA polymerase I in the presence of the two primers to give rise to a 135 bp
partial gp41 sequence. Amplified HTV sequences were hybridized with a 32-P end-labeled 40-mer
probe representing a portion of the 135 bp sequence. This was followed by digestion with Hha-I
yielding a diagnostic end-labeled 24-mer. We analyzed DNA isolated from established
HIV-infected T cell lines, uninfected T cells, T cells infected in vitro with HTV, and DNA
isolated directly from lymphocytes of sero- and culture-positive asymptomatic gay males from
San Francisco. We could readily detect, within 2 days, the 24-mer in 8 of 12 gay males tested
and in all of the infected T cells but not in any of the uninfected T cells. This technique
enables us to readily identify HIV-infected persons directly. We will present additional data
on the HTV status from a large number of persons who are: 1) asymptomatic seropositive long
term survivors; 2) sero-positive but culture-negative persons; 3) sero-negative spouses of
sero-positive persons; and 4) offspring of sero-positive mothers.
THP31 T^e Acquisition of Anti-HIV Markers during Seroconversion
observed in 40 High Risk Males.
S. JOHNSON, WILLIAM J. MASKILL, M.J. WATERS, R.J. WARREN, B.W. DWYER and
I.D. GUST. Fairfield Hospital, Melbourne, Australia.
A retrospective serological study was performed on 340 sera obtained from
39 homosexual/bisexual men and one haemophiliac male during seroconversion
after infection with Human Immunodeficiency Virus (HIV). The serial bleeds
from each patient were collected at random intervals over 4 years. Follow up
periods from the time of seroconversion range from 3 months to 3.5 years.
Tests performed on the specimens include enzyme linked immunosorbent assay
(ELISA) , radioimmunoprecipitation (RIP) test for anti-p24 and western
blotting (WB).
A 'window period' (ranging from 2 weeks to 5 months) of low sensitivity
with the ELISA as compared with the WB was observed in early specimens from
six patients. The earliest reactivity detected by WB was to core proteins
p24, p40 and p55 followed closely by reactivity to viral enzymes (p34,
p53/p68) and glycoproteins (gp41-45, gpllO). The RIP test was the least
sensitive assay. Five patients were consistently RIP negative for all
specimens, two of whom developed AIDS.
These results support recent observations concerning the poor sensitivity
of available ELISA' s in early HIV infection during which time the WB assay
detects anti-HIV core antigen reactivity.
THP29 Serological comparison of human retroviruses of West African origin.
BIBERFELD GUNNEL, J. ALBERT, U. BREDBERG, F. CHI0DI, B. B0TTIGER, E. FENY0 and
E. NORRBY, Departments of Immunology and Virology, National Bacteriological Labo-
ratory, 105 21 Stockholm, and Department of Virology, Karolinska Institute,
Stockholm, Sweden.
Among sera tested in our laboratory for antibodies to human immunodeficiency
virus (HIV) we found three anti-HIV ELISA positive sera from West African immi-
grants which by Western blot (WB) and radioimmunoprecipitation (RIP) analyses
reacted with gag and pol gene encoded proteins (p 24, 31, 53-55, 64) but not
with envelope glycoproteins (gp 41 and 120) of HIV. However, these sera reacted
with envelope as well as core proteins of the West African retroviruses human T
lymphotropic virus type IV (HTLV-IV) and lymphadenopathy associated virus type
II (LAV-II). A retrovirus (SBL-6669) was isolated from lymphocytes of one the
West African individuals, a 55-year old Gambian woman who had a decreased num-
ber of T4 cells, recurrent lower respiratory tract infections and ungal candidia-
sis. Comparison of this virus with HTLV-IV, LAV-II and HTLV-IIIB by WB and RIP
analysis showed that SBL-6669 virus was antigenically more closely related to
HTLV-IV and LAV-II than to HTLV-IIIB. The external glycoproteins of the three
West African viruses SBL-6669, HTLV-IV and LAV were indistinguishable However
there were interstrain differences in the size of core proteins and the presumed
transmembrane glycoproteins. SBL-6669 virus was associated with imrunodeficiency
like LAV-II (Clavel et al, Science 1986; 233: 343) but unlike HTLV-IV (Kanki et
al, Science 1986; 232: 238).
THP32 Live Vaccinia/HIV recombinant Viruses. An approach to an AIDS
Vaccine
MARIE PAULE KIENY*. G. RAUTMANN*, F. PLATA**, M. GIRARD***, L. MONTAGNIER**,
J-P. LECOCQ,*Transgene S.A., Strasbourg, France, **Institut Pasteur, Paris,
France, ***Pasteur-Vaccins, Marnes La Coquette, France.
Both HIV lentiviruses and HIV-infected cells are presumed to present a
single major target antigen at their surfaces. This polypeptide, the env
glycoprotein, is thought to promote HIV infection by interaction with a host
protein, possibly the lymphocyte T4 antigen. The 160 kilodalton env precursor
glycoprotein (gpl60) undergoes proteolytic cleavage in vivo, yielding a gp41
transmembrane moiety and a gpl20 extracellular component. By analogy to the
gp ' s of similar viruses, these have been presumed to remain associated at the
cell surface. We have expressed the HIV env gpl60 precursor glycoprotein gene
in a recombinant vaccinia virus. env glycoprotein encoded by the recombinant
virus VVTGeLAV is correctly cleaved to generate gp41 and gpl20. However, the
two moieties do not remain associated, gpl20 being rapidly shed from the cell
surface. We have constructed mutants of VVTGeLAV in which the env cleavage
site(s) has been removed, and the immunological properties of these second-
generation recombinants will be discussed.
168
THURSDAY, JUNE 4
THR33 LAV-2/HIV-2 infection : Clinical, epidemiological and virological features
FRANCOISE BRUN-VEZINET', M.A.REY*, M.C.DAZZA*, S.GADELLE**,
J.J.MADJAR***, IvI.HARZIC*, et al. Laboratoire de Virologie, hopital Claude Bernard*,
Paris; Diagnostics Pasteur", Paris; Universite Alexis Carrel***, Lyon - France.
In 1986 we diagnosed 18 cases of LAV-2/HIV-2 infection in patients (pts) who
have been living in France for at least one year. Six pts were assumed to have
AIDS whose 2 met the criteria for AIDS since 1983. Two pts presented with ARC
diagnosed in 1985. Ten were asymptomatic subjects (AS). Eleven pts originated from
West African countries : Cape Verde islands (2), Ghana (3), Ivory Coast (1), Guinea
(2), Senegal (2) and Guinea Bissau (1). Seven pts were european : 2 heterosexual
Portuguese couples, one French heterosexual male and a French couple of homosexual
males.
In these pts, HIV-2 transmission was likely to be acquired through heterosexual or
homosexual contacts. None was a drug abuser. In the 2 heterosexual Portuguese
couples, the mode of HIV-2 transmission is quite unclear. Vertical transmission is
studying in 3 cases of HIV-2 pregnant women. Retrovirus isolation was performed
from the peripheral blood lymphocytes from the 12 tested patients (5 AIDS, 2 ARC,
2- AS). In the supernatants of the cultures, an antigen capture assay using HIV-1
polyclonal antibody did not detect HIV-2 antigens. Isolates were characterized by
Oot Blot hybridization with HIV-1 and HIV-2 DNA probes. We are performing Southern
Blot analysis of isolates from patients originating from different countries. HIV-2
neurotropism was demonstrated by virus isolation from the CSF and/or by intrathecal
IgG HIV-2 synthesis. IgG antibodies to HIV-2 were detected by Elisa and WB (Diag-
nostics Pasteur). Since the HIV-1 and HIV-2 cross-reactivity was restricted to the
core proteins, only the presence of antibodies to HIV-2 envelope glycoproteins
demonstrated HIV-2 seropositivity. Whatever HIV-1 and HIV-2 common characte-
ristics, as lymphotropism and cytopathic effect in vitro, question is asked about a
difference of pathogenicity.
THR36 Isolation and Characterization of a Bacterially Expressed
Reverse Transcription of HTLV III/LAV
Karin Moellinq, J. Hansen, T. Schulze, and S. Sukrow,
Max-Planck-Institut fur Molekulare Genetik, Abt. Schuster,
1000 Berlin 33, IhnestraSe 73, Germany.
Various fragments of the "pol" region of HTLV III/LAV were
cloned into different expression vectors. Enzymatically active
reverse transcriptase was detected with two of them in transformed
bacteria. Furthermore, two protein bands of 66 and 51 kD were de-
tected in bacterial lysates using patient sera suggesting that
they represent the reverse transcriptase subunits 8 and a . Pro-
cessing from larger molecules, which presumably represent precur-
sor forms, could be followed with time. The enzyme activity was
purified by means of DEAE-Sephadex, phosphocellulose, mono S and
immuneaf f inity column chromatography. Biochemical parameters of
the bacterial polymerase were compared with virion-associated
reverse transcriptase. Inhibitor studies as well as fidelity stud-
ies were performed and will be presented. The enzyme should be
useful for large scale screening of reverse transcriptase in-
hibitors.
THP34 Evaluation of Microinjection of Cloned Genes as an Effective Method
of Genetically Engineering Mammalian Cells to Produce Human Immuno-
deficiency Virus and Envelope Protein
V. ANN BOYD*. T. G. WOOD**, R.V. GILDEN***, and M.A. GONDA*, *Laboratory of
Cell and Molecular Structure, and **Recombinant DNA Laboratory, ***Prograra
Resources, Inc., NCI-FCRF, Frederick, MD.
A cloned HIV, strain HTLV-IIIB (pHXB-2) , infectious provirus was microin-
jected into the cell nucleus of six non-lymphoid cell lines from caprine,
ovine, bovine, and human species. For each cell line, 100-200 cells were
microinjected with pHXB-2. An immunofluorescence assay ( IFA) for HIV p24
demonstrated virus replication 24-48 hrs after microinjection in 5* of the
cells. Virus was recovered from all cell lines regardless of tissue or species
of origin by cocultivating T4-positive human lymphocytes (H-9) with the
microinjected cells 48 hrs after microinjection. Confirmation of infectious
virus release from injected cells was demonstrated by syncytia formation,
electron microscopy, reverse transcriptase, and radioimmunoassay for HIV p24
in cocultures. Syncytia in cocultivated H-9 cells were apparent on days 7-10
and was both the earliest indicator and most reliable assay for demonstration
of infectious virus release. A complete envelope subgenomic fragment of pHXB-2
flanked by 5' and 3* LTRs (pLVWT) was constructed and introduced into
mammalian cells in an attempt to create a cell line expressing high levels of
the HIV envelope free of infectious virus. Using an antiserum to gpl20, the
major outer envelope protein of HIV, 5-20* of the microinjected cells were
found to express low levels of envelope proteins by IFA. No replicating virus
was detected and the duration of expression has not yet been determined. These
results suggest a possible approach to producing antigens in mammalian cells
and may have relevance for vaccine development.
THP37 Inactivation of HIV by Disinfectants and Spermicides
YVETTE HENIN, V. MARECHAL, F. BARRE-S INOUSS I and J.C. CHERMANN,
Institut Pasteur, Viral Oncology Unit, Paris, France.
Various disinfectants and spermicides have been tested for their efficacy to
inactivate in vitro the reverse transcriptase and the infectivity of HIV for
human peripheral blood lymphocytes. Disinfectants commonly used in hospitals
for cleaning floors and benches were containing alcohol in quaternary ammonium
or aldehyde complex solutions or glutaraldehyde in quaternary ammonium solu-
tions. All these solutions were found to be effective either undiluted or at
concentrations ranged between 0.25 % and 25 % with a time of treatment varying
from 1 to 10 min. at room temperature. Disinfectants for medical instruments
were mainly aldehyde solutions and were also destroying viral activities. Com-
mercialized solutions for body hygiene are often a mixture of alcohols with
other compounds such as quaternary ammonium salts or chlorohexidine for exam-
ple. Five of them were tested and found effective at various concentrations
(0.5 % to 50 %) in a short time of contact with the virus (30 sec. to 5 min.).
Inactivation of HIV by spermicides containing cationic detergent (benzalko-
nium chloride or alkylbenzyldimethyl ammonium chloride) has also been shown
to inactivate HIV infectivity in vitro at low concentrations in a relatively
short period of treatment (10 to 60 min.) . The effects of other spermicides
and disinfectants will also be discussed. These results might be of interest
for the prevention of the sexual transmission of the disease and for the sa-
fety in hospitals and laboratories.
THR35 "^ Neutr^izi™? Antibodies and Cellular Immunity Elicited by a
Recombinant Virus Envelope Produced in Insect Cells
CINDY LOU jTT.T.Tq*, J. RUSCHE*, K. KRDHN**, T. MATTHEWS***, M. ROBERT-GUROFF** ,
S. PUTNEY*, et al., *Repligen Corporation, One Kendall Square, Building 700,
Cambridge, MA, "Laboratory for Turror Cell Biology, National Cancer Institute,
National Institute of Health, Bethesda, MD, '"Department of Surgery, Duke
University Medical School, Durham, NC.
The HTV envelope (gpl60) was produced in insect cells using a baculovirus
expression vector encoding the HTLV-IIIg envelope. Antibodies from animals
immunized with this protein neutralize the HTLV-IIIB virus and the neutraliza-
tion titer of this antisera is approximately five-fold higher than that of
antisera to native gpl20 isolated from the virus. The neutralization of the
gpl60 antisera is type specific in that it does not efficiently neutralize the
heterologous variants, HTLV-IIIjflj and HTLV-IIIpp. In addition to eliciting
a humoral irrtnune response, gpl60 elicits cellular immunity as measured by
T-cell proliferation upon stimulation by virion or native gpl20. In contrast
to the humoral response, cellular immunity is not HIV isolate specific. We
are preparing the envelope from other viral variants to obtain a more broadly
neutralizing response and to evaluate these proteins as a vaccine.
THR38 A "ONOCLONAL ANTIBODY TO GENETICALLY ENGINEERED NON-GLYCOSYLATED
GP120 PRODUCED IN YEAST NEUTRALIZES HIV. J.C. STEPHANS and
K.S. STEIMER. Chiron Corporation, Emeryville, California, U.S.A.
A murine monoclonal antibody specific for a genetically engineered
polypeptide produced In yeast corresponding to amino acids 28-491 of the
envelope gene product of the ARV-2 isolate (now designated HIV-SF2) of
human immunodeficiency virus (HIV), is able Co neutralize the
infectivity of HIV-SF2 In vitro. This monoclonal antibody, referred to
as 95C9, reacts with glycosylated HIV-SF2 gpl20 In lmmunoblot assays. In
addition, It also reacts specifically In Immunofluorescence assays with
acetone-fixed HIV-SF2-inf ected cells. By using recombinant HIV-SF2
antigens corresponding to subreglons of gpl20, 95C9 was shown to react
with an epitope between amino acids 28 and 277 of the HIV-SF2 env gene
product. Assays with other HIV Isolates, showed that 95C9 was reacting
with an epitope that was not conserved among all HIV Isolates; 95C9 did
not react in either lmmunoblot or Immunofluorescence assays with HIV-Zr6
or LAV-B"RU, two virus strains which show considerable divergence from
HIV-SF2 In their gpl20 coding regions. Neutralization assays with these
two Isolates, and other HIV strains, are In progress. In addition we are
attempting to map the precise location of the 95C9 reactive epitope.
169
THURSDAY, JUNE 4
TUpOQ Stability of RNA stem-loop Structure and Distribution of Non-Random
Structure in Human T-cell Lymphotropic Virus Type III
SHU-YUN LE, J-H. CHEN*, J.V. Maizel, Jr., Laboratory of Mathematical Biology,
NCI, NIH, *ASCL NCI/FCRF, Frederick, MD.
The stability of predicted RNA stem-loop structure in human T-cell lympho-
tropic virus type III has been tested statistically using a Monte Carlo simula-
tion method . The distribution of statistically significant stem- loop structure
have been obtained. We can find the characteristic patterns in the 5' non-coding
region, boundary region between the protein coding frames and 3' non-coding
region. Especially, the size of the distinct and significant secondary structure
occurring in the 5' terminal region has been assessed under different window
sizes using Monte Carlo method above. The predicted secondary structure with
about 100 nucleotides is preferable to those with other size in 5' non-coding
region. Moreover the distributions of significant stem-loop structures in the 5'
terminal of ARV-2, LAV and H9/HTLV-III have also been computed. The possible
correlations between the AIDS virus genome biological function with the pre-
dicted non-random, significant stem- loop structures are discussed. Our results
support recent experiment results, in which the possible stem-loop structure of
the 5' region of HTLV-III mRNA is involved in translational control.
THP42 Human Immunodeficiency Virus Viremia in Homosexual Men
with Lymphadenopathy
JONATHAN E. KAPLAN, T.J. SPIRA, P.M. FE0RIN0, D.B. FISHBEIN, D. WARFIELD,
Centers for Disease Control, Atlanta, GA.
Seventy-five homosexual men with lymphadenopathy syndrome (LAS),
defined as lymphadenopathy in 2 or more extrainguinal sites for >3
months , were enrolled in a prospective study in Atlanta in 1982-1983.
All were seropositive for antibody against human immunodeficiency virus
(HIV). As of January 1987, 16 (21%) of these men have developed the
acquired iramunodef iciency syndrome (AIDS). Cultures for HIV were
performed on lymphocytes from 109 peripheral blood specimens from 66 of
the 75 study participants, including 12 who subsequently developed AIDS.
Cultures were screened for up to 4 weeks for reverse transcriptase (RT)
activity. Of 23 men with positive results (defined as M0000 RT
counts/0.4 ml) on the first sample, 15 were cultured a second time; all
but 2 remained positive. Of 43 men with negative results on the first
sample, 12 were cultured again up to 36 months after the first sample was
obtained. Three were positive on the second sample and 3 others on the
fourth; 6 have remained culture negative in up to 5 specimens. Men who
were initially culture positive and men who were culture positive on any
occasion were more likely to progress to AIDS than culture negative men
(9/23 vs. 3/43, p=.002; 10/29 vs. 2/37, p=.003; respectively). Culture
positivity is a marker for progression to AIDS and is likely to develop
in most men with LAS. The confidence that there exists a subgroup of men
that remain culture-negative and have a better prognosis is diminishing
with time.
THR40 Tests for Virus Yield Control in HIV Infected Cell
Culture During Preparation of Test-System for AIDS
Serodiagnostics •
O.G.ANDZHAPARIDZE, SVETLANA..S .MARBNNIKOVA . G.R.MATSEVICH,
L.G.STEPANOVA, S.M.KLBffENKCTand VJfi. ZHDANOV*
Institute of Viral Preparations, Institute of Virology, Moscow,
U.S.S.R.
Conventional variant of immuno- enzyme test-system based on pu-
rified and concentrated HIV antigen has been developed. To obtain
the antigen, HIV strain IVA 85 isolated at the Ivanovsky Insti-
tute of Virology in 1985 and adapted to continious lymphoid cell
line has been used. During productivity control of chronically
infected IVA 85 culture for cell fraction control, electron
microscopy, indirect Immunofluorescence, and immuno— enzyme assay
with cell suspension adsorbed on plates or their lysates in va-
rious concentrations were applied. HIV antigen in liquid fraction
was determined by
i SIA-capture with human IgG to HIV adsorbed on plates and
with the same antibodies labeled by horse-radish peroxidase,
ii indirect EIA with the adsorbed on the plates dilutions of
100-fold concentrates of cultural fluid.
Along with that, rate of virus accumulation in the cells in cul-
tural fluid was evaluated by hybridization with molecular probe.
Complex of the methods used gave possibility to choose an op-
timal passage scheme. Until now, IVA 85 culture passed 70 con-
sequent passages without fresh lymphoid cells addition with
70-85% of antigen-containing cells. Data of examination of 600
sera prove system specificity to be 99«6-100%#
THP43 Frequency of Clinical and Laboratory Abnormalities among HIV
Antibody Seropositive and Seronegative Gay Men.
WALTER KRAMPF, D.OSMOND, P.BACCHETTI, A. MOSS, UCSF and SFGH, San Francisco,
CA, USA.
We report frequency of clinical and laboratory abnormalities among subjects
seropositive and seronegative for HIV antibody in a prospective study of three
groups of gay men in San Francisco: an STD clinic group, a randomly selected
neighborhood group, and sexual partners of men with AIDS. Of 320 subjects seen
at one-year followup,64% (205/320) were seropositive for HIV antibody by ELISA
with Western Blot confirmation. Oral candidiasis and oral hairy leukoplakia
were clinical findings observed only in seropositives, 9% and 3% of
seropositives, respectively. Three laboratory measures were seen only in
seropositives: platelet count < 120,000 (9% of seropositives), ESR £ 22 (9%),
and H/S ratio C 0.6 (35%). Generalized lymphadenopathy was found in 55% of
seropositives and 12% of seronegatives. Frequency of other measures in
seropositives and seronegatives, respectively, are as follows: shingles, 10%
and 5%; hemoglobin < 14.2, 23% and 3; WBC ^ 4.6, 37% and 9%; lymphocytes
< 1500, 21% and 7%; and absolute T-helper count 4 400, 32% and 3%. H/S ^1.0
was found in 55% of seropositives and 15% of seronegatives, whereas H/S < 1.5
was found in 72% of seropositives and 71% of seronegatives. A significantly
higher percent of seropositives in the STD and partner groups had an H/S ratio
Cl.Q (61% and 58%) than in the randomly selected group (38%) (p=0.008),
indicating possible greater duration of infection in those groups or cofactor
effects or both.
Supported by a grant from the Universitywide Task Force on AIDS.
THP41 Bacterial Pneumonia and HIV Infection in Parenteral Drug Users without AIDS
PETER A SELWYN, AR FEItCOLD, D HARTEL, EE SCHOENEAUM/ GH FRIEDLAND, MH
ALDERMAN, et al, Montefiore Medical Ctr/Albert Einstein College Medicine, Bx, Ni, USA.
Epidemiologic data from New York City (NYC) demonstrate a sharp increase in non-AIDS
pneumonia deaths among intravenous drug abusers (IVDAs) since 198L, We studied the
incidence of bacterial pneumonia in a well-defined population of IVDAs without AIDS,
and examined the association with HIV antibody (Ab). All hospitalizations over a 12
month period were monitored among 436 IVDAs in a NYC methadone program (MMTP) enrolled
in a prospective study of HIV infection. Hospitalizations were identified through
active surveillance by MMTP staff. Both MMTP and hospital staff were blinded to
patients' HIV Ab status. Hospital charts were reviewed for all pneumonia cases.
Pneumonia was defined by infiltrate on chest x-ray; organisms were identified by Gram
stain, blood and/or sputum culture, or serology.
Surveillance began 10/1/85. At entry, there were 159 seropositives (SPs) and 277
seronegatives (SNs). By 9/30/86, 115/159 (72%) SPs and 236/277 (85%) SNs remained in
the MMTP (p<.05). Over 12 months, 14/159 (9%) SPs vs. 6/277 (2%) SNs were
hospitalized for bacterial pneumonia; odds ratio (O.R.)=4.4 (C.L. 1.6 - 11.6,
px0.005). In the SP group organisms were Hemophilus influenzae (6), Streptococcus
pneumoniae ( 5 ) , Staphylococcus aureus ( 1 ) , Escherichia coli ( 1 ) , and Legionella
pneumophila (1). In the SN group/ organisms were H. influenzae (4), S^ pneumoniae (T)
and Klebsiella pneumoniae (1). Two cases in SPs were fatal vs. none in SNs. Pneumonia
was more highly associated with HIV Ab in patients reporting no current IV drug use:
for those not using drugs at study entry, (XR.=6.7; for those still using, O.R.=2.0.
These results indicate a remarkably high incidence of bacterial pneumonia among SP
IVDAs without AIDS (minimum yearly rate = 88/1000), with a case-fatality rate of 2/14
(14%). Association with HTV Ab was not attributable to increased drug use among SPs,
The high frequency of infection with S. pneumoniae and H. influenzae suggest the need
for study of immunization of SP IVDAs against these pathogens.
THP44 HIV Seroprevalence Among Connecticut Intravenous Drug Users in 1986.
RICHARD D'AQUILA*, A.B. WILLIAMS*, L.R. PETERSEN**, A.E. WILLIAMS***
*Yale University, New Haven, CT., **Centers for Disease Control, Hartford, CT. ,
***American Red Cross, Bethesda, MD. , U.S.A.
The rising seroprevalence of HIV infection among Connecticut intravenous drug
users (IVDU) in 1986 was monitored by anonymously testing all admissions to
selected drug treatment programs for HIV antibody. The largest number of sera
(171) were obtained from entrants to the New Haven Substance Abuse Treatment
Unit. In 1986, 22.2% (38/171) of those seeking treatment for active intraven-
ous drug use were Western blot (WB) confirmed HIV seropositive. Interview
questionaire data on 114 of these entrants have been analyzed. Significantly
more of the blacks (81.8%-18/22) and of the Hispanics (40%-2/5) than of the
whites (10.4%-9/86) were WB seropositive (p<0.0001, chi-square) among this 76%
white group. Seropositives were older (mean-33 vs. 30 years, p<0,007, t-test)
and had a longer history of drug injection (mean-14.3 vs. 10.6 years, p=0.03,
t-test). There was a non-significant trend toward more needle uses in the past
year among seropositives. Sixty-eight percent (76/112) had shared needles in
the past year. There was no association between sharing and seropositivity or
between sharing and race. Most attempted to clean shared needles.
HIV seroprevalence and interview data were assessed in an additional 147 en-
trants to methadone programs in 3 other Connecticut metropolitan areas. For
entrants to all program locations, including 114 from New Haven, seroprevalence
decreased with increasing distance from New York City (p<0.01, Mantel test for
trend). Stratified analysis, controlling for program location, showed that
blacks (odds ratio-15.0, 95% confidence interval (CI)-7. 1-33.0) and Hispanics
(odds ratio-8.8, 95% CI-2.6t30.4) were significantly more likely to be sero-
positive than whites (p<10 and p<0.01, respectively, Mantel-Haenszel chi-
square) •
170
THURSDAY, JUNE 4
THR45 Cause-Specific Mortality Rates for the Acquired Immune
Deficiency Syndrome (AIDS) Dade County, Florida 1985.
DAVID G. WITHUM*, D. HOLTZMAN* , R.STEVENS*, G.METELLUS*, J.SIMS*,
J.WITTE*, et al . , *AIDS Program, Florida Department of Health and
Rehabilitative Services, Tallahassee, FL.
Dade County, Florida, which encompasses the greater Miami metro-
politan area, is situated in the lower southeastern portion of
the State of Florida. As of January 23, 1987, 869 cases of AIDS,
with Dade County morbidity, had been reported to the AIDS Program,
State Health Office, Department of Health and Rehabilitative
Services, Tallahassee, Florida.
To assess the impact of this disease for 1985 in Dade County,
deaths attributable to AIDS were identified. The Florida AIDS
case registry, death certificates, and medical examiner logs were
reviewed and 145 of the 17,324 total 1985 Dade County deaths
(0.83) were classified as AIDS deaths.
Dade County 1985 midyear population estimates (white 1,305,282;
non-white 461,670) were used to establish crude cause/race-
specific mortality rates. The crude AIDS cause specific mortal-
ity rate for Dade County was 8.2 deaths per 100,000 population.
AIDS mortality by race consisted of 77 non-white and 68 white
deaths. Population adjusted data developed a 3.2:1 non-white/
white ratio. There was a statistically significant difference
between non-white/white deaths 16.7/5.2 per 100,000. (p<.05).
These mortality rates were compared to other leading causes of
death in Dade County. AIDS non-white deaths exceeded deaths due
to motor vehicle accidents (16.7/13.4 per 100,000) and approached
white homicide deaths (18.9 per 100,000) for Dade County 1985.
Tk|P4ft Male-to-Female Transmission of Human Immunodeficiency Virus (HIV):
Current Results, Infectivity Rates, and San Francisco Population
Seroprevalence Estimates.
NANCY PADIAN*. J. WILEY*, W. WINKELSTEIN*, *U.C, Berkeley, Berkeley, CA.
Eighty-nine female partners of men who were infected with HIV or diagnosed
with AIDS or ARC have been interviewed and tested. More than 505! were the
partners of bisexual men. Overall, 20% of the women were infected (95%
confidence interval: 13%-30%). Based on the reported number of sexual contacts
with the infected partner, we were able to calculate a per exposure Infectivity
rate of .001 (95% confidence interval: 0-.0024). However, the infectivity
rate was almost 1.8 times higher for women who practiced anal intercourse than
for those who practiced only vaginal and oral sex. This higher rate is
comparable to the anal-receptive infectivity rates reported for male-to-male
exposure.
Using these estimated infectivity rates In conjunction with survey data on
the number of male partners of heterosexually active women in San Francisco,
combined with estimates of seroprevalence in their male partners, we project
that approximately 4 of 1000 such women may have been infected by these men.
We conclude that penile-vaginal contact, a well documented risk, is a less
efficient means of transmission than is penile-anal intercourse. Higher rates
of heterosexual transmission reported elsewhere are probably attributable to
factors such as greater numbers of exposures (sexual contact with an infected
partner), parenteral exposures, or to other co-factors and behaviors not
prevalent in this sample.
TUD4C Prevalence of Human Immunodeficiency Virus (HIV) Infection in Ethnic
Minority Homosexual/Bisexual Men.
MICHAEL C. SAMUEL, W. WINKELSTEIN, JR., School of Public Health, University of
California, Berkeley, CA.
Of 1034 participants in a randomly selected prospective cohort of single men
between the ages of 25 and 54, 816 (78. 9%) are homo/bisexual and of these 100
belong to ethnic minorities. We examined four minority groups and the only
significant differences in prevalence or Incidence of infection were between
black and white men. We observed a higher proportion of HIV infection among
blacks, 19 of 29 (65.5%) than among whites, 341 of 700 (48.7%). Blacks also
experienced a higher rate of HIV seroconversion than whites during the 24
months of follow-up; among the 10 HIV seronegative blacks who entered the
study, two (20%) became infected while among 359 seronegative whites, 23 (6.4%)
became infected.
To explain these findings, three established risk factors for the
transmission of HIV Infection — needle sharing, multiple sexual partners and
frequent receptive anal/genital contact — were examined. Whereas a slightly
higher proportion of whites shared needles and had multiple sexual partners
than blacks and a slightly higher proportion of blacks had frequent receptive
anal/genital contact than whites, none of the differences were significant.
Available measures of socio-economic status also did not differ by race. Other
reports have Indicated that blacks are disproportionately represented among
AIDS cases nationally, and they have suggested that the findings are due to
increased prevalence of IV drug use. Here, needle use does not explain the
difference; our findings suggest the need for further investigation into the
role of race and HIV infection.
THP49 Natural History of HIV Infection in a Cohort of Homosex-
ual Men from Los Angeles. ALEXANDRA M. LEVINE, PARKASH
S. GILL, MARK KRAILO, MARK U. RARICK, CARMEN LOUREIRO, SURAIYA
RASHEED et al . University of Southern California School of Medi-
cine, Los Angeles, California.
63 patients with biopsy-proven persistent, generalized lymph-
adenopathy (PGL), and 67 asymptomatic gay control men were evalu-
ated every six months with serial repeat node biopsies, HIV and
EBV serology and virology, and immunologic function. Median
follow-up interval is 1.3 yrs (0-53 mos). Mean age of pts was
32.4 yrs, vs. 34.7 yrs in controls. In the PGL cases, 73% were
white, 13% black, and 15% Hispanic. At study entry, 62/63 (98%)
PGL cases were HIV seropositive, vs. 36/66 (55%) of gay controls
(p<.05). With follow-up, 2 additional controls have become HIV
positive and all PGL cases are HIV positive. Rates of conversion
are as follows:
Conversion from HIV- to HIV + Control=7 . 1%/person-year
Conversion from HIV + control to any ARC=17. 3%/person-year
Conversion from HIV + control to PGL=7. 4 %/per son-year
Conversion from PGL to any AIDS condition=9 . 2%/person-year
Conversion from PGL to lymphoma=3. 9%/person-year
Two variables were significantly (p=.01) associated with increased
risk of conversion from PGL to lymphoma: increased gamma globulin
fraction, and increased IgG level at PGL diagnosis. Three variables
significantly associated with increased risk for conversion from
PGL to AIDS were (1) decreased T4, (2) decreased T4/T8 and (3)
increased IgA, at time of PGL diagnosis.
THR47 Risk Factors for Seroconversion with Human Immunodef iency Virus
Among Homosexual Men in San Francisco, 1983-1987.
RUTH M. GREENBLATT*, M. SAMUEL**, D. OSMOND***, W. WINKELSTEIN**, J. A. LEVY***,
A. MOSS***, *Robert Wood Johnson Clinical Scholars Program, San Francisco, CA,
**U.C, Berkeley, CA, ***U.C, San Francisco, CA.
Two prospective studies In San Francisco have identified 37 homosexual or
bisexual men who developed serum antibodies to human Immunodeficiency virus
(HIV) during study surveillance, 1983-1987. In the year prior to acquisition
of HIV antibody, 74% of seroconverters reported receptive anal intercourse, 77%
reported insertive anal intercourse and 100% receptive oral Intercourse.
Sixty-eight percent reported using drugs during sexual activitv.
When compared to HIV seronegative controls, men who acquired antibody had a
greater number of male intercourse partners (p<.0001), and were more likely to
have reported: receptive anal intercourse (p=.009) , receptive oral intercourse
(p=0.04) and use of either cocaine, amphetamines, depressants, or hallucinogens
during sexual activity (p=.0005). When entered into logistic analysis with
number of sexual partners and specific sexual practices, use of the above drugs
was significantly associated with antibody to HIV (odds ratio 3.29, p"0.01).
Of nine men who denied receptive anal intercourse In the year prior to HIV
infection, seven reported insertive anal intercourse. The two men who denied
both practices recalled receptive anal intercourse in the preceding 18 months.
Eight of these nine men acquired antibody late in the studies.
The proportion of men who acquire HIV infection through receptive anal
intercourse may be decreasing, and less efficient modes of transmission may
become more apparent. Use of drugs during sexual activity may contribute to
risk of HIV infection.
THP5O Laboratory and Clinical Manifestations of HI V Infection in
Patients with Conoen 1 ta I Clotting Disorders (CCD).
GEORGE F. GJERSETn, The Transfusion Safety Study Groupi) »», »Puget Sound Blood
Center, Seattle, WA , USA, mother participating institutions.
The Transfusion Safety study is a multicenter cooperative evaluation of
factors influencing risk of transfusion-transmitted hi V infection and pro-
gression. TSS has clinical and laboratory data on 456 treated CCD Patients
(426 male. 20 female), of whom 58/. are ant 1 -H I V f -«■> ■ We recorded clinical
signs (unexplained weight loss or diarrhea, generalized I ymphadenopathy ,
thrush or zoster) and laboratory findings (platelets < 100k, lymphocytes
< 1000 or T4 lymphs < 200).
A higher percentage of ant i-HI V(*l patients ( 1 9Z is 2Z, P<.001) had one or
more abnormal findings. Three patients had AIDS. Lymonadenooatny was the only
clinical sign significantly more frequent m anti-rU_y.(«) patients (P=.007).
Among laboratory findings both lymphopenia ana low T4 counts were more fre-
quent in ant i-HI V(*) patients (p<.OOU. Ant i-HI V(») patients were likelier to
have lymphopenia if 15+ years and low T4 counts if 35+ years. The likelihood
of manifestations in ant 1 -HJ_V (♦) patients did not appear to depend on type of
treatment (factor B or g concentrates or single donor components). These data
show that, thus far, most ant i-HIV(>) CCD patients are clinically well though
they may fxave laboratory manifestations of HI V infection. (Supported by Con-
tract No. NOt-HB-4-7003 of the National Heart, Lung and Blood Institute.)
171
THURSDAY, JUNE 4
THPM PREVALENCE OF HIV ANTIBODIES AMONG INTRAVENOUS DRUG USERS IN LOS
mrD1 ANGELES
LOREN LIEB*. L. MASCOLA*, L. WOODARD**, D. MC ALLISTER**, M. GILES*, S. FANNIN*,
ET AL., *Los Angeles Counly Department of Health Services, Los Angeles, CA,
**Los Angeles County Drug Abuse Program Office, Los Angeles, CAr USA
Although Los Angeles County has the third largest number of AIDS cases nation-
wide, the percent of AIDS cases who are intravenous drug users is low (ll?o) com-
pared to the East Coast rate of approximately 70!S. To assess the prevalence
of HIV antibodies in our intravenous drug addict population a random sample of
728 individuals, enrolled in either methadone maintenance or detoxification
programs, were interviewed between April and July 1986.
Detailed demographic data, medical, sexual and drug use histories were ob-
tained, and blood was drawn for determination of HIV antibody status, markers
for hepatitis B, and VDRL. Only 13 (1%) participants were seropositive. Sixty-
nine percent of the positives were white compared to 55?o of the negatives; 23?o
were hispanic compared to 34?; of the negatives; the percentage of Blacks in
both groups was the same. Seven of the HIV antibody positives were male, of
whom 5 were homosexual or bisexual. Of the 6 positive females, 3 admitted to
prostitution. Although the seroprevalence is extremely low, 92?J of the sero-
positives and 96?o of the seronegatives admitted to sharing needles. Therefore,
timely education efforts must be targeted to modify these high risk behaviors
before the prevalence rate rises precipitously.
THP54 AIDS in Women ln tne UniCed States
A.M. HARDY, MARY E. GUTNAN, Centers for Disease Control,
Atlanta, GA
Women make up only 7% of ail reported AIDS patients, but are an
under-recognized source for heterosexual HIV transmission as well as the
source for transmission to infants. As of January 23, 1987, 1,993 women had
been reported with AIDS in the United States. Their mean age was 35.1 years;
5 2% were black, 27% white, and 20% Hispanic. Pneumocystis carinli pneumonia
(PCP), the most commonly reported disease, occurred in 66% of women, while
Kaposi's sarcoma (KS) was reported in only 3%. Fifty-one percent of female
patients were intravenous drug abusers (IVDA); 27% were heterosexual contacts
of persons with AIDS or at high risk for AIDS (21% were U.S. -born women, while
6% were born in countries where heterosexual transmission plays a major role);
1U% had received transfusion with blood or blood products; for 11%, the means
of transmission was undetermined. Compared with heterosexual male AIDS
patients, women with AIDS were younger (p <0.01), but were similar by race,
residence, and disease. When female patients were analyzed by year of report,
the following significant trends (p<U.05) were noted: an increase in U.S. -born
heterosexual contact cases from 14% in 1982 to 26% in 1986; an increase in
mean age from 30.0 years in 1981 to 35.6 years in 1986; a decrease in the
proportion of females in the IVDA group between 1983 and 1986 from 59% to 48%;
a decrease in foreign-born heterosexual patients from 18% to 5%. Increases in
female AIDS patients in various risk groups were predictive of increases in
pediatric patients whose mothers were in the same groups. The data indicate
that heterosexual transmission of the AIDS virus to women is increasing.
Continued monitoring of female AIDS cases will provide an indication of future
trends in heterosexually-acquired and pediatric AIDS and information essential
for prevention efforts.
THP52 Screening of U.S. Populations for the Presence of LAV-II
G. SCHOCHETMAN, PH.D.*, CA. SCHABLE, M.S.*, L.C. GOLDSTEIN**, J. EPSTEIN,
M.D.*** and T.F. ZUCK, M.D.***, *Centers for Disease Control, Atlanta, GA,
**Genetic Systems Corporation, Seattle, WA, ***Food and Drug Administration,
Washington, D.C.
A new human retrovirus was isolated from people in West Africa and
Europe by scientists at the Pasteur Institute, Paris, France. The virus,
designated as LAV II, appears to be transmitted in a manner similar to Human
Immunodeficiency Virus (HIV) and cause similar symptoms.
A preliminary study was conducted to identify serum samples with anti-
body to LAV II from populations in the U.S. at high risk for HIV infection.
A total of 533 samples was tested using an EIA kit that included microwell
strips prepared by Diagnostics Pasteur and components of the Genetic Systems
LAV EIA. The samples included serum from 164 prostitutes in Miami, 181
Haitians in Belleglade, Florida, 164 gay men from San Francisco, and 24
seronegative people diagnosed as having AIDS.
Eighty-two of the 533 samples were positive for antibody to LAV I and
LAV II. These samples were confirmed as LAV I positive by Western blot.
The EIA results therefore represent cross-reactivity between the two viruses.
One hundred and eighty-seven samples were positive for antibody to LAV I
alone; and none of the samples was positive for LAV II alone.
The results of a research collaboration between the Food and Drug
Administration, the Centers for Disease Control and Genetic Systems
Corporation to study the epidemiology of LAV II in populations at high and
low risk to develop HIV infection in the United States will also be
presented.
THR55 HIV Exposure in New York City Streetwalkers (Prostitutes)
Wallace. Joyce I.: Christonikos, N.; Mann, J. - Foundation for Research on Sexually Transmitted
Diseases; New York , New York, U.S.A.
Eighty-one street walking prostitutes were studied in 1985, 1986, and 1987 to determine the
prevalence of HIV infection. Two health care workers and a driver found the women as they
worked. Age, number of years working, and history of drug abuse were determined. Consent
was obtained and counselling was undertaken. Arms were examined for track marks while blood
was drawn. Serum samples were screened for HIV antibodies by ELISA and confirmed by
Western blot. The ages ranged from 19 to 37 ( mean 25. ) Time spent working as a prostitute on
the streets ranged from two weeks to 20 years (mean 5.4 years. ) Three of the subjects were
men posing as women. One of them was also a drug user and was infected.
Of the 78 female subjects, twelve admitted to intravenous drug use and six (50%) were
positive. Of the 65 female prostitutes who denied drug use five (7%) were positive. This could
possibly represent heterosexual transmission. The overall seropositivity rate was 13%. There
was little difference between 1985, 1986, or 1987. These figures compare with 5% in Seattle,
25% in Miami, 6% in Athens and 88% in Rwanda. The incidence of this infection among New
York City prostitutes does not seem to have increased greatly since I982 when the principal
investigator conducted a study of T cell subsets in 33 prostitutes.
funded by New York State Department of Health
HIV antibody tests performed by the New York City Department of Health
THP53 Rapid Progression of Infection of HIV Ab+ Transfusion
Recipients from HIV-infected Donors.
JANE L. GARNER*, S.SAMSON*, K. CLAUSE*, J.HAWKINS*, J.WARD**, H.
PERKINS*, et al., *Irwin Memorial Blood Bank, San Francisco, CA.,
**CDC, Atlanta, GA.
We have followed 79 previous blood recipients of HIV-infected
donors. Thirty-three were negative for anti-HIV and 46 were
positive (Ab+) . When first evaluated, 2 of the 46 Ab+ had ARC;
none had AIDS. Six to eight months later, 10 had ARC (2 dead), 3
had AIDS (all dead) . By the third visit, one more had ARC and two
had died of AIDS. The total number of Ab+ recipients with disease
was 14 (30%) , 8 with ARC and 6 with AIDS. At the time of the
initial visit, the frequency of abnormal laboratory results in
recipients with (1) disease, (2) Ab+ but healthy, and (3) Ab-
negative were as follows:
Absolute lymphocytes «c 1500//il: 57.1%, 34.4%, and 29%;
helper/suppressor ratio <i 1.0: 85.7%, 78.1%, and 15.1%; and
beta-2 microglobulin^ .6%, 56.3%, and 26.7%. Antibody to
hepatitis B and CMV did not differ between HIV Ab+ and Ab-
recipients. The results demonstrate rapid progression of
infection in this group of high-risk recipients. On the initial
visit the likelihood of infection and subsequent disease both
correlated with the frequency of abnormal results in three tests,
but the differences were of only moderate prognostic value for
the individual case. All tests became more frequently abnormal
when signs of disease appeared, but we do not have enough serial
samples yet on healthy Ab+ patients to see whether trends in
values will be more useful prognostically .
Tupcc Decreasing Survival in Recently Diagnosed AIDS-Related
inr.au Kaposi's Sarcoma: PAUL VOLBHRDING , D.W. F3IGAL, X .
■iospitai, San Francisco,
The survival of 162 consecutive AIDS/XS patients at San Francisco
General Hospital was analyzed for variation related to the date
of diagnosis. Patients were accrued between November 1930 and
March 1984. 132 Patients are known to have died and 26 were
surviving in January 1937. 47 patients with prior or concurrent
opportunistic infections were excluded from analysis. Mean
survival of quartiles of the cohort by diagnosis date were
examined (Kaplan-Meier). Mean survival was longest in the early
diagnosis g:'oup 11151 days) and prolonged in the subsequent quar-
tiles (709,739,466 days respectively - p<.0i). This worsening
prognosis was even seen when patients with systemic signs (fev-
ers, night sweats, weight iossj were excluded. Adjusting for
orner prognostic variables ( helper/ suppressor ratio, ISR and
hematocrit) with Cox regressions also did not eliminate temporal
trends 175 survival. XS treatment had no effect on these trends.
Decreasing survival in AIDS/XS could have resulted from changes
in diagnostic practices (delayed diagnosis), increased viral
virulence, cnanges in host resistance (eg. through changes in
exposure to "cofactors" of immune deficiency) or in alterations
in therapy. Adjustment of covariab.es suggests that the worsen-
ing prognosis of AIDS/XS is due to changes in HIV virulence or in
host cofactors,
172
THURSDAY, JUNE 4
THP57 Recreational Drug Use Does Not Cause AIDS Progression, the UCSF
AIDS Registry Cohort:
AARON ROLAND, D.W. FEIGAL, D. ABRAMS. P.A. VOLBERDING, H. HOLLANDER,
J. ZIEGLER, M.A. CONANT, University of California, San Francisco, CA, USA.
A clinical cohort of 1396 patients at the out-patient AIDS clinics of the
teaching hospitals at the University of California, San Francisco, have been
recruited to participate in a registry with periodic follow-up. At entry,
51% of study participants have AIDS, 36% have ARC, and the remainder are at
high risk. At baseline 67% of the cohort reports smoking and 88% report
alcohol use. Recreational drug use was classified into three categories:
Less than
once/month
More than
once/year
to once/year
once/month
Marijuana
60%
18%
22%
Cocaine
83%
13%
4%
IV Drug
95%
2%
3%
Nitrite
83%
11%
6%
Progression was defined as developing AIDS, CDC class IVC2 (ARC),
lymphadenopathy syndrome or systemic symptoms characteristic of HIV
infection. The relationship between recreational drug use and progression
was examined with odds ratios comparing the lowest level of use to higher
levels. 78 individuals were known to have progressed. No significant
associations were found. Thus, although some types of substance use is
associated with risk of seroconversion, once infected there is no evidence in
this population that recreational drug use is a cofactor for progression.
THR60 WHENCE FOR A C00ETERMINANT OF AIHS ACQUIRE!! THROUGH RECE"TIVE
ANAL INTERCOURSE
ROGER OETELS, B VISSCHER, J GIORGI, M HO, ,) CHMIEL, I. KINGSLEY, ET AL.
Multicenter AIDS Cohort Study, NIAID, Bethesda, MO.
A cohort of 537 homosexual HIV positive men in L.A. were followed for 13
months for changes in number of CO-4 cells. Seventy-one HIV antibody posi-
tive men developed AIOS. The mean slope in CD-4 cells was -.36/day
(s.d. =.42) among men developing AIOS and -.01/day (s.d.=.01) among other
seropositives. The mean slope by level of CO-" cells at baseline was:
Subsequent AIOS Other Seropositives
< POO -.25 (s.d. = .15) .08 (s.d. = .20)
200-499 -.36 (s.d. = .38) .04 (s.d. = .26)
> 500 -.46 (s.d. = .67) -.05 (s.d. = .33)
The mean number of partners with whom cases practiced receptive anal
intercourse the six months preceding baseline was 12.3 (s.d. =27. 8) compared
to 6.2 (s.d. =11. 8) among other seropositives. The greater negative slope of
CO-4 cells and the more frequent receptive anal intercourse among cases
suggests that receptive anal intercourse is a route of entry for a factor(s)
which increases the risk of developing AIDS among HIV seropositive men.
This observation agrees with lab data that activation of CO-4 cells promotes
lytic infection with HIV. It is also possible that men frequently prac-
ticing receptive anal intercourse were infected earlier and have progressed
to AIDS by now. Follow-up of seroconverters to onset of AIDS should differ-
entiate between these two alternate hypotheses. This observation provides a
rationale for identifying agents acquired through receptive anal intercourse
which stimulate a further decline in CD-4 cells and/or increase the risk of
developing AIDS. By June data will be incorporated from an additional 1000
seropositive men in Baltimore, Chicago, and Pittsburgh.
THR58 Severe HTV-Related Morbidity and Mortality in Cases not Meeting the CDC
Surveillance Definition for AIDS.
DAVTD L. COHN, K.L. PETERSON, K.A. PENLEY, F.N. JUDSON, Denver Disease Control Service (DCS),
university of Colorado Health Sciences Center, Denver, CO, U.S.A.
In 1981, the Centers for Disease Control (CDC) developed a surveillance case definition (SD)
for AIDS, but it Is now clear that the spectrum of disease associated with HIV infection is much
broader than the original SD. In order to provide a better estimate of the true extent of severe
morbidity and mortality (SMM) associated with HIV infection in Colorado, DCS investigated cases
not meeting the SD but which seemed likely to result from HIV infection.
From May, 1982 to September, 1986, there were 239 cases of CDC-defined AIDS reported to DCS.
During the same surveillance period, there were 33 cases of SMM reported and investigated. Five
cases since have been diagnosed as CDC-defined AIDS. Nine of the remaining 28 are living and
still may develop AIDS. The reasons for exclusion by the SD were: 17 cases (61%) the disease was
not considered indicative of cellular iimunodeficiency (CTD); 7 (25%) a prior or concomi-
tant iraninosuppresive condition was present; and 4 (14%) the diagnosis was not reliably es-
tablished. Diseases not considered indicative of CID included bacterial pneumonia, bacteremia,
Candida endocarditis, Listeria meningitis, tuberculosis, disseminated sporotrichosis, Hodgkin's
lymphoma, and ATDS-dementia complex. Therefore, there are at least 19 and as many as 28 cases of
SMM outside the SD, representing 8% to 12% of reported AIDS cases. This estimate does not include
cases of SMM possibly missed due to underreporting.
We conclude that the CDC SD for ADDS significantly underestimates SMSi associated with HIV
infection, that most cases of SMM are due to diseases not considered specifically indicative of
CID, and that the CDC case definition should be expanded. In the meantime, inclusion of such
cases and other manifestations of HIV infection In surveillance registries will provide a better
estimate of the true spectrum of illness associated with HIV, as well as useful information about
the natural history and prognosis of such patients.
THP61 POSSIBLE C0-FACI0RS OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTION
AMONG CENTRAL AFRICAN PATIENTS.
P. HERMANS, F.K. LEE, M. P0NCIN, P. VAN de PERRE, A. NAHMIAS, N. CLUMECK.
(St Pierre University Hospital, Brussels, Belgium, and Emory University,
Atlanta, Georgia, USA).
Parasitic and viral serology were performed among 445 central African
people (CAP) (sex ratio: 1:1). There were 4 groups matched for age and sex: 94
CAP seen in Brussels with a clinical HIV infection (PBr), 148 CAP living in a
Central African city (K), 121 healthy CAP living in Brussels (HBr) and 82 CAP
from a rural equatorial area (R). HIV antibodies were detected by ELISA and
Western blot techniques. Antibodies for Trypanosomia brucei (TB), Plasmodium
falciparum (PF) and Entamoeba histolytica (EH) werescreened by immunofluores-
cence. Herpes type I (HSV1) and type II (HSV2) serology was performed by immu-
nodot Enzyme Assay using monoclonal antibodies against HSV1 and HSV2 purified
glycoprotein. HIV seroprevalence among the various groups was: 99?o (PBr), 19S
(K), 2?o (HBr) and 0% (R). Previous parasitic infection was more frequently
found among rural (R) than urban (K) people (p<0.001 for all parasites) inde-
pendly of their HIV serologic status. HSV1 was commonly found in all groups
(83 to 93X). HSV2 antibodies were found in 82X of HIV positive CAP compared
with 38?o of the negative patients (p<0.001). HIV and HSV2 prevalence was more
marked among urban CAP (K) than rural people (respectively 19!i vs OS for HIV:
p< 0.001; 50?S vs 30?; for HSV2: p<0.005). Among CAP living in Brussels, HSV2
seropositivity was strongly correlated with HIV seropositivity (p^O.001).
HSV2 seropositivity was similar (41S vs 29?i) among HIV negative urban or rural
people.
This study shows that HSV2 seropositivity is strongly associated with HIV
infection in Central Africa. Herpes type II could be a co-factor of HIV infec-
tion among promiscuous heterosexual Africans.
TUDCQ Analysing special features of a human lentivirus (HIV) infection
and predicting the future development using computer based
modeling (ASSP, AIDS Spread Simulation Program)
Michael G Koch , Jose J Gonzalez , Dietrich Dorner
Stehr"""", Ulrich v Welck*****, Magne Myrtveit******
VaC Karlsborg, Sweden, AID, Grimstad, Norway, I
University Bamberg, FRG, ****Robert Koch-Inst, Berlin
Munich, FRG, **** Inst f Informatlc
Johanna L'age-
t £ Psychol,
FRG, * ACS,
University Bergen, Norway
The AIDS epidemic is a lentivirus infection, the unusually long and varying
incubation period of which gives rise to several uncommon and insidious
features in the epidemic's development, such as "transients" and delayed
effects which may cause severe biases. These are described.
Indications are increasing for the possible role of macrophages as primary
target cells for the HIV-inf ect ion, reason enough to consider the
consequences of this hitherto underestimated virus survival in phagocytotlc
cells and what this would mean for the seroconversion latency. Many
important conclusions follow from these assumptions.
Different ways of forecasting are compared to each other with regard to
their efficacy for various purposes. The methods of curve fitting
(extrapolation), analogous calculation (interpolation), mathematical
modelling (formalising), and computer-based structural models (simulation)
are applied to various countries and to short and long term predictions.
The development of a compartment-based computer program for simulating
virus spread in large populations is described, the multinational modelling
project ASSP (AIDS Spread Simulation Program).
THP62 Epidemiologic observations and predictive factors for AIOS
in a cohort of New York Homosexuals: 5 year follow-up. M. LANGE,
E.B.KLEIN. Y. INADA, G. McKINI.EY. W. RAMEY , M.H. GRIECO, St. Ijuke 'S/Roosevel t
Hospital Ctr, Columbia University, New York, N.Y. USA.
104 Havosexual Volunteers (H/S) have been followed at 6 month intervals for 5
years. Of 56 volunteers seropositive for the human immunodeficiency virus
(HIV-pos) at entry into the study, 24 (42.8%) developed AIDS (1 in '82, 4 in
'83, 8 in '84, 6 in '85, 5 in '86) and 8 developed ARC (14.3%). Of 48 HIV
seronegative (HIV-neg) volunteers, 5 serconverted to an HIV-pos state but have
remained asymptomatic. Cytomegalovirus (CMV), Enteroviruses (EV) were cultur-
ed with high but approximate equal frequency from both HIV-Pos and HIV-Neg
volunteers from one or more of five sites (Blood. Semen, Urine, Throat, Rec-
tum). Of multiple laboratory parameters performed prospect ively at 6 month
intervals, the combined appearance of acid-labile interferon Alpha (AL-IFN),
disappearance of the Erythrocyte receptor for complement 3B (E-CRl) and app-
earance of a triple positive coombs test (positive for IgG, IgM, complement
3B) in an HIV-Pos individual invariably heralded progression touarrts overt
AIDS within 6 to 21 months. This combination of parameters \ias not found in
HIV-neg individuals including those with CMV-viremia.
Our observations suggest I. Culture-positive CMV infection is frequent in
N.Y.H.S. and is unrelated to the HIV infectious status. 2. The appearance of
/U..-/r7V, triple positive direct Coombs'test and absence of E-CRl in HIV-pos
subjects reflects active pathogenic processes directly related to the progres-
sion towards AIDS that are not dependent on the reactivation of CMV.
173
THURSDAY, JUNE 4
THPfi^ HIV Antibody Prevalence in Pregnant Haitian Women
NEAL A. HALSEY, R. BOULOS, J.R. BRUTUS, T. QUINN, E. HOLT,
C. BOULOS, Johns Hopkins University School of Hygiene and Public Health and
School of Medicine, Baltimore, MD, Tulane University School of Public Health
and Tropical Medicine, New Orleans, LA and Port-au-Prince, Haiti.
Pregnant women residing in an impoverished urban slum were screened for
antibodies to HIV. Of 1240 women tested in 1986 by ELISA, 114 (9.2%) were
positive and 104 (917.) were confirmed by Western blot with antibody to both
env. and gag. proteins for an 8.4% confirmed antibody prevalence rate. Four
additional ELISA positive specimens contained antibody to env. or gag. only
and were considered indeterminant.
The prevalence rates of antibody in the 55% of married women was 11.5%
versus 4.5% to 7.5% in women with less formal bonding to men. The
prevalence rates by age groups were:
Age in Years
15 - 19 7.5%
20 - 24 11.2%
Age in Years
25 - 29 8.6%
30 - 34 6.5%
Age in Years
35 - 39 8.9%.
The 8.4% prevalence rate of WB confirmed antibody to HIV in 1986 was only
slightly higher than the 7.6% rate observed in a sample of 533 mothers of
young infants bled in 1982. Aliquots of sera tested in 1982 were retested
with second generation ELISA and WB assays and found to give virtually
identical results. Thus, the rate of increase in HIV antibody prevalence
in this population does not appear to be as rapid as reported in other high
risk populations in Africa or in the U.S.
THP66 Epidemiologic Characteristics of Women with AIDS in Hew York City
HARY ANN CHIASSOH. E. FLEISHER, D. PETRUS, B. MILLER, New York
City Department of Health, NY, NY.
The annual death rate due to AIDS per 100,000 women 25-44 years of age in
New York City (NYC) has increased from 0.4 in 1981 to 15 in 1986 (based on
the AIDS case, registry) . In order to identify women most at risk for
infection, the characteristics of women with AIDS in NYC were determined
through an analysis of surveillance data. The 86 7 female cases in NYC
represent 10% of all NYC cases and 45% of all female cases reported
nationally. In 1986 the incidence of AIDS per 100,000 women 25-44 years of
age in NYC was 48 for blacks, 8.5 for whites, and 36 for Hispanics . The
major risk behavior reported was IV drug use (IVDU) by the women (61%) or
their sex partners (18%). In addition, 3% were sex partners of other at risk
individuals, 4.5% were from countries where risks are unclear, 3.5% were
recipients of blood or blood products, 2.5% had no identified risk
factor(NIR) , 2.5% were lost to follow-up, and 5% were under investigation.
The average age of the IVDUs, the sex partners of at risk individuals, and
women from countries where risks are unclear was 33, while that of
transfusion recipients was 50, and that of the NIRs was 38. In NYC, 51% of
the female IVDUs with AIDS are black, 15% are white, and 34% are Hispanic.
Among the female sex partners of at risk individuals, 41% are black, 16% are
white, and 43% are Hispanic. Of the female transfusion cases, 25% are black,
68% are white, and 7% are Hispanic. In 1985 AIDS was the leading cause of
death among women 25 to 29 years of age in NYC. These data show that in NYC
AIDS is a leading cause of morbidity and mortality among women 25-44 years
of age and that women who are IVDUs or sex partners of IVDUs are at greatest
risk of infection with HIV.
THP64 Incidence of AIDS Related Clinical Manifestations in a
Large Cohort of Gay/Bisexual Men
RICHARD A. KASLQW, W . C . BLACKWELDER , J.P.PHAIR, D.LYTER, R.F0X, B.VISSCHER for
the MULTICENTER AIDS COHORT STUDY(MACS), NIH, Bethesda, MD, USA
Few studies have documented the incidence of new AIDS related clinical
manifestations. We analyzed these clinical features in a prospective study of
gay/bisexual men examined semiannually. Combinations of symptoms, physical
signs, and lab abnormalities that correlated best with a low CD4 count or
eventual AIDS were used as an index of clinical involvement. Within 18 months
of follow up, at least 231 HIV+ men newly developed substantial clinical
involvement (a high clinical index score). Life table probabilities of
reaching this threshold score are shown for men who were HIV+ (Initial
N=1809) and men who were HIV- (Initial N=2864) throughout the interval.
% with substantial AIDS related clinical involvement
At
entry
HIV(-) 1.3
HIV(+) 5.3
(+), Entry CD4=700+ 3.2
(+), 400-699 3.7
(+), 0-399 11.9
The 18 month cumulative incidence of substantial clinical involvement in
seropositives was 17.2% and varied with initial CD4 count from 10.8% to
32.3%. The data also suggest that the probability of reaching a high clinical
index score in a 6 month period was not constant but rose with time
regardless of initial CD4 count. It is not yet clear whether this steadily
increasing incidence of AIDS related manifestations correlates with the
likelihood and rate of progression to AIDS.
THP67 Evidence for a Causal Association Between HIV Infection and
Increasing Tuberculosis Incidence in New York City.
RAMP L. STONEBURNER* . D. Des Jarlais**, J. Hilberg*, S.R. Friedman***,
Newly
reached in:
Cumulative
st 6 mo
2nd 6 mo
3rd 6 mo
(%)
0.7
0.9
1.1
2.7
4.1
6.0
8.1
17.2
2.4
1.9
6.7
10.8
2.7
6.5
7.4
16.1
7.8
14.1
14.4
32.3
J.L.Sotheran***. The New York City Depart, of Health*, The N.Y.S. Div. of
Substance Abuse Svcs.**, and Narcotic and Drug Research Inc.***, NY, MY.
Concurrent with the AIDS epidemic, New York City tuberculosis (TB)
incidence rates have increased 60%, from 20/100,000 in 1980 to 32/100,000 in
1986. The groups with the largest increase in incidence have been males aged
25-44 who are black (from 96 to 231 cases per 100,000) and Hispanic (from 35
to 103 cases per 100,000). These groups also account for 52% of all NYC AIDS
cases aged 25-44. In order to - investigate the association between HIV
infection and TB, two studies were undertaken: we matched the NYC TB and
AIDS surveillance registries to determine TB incidence among AIDS cases; and
we used the TB registry to determine TB incidence in 519 intravenous drug
users (IVDU) enrolled in a study of risk factors for HIV infection and AIDS.
Of 6,365 AIDS cases diagnosed from 1982 through April, 1986, 266 (4.2%) also
matched with the TB registry. Compared to AIDS cases with the lowest risk
for TB (whites and gay men), groups at high risk for TB were blacks (OR
4.5,95% CI=3.2-6.2), Hispanics (OR 2.9 95% CI=2.0-4.3), and IVDU (OR 3.6 95%
CI=2. 7-4 .8) . Among the 519 IVDU, 12 cases of TB were identified and all
occured among 279 persons with serological evidence of HIV infection or
clinical AIDS (p<.001). These data support the hypotheses that persons
co-infected with TB and HIV are at a higher risk of TB disease than similar
persons without HIV infection, and that AIDS and HIV infection are causally
related to increasing TB incidence in NYC. Areas with populations that have
a high prevalence of TB and HIV infection should anticipate similar
increasing TB trends and plan prevention and control strategies accordingly.
\/
THR65 Reactivity of Ghanaian Sera to Human Immunodeficiency Virus (HIV)
and Simian T-Lymphotropic Virus HI (STLV-HI).
JULIUS A. A. MINGLE^, M. HAYAMI***, M. OSEI-KWASI**, Y. ISHIKAWA***, A.
R. NEEQUAYE*, V.NETTEY***, et.al. *University of Ghana Medical School, Accra,
**Noguchi Memorial Institute for Medical Research, Legon, Accra, ***Institute of
Medical Science, University of Tokyo, ****St. Joseph Hospital, Koforidua, Ghana.
Acquired immunodeficiency syndrome (AIDS) in Africa which was previously confi-
ned to the East and Central African countries is now in West Africa. The disease
in Africa may take an epidemic character if measures are not taken to check its
spread. Prevalence rates and the risk groups therefore need to be assessed and
identified. Detection of antibodies (Abs.) to HIV and STLV-in antigens (Ags.) was
carried out in human sera from blood donors, prostitutes, sickle cell disease patie-
nts and others. The ELISA and Immunofluorescence (IF) techniques were used for
HIV Ags. and IF for STLV-HI.
Out of a total of 997 samples (226 from prostitutes) examined for HTV and 737 for
STLV-m. Abs. 93 including 57 prostitutes were positive for HTV and 18 for STLV-
HI. Abs. Some of the sera reacted better to STLV-m Ags. Western blotting test al-
so confirmed these differences.
Reports on Senegalese showed that some reacted to STLV-HI Ags. without any di-
sease. The Ghanaians reacting to STLV-HI showed disease. The Western blotting
reaction suggests that some of the Ghanaians have been exposed to a virus which
may be closely related to STLV-HI.
A new virus HTLV-TV has been reported from Senegal. Retrovirus infection in
Africa may therefore be more varied than in the Western Hemisphere. Isolation
and characterization of local strains of HTV and their inclusion in tests as Ags. may
be necessary to determine the incidence rates in some of these African countries.
Work is currently going on in this direction.
THR68
RUTH
Genital Ulceration As a Risk Factor For Human
Immunodeficiency Virus Infection In Kenya
M. GREENBLATT.. SL. LUKEHART», FA. PLUMMER.., TC.
QUINN»»», CW. CRITCHLOW., LJ. D'C0STA»«»*, et al. , .University
of Washington, Seattle, Washington, USA; ..University of
Manitoba, Winnipeg, Manitoba, Canada; ... Johns Hopkins
University, Baltimore and the National Institute of Allergy and
Infectious Diseases, Bethesda, Maryland, USA; ....Nairobi City
Council Sexually Transmitted Diseases Clinic, Nairobi, Kenya.
We studied 115 heterosexual men with genital ulcers in a
sexually transmitted diseases clinic in Nairobi, Kenya and
found the prevalence of serum antibody to human
immunodeficiency virus (HIV) in this population was 16.57. vhich
is higher than the prevalence reported in other groups of men
in Kenya. Our results also indicate that genital ulcer disease
may increase risk of infection with HIV. Of 19 men with
antibody to HIV, 12 (63.2*/.) reported previous genital ulcers,
versus 30 (31.3%) of the 96 men without antibody to HIV
(p=.008). Logistic regression analysis showed that antibody
was significantly associated with a past history of genital
ulcers <p=.03, odds ratio 3.71, 95% confidence limits = 1.14-
11.42) but not current or previous episodes of other sexually
transmitted diseases, or the etiology of current genital
ulcers. Genital ulcers are a common sexually transmitted
disease in Africa and may contribute to the increased risk for
HIV apparent among heterosexuals in this region.
174
THURSDAY, JUNE 4
THP69 Cohort study of New York City male homosexuals, 1981 -8§ .
H. MARMOR , ANNE ZE^NIUCH-JACQUQTTE , S. ZOLLA-PAZNER , W. EL-
SADR , P. THOMAS , T.J. SPJRA , et al . , New York University Medical
Center New York, NY, USA, New York City Department of Health, New York,
NY, Centers for Disease Control, Atlanta, GA, USA.
Eighty-six male homosexuals who participated as controls in case-control
studies of AIDS have been followed prospectively. Minimum cumulative HIV
infection was 30% (21/69) in 1981-2, 39% in 1982-3 (31/79), 48% (41/85) in
1984, 48% (41/86)in 1985, and 51% (44/86) in 1986. Seven cases of AIDS have
occurred. The longest follow-up of AIDS-free, HIV-infected subjects was for
8 persons who were seropositive in 1981-2. The median 0KT4/0KT8 ratio of
these 8 in 1986 was 0.36 (mean 0KT4 cells=421, SD=178 cells/mmJ); 7 of the
8 have shown continual declines in 0KT4/0KT8 ratios. Another 8 AIDS-free
subjects have seroconverted. In the combined group of 8 subjects who were
seropositive on enlistment and 8 seroconverters mean 0KT4 cell counts de-
clined with duration of follow-up. Interviews revealed that 12/65 (18%)
subjects had been celibate in the 6 months prior to interview in 1986 and
an additional 3 (5%) had adopted strict "safe sex" guidelines including
100% use of condoms during anal intercourse. Although the cohort as a
whole showed a decline in the number of sexual partners between 1985 and
1986, subjects who eliminated all risk of sexually-transmitted AIDS were
significantly more likely to be seronegative than those who continued to
place themselves or others at risk. These data suggest (a) that duration of
infection is associated with severity of AIDS-related immunologic
abnormalities, and (b) that educational efforts to reduce HIV transmission
among homosexual men have not strongly affected those who have been so ac-
tive sexually as to have become HIV infected.
THR72
Heterosexual Transmission of AIDS in Canada - National Surveillance
KIMBERLY D. ELMSLIE, Alastair J. Clayton, Laboratory Centre for Disease Control
Department of National Health and Welfare, Ottawa, Ontario, Canada.
Between February 1982 and January 1987, 843 adult AIDS cases were reported to
the national surveillance program in Canada. Risk factor data indicate that al-
though homosexual men have accounted for an increasing proportion of the total
reported cases, heterosexual AIDS cases were observed very early in the course
of the epidemic, and have been reported consistently over time. In 3.6 percent
of all AIDS cases reported, heterosexual activity was considered the probable
risk factor for HIV infection. Nine cases were white males aged 35-57 years
(median 45 years); 11 were white females aged 24-58 years (median 40 years);and
10 were Haitian females aged 25-32 years (median 29 years), who had emigrated
to Canada prior to 1980. Six of the males reported sexual activity with female
prostitutes, two had multiple female sex partners, and one had a sex partner
who developed AIDS. The female cases were attributed to sexual activity with
individuals who later developed AIDS or whose lifestyle included activities
known to increase the risk of exposure to HIV.
The first AIDS case in Canada attributed to heterosexual activity was diag-
nosed in 1981. In each of the five subsequent years to the end of 1986, 2 per-
cent to 4 percent of AIDS cases reported this risk factor. These surveillance
data indicate that heterosexual transmission is not a new phenomenon in this
country and this mode of transmission has accounted for a small but consistent
proportion of AIDS cases diagnosed each year. Bidirectional sexual transmission
of the infection is supported by the sex distribution observed among these cases.
The cases were reported fromthe large urban centres where HIV infection is most
prevalent.
THR70
AIDS in New York State Prison Inmates
DALE L. MORSE*, J. HANRAHAN* , B. TRUMAN*, J. FECK*, M. WOELFEL* ,
R. BROADDUS*", et al., "New York State Department of Health, Albany, NY,
New York State Department of Corrections, Albany, NY, USA.
Through January 15, 1987, 347 cases of AIDS had been reported among prison
inmates in New York State correctional facilities. This represents approx-
imately half of the inmate AIDS cases in U.S. state and federal systems. An
analysis of epidemiologic data on these cases has shown an increase in cases
yearly from 2 in 1981 to 107 in 1986, with an incidence of 302 cases per
100,000 inmates per year over the past 2 years. Case ages ranged from 18 to
59 years: 335 (972) were male, 12 (32) were female. Forty-six percent were
hispanic, 392 black and 142 white. Pneumocystis carlnii pneumonia (76%) and
other opportunistic infections (172) were the most common diagnoses, while
Kaposi's sarcoma was rare (32). To date, 228 have died and AIDS has become
the leading cause of death among inmates causing > 50% of deaths.
IV drug use (97X) was the major risk factor and most inmates had lived in
the NYC area prior to incarceration. Only 122 gave a history of homo-
/bisexuality and 802 of these used IV drugs. A comparison of 52 cases with
101 matched controls, showed that inmates who developed AIDS had sig-
nificantly (p >.01) lower entrance WBC counts, hematocrit, and albumin, and
higher globulin and SGOT values. Logistic regression analysis of the 52
cases and 196 random controls showed previous IV drug use, low WBC count,
elevated serum SGOT and globulin, and race to be risk factors for develop-
ment of AIDS. No long term inmates (>_7 years of continuous state incar-
ceration or admission prior to, 1978) have developed AIDS, but a more
definitive study on risk of transmission during incarceration is needed.
THR73 Cohort Study of HIV-seronegative Homosexual Men:
Predictors of Seroconversion and Clinical Course of
Early HIV Infection
ANN C.COLLIER1, V.L. Murphy1, P.L.Roberts1, H.H. Handsf ield1 ' 2
University of Washington and Seattle-King Co. Dept. of Public
Health2, Seattle WA, USA.
Most data on factors associated with HIV infection in homo-
sexual men(HM) are based on case control studies comparing HIV-
seropositive (HIV+) with HIV-seronegative (HIV-) men. We have
followed a cohort of HIV-HM and prospectively examined factors
associated with HIV seroconversion. Among 92 HM without clinical
problems suggestive of HIV infection examined in 1982-85,
25(27%) were HIV+. Of 67 HIV-HM, 45(67%) were followed for 18-47
mo(med-ian 39 mo). Among these, 14(33%) became HIV+ after 2-44
mofmedian 21 mo). Compared with the 29 persistently HIV-HM, the
14 ser-oconverters had more sex partners in the interim before
serocon-version (median 6 vs 2 partners, P=0. 017) ; more commonly
had a new partner in the preceding 1 mo(ll/13 vs 11/28, P=0 . 009) ;
and more commonly participated in receptive anal intercourse
with rectal ejaculation(10/ll vs 13/28 , P=0. 012) . There was no
difference in overall secretion exchange during sex(ll/12 vs
23/29, P=NS) . Nine seroconverters developed generalized
lymphadenopathy (GL) (detected when first HIV+ in 6, and 3-24 mo
later in 3). GL persisted >3 mo in 8. These results support the
hypothesis that receptive anal intercourse and increased numbers
of sexual partners are specific risk factors for acquisition of
HIV in HM, and suggest that most recent HIV infections are
associated with clinical findings.
THP71 Evaluation of HIV IgM and Antigen Assays for Determination
of Perinatal Infection with HIV. SHELDON LANDESMAN*, H.
MENDEZ*, B. BIGGER*, C. LANE*, A. WITTEK***, S. ALEXANDER****, J.
GOEDERT**, et al. SUNY Health Science Center at Brooklyn*, NIH**, FDA***,
Biotech****, Washington, D.C.
No serologic assays are available to distinguish HIV infection during
infancy from passive maternal antibodies against HIV. Coded sera from
14 third-trimester pregnant women and serial specimens from their
offspring (up to 3-9 mo. of age) were tested blindly for HIV-p24 antigen
(HIV-Ag), for anti-HIV IgG and IgM by whole virus Western Blot (WB)
and by ELISA using recombinant env and gag proteins. By conventional
whole virus ELISA and WB, 8 mother-infant sets were positive and 6 sets
negative. There was serologic evidence of infection in two sick babies;
one with HIV-Ag env-IgM(6 months), env-IgG and gag-IgG; the other had
no HIV-Ag but transient gag-IgH (age 1 mo) and env-IgM (ages 1-2 mo)
with a subsequent increase in gag-IgG and env-IgG (ages 2-6 mo). A third
baby had no HIV-Ag or IgM by ELISA, but at ages 2-6 mo did have a modest
increase in gag-IgG, env-IgG, WB-IgG (pl7 p24 p55). The remaining 5
infants of seropositive mothers had no HIV-Ag, no IgM by ELISA, and
declining IgG by ELISA and WB: one of them is symptomatic. All 14 babies
had faint WB-IgM bands especially at p24. Two seronegative mothers had
env-IgM and gag-IgM without HIV-Ag, IgG, subsequent seroconverison (after
3-6 mo) or evidence of HIV in their babies. These data suggest either
that relatively few (perhaps 2/8) babies of HIV-seropositive mothers
are infected or that HIV assays for IgM and Ag require improved
sensitivity and specificity to distinguish HIV infected babies during
the first 6 months of life.
THR74 Statistical analysis of European AIDS surveillance data: trends and predictions.
ANGELA M. DOWNS* , R.A. ANCELLE*, J.C. JAGER**, J-B. BRUNEI*, *VHO Collaborating
Centre on AIDS, Paris, France, **National Institute for Public Health and Environmental Hygiene,
Bilthoven, Netherlands.
European AIDS surveillance data have been analysed statistically to assess incidence trends
and to provide short-term predictions. After adjustment for estimated reporting delays, the
data (cases per half-year of diagnosis) ifere fitted to an exponential model. For the European
Cannunity (E.C.) as a whole (90% of European cases reported) and for 10 individual countries
(those with at least 50 reported cases by 30 June 1986) , the temporal evolution of the epidemic
was assessed by performing regression analysis over a succession of time intervals (windows) .
For 3 countries, separate analyses have also been carried out for the two main risk groups
(hcoo/bi-sexual men; IV drug abusers) . Predictions to mid-1988 have been made by extrapolation
based on estimated current doubling times. Available results are based on data reported as of
30 June 1986. Reporting delays were found to show considerable between-country variation. For
the E.C. overall and for most individual countries (with the exception of Italy, Spain and
Switzerland), doubling times were found to be increasing with time (for the E.C, from 6.5
months to 9.4 months over 2.5 years), as observed in the U.S.A. Preliminary analyses by risk
group strongly suggest that the different evolutions in Italy and Spain may be related to the
much larger proportion of cases among IV drug abusers in these countries, but this result is not
yet statistically significant. Estimates of current doubling times range from 4.3 months
(Italy) to 17.7 months (Denmark). If the doubling time for the E.C. as a whole were to remain
at its currently estimated value of 9.4 over the next two years, the cumulated total of cases
diagnosed in the E.C. could reach around 19,000 by mid-1988. Hopefully, this should represent an
overestimate as doubling times are likely to continue to increase. Results will be up-dated to
include all cases reported as of 31 December 1986.
175
THURSDAY, JUNE 4
TMP7R Seroepidemiological Study of HIV1 and HIV2 Infection in Guinea-
Conakry
Christine KATLAMA* , M. HARZIC*. K. KOUROUMA'*, M.C. DAZZA* , F. BRUN-VEZINET**
♦Hopital Claude-Bernard , Paris , France , **Comite SIDA , Ministere de la Sante,
Guinee-Conakry
LAV2/HIV2 is a human retrovirus recently described in patients from Western
Africa. To evaluate the presence of HIV infection in Guinea-Conakry, sera were
collected, in October 1986, from 914 subjects (518 males, 396 females) in two
areas - Conakry, the capital (756 subjects) and Labbe, a city of the north-east
country (158 subjects). Sera were tested for antibodies to HIV1 (HIVl-Ab) and
HIV2 (HIV2-Ab) by Elisa (Diagnostics Pasteur) and confirmed by Western blot(WB)
In Conakry, HIV seropositivity was found in 8/756 subjects : 2/81 were
patients hospitalized in medicine ward, 5/121 patients with tuberculosis and
1/277 was hospital health-care worker; 6 were HIVl-Ab © and 2 HIV2-Ab 9. No
HIV-Ab were found neither in 167 females attending gynecology/obstetrical
clinics nor in 110 military recruits. In Labbe, 1 hospitalized patient had
HIVl-Ab @ while 127 subjects from general population were HIV seronegative.
This study shows a prevalence of HIV infection of - 1% (9/914) in this
tested population; the highest rate was found in tuberculosis patients (4/121).
Besides, 4 sera were repeatedely HIVl-Ab © by Elisa; when analysed by WB, they
exhibited only antibodies to gag (pl8-p25-p40-p56) and pol (p34-p38) gene
products with no Ab to the envelope glycoproteins of HIV1 (gpl60.110.41) or
HIV2 (gpl30.105). Presence in Guinea of both HIV1 and HIV2 is evidenced by this
study; a low prevalence of HIV infection in countries as Guinea is an argument
to undertake rapidly management for prevention of transmission, such as blood-
bank screening, before the extent of retroviral infection.
We thank C.E. DE TSERCLAES for assistance.
THR78
Prevalence of HIV- and HTLV IV-infections in Angola.
B. BOTTIGER, I. BERGGREN, J. LEITE DA COSTA, M. MARLENE, L. LUZIA, G.BIBERFELD.
National Bacteriological Laboratory and Danderyds hospital, Stockholm, Sweden.
Ministry of Health and the National Blood Bank, Luanda, Angola.
A seroepidemiological study of HIV and HTLV-IV infection was performed in the
capital Luanda and in the Cabinda district, which is situated as an enclave be-
tween Kongo and Zaire, in Angola in October 1986. Until October 1986 five cases
of AIDS had been registered in Angola. During this study another three cases
with clinical AIDS, as defined by the 8angui criteria, were found and confirmed
by HIV-serology . Sera from groups of healthy persons and groups of patients
were screened for HIV-antibodies by ELISA(Organon-Teknika) and for HTLV IV-anti
bodies by immunofluorescence on HTLV IV-infected HUT-78 cells or by dot immuno-
binding. All screening positive sera were tested by Western blotting with HIV-
and/or HTLV IV-antigens. In Luanda HIV-antibodies were demonstrated in 2/452
(0.4?0 male blood donors, in 1/357 (0.3?o) pregnant women, in 1/100 (1%) pati-
ents hospitalized with tuberculosis, in 4/94 (4?o) patients at medicine wards
and in 0/22 women hospitalized with pelvic infections. Two known male AIDS-
patients and two of their three wifes were also HIV-seropositive. In Cabinda
4/38 ('\'\%) women at a maternity ward were found HIV-seropositive, but only 1/52
(2?o) of other hospitalized patients and none of 31 male blood donors or 59 heal
thy persons in a village on the border of Zaire. Specific anti'viiies to HTLV IV
were not found in any of 177 blood donors or 100 patients from Luanda. However,
eight out of nine HIV positive sera crossreacted with HTLV IV by immunofluore-
scence and with HTLV IV gag proteins by Western blotting. HIV infection exists
in Angola, but not to the same high extent as in some neighbouring countries in
Central Africa.
THP76 Predictives of AIDS in a clinical cohort of HIV infected patients.
" VICTOR DE GRUTTOLA*, J. LIVART0WSKI ** , W. R0ZENBAUM**, P.SETTE**,
B. AUTRAN**, F. DE VATHAIRE***. *HARVARD MEDICAL SCHOOL USA, **PITIE SALPETRI-
ERE HOSPITAL, ***GUSTAVE R0USSY INSTITUTE PARIS FRANCE.
Since 1983 > over 500 patients with confirmed HIV infection, but initially
without AIDS , have been followed. Of these patients, 22 developed clinical
AIDS in follow-up of 1 to 3 years. Of these, 14 had ARC at their examination
6 had lymphadenopathy , and 2 were asymptomatic. To determine the power of
a variety of laboratory tests to predict the development of AIDS , a matched
case-control study was performed. Each patient who developed AIDS in the course
of follow-up was matched with a control who had the same initial clinical
findings at that time. These data were analyzed using matched logistic regres-
sion analysis. The variables analysed were the numbers of white blood cells,
lymphocytes , T4 and T8 cells , the levels of serum B2 microglobuline IgG and
IgA level. The most important predictor for the development of AIDS was the
absolute number of T-helper cells(T4) followed by the level of beta2-microglobu
line(B2). From univariate analysis, the crude odds ratios for the development
of AIDS were .08 for TU > 400 vs. T4 *400(p=.02) and .18 for B2 4. 350 vs B2
> 350 (p=.09). When both variables were entered simultaneously in the logistic
model, the regression coefficients were not much changed although the signifi-
cance levels associated with them were higher. Thus, level of beta2-microglobu-
line appears to provide more information than does T-helper count alone concer-
ning the risk of developing AIDS, but larger sample sizes will be needed to
confirm this hypothesis. Linear regression analysis demonstrated that the
most important predictor of the level of T4 cells 6 months after the initial
clinical visit was the level of T4 at the initial visit but the level of B2
microglobuline also had a predictive value.
THR79 Differential Participation Rates and Epidemiologic Estimates of AIDS.
LAURA DEAN, J.L. MARTIN, Columbia U. .School of Public Health, N.Y.C.
Studies on AIDS among gay men and IV drug users show a high degree of vari-
ability in prevalence rates of HIV infection, ARC and AIDS, and it is clear
that a significant amount of this variation is due to methodological biases,
including recruitment procedures and attrition rates. This presentation begins
to address this problem by describing the relationship between differential
rates of participation and attrition and ethnic and sexual behavior factors in
a gay male NYC cohort of 745 men recruited for a longitudinal AIDS study in
1985. This group was selected from diverse community channels with special
efforts made to recruit black and Hispanic men. Even with these efforts black
and Hispanics made up only 13% of the sample. Surveillance data at that time
indicated that 33% of gay/bisexual AIDS cases in NYC were minority group
members. This initial bias was compounded by differential attrition rates of
whites and non-whites at one year follow-up. The overall attrition rate was
11%. However, black and Hispanic men were more than three times as likely to
be lost to follow-up (25%) as were white men (8%) due to more often refusing
to be reinterviewed, posing insolvable logistics problems and being ill or
dead due to AIDS. This difference is problematic because men who declined to
be reinterviewed reported having more than twice as many sex partners in the
year before they learned about AIDS (mean=241) than did men who were inter-
viewed at both times (mean=108) . These men were also more than five times less
likely to have enrolled in the HIV antibody evaluation component of the study
compared to those who were reinterviewed (9% vs 50% respectively). These
results suggest that the highest risk individuals, the highest rates of HIV
infection, and the highest rates of AIDS are to be found in the subset of
individuals who never enroll or are unwilling to continue participation in
behavioral and serologic AIDS studies.
THR77
TIMOTHY J.
Is HIV Infection Increasing in the United States? A Review of
Evidence from Sentinel Populations
D0NDER0* J.R. HERBOLD**, J. BIRCHER**, R.Y. DODD***, J.B.
SCHORR AIDS Program, CID, Centers for Disease Control, Atlanta, GA,
Department of Defense, Washington, D.C., American Red Cross, Washing-
ton, D.C.
It is widely assumed, though without evidence, that human immunodeficiency
virus (HIV) infection is increasing in the United States, since reported
AIDS cases continue to increase. We reviewed divergent infection trend
information from two large volunteer groups: military recruit applicants and
American Red Cross blood donors. To date, approximately 900,000 recruits and
7,000,000 donors have been tested for HIV antibody by ELISA and, when
reactive, confirmed by Western blot. Overall, 1.5 of every 1,000 recruits
tested were positive (1.2/1,000 when sex adjusted). Infection rates vary by
age (17-20 yrs., 0.6/1,000; 21-25 yrs., 2.5/1000; ^ 26 yrs., 4.1/1,000), sex
(males, 1.7/1,000; females, 0.7/1,000), race/ethnicity (whites, 0.8/1,000;
blacks, 4.1/1,000; Hispanics, 2.1/1,000), and geographic area. However,
during the observation period, the level of infection did not significantly
change either in the aggregate or by demographic or geographic subgroup.
Blood donors averaged 0.23 per 1,000 tested, varying by sex (males,
0.29/1,000; females, 0.07/1,000) and geographic area. Detection rates
decreased from the initial 0.38/1,000 level, due to the elimination of
previous positives among repeat donors. However, preliminary analyses of
first-time donors suggest that rates in that group doubled over a 1-year
period. Reasons for the apparent divergence between recruit and new donor
trends are unclear. The groups differ in socioeconomic, geographic, and age
composition; degree of exclusion of persons with exposure risks; and
likelihood that some participated specifically to determine their HIV-
antibody status. Evaluation of these trends by a monitoring system indepen-
dent of self-selection bias, such as the sentinel hospital based sur-
veillance, is essential.
THP80 IV Dru9 Abusers with Homosexual Activity: An Ethnographic Study
of Subtypes of Men with Two Risk Factors
Ronald Stall*, W. Wiebel**, Ostrow ***, *Rutgers University, New Brunswick, NJ,
**University of Illinois, Chicago, IL, ***University of Michigan, Ann Arbor, MI.
Men who are IV drug abusers (IVDA) and have male sexual partners are of spec-
ial interest in terms of the epidemiology and prevention of HIV transmission
since they are at high risk of exposure through two independent mechanisms and
may serve as a link to heterosexual transmission. A methodologically rigorous
estimation of the absolute numbers, social characteristics, and behaviors of
such men is difficult to obtain. We will present information obtained from
several ethnographic studies which support the existence of at least 2 sub-
groups of such men:
1. Men with prijnary identification with the IVDA subculture: Such men share
the general characteristics of inner city IVDAs, including lower SES, chronic
use of drugs such as heroin, regular sexual contact but a low level of social
identity with the gay subculture, homosexual contacts are highly stigmatized
and often are furtive and include the exchange of money, poorly informed about
the sexual transmission of HIV and are unlikely to be reached through research
and educational outreach to the gay community.
2. Men with primary identification with the gay subculture: Such men are
relatively rare and tend to be older and of higher SES than the first group of
men. They are relatively well informed about the sexual transmission of HIV
but may be uninformed about the risks of needle sharing. Their IVDA tends to
be of an episodic and recreational nature, often associated with sexual activi-
ties or gay social settings. Drugs used IV tend to be cocaine, amphetamines
and MDA rather than heroin and they tend to view messages aimed at IVDAs as
irrelevant .
Designing interventions aimed at these two subgroups appears warranted.
176
THURSDAY, JUNE 4
THP81 AIDS Surveillance in Europe
R.A. ANCELLE, J-B. BRUMET, A.M. DOWNS, WHO Collaborat-
ing Centre on AIDS, Paris, France.
A WHO Collaborating Centre on AIDS was set up in April 1984 at
Claude Bernard Hospital in- Paris (France) in order to collect
epidemiological information from the AIDS surveillance systems in
European countries. The Centre uses the CDC case definition; the
data are provided by one source per country which is recognized
by the respective national health authorities, and quarterly
reports of the situation are published . By December 1 9 86 , 2 7
countries were reporting to the Centre. Although France reports
the greatest number of cases (1350), the rates per million popu-
lation are higher in Switzerland and Denmark (29.5 and 25.7). The
trends of these rates show that most countries are now facing an
epidemic. Overall, the majority of cases have been diagnosed
among homosexuals (69%) but a steady increase is noted in the
IVDA group (14%) . There are geographic variations between the
northern countries (predominance of homosexuals) and southern
countries (predominance of IVDA) . The majority of the paediatric
cases are children whose mothers belong to one of the groups
highly represented in the country of diagnosis. This network
enables comparative views on specific problems (e.q. public
health), initiation of collaborative studies, and information
exchange for ongoing studies in the European region. An update
of the situation by March 1987 will be presented.
THP84 ^P^ spread of HIV infection in a rural district in North Uganda.
F. DE LALLA*, MASSIMO GALLI, F. CIANTIA**, P.L. ZELI*, G. RIZZARDI-
NI**, A. SARACCO et al., Clinic of Infectious Diseases, University of Milan,
♦Infectious Diseases Department, St. Anna Hospital, Como, Italy, **Kitgum and
Kalongo Hospitals, Uganda.
Spread of HIV infection in Central Africa is rapidly increasing: a rising num
ber of AIDS cases and a high prevalence of anti-HIV antibodies have been recen
tly demonstrated both in urban and rural areas. Results of a sero-epidemiologi^
cal survey in a rural district in North Uganda (East Alcholi) are reported.
During 1984 sera were collected from 111 subjects living in a rural area of the
disctrict and mainly affected with malaria or dracunculiasis . In 1986 another
group of sera was obtained from 491 subjects including 50 inpatients affected
with TB, 246 inhabitants of 2 small villages, 37 soldiers from an army settle-
ment, 158 members of 3 hospitals staffs of the district (Kitgum, St. Joseph and
Kalongo hospitals). Sera were tested by 2 commercially available ELISA methods
and by IFA. In the ones resulting positive by at least one method, W.B. confir
mation was sought for. In the first group (1983-84), only 1 out of 4 ELISA po-
sitive samples was WB confirmed (0.9%). In the second group (1986), overall po
sitivity rate was 13.2%. No significant differences were observed between the
different groups: soldiers 17%, pregnant women 12%, TB patients 10%, Hospital
staff 13.2%, rural population 13.8%. The great increase of anti-HIV seropositi
vity in such a short time indicate the dramatic spread of the epidemic even in
remote rural areas of Central Africa.
THP82 Risk of Heterosexual and perinatal transmission of Human
Immunodeficiency Virus Infection (HIV) Among Spouses and Children
of Hemophilic Patients with AIDS
Hugh C. Kim. K.Raska, Jr.. J.Eisele, L.Matts, K.Raska, P.Saidi, UMDNJ-Robert
Wood Johnson Medical School. New Bran-wick, NJ.
The risk of heterosexual and perinatal transmission of HIV infection is a
major public health concern and still not fully understood. From 1981 to 1986
ten hemophiliacs were diagnosed to have AIDS with a latency period of ranging
from 27 to 60 months (median of 36 months) as determined by the time from the
seroconversion to HIV to the onset of AIDS. Their spouses and children who were
conceived and born during the latency period of AIDS are at risk for HIV
infection. Five wives and 4 children conceived during the time of their
fathers' seroconversion to HIV were identified and tested for HIV antibody and
immune status following the diagnosis of AIDS were established. Four of 5 wives
were negative for HIV antibody with normal ranges of T4 (729+133/cmm
mean+s.d.), T8 (430+152) .and T4/T8 ratio(2.0+0.6) . One spouse with a history of
multiple sclerosis and immunosuppressive therapy, but no other risk factors for
HIV infection, was tested positve for HIV antibody by ELISA and Western blot
technic, and reduced T4 (82/cmm) count while remaining asymptomatic. Four
children from 2 families conceived while their fathers were positive for HIV
antibody were also seronegative for HIV while maintaining normal T4 and T8
counts. This finding suggests that a large number of hemophiliacs through their
exposure to contaminated clotting factors are at risk for HIV infection, but
the risk of transmission to their spouses and children conceived during the the
period of seroconversion to HIV may be small. Nevertheless, until the real
magnitude of this risk is defined, a judicious measure to prevent the risk of
transmission is warranted.
tudor HIV antibodies in blood bank donors, hemophiliacs, homosexual men,
prostitutes and hemodialysis patients, in Brasil
ZULMA F. PEIXINHO*, N.F. MENDES*, A.S.D. NUNES*. C.C.C. GUERRA**, L.G. R0SEN-
FELD**, N. HAMERSCHLACK**, et al., *Escola Paulista de Medicina, Division of
Immunology, Sao Paulo, SP, Brasil, **Centro de Hematologia de Sao Paulo, Sao
Paulo, SP, Brasil.
In 22,245 serum samples from Sao Paulo City blood bank donors obtained from
June 19SS to November 1985, studied by HIV ELISA test and H9 control plates
(Electro-Nucleonics) and Abbott HIV Confirmatory EIA, 40 (0.I870) were positi-
ve. In 1986, 73.21% (41/56) of patients with hemophilia A (treated with local
and/or imported factor VIII concentrate) and 30.9% (17/55) of homosexual- men
from Sao Paulo were positive. No antibodies to HIV were found in 176 prostitu
tes from Sao Paulo. The study of 938 serum samples from polytransfused hemo-
dialysis patients from Sao Paulo, tested retrospectively from 1985 to 1976, re
vealed that 1.61% (2/124) of the samples obtained in 1986 and 4.80% (5/104")
in 1985 were positive; no positiveness was observed in sera from 1984 or pri-
or to it. There were 6.18% (58/938) of false positive reactions due to antibo
dies against H9 antigens. Serum samples obtained from patients with hemophilia
A in Rio de Janeiro City during 1983-1984 revealed 98.24% (56/57) of positive
ness to HIV antibodies (treated mainly with factor VIII concentrate prepared
from locally collected plasma).
THR83 Opportunistic Diseases in Florida AIDS Cases: Risk Croups and Time
Trends
DEBORAH H0LT2MAN, S. LIEB, R.A. STEVENS, G. METELLUS, J. SIMS, J.J. WITTE,
Florida Department of Health and Rehabilitative Services, Tallahassee, FL, USA
As of January 23, 1987, 2,050 cases of AIDS meeting the Centers for Disease
Control definition were reported from Florida, of which 1,213 were homosexual/
bisexual (H0/BI) , 286 IV drug users, 251 persons born in "No Identified Risk"
(NIR) countries, and 300 in other risk groups. For the total cases, 2,569 op-
portunistic diseases were reliably diagnosed. An analysis of surveillance data
was conducted to describe changes in the occurrence of selected opportunistic
diseases by risk group. Five diseases accounted for 86% of the total: Pneumo-
cystis carinii pneumonia (PCP) 46%, Kaposi's sarcoma (KS) 16%, Candida esopha-
gitis (GC) 14%, toxoplasmosis (TP) 5%, and cytomegalovirus (CMV) 5%. The dis-
tribution of each disease within the three largest risk groups was as follows:
Disease
PCP KS
Risk Group
Homosexual/Bisexual Male
IV Drug User
Persons Born NIR Countries
From 1981-1986, the cumulative incidence of KS showed a slight decrease rela-
tive to the other opportunistic diseases (17 to 14%), a decline which was most
pronounced among persons born in NIR countries. PCP increased over this time
period (32 to 48%), mostly due to an increase of PCP in H0/BI males. GC showed
a decrease after 1983, primarily as a result of a decline among persons born in
NIR countries. Persons born in NIR countries also showed a decrease in TP and
CMV. The clinical diagnosis and treatment of AIDS will benefit from maintaining
a high index of suspicion for risk group-specific opportunistic diseases.
PCP
KS
GC
TP
CMV
(N=1201)
(N=406)
(N=405)
(N-162)
(N-161)
56%
76%
42%
41%
50%
13%
3%
19%
14%
8%
9%
6%
14%
25%
10'
jupQC Tuberculosis and the Acquired Immunodeficiency Syndrome -
Florida
Hans L. Rleder*, A.B. Bloch*. C.H. Cole**, J.J. WItte**, D.F. Snider, Jr.*,
*Centers for Disease Control, Atlanta, GA, **Department of Health and
Rehabilitative Services, Talahassee, FL.
To determine the impact of AIDS on tuberculosis morbidity in Florida, the
State AIDS and tuberculosis registries were matched. Of the first 1,094
AIDS cases reported from Florida through December 1985, 109 (10%) were
determined to also have had tuberculosis. Tuberculosis preceded the
diagnosis of AIDS in 57%, was concurrent with in 28% and followed the
diagnosis of AIDS In 16%. Patients with AIDS and tuberculosis (AIDS/TB)
were younger than AIDS patients without tuberculosis (AIDS/non-TB) (median
age 34 years vs. 35 years); were more likely to be black (81% vs. 21%) and
less likely to be white (11% vs. 50%); were less likely to be
homosexual/bisexual men (21% vs. 62%); and were more likely to be
foreign-born (60%) than AIDS/non-TB patients (25%). The 105 tuberculosis
patients with AIDS (TB/AIDS) who were reported to have tuberculosis from
1981 to 1985 were compared to the 7,136 tuberculosis patients without AIDS
(TB/non-AIDS) reported during the same period. TB/AIDS patients were found
to be younger (median 33 years vs. 49 years) and were more likely to be
black (79% vs. 51%) than TB/non-AIDS patients. They were less likely to
have pulmonary tuberculosis (62% vs. 89%); were less likely to have pleural
tuberculosis (0.1% vs. 3.0%); and were more likely to have lymphatic (19%
vs. 2.3%) and miliary tuberculosis (9.5% vs. 1.3%) than TB/non-AIDS
patients. These data suggest that tuberculosis is common in AIDS patients
in Florida and that AIDS/TB patients differ In many demographic and clinical
aspects from AIDS/non-TB patients and TB/non-AIDS patients.
177
THURSDAY, JUNE 4
THR87 Descriptive Epidemiology of Acquired Immune Deficiency
Syndrome Cases Among Native Born Black Persons in the
United States Reported June 5, 1981- April 14, 1986
MENCER DONAHUE EDWARDS, Spectrum AIDS Education Project, Wash.,D.C.
Research was undertaken to determine the descriptive epidemi-
ology of AIDS cases among native Black Americans. From June 5, 1981
- April 14, 1986, 4,362 cases of AIDS were reported among Black
persons born in the U.S. 4,195 were adults/adolescents, and
i67 children. 2,510 of these are known to have died, a case fatali
ty rate of 57.5%. Among adult patients, 4i% were gay /bisexual
males , and 39 .31% intravenous drug abusers . Patients with
Pneumocystis carinii Pneumonia only accounted for 65% of all cases
Over 40% resided inthe North-East SMSA . The annual incidence rate
in this selected sub-population of Black cases was 0.85 cases per
100,000. Comparison with a control group consisting of the remain-
ing 15 , 19 8 cases as of April 14, 1986 yielded statistically
significant differences : the study group included 9 .1% more
females; 2.4% fewer cases age 30-49; 32.3% fewwrgay or bisexual
male patients ; and 1 .8% more cases in the ' no known risk group '
category and 11.1% fewer and 10.6% more diagnoses of Kaposi 's
Sarcoma and Pneumocystis carinii Pneumonia only respectively.
Implications of these results are discussed in light of
recently described epidemilogy of all AIDS cases among Black
persons , native and non-native, in the U.S.
TUpnn Comparison of a novel RIPA/SDS-PAGE to immunoblotting and
vicusculture
HAN HUISMAN, M.TERSMETTE, N.LELIE, C.v.d . POEL' , J.M.A.LANGE" and F.MIEDEMA.
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service,
incorporating Lab. of Exp. and Clin. Immunology University of Amsterdam;
'Blood Bank Amsterdam; "Dept. of Med. Virology, University of Amsterdam.
A RIPA using 125I-labeled HIV antigens, enriched for gpl20/41env
(GRIPA) was compared to immunoblotting (IB) for sensitivity and specificity
for HIV antibodies. Sequential sera from 8 seroconverted homosexuals were
tested. In all cases antibodies to gpl20/41 and more prominent to p24, were
found. In two cases these antibodies were detected earlier than by IB. It
appeared that the GRIPA was 10 times more sensitive for anti-p24 in serial
dilutions of eight serumsamples, while the detection of anti-gpl20/41 was
similar in IB. In one of 78 randomly chosen EIA-negative sera from
homosexuals, antibodies to p24 could be detected. This early seroconversion
was confirmed three months later by IB. The specificity of the GRIPA was
demonstrated by analyzing 10 EIA- negative sera from homosexuals collected
during two years. All sera were found negative in the GRIPA and the persons
revealed no signs of HIV infection. Six blood donors reactive for p24 in IB
for two years but negative in the GRIPA, were also studied. Virusculture was
attempted with six seropositive asymptomatics as a positive control group. The
six p24 IB positive persons were culture negative, while a 100% correlation
existed between GRIPA and virusculture. It is concluded that reactivity in IB
to p24 may be false positive, whereas reactivity in the GRIPA to p24 only Is
highly suspicious. This feature in addition to the high sensitivity for
gpl20/41 makes the GRIPA an useful confirmatory assay in sera with conflicting
results in other HIV antibody assays.
THfiuO HIV infections in rural areas of West Africa(Guinea Bissau)
F.ANTUNES*.M.ODETE SANTOS FERREIRA**M.H. LOU RENCO**C. COSTA***, M.PE-
DRO****,*lnstituto de Higiene e Medicina Tropical, Faculdade de Medicina de Lisboa,
**FacuIdade de Farmacia de Lisboa, ***Ministerio da Saude,Bissau,****Hospital de San-
ta Maria, Lisboa.
In November 1985, sera from 98 individuals has been taken in two rural areas in Guinea
Bissau, used for trypanosomiasis studies, and stored until now. In the first area,Biombo,we
studied U8 sera from the inhabitants of village("tabanca")Cupedo,50 km from the capital
Bissau. In the second area,S.Domingos,in the north of the country, a few kilometres from
the border of Senegal we studied 50 sera from the inhabitants of two villages, 26 from
"tabanca" Djugul and 24 from "tabanca" Colage.
We used the ELISA and the Western blot both to HIV type 1 and HIV type 2,and the IFAT
to HIV type 2 in the 98 sera.
HIV 1 antibodies were detected in 6 of 48 inhabitants of Cupedo(12.5%),5 males and 1
female;in Djugul HIV 1 antibodies was detected in 1 female over 26 inhabitants(3.8%),
and in Colage in 1 female over 2U inhabitants(4.2%).
In Cupedo we have finded 5 positive cases over 48(10. 4?6}for HIV 2,1 male and 4 females;
in Djugul HIV 2 antibodies were detected in 7 individuals over 26(26.9%),! male and 6
females, and in Colage HIV 2 antibodies was detected in 1 female over 24 individuals(4^2?6).
These findings indicates that HIV 1 and HIV 2 may be endemic in certain West Africa
countries.
THP91 Mothers of Infants With HIV Infection: Outcome of Subsequent
Pregnancies
GWENDOLYN B. SCOTT , M.T. MASTRUCCI, S.C. HUTTO, W.P. PARKS,
Department of Pediatrics, University of Miami School of Medicine, Miami, FL
One hundred and thirty-four cases of perinatal HIV infection have been
identified in South Florida between January 1981 and December 1986. These
infants were born to 109 HIV infected women. Risk factors identified
include drug abuse in 22% of the mothers and the remainder had no
identifiable risk factor other than heterosexual contact with an infected
person. All but one of the mothers were clinically well at the time of
delivery of their first infant with HIV infection emphasizing that the
infected child is frequently the first member of a household to be
identified as infected. Subsequent to the birth of the index pediatric case
33 (30%) of the 109 women have developed ARC or AIDS and 18 (17%) have
died. Twenty-five women have had 42 subsequent infants after the index
case. Two women and their 3 children have been lost to follow-up. The
remaining 23 women and their infants have been followed prospectively.
Length of follow-up families ranges from 6 months to 5 years with a mean of
32 months. Fifteen women have more than 1 infected child. Of the subsequent
siblings, 21 (54%) are infected and 18 (46%) are not infected. Of the 21
infected siblings 12 have died (60%). None of the unaffected siblings have
died. Family patterns of disease include families that have 2 children with
encephalopathy, one family that has 3 children with wasting syndrome and 1
family that has 2 children with severe lymphoid interstitial
pneumonia. Infants born to HIV infected women who have delivered a previous
HIV infected infant are themselves at significant risk for infection. These
results may reflect a special population of women and further studies are
required to determine also the risk of having an infected child in women
without previously infected children.
TUDQQ Acute Infection by H.I.V. in Drug Addicts.
inr.03 RAFFAELE PRISTERA'*, C. SEEBACHER* M. CASINI*. A. LAZZARIN**,
Department of Infectious Diseases, Bolzano, University Clinic of Inf.
Dis. , Milan; Italy
The diagnosis was established in 17 out of 365 DA for onset of
mononucleosis- like syndrome and of H.I . V.-Ab seroconversion. The duration
of the acute illness ranged from 15 to 66 days. The incubation period was
2-3 months in 4 DA with chain transmission (syringe sharing among them and
subsequent infection during this phase) , but unknown in the other 13 for
previous repeatedly sharing . Seroconversion occurred about 1 month after
disease onset.
The acute phase was characterized, when compared with control seronegative
DA, by an increase of WBC (x": 9350), lymphocytes (not as relative countl)
and especially of CD8 (x: 1626, 44%) and by a moderate reduction of CD4 .
This picture might stand for the immune response to the infection,
particularly characterized by the increase of the cytotoxic portion of CD8 ,
as it happens during other viral infections (CMV, EBV, HSV). On the other
hand, 3 patients did not show this picture: neither WBC, nor lymphocytes,
nor CDS (x: 935) were increased, whereas CD4 were even more reduced. They
had all a severe post- infect ious chronic active hepatitis and thus likely a
pre -existent alteration of the immune system (IS), which might have
prevented CDS from their cytotoxic response.
Consequently the CD8 increase lack might suggest a functional failure of
the IS, particularly of CD4, and predict an unfavorable evolution. As a
matter of fact these 3 patients showed later on a CD4 fall, which was
considerably stronger, if compared with that of the other 13.
THP92 Heterosexual Transmission of Human Immunodeficiency virus (HIV):
Relationship of Sexual Practices to Seroconversion.
MAftGARET A FISCHL, GM DICKINSON, A SEGAL, S FLANAGAN, M RODRIGUEZ. University
of Miami, Miami, Florida.
To evaluate the efficacy and potential role of condom use In the prevention
of heterosexual transmission of HIV, spouses of patients with AIDS and AIDS-
related complex were evaluated. Evaluation included a medical history,
physical examination, standardized interview, and blood tests. All spouses
were counseled and followed every 4 months. Forty-seven seronegative spouses
were studied. Twelve were men and 35 were women. None had risk factors for HIV
infection. The median length of followup was 18 months. Seventeen (36%)
developed antibody to HIVj 4 (33%) were men and 13 (37%) were women. The
relationship of sexual practices after enrollment to the development of
antibody to HIV is shown below.
number HIV antibody percent
positive negative converted
0 17 0%
3 15 17%
14 3 82%
The frequency of sexual Intercourse and types of sexual activity were not
different for spouses using condoms compared to those not using them. In
evaluating couples who used condoms, breakage, improper use and fellatio
without condoms was not uncommon. Although condom use appeared to decrease the
rate of HIV transmission, seroconversion occurred. These data suggest that
condom use may not afford complete protection against the heterosexual
transmission of HIV.
abstinence
12
condom use
18
no condom use
17
178
THURSDAY, JUNE 4
THR93 Prevalence of HIV-1 and HIV-2 antibodies in a selected Malawian
population
LUT2 G. GURTLER, G. ZOULEK, G. FROSNER, F. DEINHARDT et al., Max von
Pettenkofer Institute, University of Munich, Federal Republic of Germany and
G. LIOMBA, H.J. SCHMIDT et al,, Queen Elizabeth Central Hospital, Blantyre,
Malawi
Screening for HIV infections in Malawi was began in 1986 to evaluate the
prevalence of HIV-1 and HIV-2 in this part of Africa. 96 antenatal mothers,
265 female prostitutes and 32 male prisoners were screened with a
commercially available ELISA for HIV-1 and an ELISA prepared in our
laboratory for HIV-2 using LAV-2, kindly provided by L. Montagnier. Positive
reaction in the ELISA tests were confirmed by immunofluorescence and immuno-
blot. In addition, the presence of markers of infection with other sexually
transmitted agents, i.e. hepatitis B virus (HBV) and treponema pallidum (TPA)
was determined.
The results are given in the table as positive/number tested (percent) .
markers for HIV-1 HBV TPA
antenatal mothers 4/96 (4%) 67/96 (70%) 26/96 (27%)
female prostitutes 148/265 (56%) 219/265 (83%) 143/265 (54%)
male prisoners 10/32 (31%) 18/32 (56%) 11/32 (24%)
oO oT the sera of prostitutes positive for anti-HIV-1 also were screened for
anti-HIV-2. Antibodies specific for HIV-2 antigens were not detected.
However, crossreactions of anti-HIV-1 with HIV-2 antigens were observed,
particularly reactions of anti-HIV-l-p24 core with HIV-2-p27. The results
show that infections with HIV, HBV and TPA are common in this part of Africa;
but it is not justified to calculate from only 393 individuals investigated
so far the prevalence of anti-HIV in the 7 million inhabitants of Malawi.
Ongoing studies should clarify this further.
THR96 '9M Antibodies to HIV in Sera from HIV-infected Homosexual Men in
Montreal
SWEE-LENG TAN, D EYMARD, N GILMORE, M ROZAKIS, S JOTHY , E GOLDBERG, R LEBLANC,
0 ROSENGREN, M 0 ' SHAUGHNESSY, P GILL. Division of Clinical Immunology and
Department of Pathology, Royal Victoria Hospital, McGill University, Montreal;
Laboratory Centre for Disease Control, Ottawa, Canada
Sequential sera from 163 homosexual men, infected with HIV confirmed by IgG
seropositivity, were assayed for IgM antibodies to HIV. They were selected
from a private practice, and consisted of 28 men who IgG-seroconverted; 12 men
who reverted from IgG-seropositive to negative; and 123 men who were persist-
ently IgG-seropositive. 133 men were asymptomatic at the time of serum collec-
tion; 30 men had ARC; and 10 later developed AIDS. Duration between serum
samples was 9.8 months ± 4.6 (SD). IgM antibodies were detected by IgM-ELISA
after rheumatoid factor adsorption. Cut-off for this assay was 7 SD above the
mean of IgM-seronegative controls. Specificity of IgM antibodies was confirmed
by IgM-Western blotting.
IgM antibodies were detected in the sera of 14 men, or 8.6% of this cohort: 2
of 28 men who IgG-seroconverted, including one man who had IgM antibodies when
IgG antibodies were undetectable; none of 12 men who IgG-seroreverted; and 12
of 123 men who were persistently IgG-seropositive, including 3 men who develop-
ed IgM antibodies when already IgG-seropositive and 6 men who remained persist-
ently IgM-seropositive. 8% of asymptomatic men, 10% of men with ARC and 10% of
men who subsequently developed AIDS had IgM antibodies detectable in their
sera. Western blotting showed IgM antibodies reacted with recognized HIV anti-
gens but with a different pattern than that of IgG antibodies.
These data show that IgM antibodies to HIV are detectable at low frequency in
sera of HIV-infected homosexual men, and appear unrelated to IgG antibody
responses or to HIV disease manifestations.
THR94 Berlin prospective Study on 35 HIV (human immunodeficiency virus)
Antibody-Positive Newborns
ILSE GR03CrH\0RNER*,S.KOCH*,B. STOCK", J.Woweries***,B.Z0RR**** .A.SCHfiFER*****,
et al. ,*Uhiversitats-Kinderklinik Berlin, "Kinderklinik RVK Berlin, ***Kinder-
klinik Neukolln Berlin, ****Institut fur experimentelle Virologie Berlin,*****
Universitats-Frauenklinik Berlin
The presence of HIV-IgG-antibodies (AB) in newborns (NB) of HiV-AB-positive
mothers does not provide conclusive evidence of an actual infection with the
virus. This is determinable only by longterm observation of the patients, con-
cerned in accordance with immunological, virological and clinical criteria.
Consequently, since July 1985, all NB of HiV-AB-positive mothers are being
kept under close observation at the Berlin University Children1 Hospital and
35 newborns have so far been icluded in the study.
During an observation period of now over 18 months, none of the children ha-
ve as yet contracted AIDS. A slight neurological abnormality was apparent in
2 children. One child who suffered a bacterial meningitis at 11 months of age
had become seronegative at 6 months of age. The Hi-virus was identified in CSF
at the time of meningitis despite further seronegativeness.
One child whose clinical course was extraordinary (weight stagnation, re-
currences of Candidiasis) died at 7 months (sudden infant death).
As expected, 15 children whose virus culture was negative, became seronega-
tive at between 3 to 7 months, however also 4 children with a positive virus
culture became seronegative.
The results clearly show that AB-Screening is not a sufficient method of
course control, but that longterm observation is essential for accurate
classification of HIV-AB-positive newborn children.
THP97 Hi9h Prevalence of Serum Antibodies to HTLV-III p66/p51. A.L.
DeVICO*, F. diMARZO VERONESE*, R.C. GALLO*», M.G. SARNGADHARAN* ,
*Bionetics Research, Inc., Rockville, MD; **Lab. of Tumor Cell Biology, NCI,
Bethesda, MD.
The reverse transcriptase of HTLV-III is detected in immunoblot assays as a
pair of 66 kD and 51 kD proteins (p66/p51). These proteins share a common
NH2 terminal amino acid sequence; whether both proteins are enzymat ically
active has not been determined. A preliminary study indicated a high
seroprevalence of RT antibodies in HTLV-III antibody-positive individuals
tested by the viral immunoblot technique. Further, some individuals had
serum antibody reactivity with only p66. To more accurately determine the
frequency of serum antibody reactivity with RT, the results of 700 immunoblot
assays of HTLV-III antibody-positive sera were examined. Seropositivity was
determined by reactivity with gp41, p24 or both. Of the sera selected, 79%
were positive for antibodies to p66/p51. Such immunogenicity for RT has not
been demonstrated for any noncytopathic mammalian retroviruses including
HTLV-I and -II. The seroprevalence of reactivity with RT seems to vary with
the stage of the disease. Out of the 700 sera 360 for which a diagnosis was
available were divided into 4 groups consisting of asymptomatic individuals
at high risk, ARC patients, AIDS patients and AIDS patients with Kaposi
sarcoma. Seroreactivity to p66/p51 was found in 75%, 85%, 77%, and 78% of
the individuals in each group, respectively. Serum from the individuals with
antibody reactivity to only p66 were retested in an immunoblot assay using
purified enzyme bound to nitrocellulose. All of the individuals tested had
serum antibody reactivity with p51 but the level of reactivity remained much
lower than that for p66.
THP95 The Geo6raphic Distribution of Human Immunodeficiency Virus
(HIV) Antibodies in Parenteral Drug Abusers (PDAs)
W. ROBERT LANGE*, B.J. PRIMM**, F.S. TENNANT , J.T. PAYTE *,
CM. LUNEY", J.H. JAFFE* et al., *NIDA-ARC, Baltimore, MD, **ARTC, Brooklyn,
NY, Community Health Projects, W. Covina, CA, ' Drug Dependence
Associates, San Antonio, TX, #DACCO, Tampa, FL.
Opioid dependence treatment programs in 5 regions of the US collaborated
in a study aimed at monitoring trends in seroprevalence of HIV antibodies.
After informed consent, 1,650 PDAs volunteered to provide blood specimens
and data on health history and patterns of drug use. While this sample
cannot purport to be representative of PDAs in the region, nor even of PDAs
in treatment within the region, the wide disparities in HIV seroprevalence
in the face of similarities in drug using behavior have important
implications for prevention. In the New York area (Harlem, Brooklyn), 61X
of samples (N-280) obtained in late 1986 were positive, up from 501 of
samples (N-585) from the same program taken in early 1984. In Baltimore,
29X of samples (N-184) representing 11 programs were positive. Significant
sex and ethnic group differences were apparent. In contrast, samples from
programs distant from the Northeast corridor had far lower rates: San
Antonio, 2X (N-106); Tampa, OX; Southern California, 1 . 5X (N-413, with
samples from programs from Fresno to San Diego). Contrary to expectations,
there was no corresponding difference in lifetime needle sharing
experiences, which ranged from a low of 701 in New York to 99X in San
Antonio. Because needle sharing is practiced by PDAs in areas where
seroprevalence is still relatively low, these areas are vulnerable to the
same catastrophic spread seen in the Northeast. But a window of opportunity
where prompt, vigorous, and aggressive efforts at prevention could have
major impact.
THP98 Recreational Drugs and HIV Infection: Relationship to Risk of
Infection and Immune Deficiency. Cladd E. Stevens, Patricia E.
Taylor, Santiago Rodriguez and Pablo Rubinstein.
310 East 67th Street, New York, New York, U.S.A.
New York Blood Center,
In early 1984 the Laboratories of Epidemiology and Imrnunogenetics at the
New York Blood Center began a prospective study of the acquired immune defi-
ciency syndrome (AIDS) in a cohort of 850 homosexually active men in New York
City. At the time of entry into the project in 1984, each participant com-
pleted a self-administered questionnaire which contained quantitative questions
regarding use of 21 recreational drugs or categories of drugs, including amyl
and butyl nitrite. Participants have returned every four months at which time
an interim history is obtained and cellular immune function is assessed.
At the time of entry 42.3% of the men were anti-HIV positive. Anti-HIV
prevalence at that time correlated with the use of each of the 21 recreational
drugs for which we solicited information. However, recreational drug use also
correlated with sexual activity. Including numbers of sex partners and fre-
quency of high risk sex practices, factors which were the strongest predicters
of anti-HIV posltivity. No consistent association between history of use of
any drug and defects In cell mediated immunity detected among anti-HIV positive
men at entry was observed. Over the past two-and-a-half years, 47 of the
participants have been diagnosed as having AIDS. No association was found
among the anti-HIV positive men between history of drug use and the subsequent
development of AIDS.
These preliminary data suggest that the relationship between recreational
drug use and the risk of HIV infection is secondary to the association with
sexual activity and that drug use had no subsequent influence on the develop-
ment of defective CMI or AIDS.
179
THURSDAY, JUNE 4
THR99 Correlation of HIV Isolation Rate and Stage of Infection. RR
REDFIELD, DC WRIGHT, NC KHAN, DS BURKE, WRAIR, Washington, DC.
HIV infection causes a spectrum of disease which can be placed in a
working framework of progressive stages of viral-Induced immune
dysfunction as proposed by the Walter Reed Staging Classification. We
investigated the ability to Isolate HIV from perpheral blood mononuclear
cells (PBMC) of patients with different stages of HIV infection. All
retroviral cultures were performed and Interpreted blindly with respect to
clinical status. Cultures were performed using patient PBMC obtained by
Ficol hypaque separation from 30 ml of whole heparlzed blood which were co
cultivated with PHA-stiraulated normal donor PBMC. Cultures were monitored
for viral production by both reverse transcriptase and HIV antigen-
specific assays for 30 days. Results are summarized in tables below.
TABLE 1
TABLE 2
WR STAGE
N
#P0S
%P0S
T4tf
N
!?P0S
%P0S
1
3
0
0%
>800
8
1
13%
2
34
9
26%
600-799
16
2
13%
3
3
1
33%
400-599
13
6
46%
4
3
1
33%
200-399
6
3
50%
5
6
5
83%
100-199
5
3
60%
6
5
4
80%
<100
6
5
83%
TOTAL
54
20
37%
TOTAL
54
20
37%
THP102 lmmune Response and Challenge of Chimpanzees Immunized with a gp41
Synthetic Peptide. G.R. DREESMAN*. T.C. CHANH*, P. KANDA*, J.W.
EICHBERG*, R.C. KENNEDY*, J.S. ALLEN**, et al. *Southwest Foundation for
Biomedical Research, San Antonio, Texas, **Harvard School of Public Health,
Boston, Massachusets.
Two chimpanzees were immunized with a synthetic peptide containing
amino acid residue 735-752 of gpAl transmembrane glycoprotein of HIV
coupled to KLH. A third animal was inoculated with an unrelated
peptide KLH conjugate. Both animals immunized with the gp41 peptide
produced an antibody response which reacted with native gp41 and
gpl60. The three animals were challenged with HIV-NY5 isolate after 4
injections of Immunogen and have been studied for 24 weeks post
challenge for antibody response and virus isolation. Antibody
response to viral protein p24 and gpl20 was similar between the con-
trol animal and the first peptide immunized animal. However, antibody
to these proteins were delayed approximately 4-6 weeks in the second
animal. Virus isolation studies are In progress.
These data demonstrate a significant correlation (P<0.001) of the ability
to isolate HIV from PMBC with (1) Walter Reed stage and (2) T-helper cell
number. The biological explanation of these differences is currently
under investigation.
THR100 Serial T Cell Phenotypes in Homosexual Men Who Did or Did Not
Progress to AIDS.
JANET K.A. NICHOLSON, T.J. SPIRA, B.M. JONES, J.S. McDOUGAL, Centers for
Disease Control, Atlanta, GA.
A cohort of 75 HIV-antibody-positive homosexual men with chronic
lymphadenopathy has been studied serially for the last 3-4 years in Atlanta.
As of January 1987, 21 have developed acquired immunodeficiency syndrome
(AIDS). To determine whether those who developed AIDS are immunologically
different from those who did not develop AIDS, we retrospectively examined the
distribution and number of subpopulations of CD4 and CD8 lymphocytes in 5 men
who progressed to AIDS and 10 men who did not over the last 3-4 years.
Two-color immunofluorescence studies were done with combinations of monoclonal
antibodies to detect functionally defined subpopulations of CD4 cells
(helper-inducer [CD4+4B4+], suppressor-inducer [CD4+2H4+], and
"activated" [CD4+HLA-DR+] ), CD8 cells (cytotoxic [CDS+LeulS-] ,
suppressor [bright CDS+LeulS"1"], "reactive" [CD8+Leu7+] , and
"activated" fCD8+HLA-DR+] ), as well as phenotypes associated with natural
killer (NK) activity (dull CDS+LeulS"1" and Leu7~Leul 1+). CD4 cells
declined more rapidly in patients who progressed to AIDS, than In those who
did not. None of the CD4 subset, CD8 subset, or NK-associated subset
enumerations clearly distinguished progressors from nonprogressors. However,
each progressor had a unique phenotype change that progressed with time, such
as a severe depression in Leull+ cells, increases in CD8+HLA-DR+ cells,
increases in the proportion of CD3 cells that are Leu7+, and the proportion
of CD4 cells that are 4B4+ or 2H4+. These changes were seen in only 2 of
the 10 nonprogressors; the remaining 8 had stable phenotypes. These unique
changes may reflect a falling immune system.
THR103 Pediatric HIV infections in HIV-ELISA negative individuals: a report of 10
cases.
W. BORKOWSKY, K. KRASCNSKI, D. PAUL*, T. MOORE, D. BEBENROTH,
AND S. CHANDWANL NY U-BeUevue Hospital Ctre. New York, NY, *Abbott
Laboratories, North Chicago, H*
The presence of HIV specific antibody has been used to document HIV infection in
patients. Both ELISA and im munofluorescence (TFA) have been used for screening.
Rarely, sera considered negative by HTV-ELTSA assay is found to be reactive with virus
specific bands on Western Blot assay (WB). Although these assays can produce false
positive results in children below 1 year of age due to the presence of transplacentally
derived maternal HIV specific IgG, we have found that false negative responses may be
more com mon than previously suspected. We have identified about 90 children infected
with HIV. Ten of these were considered to be HTV-ELISA negative but found to possess
HIV antigen in their plasma, as measured by an antigen capture ELTSA assay, with
estimated viral antigen concentrations of 13 to 756 pg/mL Five of the ten have died of
AIDS. Nine of the ten were born to drug abusing mothers. Five of the mothers had HTV-
ELISA antibody tests performed on their sera and all were positive. Nine of the children
had decreased helper T cells. IFA performed on 6 of the sera was negative. WB assays
performed on 5 of the sera were negative. Four of the children had supporting evidence
of HIV infection as determined by the presence of anti. pl21 antibody found with a
com mercial assay which employs recombinant antigen (ENVACOR). Since HIV infected
infants have impaired primary antibody responses to other antigens, a comparably
impaired response to HIV antigens may result in negative antibody assays. HIV antigen
measurement appears to be an important tool to identify these infants.
TUDini Abnormal Lyraphokine Activated Killer Cell (LAK) Induction in
inn IUI peripheral Blood Mononuclear Cells (PBMC) in Patients Infected
with the Human Immunodeficiency Virus (HIV)
ALAN LANDAY*, J. HARRIS*, L. FALK**, D. PAUL**, H. KESSLER*, D. BRAUN*, et al .
*Rush Medical College, Chicago, IL, and **Abbott Laboratories, North Chicago,
IL
The ability to generate LAK cells from the PBMC of asymptomatic homosexual
males (AHM) with serologic evidence of HIV infection (n=25) was evaluated.
HIV infection was determined by the presence of antibodies (Ab) to HIV
proteins or by the presence of HIV core antigen (Ag). LAK cell generation was
normal in HIV Ab+ Ag~ AHM (mean % cytotoxicity = 46+13 compared to a control
group of seronegative AHM where mean % cytotoxicity = 45±16). In contrast,
the LAK cell Induction was significantly impaired in AHM who were HIV Ab+ Ag+
(mean % cytotoxicity = 16±9, p<0.01 compared to controls). The mechanism for
suppressed LAK induction was evaluated and found to be due to an Indomethacin
(indo) sensitive suppressor function. Thus, the addition of indo to cultures
of cells from Ab+ Ag+ AHM restored their LAK function to control levels (mean
% cytotoxicity = *J6±9). The presence of this indomethacin sensitive
suppressor in Ab+ Ag+ AHM was also documented in mitogen stimulated
blastogenesis and IL-2 production assays and was correlated with significant
depression of monocyte HLA-DR expression (32±11$ LeuM3+ HLA-DR+ monocytes vs
82+15$ LeuM3+ HLA-DR+ monocytes in controls, p<0.01). The deficits in LAK
cell induction and mitogen stimulated blastogenesis which were observed in the
group of patients who were Ab+ Ag+ were associated with HIV recovery from the
monocytes of these individuals. These findings have important implications
for our understanding of the pathogenesis of HIV infection and may point the
way to new methods for therapeutic intervention.
TUpiflJ. Viruses of Human Immunodeficiency Virus Family Induce Expression
inr. IU*» of Class I3- Major Histocompatibility Complex Structures on
Infected Target Cells ^n Vitro
MARI KANNAGI, NORVAL W. KING, NORMAN L. LETVIN, Harvard Medical School, New
England Regional Primate Research Center, Southborough, MA.
The human immunodeficiency virus (HIV) and the closely related simian
immunodeficiency virus (SIV) induce profound immune dysfunction in primate
species. We have now shown that cell populations infected in vitro with
these viruses exhibit increases in major histocompatibility complex (MHC)
class II antigen expression. Cell lines chronically infected with both the
monkey and human viruses express substantially more MHC class II but not
more lineage-restricted or activation antigens on their membranes than do
uninfected cell lines. No serologic cross-reaction was observed between
MHC class II and viral specific antigens. MHC class II induction does not
appear to be mediated through the production by infected cells of a soluble
factor such as gamma interferon. Studies of the kinetics of antigen
expression by cell lines following SIV-infection indicate that induction of
MHC class II structures is a late event- Immunoelectronmicroscopy revealed
that MHC class II antigen is expressed not only on the surface of the
SIV-infected cells, but also on the envelope of virus particles derived
from those cells. MHC antigen expression on virus infected cells and
expression of those determinants by the virus may play a role in the
pathogenesis of AIDS and the autoimmune abnormalities observed in HIV
infected individuals.
180
THURSDAY, JUNE 4
THR105 CORRELATION OF DELAYED HYPERSENSITIVITY SKIN TESTING AND ABSOLUTE
T4 NUMBER AND T4/T8 RATIO. D.L. Blrx, J. Rhoads, L. Smith,
C. Wright, D. Burke, R. Redfield. Walter Reed Army Medical Center and Walter
Reed Institute of Research, Washington, D.C. USA.
We have evaluated 400 consecutive HIV ELISA and Western Blot confirmed
seropositive patients who presented for evaluation and staging. Each indivi-
dual underwent anergy screening with simultaneous, absolute lymphocyte and
T4 counts, and T4/T8 ratio. The anergy panel consisted of PPD 5TU, two
concentration of tetanus toxiod (TT) and Candida albicans (CA) O.lLf, 1.0 Lf
and 1:10 w/v 1:100 w/v respectively, mumps, and trichophyton. 5x5 mm indur-
ation was considered positive at 48 hrs . Complete data is presented on 337
patients in tabular form.
T4 (#/mm3)+SDx2 T4/T8 ratio + SDx2
skin test results
(n)
1.
anergy
45
172 + 152
.27 +
.20
2.
TT (lLf)CA(l:10 w/v)
39
412 + 237
.56 +
.39
3.
1/5-v
61
481 + 299
.64 +
.41
4.
2/5 )
77
530 + 250
.64 +
.29
5.
3/5 VTT (0.1 Lf)
71
637 + 263
.84 +
.46
6.
4/5 \CA (l:100/v)
39
614 + 374
.75 +
.46
7.
5/5~>
5
550 + 160
.67 +
.31
There is statistical significance between the T4 counts and ratios of
those who are anergic and all other catogories p^O.Ol, as well as, those
who are only positive to the higher concentration of TT and CA (# 2 vs // 5)
p<0.05. A trend can be seen between the number of positive skin test
responses and T4 counts and T4/T8 ratios. All individuals are being
followed for correlation with disease progression.
THR108 Intrathecal Synthesis of IgG OligoclonaJ Bands with Specific Activity
Against Human Immundeficiency Virus (HIV) in AIDS Patients with
Encephalopathy
MAURO CERONI, G. STONE, P. PICCARDO, D. MADDEN, 3. SEVER, NINCDS,
NIH, Bethesda, MD.
Involvement of the nervous system, including encephalopathy, is increasingly
recognized as a frequent finding in AIDS. Evidence is accumulating that the HIV
virus not only attacks the immune system but also affects the central and
peripheral nervous system. The pathogenesis of the neurological damage however
is very poorly understood. It has been demonstrated that HIV antigen and specific
antibodies can be found in cerebrospinal fluid (CSF) with and without signs of
encephalopathy. Usually encephalopathy is accompanied by intrathecal synthesis
of IgG as demonstrated by quantitative indices of IgG and appearance of
oligoclonal IgG bands in CSF. Our studies using isoelectric focusing of serum and
CSF from patients with AIDS-related encephalopathy confirmed the presence of
oligoclonal IgG banding. Some bands were common to serum and CSF and others
present only in CSF. Using an immunoblot technique employing HIV precoated
nitrocellulose paper, we have also demonstrated the presence of several HIV
specific IgG bands in the sera and CSF of patients with AIDS-related
encephalopathy. Most HIV antibody bands are present in both serum and CSF; some
are present exclusively in the serum or CSF. Negative controls included sera from
patients with gammopathy and HIV antibody positive samples blotted to
nitrocellulose paper precoated with control, non-infected H-9 cell culture
preparations. These findings demonstrate that HIV antibodies develop in the CNS
and specific B-lymphocyte clones are stimulated to produce monoclonal IgG
antibodies to HIV in the CNS. These findings strongly support a direct causative
role of HIV in AIDS-related encephalopathy.
THR106
Anti Nucleo-Capsid antibodies and
with blood T4 cell counts and clinical status
D. MATHEZ*, D. PAUL**, G. SAIM0T***, D. JAYLE
Raymond Poincare, Garches, FRANCE^ **ABB0TT R
Park, 111, USA; ***Hdpital Claude Bernard, Pa
Paris, FRANCE.
Serum HIV antigen concentration was measure
ted serum is incubated with solid phase human
with rabbit IgG recognizing HIV (mainly) core
antibody assay used recombinant (mainly) P24
competing human anti-HIV IgG. Inhibition > 85
rily defined a high (af f inity/titers) NCA ant
A reciprocal distribution between S-HIV-Ag
Ag positive among 98 without H-NCA-Ab compare
versus 11.5%). S-HIV-Ag was detected in 41/72
26/74 with T4>700 while H-NCA-Ab were detecte
tively. Among patients without H-NCA-Ab, 5-HI
of T4 counts. These results suggest that S-HI
anti-Core antibody (in our serially tested pa
factor in the pathogenesis of T4 lymphopenia
In contrast, 12/18 Kaposi patients with T4
compared with 36/111 non-Kaposi patients. Con
3/20 Kaposi patients vs 102/195 non Kaposi ( 15
could play an active part in pathogenesis of
process leading to T4 lymphopenia. According
kaposigenic factor.
S-HIV antigenemia: correlations
>***, J. LEIBOUITCH*. *Hepital
esearch and Developpment, Abbott
ris, FRANCE; ****H6pital Tarnier,-
d by immune capture where untrea-
anti-HIV IgG and further reacted
antigen (P24) . Anti-Nucleo-Capsid
protein (solid phase) and
'/. that of anti-HIV IgG arbitra-
lbody specimen (H-NCA- Ab).
and H-NCA-Ab was found: 71 S-H1V-
d with 6/57 with H-NCA- Ab (807.
patients with T4 <200/ul and
d in 16/82 and 53/90, respec-
V-Ag distribution was independent
V-Ag may contribute to declining
tients) but that it is not a main
200 had detectable S- HIV-Ag
ersely H-NCA-Ab were found in
7. vs 52*/.) .Soluble viral products
Kaposi independently of the
ly, H-NCA-Ab would act as anti-
THR109 Differential Susceptibility of CD4 T Lymphocyte Clones
to HIV Infection
GERALD LINETTE*,S. K0ENIG**,F. R0BBINS*,T. FOLKS**, R. HARTZMAN***,A. FAUCI**;
*Georgetown Univ., Washington, DC; **NIH, NIAID, and ***NMRI, Bethesda, MD.
It has been reported that only 10- 15% of normal circulating lymphocytes will
avidly bind and support replication of HIV in vitro. To evaluate the differ-
ential susceptibility of T4 cells to HIV infection, a panel of 10 CD4 CD8",
IL-2-dependent alloreactive clones were generated from a healthy HIV seroneg-
ative volunteer. The clones were infected with HIV-1 at a multiplicity of in-
fection of 0.1 and 1.0. HIV infection was monitored for 21 days by examination
of cultures for cytopathic effects and by assay of supernatants for reverse
transcriptase (RT). Eight of 10 clones showed no evidence of HIV infection.
Two clones, one supporting HIV replication (CL62) and another showing no
evidence of infection (CL40), were used for subsequent studies. Prior to
exposure to HIV, both clones expressed similar levels of CD4, HLA-DR, and TAC
antigens and showed comparable levels of alloantigen specific-proliferation in
a 4 hour H-TdR incorporation assay. Fourteen days following HIV infection of
CL62, peak RT activity was measured. Ten to 50% of these cells were infected
as detected by in situ hybridization for HIV RNA. No viable cells were present
in these infected cultures after 30 days. In contrast, CL40 produced no detect-
able RT activity or HIV proteins in an antigen capture assay and continued to
proliferate and expand 2-3 fold over the same time interval. However. 0.1% of
CL40 cells contained HIV RNA by in situ hybridization and virus from the cell
free-supernatants of these cultures could be passaged to normal PHA-stimulated
lymphocytes. Differential susceptibility to infection of normal T4 cells with
HIV may be determined by cellular factors exclusive of specific receptor
expression (CD4) and cellular activation.
Inr. IU/ xne Thymus-AIDS Connection: HIV pl7 Protein Contains an Epitope
Immunoreactive with Antisera to Thymosin a and HGP-30, a Synthetic gag
Peptide Analogue
PAUL H. NAYLOR*, A.L. GOLDSTEIN*, P.S. SARIN**, M. BADAMCHIAN*, S. WADA*.
C.W. NAYLOR* et al., *The George Washington School of Health Sciences,
Washington, D.C, **National Cancer Institute, Bethesda, MD.
The p 1 7 protein of Human Immunodeficiency Virus (HIV) contains an epitope
which has a 44-50% homology with an 18 amino acid region of thymosin o.
(Ta. ) , a thymic hormone. Using solid phase peptide synthesis we have
synthesized a 30 amino acid analogue of this pl7 epitope which we have
termed HGP-30 (HIV pl7 gag synthetic peptide — 30 amino acids). Using
high performance liquid chromatography, radioimmunoassay (RIA), and Western
blot analysis, the presence of this immunoreactive epitope in a 17 ,000
dalton protein from an HTLV-IIIB viral extract has been identified. No
significant immunoreactivity was found in a number of other retroviral
extracts including those obtained from feline , bovine , simian and murine
retroviruses. These results, coupled with our previous studies
demonstrating immunoreactive but non-authentic Ta -like material in serum
from viral infected individuals at risk for or with frank AIDS confirms our
hypothesis of a Thymus-AIDS connection. The demonstration that an antisera
to HGP-30 cross-reacts with HGP-30 but not with Ta , and identifies the
same protein as a pl7 monoclonal antibody suggest that an ELISA or RIA can
be developed that would be diagnostic for the presence of antibodies or
antigens in individuals that are seropositive for the AIDS virus.
(Supported in part by grants and/or gifts from the NCI (CA24974), Alpha 1
Biomedicals, Inc. and Viral Technologies, Inc.)
THP110 Abrogation of Mitogen Response of Normal Lymphocytes by Anti-
lymphocyte Antibody Positive Sera of AIDS and ARC Patients.
BRENT DORSETT, DAVOR SKLIZOVIC. WILLIAM CRONIN, HARRY L. IOACHIM, Department
of Pathology, Lenox Hill Hospital, New York, N.Y.
We have previously reported the presence of elevated levels of antilymphocyte
antibodies (ALA) in the sera of patients with acquired immune deficiency
syndrome (AIDS) and AIDS related complex (ARC). In addition we have demonstra-
ted that ALA are statistically linked to disease progression. In order to
determine whether sera containing elevated levels of ALA might affect
lymphocyte function we have examined their effect on the mitogen response of
normal peripheral blood lymphocytes. Whole blood from healthy volunteers was
cultured in RPMI 1640 in the presence of mitogenic levels of Phytohemagglu-
tinin (PHA). Cultures were treated with -ALA positive AIDS and ARC sera as well
as ALA negative control sera. At various intervals cells were harvested and
hypotonically lysed in the presence of Propidium Iodide. After treatment with
Rlbonuclease the relative level of lymphocyte stimulation was determined by
flow cytometric measurement of the proliferating cell compartment. The
mitogenic effect of PHA on normal lymphocytes was substantially reduced by
treatment with ALA positive sera. Reductions varied from 40 to 95Z. Treatment
with ALA negative sera failed to affect mitogen response.
181
THURSDAY, JUNE 4
JHR111 IDENTIFICATION AND CHACTERIZATION OF AN IMMUNODOMINANT EPITOPE ON THE
GP41 HIV ENVELOPE PROTEIN. R. WISNIEWOLSKI , P. D. CHEN, J.G. WANG,
W.WALTERS AND C.Y.WANG. United Biomedical, Inc. Lake Success, N.Y.
We have previously identified a peptide 21 residues in length corres-
ponding to a highly antigenic segment of HIV gp41 envelope protein(PNAS 83:
6159,1986) and included this peptide in a synthetic mixture as the solid phase
immunoadsorbent for the detection of anti-HIV in individuals with HIV
infection.
When this peptide was conjugated to a protein carrier (HSA) and used as an
immunogen, high level of antibodies directed against this peptide was found to
cross-react with the whole HIV lysate.
When attenuated HIV was used as the Immunogen, after fusion with NS-1
myeloma cells, a high frequency ( 80%) of monoclonal anti-HIV antibodies
screened out by Enzyme Immunoassay on HIV lysate fixed plates were found to be
negative by Western Blot (WB) analysis. These EIA-positive WB-negative HIV
antibodies, frequently discarded by investigators due to their seemingly low
affinity nature, were found to react specifically with the 21mer antigenic
peptide .
Further analysis of these monoclonal anti-HIV gp41 antibodies, developed
through immunization with either the peptide-conjugate or the HIV lysate, with
peptide analogs of this 21mer has enabled us to precisely delineate each of
their corresponding epitopes at a single amino acid level. Although no
inhibition of HIV binding to CEM-T cells were observed with these antibodies,
preferential recognition of this gp41 epitope may indicate an important
functional role of this region in the initiation of an immune response through
antigen presentation or T cell activation.
THP114 Cellular Pathogenesis Induced by Human Immunodeficiency Virus
DOROTHY E. LEWIS*, B. YOFFE° , C.G. BOSWORTH* , F.B. HOLLINGER0, &
R.R. RICH*, *Howard Hughes Medical Institute, Departments of Microbiology &
Immunology and "virology, Baylor College Medicine, Houston, TX, USA.
We developed an in vitro system to study cytopathology induced by human
immunodeficiency virus (HIV) . We mixed an irradiated infected tumor cell
line, H9, with peripheral blood mononuclear cells (PBMCs) and monitored the
phenotype of lymphocytes. Rapid reduction of CD4+ numbers occurred after
3-5 days in cultures containing irradiated H9/HIV. In contrast, no depletion
occurred after incubation with K562 or uninfected H9 cells. Similarly, no
depletion occurred after incubation of H9 cells with free virus in 5 days.
Because we thought that antigen activation might play a role in the rapid CD4
depletion and because the quantity of free HIV may be different from that
associated with H9/HIV cells, we examined the response to irradiated infected
PBMCs. Allogeneic or autologous mixtures of PBMCs from person "A" or "B"
were examined in cultures containing irradiated infected cells from person
"B". In some A + B/HIV cultures, we noted dramatic depletion of cells within
5 days; in others only a modest reduction occurred. In B + B/HIV cultures,
however, no reduction in CD4+ numbers occurred after 5 days in culture
although surface inter leukin-2 receptor expression did occur. We, therefore,
used PHA or CD3 Sepharose to provide a T cell receptor signal to the B +
B/HIV cultures. We found that dramatic depletion of CD4+ numbers occurred
after PHA addition. CD3 also induced CD4 cellular depletion but to a lesser
extent than did PHA. These results suggest that HIV must be associated with
cells for optimal cytopathology and that lymphocyte activation, perhaps via
allogeneic recognition, may be a primary mechanism involved in the acquisi-
tion of HIV in vivo. Supported by NIH grants AI22549 and AI21289.
THP112 UV-HIV Immunosuppression of Mitogen Responses by Normal PBL Can
Occur in the Absence of Cytopathology
NASAR QURESHI, R.F- GARRY, and L.A. HENDERSON, Department of Microbiology and
Immunology, Tulane Medical School, New Orleans, LA.
Decrease in T4 cells cannot account for the full extent of the immune
defects seen in AIDS or ARC patients. Immune defects can be demonstrated in
seropositive patients with T helper/T suppressor cell (T4/T8) ratios in the
normal range. Normal peripheral blood lymphocytes (PBL) incubated with PHA
and uv-inactivated HIV (UV-HIV) were examined with specific monoclonal
antibodies to various T cell subsets by flow cytometry. Three out of 7
individuals tested exhibited a 25-30% decrease in Leu 3a positive cells, and
a marked decrease in T4/T8 ratios over a 7 day incubation period. This
decrease was accompanied by a varied but consistent increase in Leu 2a
positive cells. Preactivation of PBL' s with PHA alone and subsequent ex-
posure to UV-HIV in the presence of PHA exhibited inconsistent Leu 3a killing
and T4/T8 ratio changes in susceptible individuals tested in repeated experi-
ments. The effects of UV-HIV on the proliferation of normal PBL' s cultured
in the presence of PHA were studied. UV-HIV, intact or detergent solublized,
suppressed PHA stimulated proliferation of donor PBL's over a broad range of
PHA concentration even in the absence of cell killing. This effect was
dependent upon the quantity of UV-HIV or solublized UV-HIV. The elaboration
of a putative suppressor factor from cultures of UV-HIV treated PBL's in the
presence of PHA will be discussed. Demonstration of marked immunosuppression
in the absence of Leu 3a killing and changes in T4/T8 cell ratio, indicates
the possibility that the two phenomena may be mediated by two different
proteins or the same protein may serve several functions.
THP115 Antibodies to HIV are produced within the Central Nervous System of
all subjects with all categories of HIV Infection
ANDREW LLOYD, J.M. DWYER, P. ROBERTSON, D. WAKEFIELD, Departments of Clinical
Irmiunology and Pathology, The Prince Henry/Prince of Wales Hospitals of the
University of New South Wales, Sydney, Australia.
Anti-HIV antibodies were found in the cerebrospinal fluid of all 41 subjects
tested whose serum contained these antibodies. To ensure that locally produced
antibody was being detected, a sensitive assay was used to demonstrate the
integrity of the blood-brain barrier. Antibodies to ubiquitous adenovirus
group antigens were sought, simultaneously, in CSF and serum. A lack of adeno-
virus antibodies in CSF of subjects seropositive for adenovirus was required
before CSF anti-HIV antibodies could be considered to be produced within the
central nervous system.
Of the forty-one subjects tested eight were asymptomatic, eight were clinic-
ally well but had significant lymphadenopathy, fourteen were immunodeficient
and had constitutional symptoms ( AIDS-related complex or ARC) and eleven had
AIDS. Oligoclonal banding was detected in the CSF of sixteen subjects and a
pleocytosis was present in twenty-four. Neither finding clustered with a
particular stage of infection. It appears that serological evidence of HIV
infection of T lymphocytes and of the central nervous system occurs simultane-
ously. All HIV infected subjects are at risk of developing primary neuro-
logical as well as immunological sequelae. Similarly, currently poorly under-
stood resistance factors must protect both lymphocytes and nervous system
tissue from damage by the HIV virus, as to date, the majority of infected
subjects have not become immunodeficient or developed neurological disease.
THR113 Patterns of Lymphocyte Subset Alterations in SIV/Delta Infected
Rhesus Monkeys.
LOUIS N. MARTIN, M. MURPHEY-CORB , E.A. WATSON, G.B. BASKIN, Delta Regional Pri-
mate Research Center, Tulane University, Covington, LA. U.S.A.
Simian Immunodeficiency Virus (SIV/Delta) infection of rhesus monkeys induces
immunodeficiency, opportunistic infections (01) and death. 01 manifestation
postinoculation varies from 2 to 21 months. Studies of lymphocyte subsets by
staining with monoclonal antibodies revealed two patterns of alterations in
SIV/Delta infected monkeys, one of which may be prognostic of imminent 01.
Monkeys dying with 01 by 8 months after SIV/Delta inoculation developed in-
creased percentages of T-ll (erythrocyte receptor) and Leu 2a (suppressor/
cytotoxic) cells. Depressed helper/suppressor (H/S) ratios resulted from the
increase in the percentage of Leu 2a cells. Although these animals had nor-
mal percentages of Leu 3a (helper/inducer) cells, the percentages of these
cells staining with 4B4 was decreased, indicating a defect in a more restricted
helper/inducer subset. Five of the 7 inoculated monkeys which exhibited this
pattern of subset alterations died within 8 months postinoculation, and A of
the 5 monkeys which died also had progressive decreases in serum IgG concentra-
tions. Monkeys which survived longer than 8 months developed decreased per-
centages of T-ll and Leu 3a cells and increased percentages of B-l cells.
Depressed H/S ratios in this group resulted from the decrease in Leu 3a cells.
Although the percentage of Leu 3a cells was depressed, the percentage of these
cells staining with 4B4 was normal. All 6 inoculated monkeys which exhibited
this pattern of subset alterations, including increased B-cell percentages, had
progressive increases in serum IgG. One monkey in this group died 309 days
postinoculation with a B-cell lymphoma. Seven of 9 monkeys tested had defec-
tive antibody responses to tetanus toxoid.
THP116 IMMUN0L0GICAL PARAMETERS IN HIV-INFECTED SPANIARDS : HIGH MONOCYTE NUM-
BERS IN PERSISTENT LYMPHADENOPATHY PATIENTS. Arnaiz-Villena A, Alcami
J, Regueiro JR.. Inmunologia, Hospital Primero Octubre, 28041 MADRID. SPAIN. The
paleo-North African origin of the Spanish population makes it an interesting eth
nic group for the study of AIDS in Caucasians. We have thus established the immu-
nological status of the different stages of HIV infection in Spaniards. One hun-
dred HIV+ patients (as assessed by both Elisa and Western blot tests) were stu-
died(81 drug addicts, 7 homosexual, 4 post-transfusional, 2 heterosexual transmi.
ssions,2 mother/child infected couples and 2 belonging to no obvious risk group)
The following parameters were studied: peripheral blood mononuclear leukocytes
(PBML) subpopulations (CD3,CD4,CD8,CD11 and CD20), serum immunoglobulins, in vi-
tro proliferative response to phytohaemaglutinin (PHA), anti-CD3 and pokeweed,
and anti-HIV proteins (pl5, 24, 31 ,41 ,53,55,64 and 120) serum IgG antibodies. CDC
clasif ication criteria, were used:27 asymptomathic(AS) ,27 with persistent lympha-
denopathy (LAP) ,26 with AIDS-related complex (RC) and 20 full-blown AIDS were ob
served . RESULTS : all patients had high polyclonal serum IgG levels and high CD8
PBML (p< 0.05) as compared to healthy controls. Interestingly , LAP patients showed
high monocyte numbers (510 vs 331, p<0.05) and CD11+PBML (594 vs 282, p< 0.001)
as compared to AS group, but both variables were back to normal values in RC and
AIDS subsets; this may be of value for assessment of illness progress, and, in LAP
individuals, dropping CD11 PBML may indicate a poor prognosis. Compared to AS
and LAP groups, RC and AIDS patients had lymphopenia (p < 0.001) , low CD4 PBML
(p<0.001), low CD4/CD8 ratio (p<0.001) and low lymphoproliferative responses
(PHA, p< 0.001; anti-CD3,p <0.01) . Lastly, compared to all other groups, AIDS pa-
tients had high serum IgA levels (583 vs 250 mg/dl, p< 0.001) and lower pl5
(p <.0.05) and p55+ (p<0.01) anti-HIV antibodies. The use of these variables for
the diagnosis and prognosis of HIV-infected patients is discussed.
182
THURSDAY, JUNE 4
THP117 The Existence of an Inhibitory Factor(s) against HIV-Reverse Trans-
criptase in Sera from AIDS and ARC Patients.
ROBERT J. PETRELLA, Y. SEI, M.M. YOKOYAMA, J.G. BEKESI, Mount Sinai School of
Medicine, New York, New York 10029 USA
We have investigated inhibiting and enhancing effects of HIV infected indi-
viduals' sera on HIV-reverse transcriptase (RT) activity in vitro. The modula-
ting effects were not observed in assays containing sera taken from HlV-unin-
fected homosexuals and heterosexual controls, suggesting that the inhibitory
and enhancing phenomena are associated with HIV infection. The presenting
study has focused on the inhibitory function of the sera. 4 of 20 (20%) AIDS
and 5 of 33 (15%) ARC patients sera showed the inhibitory effect. The effect
was not observed in either 20 HIV(-) homosexuals or 28 heterosexual controls.
Enzyme kinetic study showed that sera with the inhibitory property lowered the
maximum velocity attainable with a given amount of enzyme (Vmax), but did not
affect the dissociation constant for the enzyme with its RNA substrates. The
result suggests the presence of one or more non-competitive inhibitory factor
(s). Furthermore, the inhibitory function of sera was completely absent in
the eluates of protein A-agarose affinity chromatography columns. These re-
sults indicate that the inhibitory factor is probably an antibody that binds
at a site on HIV-RT other than the RNA binding site. In addition, sera from
AIDS subjects that displayed RT-inhibit ing effects showed significantly
greater neutralizing activity than non-inhibitory sera, implying that the
inhibitory antibody may contribute partially to the sera's neutralizing
activity against HIV infection. The existence of this inhibitor points out
several diagnostic problems and therapeutic possibilities.
THP120 Cross-Reacting Neutralizing Antibodies Against Three Different
Strains of Human Immunodeficiency Virus (HIV).
LUBA K. VDJCIC, D.H. SHEPP , AND G.V. QUINNAN, JR., Division of Virology, OBRR,
FDA, Bethesda, MD, USA
The cross-reactivity of neutralizing antibodies against different strains of
HIV is of interest with regard to potential vaccine efficacy. Sera from
patients infected with HIV were tested against the Illn. LAV, and RF-II
strains of HIV for neutralizing antibodies. The IIIr and LAV strains are
closely related, but both are distantly related to the RF-II strain. The
methods used for this rapid microneutralization assay have been described
previously. Briefly, sera and virus were incubated for 90 minutes followed by
the addition of Molt-3 cells as the indicator cell line. Four to five days
later neutralization was determined by a 50% reduction in giant cell
formation. In this system giant cell formation correlates with other
parameters of viral replication. To date 15 healthy asymptomatic patients and
8 patients with AIDS have been tested against all 3 strains of HIV. Of these
sera, 86% neutralized the Illg strain with a geometric mean titer (GMT) of
1:79 for the positive samples, 78% neutralized the LAV strain with a GMT of
1:75, and 59% neutralized the RF-II strain with a GMT of 1:17. The results
obtained with the Illg and LAV strains were 95% concordant. The results
obtained with the RF-II strain were 68% concordant with those obtained with
the other strains in terms of presence or absence of neutralizing antibodies.
The results indicate that HIV often induces cross-reactive antibodies. It is
unclear whether a vaccine based on antigens of a single strain would induce
immunity protective against distant variants of HIV.
THR118 Defective T Cell Mediated Natural Anti-Bacterial Activity in HIV-
infected Patients
GUIDO POLI*, L. NENCIONI**, M. ROMANO**, A. LAZZARIN***, A. MANTOVANI*, and
A. TAGLIABUE**, Mstituto M. Negri, Milano, Italy, **Centro Ricerche Sclavo,
Siena, Italy, *** Istituto Malattie Infettive, Milano, Italy.
Circulating mononuclear cells (PBM) of healthy subjects possess an in vitro
natural activity (NA) against enteropathogenic bacteria, including
Salmonella. The effector cell is characterized as a CD4(+)/CD8(-)/Leu8(+) T
lymphocyte, acting against bacteria by an ADCC mechanism, via cytophilic
IgA. Because AIDS is a profound immunodeficiency caused by human
immunosuppressive virus (HIV) involving primarily CD4 lymphocytes, it was of
interest to assess NA of HIV-infected subjects at various stage of disease.
Results indicate that NA against Salmonella typhi is significantly decreased
in AIDS as well as ARC and LAS patients. Worthy of note, CD4(+)/Leu8(+)
lymphocytes were previously demonstrated to be the most susceptible
subpopulation of T lymphocytes to HIV infection. Anti-S. typhi IgA levels
were studied in HIV-infected population and in healthy subjects. Despite
an increased level of total IgA, AIDS and ARC patients show a profound
depression of specific anti-S. typhi LPS IgA. Therefore, both the cellular
and humoral components of anti-Salomonella NA are profoundly depressed.
These data can provide an explanation for the increased incidence of
bacterial infections in AIDS and ARC patients, including Salmonellosis.
THP121 Increased B-Cell Activation and Immaturity Associated
with Human Immunodeficiency Virus (HIV) Infection
O. MARTINEZ-MA2A*. E. CRABB* , R.T. MITSUYASU**, J.L. FAHEY*, AND
J.V. GIORGI**, *Depts. Micro. & Immunol, and **Medicine, Jonsson
Comp. Cancer Ctr. , UCLA School Medicine, Los Angeles, CA 90024
The expression of phenotypic markers on B lymphocytes in
patients with AIDS, in HIV-sero(+) individuals, and in healthy
HlV-sero(-) donors was examined by two-color flow cytometry.
Patients with AIDS and HIV-sero(+) individuals showed an elevated
percentage of B cells (Leu 16+, CD20) bearing an activation
marker, the transferrin receptor, when compared to donors not
infected with HIV. A decrease in the percentage of resting (Leu
8+) B cells was also seen in AIDS patients and HIV-sero(+)
individuals. An increased percentage of circulating, immature
(CALLA-positive, CD10) B cells was seen in AIDS patients. These
phenotypic changes were accompanied by an increased level of
spontaneous IgG and IgM secretion, and increased cell size within
the total B cell population, and within some B cell
subpopulations, in patients with AIDS and in HIV-sero(+)
subjects. These results demonstrate that phenotypic changes
indicative of in vivo B cell activation and immaturity accompany
the polyclonal production of Ig seen in HIV-infected individuals.
This work was supported by NIH grants AI15332, AI52573, and
CA00132, grant 86LA012 from the California Universitywide Task
Force on AIDS, and funds from the Will Rogers Memorial Fund.
This work is based on work supported under a National Science
Foundation Graduate Fellowship to E. Crabb.
THR119 Randomized Clinical Trial of Plasma and Recombinant Hepatitis B
Virus Vaccines in Gay Men
N. Qdaka*. L. Eldred*, S. Conn*, A. Munoz*, H. Fields**, F. Polk*, et al.,
*Johns Hopkins School of Hygiene and Public Health, Baltimore, MD, **Centers
for Disease Control, Atlanta, GA.
A randomized, double-blind comparative study of plasma (20ug/dose) versus
recombinant (lOug/dose) hepatitis B virus (HBV) vaccine (both provided by
Merck Sharp and Oohme) was conducted in 186 gay men without serologic evi-
dence of prior HBV infection. Vaccine was administered intramuscularly in the
deltoid at 0,1, and 6 months: serum was obtained at 0,1,6 and 9 months and
assayed for anti-HBs by radioimmunoassay. HIV serologic status was determined
by EIA and immunoblot. Results among 158 who received all 3 doses and from
whom 9-month serum was available were:
Plasma
Recomb
nant
HIV neq
HIV pos.
HIV neg
HIV pos.
Seroconversion
60/69 (
87)
2/8 (.25)
51/72 (
71)
1/9 (.17)
(>20 mlU)
In anti-HBs
level
0
0
0
0
0
1 mo.
0.46
0.09
0.38
0.01
6 mo.
3.09
1.34
2.43
0.67
9 mo.
4.11
1.63
3.48
0.99
Multivariate analysis of data from all 186 participants, with an
autoregressive model, demonstrated that the plasma derived HBV vaccine was
significantly more immunogenic than the recombinant vaccine, and that HIV
infected men were significantly less likely to respond to either vaccine than
were HIV seronegative men.
THP122 Human Immunodeficiency Virus (HIV; Antigen (Ag) and Antibody (Ab)
Profiles in Children with HIV Infection: Correlation with Clinical
Status. N. KAMANI*. L.R. KRILOV*. K.M. HENDRY**, A.E. WITTER**, and G.B.
QUINNAN**" *SUNY Stony Brook & Schneider Child Hosp of Long Island Jewish Med
Ctr, Dept Peds, New Hyde Park, NY, **Div of Virology, FDA, Bethesda, MD.
HIV Ag and Ab profiles were determined on sera from 25 children (loo-*, 9£)
with HIV infection. 6 children (ages 4-84mos; median 5mos) had CuC-defined
AIDS with opportunistic infections (01); 2 children (ages 12 & 75mos) had his-
tologically confirmed lymphoid interstitial pneumonitis (LIP) ; 17 children
(ages 4-108 mos; median 39mos) had AIDS-related complex (ARC) with persistent
generalized lymphadenopathy, HIV p24 Ag was detected in serum by enzyme Immuno-
assay. Western blot analysis of Ab responses to multiple HIV Ags revealed 3
patterns of response: (A) strong total IgG and IgGi responses to all viral Ags
including p24 and detectable IgA, IgM &/or IgG2-4 responses to multiple viral
Ags; (B) weak or absent IgG and IgGl response to p24 Ag with significant Ab
responses to other Ags; (C) weak or absent IgG and IgGi response to p24 Ag and
at most minimal Ab response to other viral Ags. Clinical status and Ag/Ab pro-
files are tabulated below.
Clinical Status p24 Ag Ab profile pattern
++ + NEG (A) (B) (C)
3 1 1-5
1 1
5 11 14 1 1
AIDS with 01 2
AIDS with LIP 2
ARC
The presence of Ag in the absence of a significant Ab response to p24 corre-
lates with AIDS and a strong Ab response to p24 Ag plus detectable Ab to other
HIV Ags in multiple Ab subclasses correlates with a more stable clinical
status. The longitudinal evaluation of Ag/Ab profiles may help in the assess-
ment of clinical prognosis for children with HIV infection.
183
THURSDAY, JUNE 4
TI4D19Q Frequency and significance of serum monoclonal IgG at various stages
of HIV-1 infection.
D. B0USCARY, R. FIOR, L. INTRATOR, C. PICARD, A. SOBEL. Departement d* immunolo-
gic, Faculte de medecine, Creteil 94010, France.
A number of HIV-associated abnormalities, such as alteration of regulatory
T-cell functions, viral reactivations, B-cell hyperreactivity and B-lymphomas,
suggest the possible emergence of B cell derived monoclonality . Indeed, oligo-
clonal bands have been occasionaly reported in patients with AIDS. A systematic
investigation was realized in 150 consecutive patients with HIV-1 infection.
Monoclonal immunoglobulins were detected by electrophoresis and immunof ixation
in agarose. A monoclonal IgG was found in 18 cases (12 %) . 20 % of these had at
least a second peak. Most of the peaks were IgG K (95 %) and did not exceed 2
g/1. The patients with M-IgG (group I) were compared to the 132 patients without
M-IgG (group II), for a 4-15 months observation period. Both groupsdid not dif-
fer in terms of clinical status (asymptomatic carriers, LAS, ARC or full-blown
AIDS), above 70 % of the individuals being in both former categories. M-IgG was
not related to the presence of Kaposi sarcoma. Blood transmitted HIV (drugs u-
sers and transfusions) were slightly more frequent in group I (72 % vs. 42 %) .
Polyclonal hypergammaglobulinemia was more frequent in group I (71 % vs. 44 %) .
Mean lymphocyte counts, T4 (760 vs. 618), T8 (930 vs. 757) counts were compara-
ble in both groups. Viral serologies were similarly distributed. During the ob-
servation period the M-IgG persisted in 3 patients, disappeared twice. None of
the 150 patients had lymphoma. These data confirmed the high frequency of M-IgG,
even at early, poorly symptomatic stages of HIV-1 infection, when immune defi-
ciency is likely to be limited. B-cell hyperreactivity was commonly associated
without evidence of EBV reactivation. Nevertheless, this study supports the hy-
pothesis that genetic rearrangements of B-cells occur early and frequently, pro-
viding favorable conditions for a multistep process of lymphomagenesis .
THP126 Abnormal leukocyte functions In HIV-infected asymptomatic homosexual
men with normal CD4+ T-cell numbers
FRANK MIEDEMA, A.J.C. PETIT, F.G. TERPSTRA, J.K.M. EEFTINCK SCHATTENKERK*, F DE
WOLFF**, P.Th.A. SCHELLEKENS et al., Central Lab. Netherl. Red Cross Blood
Transfusion Service, incorporating the Lab. of Exp. and Clin. Immunology of the
Univ. of Amsterdam, *Dept. of Internal Medicine of the Univ. of Amsterdam,
**Municipal Health Service, Amsterdam, The Netherlands
To investigate early effects of HIV infection on the immune system, we stud-
ied leukocyte functions in HIV+ asymptomatic homosexual men (n=14) classified
in group II, compared to HIV- homosexual men (n=20) . All HIV+ men, except one,
had normal absolute CD4+ T-cell numbers, in 7 men CD8+ cells were elevated.
CD20+ B cells were low in 5 HIV+ men, monocyte numbers were normal. Compared
to HIV- homosexual men, the HIV+ men showed decreased T-cell proliferation in-
duced by CD3 Mab in the presence of normal accessory cells. T-helper activity
for polyclonally (PWM) -stimulated normal B cells was decreased in HIV+ but not
in HIV- men. Accessory cell function of monocytes in CD3 Mab-Induced prolifera-
tion of purified normal T cells was decreased In HIV+ men compared to HIV- men.
Immunoglobulin (Ig) synthesis In the PWM-driven system by B cells of HIV+ men
was severely deficient and was not restored by addition of normal CD4+ T cells
or depletion of CD8+ suppressor cells.
In the microculture system (80,000 MNC/well) only MNC of HIV-homosexual men
showed spontaneous Ig production. Both HIV- and HIV+ homosexual men showed a
decreased abnormal in-vivo antibody response to Immunization with Keyhole-
limpet hemocyanln. Our results suggest that HIV induces immunological abnorma-
lities before CD4+ T-cell depletion occurs.
THR124 AlPna Interferon of a Marker and a Secondary Pathogenic Factor in
AIDS
BERNARD BIHARI, F. Drury, V. Ragone, G. Ottomanelli, E. Buimovici-Klein
Several prospective studies of high risk groups have suggested that alpha
interferon (alpha IFN) in an acid labile form, is a marker for the future devel-
opment of AIDS. In our low dose naltrexone study reported elsewhere at this
conference, the mean admission alpha IFN level was 160 i.u. Sixty percent of
the patients showed a gradual sequential decline in alpha IFN levels, plateauing
at 8 i.u. and 40% showed no such drop. The first group, called responders, had
a much higher 12-month survival rate than the nonresponding group, (83% vs 19%
p<.01) and fewer major 0.1. 's (p<.01). The results suggest that lowering the
pathologically high levels of alpha IFN has a protective effect. Of interest
was the finding of an inverse relationship between the admission absolute
number of T4's and the admission alpha IFN level in the responder group (p<.01)
not exhibited in the nonresponder group. These results support the hypothesis
that alpha IFN is an important marker both for disease progression and for
treatment response. They also suggest that alpha IFN is a major secondary
pathogenic factor in the disease. This is supported by the experience with
recombinant alpha IFN in animal studies and in clinical trials with cancer
patients, demonstrating significant suppression of cellular immunity, including
T4 number and function. In addition, alpha IFN acts in vivo as an opioid, and
in high levels is likely to down regulate opiate receptors on imriunocytes and
pituitary beta endorphin production, thereby disturbing endorphinergic cor-
rection of immune system dysf unction.
THR127 T8+Leul5- Cytotoxic Cells 1n AIDS-related Diseases in Hemophiliac
Patients
ALAN P. KNUTSEN, J.D. BOUHASIN, J.H. JOIST, S.T. ROODMAN, St. Louis University
Medical Center, St.- Louis, MO, USA.
The purpose of this study was to quantitate T cytotoxic cells in HIV sero-
positive hemophiliac subjects and to correlate these to disease state. Defic-
ient T cell cytotoxicity to viral-infected target cells has been reported in
patients with ARC and AIDS. Recently, Nicholson et al reported elevated num-
ber of cytotoxic T cells in the blood of HIV-seropositive asymptomatic homo-
sexual men. In our study, the percentage of T8 suppressor/cytotoxic cells
were elevated in HIV-seropositive hemophiliacs who were asymptomatic (N=41),
had ARC (N=6), or AIDS (N=7) compared to seronegative hemophiliacs (N=24),
44.9, 45.3, 51.8 vs 31.4% {P<0.01, <0.01, <0.01, respectively). However, the
absolute number T8 cells were not statistically different among these groups
of hemophiliacs. Phenotypic analysis of dual-labelled T8Leul5 cells revealed
that seronegative hemophiliacs (N=7) compared to normal controls had increased
percentage of T8+Leul5- cytotoxic cells, 94.2 vs 69% (P<0.01). Similarly, se-
ropositive hemophiliacs of all 3 groups had increased percentages of T8+Leul5"
cells though not statistically different from seronegative hemophiliacs. Se-
ropositive asymptomatic hemophiliacs (N=30), however, had increased number of
T8+Leul5" cells compared to seronegative hemophiliacs and controls, 704 vs 488
and 301 cells/mm3 (P<0.01, <0.01, respectively). Furthermore, T8+Leul5" cells
were decreased in hemophiliacs with ARC (N-5), 531 cells/mm3 (P=NS), and with
AIDS (N=4), 259 cells/mm3 (P<0.01). In summary, T8+Leul5" cytotoxic cells
may be important in controlling HIV Infection, evident as an increase in our
seropositive asymptomatic hemophiliacs. A decrease of T cytotoxic cells may
have predisposed some to develop AIDS or be a reflection of disease activity.
THP125 Recombinant HIV env Gene Products Induce Human Immune-Specific
Lymphocyte Responses In Vitro.
JOHN W, TORSETH , P.W. BERMAN**, AND T. C. MERIGAN*. *Stanford University
School of Medicine, Stanford, CA, Genentech, Inc., South San Francisco, CA
Peripheral blood mononuclear cell cultures were established from 56
patients with antibody to human immunodeficiency virus . Asymptomatically
infected patients (7/11) had significant immune responses induced in culture
by an immunoaf f inity purified, recombinant glycoprotein (gp-130) from the
virus . In addition to stimulating the production of gamma interferon, this
recombinant version of gp-120 protein induced transformation responses which
predicted clinical disease status as well as correlated directly with
circulating levels of helper/ inducer lymphocytes (r-0.43, p 0.01) and
indirectly with virus antigen (p=0.025). Three of 27 patients with AIDS-
related complex (ARC) also responded to this protein. However, these
responses occurred significantly less frequently than responses to herpes
simplex virus and cytomegalovirus antigens in the same seropositive
patients. Neither this protein, nor two other immunore active, recombinant
HIV proteins induced such in vitro responses in 11 seronegative subjects,
thus the antigenic responses are immune- spec if ic . Our findings suggest that
HIV- specific cellular immune responses to gp-130 decline in association with
disease progression, and become undetectable in frank AIDS. In addition,
they appear to serve as a marker for immune responses important in
prevention of blood borne dissemination of free virus (as detected by serum
HIV antigen assay).
THP128 DIRECT DETECTION OF HTLV-III ANTIGENS ON LYMPHOCYTES FROM PATIENTS
WITH AIDS AND AIDS RELATED COMPLEX.
Denis Burger, Mark Loveless, Patricia Watson Martin, Randy Hodges, Sue Caouette,
Paul Yoshihara, and Andrew Goldstein, Epitope, Inc., Portland, OR 97006.
Monoclonal antibodies were produced against HTLV-III, the etiologic agent of
AIDS and ARC. One of these monoclonal antibodies, designated 3D8, was reactive
with the viral core protein (gag), by Western blot analysis against viral
lysates and by ELISA assay versus cloned gag product. Antibody 3D8 was used
to detect expression of HTLV-III antigens on the H9 cell line following viral
infection as well as on lymphocytes from seropositive patients. Virally-
infected H9 cells were found to be highly reactive with antibody 3D8 by FACS
analysis. Forty-five Western Blot-positive patients representing AIDS, ARC and
an asymptomatic group were studied using flow cytometry. A significant
percentage of T4-positive lymphocytes from individual patients were stained
with antibody 3D8. The highest percentage of HTLV-III positive cells came
from patients with AIDS (up to 50% staining of T4 cells) although patients with
ARC and patients without symptoms also demonstrated significant expression of
HTLV-III antigens. Moreover, there was a correlation between the number of
patients expressing HTLV-III antigens on T4 cells and clinical grouping. These
data suggest that a higher percentage of T4-lymphocytes express HTLV-III
antigens than has been predicted by detection of intracellular HTLV-III mRNA.
184
THURSDAY, JUNE 4
THR129 IMMUNOPHENOTYPES BY FLOW CYTOMETRY:
A LONGITUDINAL STUDY IN HEALTHY INDIVIDUALS
PHILIPPE C. BISHOP, D.C. BOONE, J.W. PARKER, USC School of Medicine, Los
Angeles, CA.
The study was undertaken to assess the variations in the immunological
phenotypes of peripheral blood lymphocytes and monocytes in repeated
samples from five healthy volunteers who were not at risk for AIDS. Weekly
samples were obtained for 13 weeks. Monoclonal antibodies to seventeen
lymphocyte and five monocyte antigens were evaluated using two color flow
cytometry. Individual and group mean (s.d.) differences were calculated
from data for consecutive weeks to determine overall variation. Average
week to week differences were less than 5% with the exception of 12+
(17.1%, s.d. 14.7), NKH+ (6.2%, s.d. 4.3), M01+ (9.8%, s.d. 6.6), and M02+
cells (7.2%, s.d. 5.4). During the course of the study, one subject had
symptoms associated with a common influenza-type viral infection and showed
a temporary reversal in the helper /suppressor ratio (0.82) which reverted
back to normal (1.83) the following week. Overall, most of the phenotypes
remained relatively constant with the exception of those associated with
activated lymphocytes, natural killer cells, and monocytes. The observed
variations presumably reflected both technical inconsistencies and
responses of the immune system to daily environmental stimuli. Because
patients also undergo the same types of environmental insults, but may have
a more labile immune system, serial phenotypic measurements are essential
to adequately assess their immunological status.
THR 132 Lymphocyte circadian cycles in HIV infected individuals : abnormalities of both CD4
and C08 cells.
ERIC MARTINI' , C, DOINEL'* , J.Y. MULLER* . CH. SALMON- ■ CNTS-lnstitut , *INSERM , Paris. France
Physiological circadian variations are observed in peripheral blood lymphocytes counts. The nadir
occurs around 8.00 a.m. and the peak value at midnight.
In HIV infected individuals, lymphocyte function abnormalities are frequent. So, we developed a
protocol to search for modifications in the CD4 and CD8 lymphocyte cycles
Peripheral blood samples were obtained from 9 healthy controls and 16 HIV infected patients : 9 were
asymptomatic or lymphadenopathic seropositive patients (CDC group ll-lll), 7 were ARC or AIDS
patients (CDC group IV),
CD2-0KT 1 1 , CD4-0KT4 and CD8-0KT8 cells were determined using fluorescein labelled monxlonal
antibodies and a flow cytometer (Spectrum III with a 21 40 analyzer, Ortho Diagnostic Systems). Samples
were obtained at 8.00 a.m., 4.00 p.m. and midnight. Using absolute number of cells, results were
expressed in terms of a "Nycthemeral ratio"(NR) I.e. midnight count : 8.00 a.m. count.
In controls, variations were noted for all lymphocyte subpopulations ; CD4-NR was1.6±04 andCD8-
NR l.4±0.2. In CDC group IV patients, cycles were always impaired : CD4-NR were less than 1.1 and
CD8-NR less than I. In the 9 CDC group ll-lll patients, 5 had cycles comprised tn the normal range, 4
had both CD4-NR andCD8-NR decreased.
It is of Interest that there is no correlation between the absolute number of any lymphocyte subset and
any NR value. So, CD4 lymphocyte cycle abnormalities were observed even in patients with normal CD4
absolute count. Furthermore, even for CD8 cells (that are not infected by HIV) NR values were low,
independently of their absolute count
Because all CDC group IV patients had lymphocyte cycles abnormalities, the evaluation of NR might
become an early prognosis factor. This would be of great interest to CDC ll-lll group In keeping with their
nycthemeral cycles
THR130 Oligoclonal IgG bands on Serum-electrophoresis in a Cohort of Homo-
sexual Men in Stockholm, Sweden.
GORAN 8RATT, L WALDENLIND, G v KR0GH, A KARISS0N, L M0BERG, E SANDSTROM. Dept.
of Clinical Chemistry and Venhalsan, Dept. of Dermato-venereology, Sodersjukhu-
set, Stockholm, Sweden.
As part of a health screening project for asymptomatic gay men in Stockholm,
sera from 145 men collected 1983 and 1984 were examined with agarose electropho-
resis and immunofixation with IgG, IgA, IgM and kappa/lambda antisera (Dako-
patts, Denmark). HIV-seropositive men were reexamined in 1985 and 1986. 100 age
matched healthy male blood donors served as controls. The results were as
follows:
HIV-serology n Individuals with oligoclonal bands, (IgG level (g/D)
1983 1984 1983 1984 1985 1986
NEG NEG 110 1(11.2+2.2)0(10.9+2.1)
NEC POS 10 2 (10.6 +1.0) 1 (11.4 +1.9) 4
P0S POS 25 14(14.8+2.8)15(15.4+2.9)11
CONTROLS 100 0 (11.6 + 1.6)
All the oligoclonal bands consisted of IgG with either kappa or lambda light
chains. During the 3 year follow-up 3 of the 25 men, who were HIV-positive in
1983, developed AIDS. All had oligoclonal bands and IgG levels >15.4 g/1 in
1983. Oligoclonal bands seem to be a common finding that parallel high IgG
levels in HIV-positive gay men. It is not an early finding after seroconversion.
Over 50?; of the men who were HIV-positive in 1983 had oligoclonal IgG bands and
this finding seemed to be constant over the follow-up period.
(13.6
(16.0
2.1) 5 (14.0 + 1.5)
3.4)11 (16.3 + 3.9)
THP133 Zinc Deficiency and Human Imminodef iciency Virus Infection.
JULIAN FALUTZ, C. TSOUKAS, J. WOLSKA, J. SAMPALIS, P. GOLD.
McGill University, Montreal, Quebec, Canada.
The role of co-factors, including malnutrition, In the observed immuno-
suppression associated with the human Immunodeficiency virus infection (HIV)
is unknown. Zinc deficiency predisposes to reversible abnormalities of cell-
mediated immunity, as well as thymic atrophy and dysfunction. To assess the
possible role of low zinc as a co-factor In the severe immunosuppression
characteristic of advanced HIV disease, we measured serum zinc, albumin, and
T cell numbers in CDC determined subgroups of HIV infected individuals. Zinc
was measured by atomic absorption spectrophotometry. T cell subsets were
measured by monoclonal antibodies. Comparisons were for groups versus
controls. Results are expressed as mean ± S.D.
Control Group II Group III Group IVA Group IVC1 Group IVD
n = 22 7 19 5 14 6
Zinc racg/dl 1.17+0.2 1.32+0.3 1.05±0. lc 0.96±0. lc 0.79±0.2e 0.92±0.1d
T helpers /mm3 935±376 534±264c 675±330b 289±317d 40±60d 104±128d
Albumin g/dl 5.12±0.3 4.5±0.5a 4.9+0.53 4.3±0.6a 3.8±0.8e 4.2±0.6b
T Test a=p<0.05 b=p<0.01 c=p<0.005 d=p<0.001 e=p<0.0001
Group IV patients had significantly decreased zinc levels, which correlated
with the decline in Immune status, as assessed by T helper cell numbers
(r=0.43, p<0.002) Albumin was significantly decreased in all Group IV pa-
tients. The etiology of the decrease In zinc with progressive HIV disease is
likely multifactorial. We hypothesize that low zinc may exert an addition-
al Immunosuppressive effect In HIV disease, and that >:lnc repletion may have
a beneficial role In retarding an otherwise progressive decline In immunity.
THR131 Antibody Response to a Recombinant Hepatitis B Vaccine in Anti-HIV
Positive vs. Anti-HIV Negative Persons
MICHAEL GESEMANN*. N. BROCKMEYER**, N. SCHEIERMANN*, E. KREUZFELDER*,
A. SAFARY***, E. SIM0EN***, et al., *Institut fur Medizinische Virologie und
Immunologic, Universitatskl inikum, Essen, FR Germany, **Dermatologische
Klinik, Universitatsklinikum, Essen, FR Germany, ***SmithKline-RIT,
Rixensart, Belgium.
To determine the influence of HIV (Human Immunodeficiency Virus) infection
on the outcome of hepatitis B vaccination, 19 homosexuals seronegative
(group I) and 8 persons anti-HIV positive (group II) were vaccinated with
20 meg doses of a yeast-derived hepatitis B vaccine (SmithKline-RIT, Belgium)
at months 0, 1, and 6. Another 12 anti-HIV positive persons (group III) with
evidence of past exposure to HBV (Hepatitis B Virus) (anti-HBc positive,
HBsAg negative; RIA, Abbott) also received a full course of vaccination.
Anti-HBs (RIA, Abbott) levels were measured at months 0, 1, 2, 6, and 7.
By month 7, 89 % of group I, but only 3 of 8 anti-HIV positive vaccinees
(group II) had seroconverted (p=.005; Chi square test). Increases of anti-HBs
levels from month 6 to month 7 averaged 230fold in group I (n=10) but only
by factor 8 in groups II (n=2) and III (n=10) (p=.002;; Wilcoxon, Mann and
Whitney rank sum test).
Total and T4 lymphocyte counts determined at least once during the course of
study were significantly higher in anti-HIV negative than in anti-HIV positive
vaccinees (mean + std. dev. ; total lymphocytes:/2926 ± 918 vs. 1562 ± 736,
p=.002; T4: 1048 ♦ 413 vs. 398 ! 206, p=.002; respectively).
These data show that this yeast-derived hepatitis B vaccine is immunogenic
in population at risk for acquiring HBV and HIV infection, but immune
responses as measured by anti-HBs production are impaired in parallel to the
decrease of T4 lymphocytes in the course of HIV infection.
THPI^d Human Monocyte Cytotoxicity for Candida Albicans Can Be Augmented
with Gamma Interferon and Muramyl Tripeptide.
Phillip D. SMITH, R.A. CALDERONE, L.M. WAHL and S.M. WAHL. NIDR, NIH,
Bethesda, MD 20892 and Dept. of Microbiology, Georgetown University,
Washington, DC 20007.
Candida albicans (CA) is an opportunistic fungus commonly found in the oral
cavity and esophagus of AIDS patients. Monocytes, which may exhibit impaired
functional activities in AIDS patients, contribute to host defense against CA.
To explore possible mechanisms for augmenting monocyte antifungal activity, we
developed a new microassay for measuring cytotoxicity of CA. Monocytes,
purified by countercurrent centrifugal elutriation, were cocultured for 4 hr
at varying effector to target (E:T) ratios with pulse-labeled (3H-leucine) CA
yeast cells (strain 4918). Increasing the E:T ratio correlated directly with
increased 3H release and Inhibition of CA colony formation. Inhibitors of
oxidative metabolism, myeloperoxidase, and phagocytosis caused a marked
reduction in monocyte cytotoxicity for CA, confirming in our assay that
killing of CA was dependent upon reactive oxygen ^Intermediates and
phagocytosis. In experiments designed to determine whether this cytotoxic
activity could be augmented, we found that recombinant gamma interferon or
muramyl tripeptide (delivered in liposomes) alone did not increase monocyte
cytotoxicity for CA but acted synergistlcally to augment cytotoxicity
several-fold.
Thus, the ability to enhance monocyte antifungal activity of CA may have
clinical relevance for Immunocompromised hosts, in particular AIDS patients
with CA and other fungal infections.
185
THURSDAY, JUNE 4
THP135 Tne Generation of Natural Killer and Lymphokine
Activated Killer Cells in HIV-infected Individuals.
JAMES REUBEN, A. RIOS, G. BREWTON, AND P.W.A. HANSELL. M.D.
Anderson Hospital and Tumor Institute, Houston, TX., U.S.A.
Individuals infected with HIV usually lack natural killer (NK)
cell activity; however, NK activity can be restored in vitro by
the addition of interleukin-2 (IL-2). The addition of IL-2 also
gives rise to another effector , the lymphokine-activited killer
(LAK) cell. We investigated the ability of IL-2 to restore NK as
well as to generate LAK activity in 15 patients with AIDS-related
symptom complex (ARC) or lymphadenopathy syndrome (LAS) and 8
controls. Freshly isolated peripheral blood lymphocytes (PBL)
were assayed for NK against the target, K562, and for LAK against
the NK-resistant, Daudi cell line. In addition, PBL were
incubated in vitro for 3 days with 50 units of recombinant IL-2
(rIL-2, Cetus Corporation), harvested and assayed for NK and LAK
activity.
The results show that freshly isolated PBL from patients lacked
NK when compared to control (4.8% vs 25.2%, respectively;
p<0.01). NK activity was augmented by rIL-2 in all patients and
controls; rIL-2 generated LAK in all cases but one patient. There
was a high degree of correlation (r=0.91) between the increment
in NK by rIL-2 and the generation of LAK. These data suggest that
the same cell may mediate NK and LAK following incubation with
rIL-2. Studies are in progress to explore the generation of NK
and LAK by HIV antigens as well as to investigate their
effectiveness in the lysis of HIV-infected targets.
THR138 Financial Analysis of AIDS Programs in the Americas
DONALD S. SHEPARD", Y. KOURI*, F. ZACARIAS**, C. CAMERON*, P. ROSE-
LLO' ,"L.G.M.RODRIGUES , et al,. "Harvard Institute For International Develop-
ment, Cambridge, MA, **PAHO, Washington, D.C., 'Health Department, San Juan, PR,
" Ministry of Health, Brazil
PAHO and WHO expect to receive approximately $200 million in fiscal year 1988
for AIDS control in developing countries. To be able to make and evaluate finan_
cial commitments of such funds there is need to develop a financial system with
national program and activities components. The national system compiles the le_
vel and uses of funds by year for all activities in the country, while activi-
ties monitoring systems compile these data for individual program activities,
and relates funding to outputs. For the national system a matrix reporting sys-
tem is proposed for each year with sources (international and domestic agencies)
and uses of funds (types of AIDS program activities such as case finding, con-
tact tracing, screening, treatment, education, and research). The activities
monitoring system relates expenditures to the country's reporting system on the
magnitude and trend of the AIDS problem in the country (cases diagnosed and num
ber of deaths) and to specific indicators (e.g. number of repeatedly positive
serological tests).
A preliminary application to San Juan, Puerto Rico and Sao Paolo, Brazil,
suggests that AIDS case management and treatment is being financed primarily
from general operating expenses of public hospitals, with the likelihood of re-
ducing funds for all other treatments.
This framework is proposed as a tool for donors and national and state go-
vernments to monitor uses of funds, target requests to needed areas, and cons-
tantly improve the productivity of their expenditures.
THP136 ^ study of some immunological parameters in relation to HIV anti-
genemia in patients infected by HIV
P.SCHELLEKENS**, M.ROOS*, J.EEFTINCK SCHATTENKERK** , J.LANGE**, F.MIEDEMA*" ;
AND F. DE WOLF**, *Central Lab. Netherl.Red Cross Blood Transf. Service, in-
corporating the Lab. of Exp. and Clin. Immunology of the Univ. of Amsterdam,
**Dept. of Internal Medicine of the Univ. of Amsterdam, Amsterdam, The
Netherlands
The relation between infection with HIV and various immunological parameters
was studied in the following groups of individuals; a) healthy controls;
b) homosexual individuals from the AIDS risk group without anti-HIV antibodies;
c) idem, but with anti-HIV antibodies; d) patients with lymphadenopathy syn-
drome; e) patients with ARC; f) patients with AIDS and opportunistic infec-
tions. Each group, consisting of 15-20 individuals was tested for: absolute
numbers of T4- and T8-positive cells; ratio T4/T8; and cellular immunity both
in vivo and in vitro. Healthy HIV-antibody positive individuals and patients
with LAS showed aready a decreased ratio T4/T8, mainly due to an increase in
the number of T8-positive cells. The ratio in ARC and LAS was even lower but
now due to low numbers of T4+ cells and with normal numbers of T8+ cells. The
lymphocyte proliferative response, low in the HIV-antibody positive group, was
normal in the LAS group but profoundly decreased in the ARC and AIDS group. In
the HIV-antibody positive group the severity of the impairment of the various
parameters of immunocompetence was not related to the presence of antigenemia.
Compared to healthy controls the antibody response after immunization with KLH
was depressed (although not absent) in all groups studied.
THP139 HIV Infected African Patients With a Negative HIV ELISA Serology?
ROBERT L. COLEBUNDERS*. H. FRANCIS*, M. DUMA*, T. QUINN**, G. VAN
DER GROEN***, P. PIOT***, et al., * Projet SIDA, Kinshasa, Zaire, ** NIH,
Bethesda *** Institute of Tropical Medicine, Antwerp, Belgium.
In hoth healthy carriers and AIDS patients commercially available ELISA
kits will not detect all Western blot(+) persons. Sera of all HIVC-)
COrganon Teknika) patients with persistent diarrhea (n=25), a history of
herpes zoster (n=15), a generalized pruritic papular eruption (n=9) or a
generalized aggressive Kaposi's sarcoma (n=l), observed at Mama Yemo
Hospital, Kinshasa, between June 1985 to October 1986, were tested by
Western blot. The sera of 10 (20%) of the 50 HIV ELISAC-) patients with
AIDS-like symptoms or signs had at least the protein band p 24 on Western
blot (Du Pont strips). In 2 (4%) of these 50 patients, Western blots showed
the presence of at least the p 24 and the gp 41 band. In one ELISA and
Western blot(-) patient with persistent diarrhea, esophageal candidiasis was
found endoscopically. In the 3 HIV ELISA(-) patients in whom cultures were
performed, HIV was isolated. The sera of two of these patients were Western
blot(-) and in the other, only a p 24 protein band was present. Antibody
tests using other ELISA methods, LAV II and HTLV IV serologies are pending.
Performance of Western blot tests should be considered when evaluating
suspected HIV(-) cases of AIDS. Furthermore patients may be HIV virus
carriers without the presence of HIV antibodies detectable by either ELISA
or Western blot.
THP1^7 Prevalence of HIV among the Infectable Drug Using Population in
South London and Factors Influencing its Spread.
G WEBB*, M BURGESS*, S SUTHERLAND*
•King's College Hospital, London,
J STRANG*, T J MCMANUS*
Public Health Laboratory Service
This study surveys the HIV antibody status of 250 infectable drug abusers in
South London and includes a more detailed analysis of 100 of those tested. It
evolved from a clinically perceived need to identify rapidly common risk
factors when HIV antibody testing to include in local health education cam-
paigns. The subjects are a mixed sample comprising those who are or were
involved with various agencies and those still on the street.
The overall study also looks at the general drug taking behaviour of the sub-
jects, with particular reference to their injecting and sharing habits,
together with other facts which could influence or facilitate the transmission
of the virus within the population.
The more detailed survey focuses on past and continuing drug abuse and its
associated behaviour, together with an analysis of changing sexual behaviour
and behavioural modification linked to the awareness of the virus and its
differing modes of transmission. This gives insight in the way the virus has
passed from particular at risk communities to the more general non-drug abus-
ing population.
The surveys are being conducted over an 18 month period. They demonstrate a
five-fold increase of HIV infection in this previously HIV-free population, over
the first 12 months of the study alone. Revised figures will be included in
the survey in time for the Conference.
THP140 Tne Effect of Pregnancy on Progression of HIV Related Disease.
■ III. ITU ELLIE E. SCHOENBAUM*. PA SELWYN*, AR FEING0LD*, K DAVENNY*,
V ROBERTSON*, M ROGERS**, et. al., *Montefiore Medical Center, *Albert Einstein
College of Medicine, Bronx, N.Y. and **CDC, Atlanta, GA. , U.S.A.
It has been suggested that pregnancy adversely affects the outcome of HIV in-
fection due to the physiologic immunosuppression that occurs late in pregnancy.
We are prospectively studying the effect of pregnancy on the natural history of
HIV infection in intravenous drug abusers attending a NYC methadone program.
Women of child bearing age without AIDS or oral thrush(OT) are serially tested
for HIV antibody(Ab) , T-cell analyses and viral culture. Physical examinations
and standardized interviews are performed. Pregnancy is identified early by
routine monthly urine testing. Seropositive (SP) women delivering livebirths or
carrying *24 weeks are compared to women who did not become pregnant or who
terminated pregnancy by 13 weeks gestation.
Of 276 women tested since July 1985, 96(38%) were SP. Of these, 34 have been
rescreened over a mean 12 mos. of follow-up. Among the rescreened, 15 (Group I) had
pregnancies carried 724 weeks and were followed a mean of 6 mos. post-partum
and 19 (Group II) either did not become pregnant (14) or had pregnancies ter-
minated by 13 weeks gestation (5). The two groups were stratified by the ab-
sence or presence of generalized lymphadenopathy (GL) initially and followed
for progression to GL, OT, or AIDS.
Group Baseline Status No. Subjects No. Progressed Mean Mos. F/U
without GL
with GL
without GL
with GL
6/12 GL only*
1/3 OT**
2/7 GL only*
2/12 OT**
15
12
*py.05 **p > .05
No subject developed AIDS, although 7/15(47%) in Group I vs. 4/19(21%) in
Group II advanced in their HIV status (OR=3.3, p*.07). These preliminary data
suggest that pregnancy was not associated with the occurrence of AIDS. Further
study may confirm the trend of greater HIV disease progression due to pregnancy .
186
THURSDAY, JUNE 4
THP141 Pancreatic Disturbances and AIDS : an Anatomopathological Study
,nn,HI FRANCOIS BRICAIRE. C. MARCHE, D. ZOUBI, B. REGNIER. AG. SAIMOT,
JM. DECAZES. Hopital Claude Bernard, Paris, France.
A systematic analysis from autopsy of 113 AIDS patients has enabled us to
confirm the existence of alterations of the pancreatic gland in about half of
them. The cases studied were 99 men and 14 women whose average age was 36.8
years (22-71). Among them were 82 homosoxuals, 25 Africans or Haitians, 3 drug
abusers, 1 transfused patient, 2 without risk factors. An average of 12.4 months
elapsed between the discovery of the disease and death. Sixty seven patients
had had isolated opportunistic infections, 7 a isolated Kaposi sarcoma of lym-
phoma, and 39 had had both. Macroscopically the pancreas was normal in 59
cases ; 54 patients showed alterations of the gland such as oedema and increase
of volume (40), fibrous aspect (5), cytosteatonecrosis lesions (8), kaposian
of lymphomatosis aspect (5). Histopathology revealed that in 16 cases the pan-
creas could not be interpreted because of necrosis, alterations were found in
49 cases, aspects was normal in the remaining 49 cases. The main alterations
were largely disseminated. The forms were cytosteatonecrosis (8) or subacute
pancreatic disorder with inflammatory lesions (oedema, polymorphic granuloma)
(33), fibrosis (14), metaplasia and dedifferentiation of the ducts (14) or vas-
cular lesions (haemorrhage, thrombosis) (8). Specific lesions were observed in
21 cases, though non could be found in 28 cases. Such lesions, disseminated
both in the exocrine and endocrine tissues and in the interstitial and ducti-
cal ones, were as follows : cytomegalic inclusion cells testifying to CMV in-
fection (10), cryptococcal (2), tuberculous lesions (1), kaposian sarcoma or
lymphoma (8). In 19 cases specific lesions demonstrated were correlated to the
clinical findings.
The pathological processes observed histologically can be regarded as partial-
ly responsible for the disorders of the digestive systam characteristic of AIDS.
THP144 Combination chemotherapy (low dose adriamycin, bleomycin, vincristine)
for advanced Epidemic Kaposi's Sarcoma (EKS) . PARKASH S. GILL, MARK
U. RARICK, MARK KRAILO, CARMEN LOUREIRO, MARGORIE BERNSTEIN-SINGER, ALEXANDRA
LEVINE et al, University of Southern California School Med, Los Angeles, Calif.
Thirty homosexual men with advanced EKS were treated with combination
chemotherapy consisting of adriamycin, 10 mg/m2 (n=14), or 20 mg/m2 (n=16),
plus vincristine, 1.4 mg/m2 and bleomycin, 10 mg/m2, given IV every two weeks.
At study entry, extensive cutaneous EKS involvement was present in 29, in
whom 19 had associated lymphoedema; mucous membrane involvement was present in
17, symptomatic gastrointestinal disease in 5, lung involvement in 12. Systemic
"B" symptoms were present in 17, and hx of past Pneumocystis carinii pneumonia
in 5. At study entry, mean hemoglobin (Hb) was 12.7 gm/dl (r=9-22) ; mean absol-
ute neutrophil count was 2886/dl (r=1073-6724) ; mean lymphocytes were 1329
(r=377-3190), mean T4=146dl (r=10-412); mean T4:T8 =0.2 (r=0.03-0.8) . Chemo-
therapy was begun at a median of 4 mos from initial dx (range=0-10 mos). Res-
ponse rate was 78. 6%, with complete response in 14%, partial response in 642.
An additional 18% had minimal response, while one patient had no response, and
two are too early to evaluate. Poor prognostic indicators for survival include
current or past hx of diarrhea (p=.03) and "B" symptoms (p=.02). Involvement
of any particular visceral organ had no impact on response rates or survival.
Toxicity included nadir mean Hb of 11.4 gm/dl, neutrophils of 1589/dl (324-
5530), opportunistic infections in 7 pts. Median survival was 8 mos. Because
of these early results in pts with extremely advanced disease, we have begun a
prospective, randomized trial of adriamycin alone (20 mg/m2) vs. ABV. Results
will be presented. We conclude: (1) Low dose adriamycin, plus vincristine and
bleomycin may induce remissions in 79% of pts with advanced EKS. (2) In spite
of good responses, survival may be short, often due to other complications of
AIDS.
THP142 T"e Humoral Immune Response in HTV-Associated Periodontitis. P.A. Murray.,
' W.G. Grieve, J.R. Winkler. Univ. of California, San Francisco, CA, USA.
We have recently observed an acute, painful and rapidly progressive periodontitis in HIV-
infected individuals, which we have termed ALDS-virus associated periodontitis (AVAP).
Little is known about the etiology and pathogenesis of this infection. The purpose of this
investigation was to provide insight into the oral microbioata associated with the lesion. Since
direct culturing of the associated flora is time consuming, expensive, and complicated, we
chose to evaluate the systemic immune response to potential pathogens of AVAP. For this
prupose we studied the immune response to the following potential periodontal pathogens:
Bacteroides gingivals (33277). Fusobacterium nucleatum fl0953). and Capnocvtophaga
sputigena (33123V An indirect ELISA assay was used to measure the level of antibody (Ab) in
HIV-seropositive homosexuals, HIV-seronegative homosexuals and HIV-seronegative
heterosexuals. Formalinized, whole bacteria were used as antigen in wells of polystyrene
microtiter plates. After blocking unbound antigen sites, serial dilutions of serum were
incubated, washed and blocked. The secondary Ab was Mouse Anti-Human IgG [Fc]
Fragment, and the tertiary Ab was alkaline phosphatase conjugated Goat Anti-Mouse IgG
F(ab')2. Substrate was added and measurements taken at OD405. A reciprocal dilution of
serum required to provide a reading of 0.4 at OD405 was calculated for each patient Means
with standard deviations were then calculated for each group tested, and a t-test was applied to
determine significance. Results for B. gingivalis indicated a significantly higher antibody titer
for HIV-positive homosexuals than for HIV-negative homosexuals (p<.05), and heterosexuals
(p<,001). For the same groups of people, results for F. nucleatum indicated a higher titer,
p<0.005 and p<.01 respectively. Interestingly, the results indicated no significant difference
between the same groups of individuals for C. sputigena. Results demonstrate that bacteria
normally associated with periodontitis in normal individuals are causing elevated systemic
antibody levels in HIV seropositive individuals. Thus, these bacteria may be overwhelming
the immunocompromised patient to cause AVAP. Supported by NIH Grant T35DEO7103.
THP145 Bacterial Infections In Human Im m unodeficiency Virus (HIV) Infected
Children.
KEITH KRASINSKI, W. BORKOWSKY, S. BONK, R. LAWRENCE, AND S. CHANDWANL
New York Oniversity-Bellevue Hospital Center, New York, NY
HIV infection in children is frequently complicated by bacterial infection, and preventive
im munoglobulin (TG) therapy has been suggested. In a 3.5 year period we have cared for
70 HIV infected children (only 3 of which were treated with IG); 44 of whom had at least
one bacterial culture. There were 1163 cultures performed in these 44 patients: mean =
26.5, median = 15, range 1-126 cultures per patient. There were 97 documented episodes
of bacterial infection in 26/44 (59%) of these patients (mean = 3.7, median = 2, range 1-
11). Otitis media, pneumonia, urinary tract infections and diarrhea were the predominant
syndromes identified. There were 31 bacteremias among 17 patients (mean = 1.8, median
= 2, range 1-5). Pneumococci were the most com mon blood isolates (11/31), and types
4,6,9,14 and 19 were recovered. One patient had 3 separate episodes due to the type 6
organism . Other organisms included: P. aeruginosa 2, E. cloacae 2, j^. pneumoniae 2, S.
aureus 2, S. viridans 2, enterococcus 2; and one each of Streptococcus group A and B, S.
epidermidis, P. maltophilia, E. ooli, A. calcoaceticus, S. enterididis, bacillus species, and
diptheroids. One patient had concurrent E. cloacae and enterococcal bacteremia.
Overall 26/70 (37%) of patients with recognized HIV infection have had bacterial
infection and 17/70 (24%) have had bacteremia, all of which were associated with
infection at other body sites. One of our 3 IG treated patients developed Klebsiella
sepsis. Bacterial infection could be implicated in the deaths of only 4 patients: 1 with
enterococcal and varicella pneumonia, 1 with E. cloacae, fungal and C MV pneumonia, 1
with Pseudomonas and PCP, and 1 with pneumonia due to Pseudomonasonly. Although
bacterial infections are a frequent cause of morbidity in HIV infected children, they are
usually treatable. IG therapy might have been expected to prevent the pneumococcal
infections, its' role in preventing other bacterial infections is less clear.
THR143 Crcsvl Violet: A Rapid and Sensitive Stain for Diagnosing Pneumocystis
carinii Pneumonia by Sputum Examination.
CARLOS M. MOAS. D.A. EVANS, J. STEIN-STREILEIN. P. GANJEI, A. E.
PITCHENIK, University of Miami School of Medicine, Miami, FL.
The detection of P. carinii cysts in the sputum of patients with the Acquired Immuno-
deficiency Syndrome (AIDS) has been useful in diagnosing P. carinii pneumonia noninvasive-
ly. Gomori Methcnaminc Silver (GMS) has the advantage of staining the characteristic cyst
(which is the most commonly recognized form). However, it is time consuming, technically
involved and may be relatively insensitive for detecting small numbers of cysts in sputum.
One hundred and ten expectorated sputum samples were collected consecutively from 90
patients with AIDS and unexplained pulmonary infiltrates. Each specimen was cytoccntri-
fuged onto two slides. One slide was stained with GMS and the other with Crcsyl Violet
(CV). All slides were read by two independent observers in a double blind fashion.
Of 110 specimens, 27 (25%) were positive for P. carinii cysts by CV, and 17 (16%) were
positive by GMS. In 6 of the 10 patients whose sputa were positive by CV, but negative by
GMS, P. carinii was confirmed (by histology in 5 patients and by a typical clinical picture
with response to specific therapy in 1 patient). In 4 of the 10 patients, 3 had no follow-
up and one had no clinical evidence of P. carinii pneumonia.
These results suggest that CV is more sensitive and as specific as GMS in detecting
P. carinii cysts in sputum. CV staining of sputum is technically simple and takes only 30
min. to perform, while GMS is technically more difficult and takes 3 hrs. to perform.
Since CV stains the easily recognized P. carinii cyst form (and not the much smaller
trophozoite), it requires less special expertise than other rapid staining techniques for
P. carinii (i.e. Giemsa stain). CV may be a superior stain for diagnosing P. carinii
pneumonia by sputum examination. In patients with AIDS it could be easily adapted for
general use to expedite diagnosis and treatment.
THR146 Neuropsychological Characterization of HIV Infection.
PIM BR0UWERS*,M.C. H0BAN**, K. SQUILLACE**, R.T.J0FFE**, D.R.
RUBIN0W**, *Georgetown University, **National Institute of Mental Health,
Washington, DC, USA.
Reports that the brain may be directly and selectively affected by HIV
infection has increased the importance of neuropsychological characterization
of AIDS dementia in patients without opportunistic infections of the brain.
We previously observed significant differences in the performance of a group
of 13 patients with AIDS but without CNS opportunistic infection compared with
10 age and education matched homosexual volunteers on neuropsychological tests
sensitive to alterations in attention and motivation. In addition differences
were found on tests measuring functions that are normally considered most
resistant to global brain insult such as the vocabulary subtest of the verbal
IQ. While no significant differences between the groups were found on tests
assessing memory, both groups performed poorly on tests of verbal memory,
scoring significantly below established norms. Similar findings have been
observed in an additional 12 AIDS patients compared with 8 seroposi tive-only
patients and 8 patients with chronic active hepatitis. These results suggest
a txo factorial component to the neuropsychological profile of AIDS patients,
one component associated with attention and motivation, another with knowledge
functions. The results additionally suggest that brain areas subserving
language related functions may be selectively affected by the HIV Infection,
with the degree of impairment perhaps reflecting the status of the Infection.
Comparison of AIDS patients with Huntington's and Alzheimer's patients will be
made to evaluate similarities and differences in their dementias.
187
THURSDAY, JUNE 4
THR147 Assessment of Potential Chemotherapeutic Agents Against Mycobacterium
avium Complex Infections in Beige Mice
PATTISAPU R.J. GANGADHARAM*. V.K. PERUMAL, N.R. PODAPATI, K. PARIKH,
M.D. ISEMAN, National Jewish Center for Immunology and Respiratory Medicine,
Denver, Colorado
Mycobacterium avium complex (MAC) organisms are major opportunistic pathogens
afflicting AIDS patients. Using the beige mouse model, we have investigated the
chemotherapeutic potential of 20 compounds which showed high hi vitro
antimycobacterial activity against numerous strains of MAC. The jn vivo
chemotherapeutic activity of each of these compounds was assessed in beige mice
challenged intravenously with a virulent MAC strain, in each of 2 or 3 experiments.
Comparison of the mortality and CFU counts of organisms from spleens and lungs at
various periods of challenge between the drug-treated and control groups, enabled us
to classify these 20 compounds into three groups: active, probably active and
inactive. Activity jn vivo was defined as a statistically significant reduction in the
mortality and CFU counts of the organisms recovered in the drug treated group as
compared with the controls; inactivity was defined as having no evidence of any
difference at any point between these two groups. Drugs in the probably active group
indicated some activity after prolonged chemotherapy, suggesting that perhaps with
higher doses, these drugs would show more significant activity. By this classification,
4 drugs, amikacin, CQQ (gangamicin), clofazimine and rifabutin were classified as
active; desoxyfructoserotonin and cyclopentyl rifampin as probably active; and the
remaining 14 as inactive. These studies were extended to combination chemotherapy
among these 4 active drugs. (Supported by NIH Contract No. 42544).
THR150 Disseminated Histoplasmosis in Patients with AIDS or at
high risk for AIDS.
WILLIAM C. CARRON, R.S. FISHBACH, R.D MEYER, Cedars-Sinai Medi-
cal Center, UCLA School of Medicine, Los Angeles, CA., U.S.A.
Pour patients with AIDS and 1 at high risk for AIDS living in
Los Angeles, CA. developed disseminated histoplamosis. None of
the 5 patients had recently been in a highly endemic area for H.
capsulatum and only 2 patients had ever been in such an area in
the distant past. Histoplasmosis was the initial AIDS defining
condition in 4 patients. All patients had constitutional symptoms
of weight loss, fatigue, night sweats and unusually high fevers.
Chest radiographs and liver functions tests were abnormal in all
patients. Cultures of bone marrow in 2 of the 3 patients tested,
blood cultures in 2 patients, and biopsies of brain, adrenal
gland, and lymph node yielded H. capsulatum in separate patients.
Four patients died; only 1 patient lived more than six months
despite antifungal therapy with amphotericin B.
A review of the literature showed 54 patients with AIDS and
histoplasmosis from all areas. Disseminated histoplasmosis was
the initial AIDS defining condition in 31 of 43 patients in whom
such data were given. Commonly involved sites were blood, bone
marrow, liver, spleen, lymph nodes and lungs. Serological tests
were of little value. Improvement during therapy with amphoter-
icin B occured but outcome was very poor; relapses during ketocon-
azole therapy were common.
Disseminated histoplasmosis is an important cause of morbid-
ity and mortality in patients with AIDS or at risk for AIDS,
including those in non-endemic areas.
THR148 Preliminary observations of the effect of cow's milk
globulin upon intestinal cryptosporidiosis in AIDS.
DONALD Pj. KOTLER. St. Luke's-Roosevelt Hospital Center, Columbia
University, New York, NY
Many of the intestinal (GI) complications of AIDS result from
immune deficiency in the gut. Impaired secretory immunity in AIDS
(Dig Dis Sci 32:129,1987) could affect the clearance of parasites
from the GI tract. In this report, the preliminary observations
of the effect of cow's milk immune globulin (Stolle Research and
Development Co) upon the course of chronic intestinal
cryptosporidiosis in AIDS is presented. The globulin was prepared
from the milk of cows that had been hyper immunized with human
enteric bacterial antigens (but not Cryptosporidium) using a
proprietary, slow release vaccine. The milk was pasteurized at
low temperature under reduced pressure to prevent protein
denaturation, then was passed through a membrane to retard
molecules greater than 100,000 MW and concentrated 30 fold.
Three patients were treated. All had diarrhea with Cryptosporidia
in stool samples and on intestinal biopsy. Patients were treated
with ascending doses of the globulin given orally qid, with
NaHCOo. All 3 responded favorably, with the reappearance of some
or all formed stools. Stool examinations reverted to negative in
2 patients tested and organisms disappeared from intestinal
biopsies in 1 of 2 tested. While preliminary, the results
strongly suggest that a large molecular weight fraction in cow's
milk effectively suppresses cryptosporidiosis in patients with
AIDS.
THP151 Multiple-Dose Pharmacokinetics of Eflornithine in AIDS Patients
Treated for Pneumocystis carlnli Pneumonia.
THOMAS M. GILMAN, Y.J. PAULSON, J.L. COHEN, P. N.R. HESELTINE, C.T. BOYLEN.
University of Southern California, Los Angeles, CA, U.S.A.
Eflornithine (alpha-dif luoromethylorni thine , DFMO) is an irreversible
inhibitor of ornithine decarboxylase. We have previously reported
ef lornithine's efficacy In treating refractory Pneumocystis carlnli pneumonia
and the occurrence of severe thrombocytopenia in patients with impaired renal
function. Others have reported that the elimination of eflornithine is highly
dependent on renal function and so information about multiple-dose
eflornithine pharmacokinetics In patients with AIDS is needed to modify dosage
and avoid toxicity.
The biodisposi tion of eflornithine was studied in detail in four AIDS
patients receiving compassionate therapy for refractory Pneumocystis carinil
pneumonia. Intravenous treatment with lOOmg/kg IVPB every 6 h was given for 3
to 5 days. Serum for eflornithine assay was then obtained before and 0.5, 1.5,
3, 6, and 12 hours after a dose, while the subsequent dose was withheld. A
high-pressure liquid chromatographic assay was used to measure eflornithine
concentrations. Pharmacokinetic parameters were determined using a one-
compartment model.
Creatinine clearance ranged from 75.7 to 101.2 ml/min. At steady-state,
peaks ranged from 196.6 to 317.9 mg/L and troughs ranged from 71.3 to 113.3
mg/L. Pharmacokinetic parameters (mean + SD) were: distribution volume (Vd)
32.8 + 4.4L, half-life (tl/2) 4.1 + 0.5 hours, elimination-rate constant (Kel)
0.17 + 0.02, and total body clearance (CLtb) 92.3 + 9.9 ml/min. A one-
compartment model is appropriate to evaluate the relationship between
eflornithine pharmacokinetics and renal function in AIDS patients.
THR149 NORFLOXACIN IN THE ERADICATION OF SALMONELLA INFECTIONS IN AIDS
PATIENTS. Dennis M.. Causey.. P.N.R. Heseltine, MA. Appleman and
J.M. Leedom. University of Southern California, Los Angeles, CA, USA.
Recurrent episodes of salmonel losis, including recurrent life-threatening
bacteremias, have been well-described in patients with AIDS. Because of the
need to avoid sensitization to trimethoprim/sulfamethoxazole (TMP/SFX) in AIDS
patients and the high frequency of ampicillin resistance of salmonella iso-
lates, alternative therapies must be sought. He report the treatment of three
AIDS patients, who had recurrent salmonellosis, with norfloxacin, a new oral
fluoroquinolone which has excellent in vivo activity against Salmonella sp.
Each patient had 2-3 prior distinct clincal episodes of salmonellosis which
had failed to be eradicated with standard courses of ampicillin, TMP/SFX,
ceftriaxone, or cefotaxime. Microbiologic relapse occurred in each patient
within 2-4 weeks. Each of the salmonella strains was susceptible to norfloxa-
cin. Patients were treated with norfloxacin 400 mg bid orally for 30 days.
Stool cultures were negative at one week in all three patients. No adverse
reactions to norfloxacin were noted during the treatment period. Patients #1
and #2 remained culture negative during a 4-6 week followup period and had no
clinical recurrences until their deaths from other AIDS-related infections or
neoplasms. Patient #3 had a clinical and microbiologic relapse of salmonella
1 week after norfloxacin was stopped but responded clinically to retreatment
with norfloxacin. Norfloxacin appears effective in the treatment of salmonel-
la infectiont in AIDS patients and may be more useful than standard agents in
eradicating the organism and preventing clinical and microbiologic relapse.
Oral administration and twice daily dosing are significant advantages. Fur-
ther studies will clarify its role in the management of salmonellosis in AIDS
patients.
TLip-JCO Histologic Patterns of Lymphadenopathies in AIDS: Correlations with
inr. IUC Progress 0f Disease. HARRY L. IOACHIM, MANIMALA ROY, WILLIAM CRONIN.
Department of Pathology, Lenox Hill Hospital, New York, N.Y.
Persistent generalized lymphadenopathy (PGL) is one of the manifestations of
infection with immune deficiency virus (HIV) which often precedes the severe
opportunistic infections and neoplasias of acquired immune deficiency syndrome
(AIDS). We examined microscopically biopsied lymph nodes of 60 patients,
identified characteristic histologic lesions and correlated them with the
presence of HIV antibodies, T4/T3 lymphocytes ratios and the progress of
disease. There were 55 men and 5 women, with a mean age of 37 years. A follow
up of 3 months to 8 years showed that 37 patients progressed to AIDS including
23 who died while 23 remained in the stage of PGL. The lymph nodes were
classified in 3 types according to predominant histologic patterns:
A. hyperplasia of lymphoid follicles with germinal centers showing cytolysis
and phagocytosis. B. effaced follicles, diffuse lymphoid and vascular hyper-
plasia. C. atrophic fibrosed follicles, lymphoid depletion and hypervascularity.
The predominant lymph node pattern in 1981-83 was type A while in 1984-86
type C was more frequent. More patients with types A and B remained stationary
PGL whereas more type C patients died of AIDS. Patients with type B and C
lesions more often developed Pneumocystis pneumonia, CMV infections and
lymphoma. Nine patients had repeated biopsies which in 3 cases showed persis-
tance of types A and B for up to 2 years and in 6 cases progression from
types A and B to C. Lymph node lesions type C consistently correlated with
short survival, types A and B with better prognosis.
188
THURSDAY, JUNE 4
THP153 ^ca^es f°r tne Neurological Examination and History in the AIDS
Dementia Complex
DONNA ORNITZ, HANNAH AMITAI, JOHN J. SIDTIS, RICHARD W. PRICE, Memorial
Sloan-Kettering Cancer Center, New York, NY.
The AIDS dementia complex (ADC) is a frequent complication of HIV infection
which usually develops after the systemic manifestations of HIV infection,
but at times will precede AIDS and apparently pursue an independent course.
In order to more clearly define the epidemiology, natural history and
response to therapy of the ADC, we have attempted to develop standardized
neurological history and examination scales to complement formal neuropsycho-
logical testing. These involve ADC-directed questions related to cognitive,
motor and behavioral dysfunction that are oriented toward functional status.
The neurological examination is also scaled to evaluate these same functions
by mental status, motor and coordination tests. A long form of this examina-
tion has been developed for detailed assessment of neurological natural
history and the response to antiviral therapy, while a short form has been
developed for larger-population epidemiological studies and for screening
examinations. We have begun to use these scales together with standardized
functional status scales and neuropsychological tests in HIV-infected indi-
viduals ranging from clinically asymptomatic to severe ADC. Preliminary
analyses suggest that these neurological history and examination scales cor-
relate with traditional functional status scales (e.g., Karnofsky, Kurtzke
and Blessed) as well as with formal neuropsychological evaluation (correla-
tions ranging from r = .4 to r = .75). These instruments, which will be
described in detail, have the advantage of being brief, ADC-specific scales.
THR156 0utc
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THP"|54 Prognosis and Natural History of Pneumocystis Carlnil
Pneumonia: Indicators for Early and Late Survival"
CONSTANCE A. RAISER, D.W. FEIGAL, G. LEOUNG, M. CLEMENT, C. WOFSY, University
of California, San Francisco General Hospital, San Francisco, CA.
Prognostic Indicators of 74 consecutive patients (pts) with first episode of
Pneumocystis carinll pneumonia (PCP) at San Francisco General Hospital (SFGH)
from March through August 1985 was reviewed, a time before AZT therapy became
available. All pts were in a high AIDS risk group, had no evidence of non-
AIDS immunosuppression, and were men with a mean age of 36 years (range 22-
59). 23Z of the group already had an AIDS diagnosis, usually Kaposi's
sarcoma, at presentation with PCP.
Kaplan-Meier survival analysis showed that 27% (+5%) died within the first
four weeks after first PCP episode. Pts with initial room air arterial blood
gas P02 < 60 torr had 4 week mortality of 50% versus 14% with P02 > 60
(p=.03). Type of Initial drug therapy (trimethoprim / sulfa-methoxazole 68%,
Dapsone 20%, Pentamidine 9%, other 3%) was not predictive of early or late
mortality. Median survival after first episode was 9.8 months. Probability
of a second episode of PCP was estimated at 18% at 6 months, 46% at 9 months,
and 65% at 18 months. The second episode mortality at four weeks was 37%
(+10%): overall median survival was 4.8 months.
To create a group comparable to populations eligible for clinical trials
after PCP, survival and progression was recalculated for pts living at least 4
weeks after initial episode. 6 month mortality was 18% (+6%) and 6 month
recurrence was 18% (+6%). When planning sample sizes for trials of post PCP
pts, the correct clinical subset must be used to estimate expected survival.
I (In 101 Immunotoxicological Properties of Isobutyl Nitrite
PATTISAPU R.J. GANGADHARAM*, V.K. PERUMAL, B.T. JAIRAM, K. PARIKH,
National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado
Acquired Immunodeficiency Syndrome (AIDS) is frequent among homosexual men
who use licit and illicit drugs recreationally. We have investigated the
immunotoxicological properties of one such illicit drug, isobutyl nitrite (IBN), in
street gargon "RUSH" in beige and C57B1/6 mice. Beige mice in general tolerated a
less period of exposure to IBN as compared to the C57B1/6 mice. Beige mice were
infected intravenously Mycobacterium avium complex (MAC) and exposed daily,
alternate day and twice weekly. The groups having daily inhalation showed high and
early mortality (90%) and high CFU counts in the spleen and lungs with progressive
decrease in alternate day and twice weekly groups. Oral and rectal routes of
challenge with MAC showed similar trends. Mortality with and without IBN exposure
were 90 and 40, 30 and 0 and 30 and 0, between IBN treated and controls
respectively, with TV, oral and rectal challenges. Statistically significant differences
in CFU counts of MAC were seen between D3N treated and control animals in all
series. Exposure to 0 to 1% of IBN showed a dose related toxicity on viability of
macrophages and lymphocytes from beige and C57B1/6 mice. At the optimal
concentration, it caused diminished phagocytic indices and greater intracellular
growth of the organisms in peritoneal and alveolar macrophages. Exposure of beige
and C57B1/6 mice for 2 to 4 weeks caused increased release of superoxide anion (C^)
and hydrogen peroxide (HjOj), decreased NK cell activity but no change in the
TH:TS cell ratios. Toxicity of IBN may operate either through diminution of NK cell
activity or through increased release of HnO,, which in turn, can form toxic
complexes with methemoglobin which is a consequence of D3N administration.
(Supported by Research Grant NO. AI-21897 from NIH).
THR155 AIDS Dementia Complex associated with Brain Reactive Antibodies
MAHENDRA KUMAR',L.RESNICK",J.BERGER"'and C.EISDORFER*
Departments of Psychiatry' and Neurology*", University of Miami, School of
Medicine, Miami, FL and Mount Sinai Medical Center", Miami Beach, FL.
The cause(s) of AIDS dementia complex are unknown. It has been suggested that
dementia may be a result of direct neurologic infection by HIV, or an indirect
effect, such as autoimmune phenomenon. Although HIV has been detected in the CNS,
the target cell/s appear to be macrophages and/or glial cells but not neuronal
tissue. Brain reactive antibodies (BRAs) are present in patients with dementing
diseases such as Alzheimer's disease and Cructzfcldt Jakob disease. We present
evidence that BRAs are associated with AIDS dementia. Elcctroblots prepared from
normal human hippocampal tissue were used to analyze BRA activity. Thirty sera
samples from HIV seropositive patients, 18 with and 12 without AIDS dementia
complex were screened for BRAs. The results reveal that 78% of patients (14/18)
with dementia, and 33% of patients (4/12) without dementia were positive for BRAs
(X2-4.22, p< 04). The brain reactive protein in hippocampal tissue has an apparent
MWt of 45 kDa. We had observed earlier that although 16-30% of normal subjects
also have BRAs, the activity Is rarely directed against the 45kDa protein. The
presence of antibodies in patients without AIDS dementia complex suggests that
BRAs may be an early marker of dementia. However, prospective studies need to be
performed to evaluate the role of BRAs in AIDS dementia complex.
TUDIKD Prospective Neurodevelopmental Outcome of Infants of HIV
Seropositive Mothers and Their Controls. JOAN HITTELMAN*,
A. WILLOUGHBV**, H. MENCEZ*, J. SILCOTT*, P. SHAH*, S. HOLMAN' ET AL.
*SUNY Health Science Center at Brooklyn, Brooklyn, N.Y., U.S.A. and
••National Institutes of Health, Bethesda, Maryland, U.S.A.
As part of a prospective neurodevelopmental follow-up, the development
of 18 HIV persistantly seropositive infants is compared to that of 28
seronegative controls. The sample is drawn from 2 patient populations:
infants whose mothers attend a special substance abuse pregnancy clinic
(13 pos ; 18 neg ) or a Haitian pregnancy clinic (5 pos: 10 neg) .
Thirty-five infants have been assessed at 1 month of age using the
Einstein Scale; 23 at 3 months and 13 at 6 months using the Bayley Scales,
by an examiner blind to the infants' status. Correcting for gestational
age, 6 seropositive infants and no controls were found to be
developmentally delayed (p<.05).
No differences were found between the groups at 1 month of age. At
3 months, mental development scores were lower in the positive group
<x=-101> than the controls (x=109; p<.05).
The 6 month sample is comprised of infants of substance abusing women
only. The seropositive infants had poorer language development (p<.025)
and a trend for poorer cognitive development <p<.075> than the controls.
Two additional infants, born to seropositive mothers, seroreverted
before 6 months of age. Their data is not included in the above analysis;
their development is within normal limits.
Infants exposed to HIV appear to show specific delays and/or lowered
developmental quotients by 3 months of age.
189
THURSDAY, JUNE 4
THR159 '-)oes Concomitant HIV Injection and Measles Iniection in African Children
Lead to Increased Morbidity and Mortality?
MICHAEL G.SENSION*. N. NZILA**, M. DUMA P.**, R. RYDER**, T.C. QUINN***
M. LINNAN****,et al., *lohns Hopkins Univ. Sen. Med., Baltimore, MD, **Project
SIDA, Kinshasa, Zaire, ***NIAID, NIH, Bethesda, MD, ****CDC, Atlanta, GA.
To determine if concomitant measles and HIV infection augment childhood morbidity
and mortality, we are studying 300 children less than 6 years old admitted with
clinical measles to Mama Yemo Hospital in Kinshasa, Zaire between Jan-April, 1987.
Measles cases are confirmed by IgM serology while HIV infection is established by
detection of HIV antibodies by repeat ELISA with Western blot confirmation. From
Jan. 8-29, 62 children have been enrolled (3<f males, mean age = 15.5 months; 28
females, mean age = 18.6 months) of whom 5 are HIV seropositive (8%). Of the 5
HIV seropositive children, 2 (40%) have died, and 3 (60%) have improved during
hospitalization. Among the 57 HIV seronegative measles cases, 7 (12%) have died
and 50 have improved. History of measles vaccination was low among both groups
with 1 HIV positive (20%) and 8 HIV negative (1*%) children having previously received
measles vaccine. HIV seropositive children were more likely than HIV seronegative
children to present with polyadenopathy (60% vs. 42%), a history of diarrhea (60%
vs. 30%), or 2 or more of the following symptoms: pneumonia, diarrhea, laryngitis
(80% in HIV seropositives vs. 37% in HIV seronegatives). HIV seropositive children
were also more likely to have had previous hospitalizations than HIV seronegative
patients (*0% vs. 12%). The 2 HIV seropositive children who died had a mean WBC
of 3,800/mm3 and a mean total lymphocyte count of 970/mm3 which contrasted
with counts of 10,600 and 3,800 respectively, in the 3 HIV seropositive children
discharged with clinical improvement. Our final results in 300 children will
demonstrate whether measles and HIV infection synergistically increase morbidity
and mortality in African children.
THR162 A COMPUTERISED NEUROPSYCHOLOGICAL BATTERY FOR THE ASSESSMENT OF
HIV INFECTED ADULTS WITH EMPHASIS ON DETECTION OF EARLY CENTRAL
NERVOUS SYSTEM INVOLVEMENT
Agnes Lodynski, Clemency A. Palmer and John Green.
Psychology Department, St. Mary's Hospital, London ENGLAND.
This paper presents a new and comprehensive psychomentric assessment battery
for the detection and categorisation of the so-called AIDS Dementia Complex.
The battery includes two sets of sensitive computerized tests which even ill
subjects find rewarding and interesting. The performance of standardised
controls, asymptomatic HIV-positive, PGL, ARC, and AIDS groups were compared
in two studies, the second of which is the first stage of a two year
longitudinal project.
Early results indicated impairment in those tasks which demand more complex
information processing and it is argued that early central nervous system
involvement - the achievement of which is especially vital clinically - is
most sensitively detected by using paradigms derived from experimental work
on Attention and Performance. The effectiveness of this approach is
illustrated using results from a computer administered dual-attention task.
THP160 Detection of HIV Core Proteins in Biopsied Lymph Nodes from Patients
with AIDS-Related Complex (ARC) and AIDS.
NORA C.J. SUN, P. SHAPSHAK, K. SUGITA, D. IMAGAWA and G. BEALL, Harbor-UCLA
Medical Center, Torrance, CA 90509
Detection and localization of HIV (HTLV- 1 I l/LAV/ARV) antigen in the biopsied
lymph nodes from patients with ARC and AIDS were studied by an avidin-biot in-
complex (ABC) method using monoclonal antibodies (MoAb) against HIV core pro-
teins p24, p 1 7 and envelope protein gp 120. It was found that all MoAb were
reactive with frozen lymph nodes of some patients, but the morphology of posi-
tive cells was poor. P2l) and pi 7 were also detectable on formalin-fixed, para-
ffin embedded sections, and a stronger reaction was observed when we used MoAb
p24. Eighteen biopsied lymph nodes from ARC patients and 2 from AIDS patients
(both had Kaposi's sarcoma (KS) in the nodes) were the subjects for study of
p24 on formalin-fixed, paraffin embedded sections. Of 13 lymph nodes which
displayed follicular hyperplasia, 8 of them showed strong reaction, 3 of them
weak reaction (or occasional cells being positive), and 2 of them were non-
reactive. Five lymph nodes which displayed follicular regression and paracor-
tical hyperplasia showed that four of them were reactive with p24 MoAb and one
was negative. Lymph node biopsies from 2 patients with KS showed occasional
cells being positive. Most positive cells were present in the follicular (ger-
minal) centers, however, the interd ig i tating reticulum cells, histiocytes and
endothelial cells were also positive in some instances. T-cell subsets (T4 and
T8 cells) study was done in the same specimen (but from frozen lymph nodes)
from seven patients. It was found that there was no correlation between the
absolute counts of T4 and T8 cells in biopsied lymph nodes and the presence or
absence of HIV core protein p2*t.
THP163 identification °* Pneumocystis carinii (PC) in sputum;
underestimation of cyst number with Giemsa.
WALTER BLUMENFELD, W.K. HADLEY, J.M. GRIFFISS, University of California
San Francisco, San Francisco, CA.
The diagnosis of PC pneumonia is currently based on morphologic recognition.
The Giemsa stain demonstrates both the trophozoite and cyst forms. Its use has
led to the impression that the trophozoite predominates in AIDS. This study
was undertaken to determine which of several stains results in easiest recog-
nition of PC, and to compare cyst number as seen by different stains. 16
dithiothreitol-liquefied PC-positive, frozen induced sputums were simultane -
ously thawed. Each sputum was vc-rtexed and equally distributed onto 5 slides.
The following 5 stains were done: (1) Giemsa; (2) toluidine blue; (3) silver
methenamine; (4) toluidine blue/Giemsa; and (5) silver methenamine/Giemsa.
Each slide was evaluated for number of recognizable units of PC at lOx, and
number of cysts at lOOx power. With stains (1),(4), and (5), the size of each
PC aggregate was measured with an ocular micrometer. There was no difference
among the stains in detectable number of units of PC organisms or amount of
PC aggregate area. However, median number of cysts/sq.mm of PC aggregate area
on Giemsa was 6.1 x 10 (range Q - 11.5 x 10 , interquartile interval 3.6-6.9
x 103), compared with 16.9 x 10 with toluidine blue/Giemsa {range 0 - 62.8
x 103, interquartile interval 7.7 - 45.4 x 10 ) and 6.7 x 103 with silver
methenamine/Giemsa (range 0 - 57.6xl03, interquartile interval 0.4 - 12.7 x
103) . Cyst recognition with silver methenamine was hindered by the large
amount of nonspecific silver staining. All the evaluated stains are equally
suitable for diagnostic screening purposes. When accurate enumeration of cysts
is important, the Giemsa stain, in comparison to toluidine blue, under-
estimates the number of cysts.
THP161 Cytomegalovirus encephalitis in AIDS : an anatomo-
clinical study of 4 cases. —
C. MARCHE*, ADRIEN G. SAIMOT* , S. BARTCZAK*, S. MATHERON* ,
R. VAZEUX**, C. VEDRENNE***. Hop . CI . Bernard* , Inst itut Pasteur**,
Hop. St Anne***, Paris, France.
Post-mortem examination of 90 brains from AIDS patients
provided evidence of CMV infection in 4(4.4%). Neurological
symptoms and signs appeared 2 to 4 months before death. Early
symptoms included behavioral changes, confusion, pyramidal
tract signs and ataxia. At late stage, dementia, seizures, then
coma developed. A mild CSF pleocytosis with protein^ 100 mg/dl
was noted in 2 pts.In 3 cases CT showed cortical and subcortical
atrophia. In one case CT was normal but MRI showed ventriculi-
tis. At autopsy, gross pathologic findinds were a ventricular
dilatation with peri-ventricular hemorrhage and a rough pattern
of ventricular wall. Major histologic features were : small
and large areas of polymorphic or histiolymphocytic cells
with necrosis and microglial nodules. Inclusions typical of
CMV were present in numerous cells within or without the inflam-
matory or necrosis foci. The major lesions were periventricular
and/or disseminated in the white and gray matter. Cerebellum
was also involved. In all cases immunoperoxidase staining
proved conclusive for CMV, negative for HSV-1 and 2. HIV-RNA
and proteins were not detected in 2 brains tested for. EM
confirmed the diagnosis in all cases. CMV encephalitis was
probably the results of overwhelming disseminated CMV infection
in 2 pts, but not in the 2 others. These data suggest that
subacute CMV encephalitis is not as rare as reported in AIDS.
THR164 Evaluation of Infectious and Immunologic Status by Bronchoalveolar Lavage In
Patients with AIDS and ARC.
T. MAY", CH. KOHLER *, N. DELORME °°, H. GERARD', G. FAURE **, P. CANTON0 Services
des Maladies Infectieuses" et des Insuffisants resplratoires" - Laboratoires
d'histologie-Embryologie* et d'lmmunologie". CHRU Nancy Brabois FRANCE.
Bronchoalveolar (BAL) was carried out in 17 AIDS and in 10 ARC with the aim of
establishing an etiologic diagnosis of lung opportunist iniection and to analyse the profile of
immunocompetent alveolar cells.
In patients presenting with clinically and/or radiologically proven pneumonia, BAL
revealed at least one opportunist pathogen in every case whereas It was negative In patients
presenting neither clinical nor radiological signs of pneumonia. The analysis of the cells
obtained by BAL showed that ARC group of patients presented hypercellularity
(mean±SEM) : 295x103 C ±108x103 (ARC); 164x103 C ±29x103 (AIDS) (S 200x103
C in controls). Alveolar lymphocytosis was Increased (AIDS : 26 ± 5.7%; ARC : 25.2 ± 7.4
%; £ 15 % in control) contrasting markedly with lymphopenia In the peripheral blood
(AIDS : 33 ±7.2 cells(CD4) et 150 ± 40.8 cells(CD8); ARC : 271.7 ± 64.8 cells(CD4) et
436.7 ± 85.9 cells(CD8). Most of the alveolar lymphocytes expressed CD8 phenotypes
whereas CD4 were severely depleted (CD4/CD8ratio : 0.16 (AIDS); 0,20 (ARC).
BAL appears to be an excellent mean for the diagnosis of lung Infection but it also
provides a new approach for studying the local immunity in the Immunocompromised
patients. We have undertaken a prospective study in asymptomatic HIV positive patient. The
preliminary results in this third group suggest also modifications of the local Immunity of
the lung.
190
THURSDAY, JUNE 4
TUD1CR Echocardiography detects cardiac involvement in Acquired Immunodefi-
ciency Syndrome( AIDS) : study in 70 patients.
SALVATORE CORALLO.M.R.MUTINELLI , M.MORONI* , A. LAZZARIN** ,G.BAR0LDI*» .Cardiac, In-
■fectious Dis.*and C.N.R. PathologJ'Dpts, University of Milan, "L.Sacco" Hospital
Milan, Italy.
Little is known about cardiac involvement in AIDS. On that purpose 70 consecu-
tive patients(pts) (mean age 29+7 sd years) 54(77%) males and 16(23%) females
with AIDS diagnosed clinically and serologically were examined by means of TM
and 2D Echocardiography with the aim of detecting cardiac abnormalities(C. A. ) .
64 Pts were affected by opportunistic infections ,6 by Kaposi's sarcoma. No
pt showed clear signs of heart failure. Results: 49/70(70%) pts showed C.A.
characterized by left ventricle(LV) walls thickness (mean 8.3+0.2 mm), systolic
thickening (mean 39+3 %) and particularly LV % shortening fraction (27+5) impor-
tant reduction. 28/70(40%) Pts showed pericardial effusion, moderate in 23,cos-
picuous in 5. Moreover in 20 pts LV antero-apical dyssynergy and in 1 pt LV in-
tracavitary mass was found. In 25 pts in clinically advanced state LV was globu
lar and poorly contracting. 18 Pts died and necropsy showed in 12 pts globular
shape of the heart, four chamber dilation, and LV walls thinning. Conclusion :des
pite little clinical suspicion C.A. in AIDS are frequent. An impairment in LV
contractility appears to be the first Echo finding; followed by LV walls thin-
ning,pericardial effusion and eventually by LV cavity dilation. This evolution
is suggestive of myocardial damage induced by Human Immunodeficiency Virus.
Echocardiography proved very helpful in detection.
THR168
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of the virus, 86 (52,5%) displa
n, 27 of them having less than 1
mophlliacs _
H.H.BRACKMAMN ,
Universitatsklinik.Bonn,
logie, Bonn.FRG
stitute for experimental
, 1.75 (61%) are infected
IV) . The percentage of
umber of factor units the
s outpatients
7,5%)uere symptom
yed symptoms of t
00 CD<.+ lymphocyt
at the
less
he HIu-
es/ul
982 through January 1987 15 hemophiliacs developp
g to the CDC-criteria. 10 of them had their prima
1986 or 1987. These were opportunistic infec
neurological manifestations in 5 patients, a
patients (2 patients had more than one Initi
ed AIDS
ry mani-
tions in
nd malig-
al mani-
in
nts ,
in 2
n).
HlU-lnf ected female sexual partners of hemophiliacs in-
ed so far are symptomless carriers at present.
do not show any different natural history of HlU-inf ectl-r
mophlliacs as compared to other risk groups.
THR166 Neopterin Levels Correlate with Walter Reed Staging
Classification of HIV infection.
DIETMAR FUCHS* , H , WACHTER* , H . JAEGER** , M . POPESCU** , et al . ^Insti-
tute for Medical Chemistry and Biochemistry .University of
Innsbruck, Austria, **AIDS Study Group, Schwabinger Krankenhaus
Munich, FRG.
In vitro and in vivo data contribute to the evidence that
neopterin represents a sensitive marker for activation of
macrophages by interferon-gamma. Due to the origin of interfe-
ron-gamma elevated neopterin is also characteristic for
activation of T-cells. Since in vitro the production of HIV
strictly depends on activation of T-cells there is a basis
that neopterin might reflect the clinical state of HIV
infection. To investigate the importance of neopterin in HIV
infection 50 male subjects in different stages of the Walter
Reed staging classification were repeatedly tested for
neopterin levels in urine and serum over a three months period.
Neopterin was measured in urine samples using HPLC standard
techniques and in serum by using RIA. Urinary neopterin levels
were related to creatinine. In addition, data from the medical
history, physical examinations, whole blood cell count, blood
chemistry, HIV serology, in vitro and in vivo tests for
cellular immunity were collected.
Neopterin levels in urine and in serum showed a significant
correlation with the Walter Reed staging classification.
Neopterin levels in urine and serum rose with progression
of the disease as measured by the WR classification.
THP169 Acute hepatitis during human immunodeficiency virus
(HIV) primary infection.
PIERRE-MARIE GIRARD, S. MATHERON, M.A. REY , C. MICHON, J. P.
COULAUD, A.G. SAIMOT et al., Hopital Claude Bernard, 75019
Paris, France.
Acute hepatitis was observed in 7 adult patients (pts) (6
males, 1 female, aged from 23 to 41 years) among 15 well
documented cases of HIV primary infection. All pts had fever
with other symptoms and signs (sore throat : 6, rash : 7,
meningitis : 3, adenopathies : 10, splenomegaly : 4, dysphagia :
3, diarrhea : 6). HIV primary infection was assessed by
sequential serum ELISA and Western Blot. In the 7 pts with
hepatitis, HIV was transmitted through sexual intercourse (5
pts) and direct parenteral exposure (2 pts). Transaminases raise
was observed from 8 to 53 days after the onset of fever (mean
ASAT peak : 8.8 x normal value). Mild cholestasis (Alkaline
phosphatase : 2 x normal value) occurred in one pt. One pt was
subicteric and non specific digestive symptoms were observed in
five. Needle liver biopsy showed mild cytolysis with portal
inflammation in 2. Liver function tests returned to normal
within 10 weeks. In all pts other hepatitis agents were ruled
out by negative virus isolation (CMV), negative antigenemia
(HBV) and lack of IgM antibodies and/or seroconversion (HAV,
CMV, EBV, HSV, Treponema, Toxoplasma) on repeated tests. Acute
hepatitis seems common during HIV primary infection (46%).
Although concomitant non A-non B virus infection cannot be
definitively excluded, hepatitis might be due to HIV itself.
THP167 Flexible Fiberoptic Bronchoscopy and Bronchoalveolar Lavage (B.A.L.)
for Diagnosis of Opportunistic Infections in Pediatric Patients
with A.I.D.S.
J.A. BIRRIEL JR , S. GOLDFINGER , G. SCOTT , M. MASTRUCCI , D. VERNON
B. H0LZMAN , et.al.. University of Miami, School of Medicine, Miami, Fl .
We report our experience with the technique of B.A.L. using flexible fiber-
optic bronchoscopy in 10 children with A.I.D.S. Indication for the procedure
was worsening in pulmonary status in patients previously diagnosed as having
A.I.D.S., or evidence of interstitial pneumonia in patients with a presumptive
diagnosis of opportunistic infection. From a total of 10 patients, four la-
vages were positive for Pneumocystis carinli; one was positive for Pneumocystis
carinii and Pseudomonas Aeruginosa (cultures from B.A.L. and blood were also
positive for Pseudomonas)., and five lavages were negative. Pathological exami-
nation by way of autopsy in three patients correlated 100% with bronchoscopy
findings, (positive for Pneumocystis carinii, positive for Pneumocystis carinli
and Pseudomonas , and negative for opportunistic infection.) The most common
complication was mild to moderate epistaxis in 3 patients; one patient required
endotracheal intubation due to C02 retention.
In the majority of cases, the pulmonary involvement in pediatric patients
with A.I.D.S. is due to opportunistic infections or lymphocytic interstitial
pneumonia. The flexible fiberoptic bronchoscopy with bronchoalveolar lavage
offers an effective and relatively safe method for the diagnosis of opportu-
nistic infections in this population of patients.
THP17A Anti-D and anti-c immunoglobulin for HIV related thrombocytopenic
purpura.
Eric OKSENHENDLER*. Y. BR0SSARD" , P. BIERLING*", P.M. GIRARD"", C.
SCHENMETZLER' and J. P. CLAUVEL*. •: H5pital Saint-Louis, ": Centre d'Hemobio-
logie Perinatale, ***: Hopital Henri Mondor, ••••: Hopital Claude Bernard,
PARIS, FRANCE.
The potential risks of steroids and splenectomy in HIV infected patients
led us to evaluate the efficiency and safety of anti-D and anti-c immunoglo-
bulin in 9 adults with HIV related thrombocytopenic purpura. They were 5 drug
addicts and 4 homosexual men ; all had HIV antibodies but none had full blown
AIDS. None were splenectomized. The platelet count was below 15 x 10 /l in
all patients. The 7 Rh+ patients received 1,000 pg (12 to 20 tig/Kg) of anti-D
IgG (Bio-Transfusion, France) intravenously on 2 consecutive days. The 2 Rh-
patients were given an equivalent dose of anti-c IgG (20 ml of plasma from a
single donor). A significant platelet rise above 50.10 /l was obtained in 6
patients. Repeated boosters were efficient in 4 cases.
Direct antiglobulin test became positive in all patients and serial quanti-
tative evaluations of IgG coating of red blood cells (RBC) were performed in
4. Only one patient experienced a significant hemoglobin drop. Eluates of
platelet bound IgG were not modified by the therapy.
To further elucidate the mechanism of the therapy, two patients received
consecutively both regimens : one Rh+ (O, D+, E-, c-, e+ ) patient who
responded to anti-D IgG received one course of the anti-c regimen without any
significant response. One Rh- (C-, D-, E-, c», e*) patient did not respond to
anti-D but had a good response with anti-c IgG.
These data suggest that anti-Rh IgG can be efficient and safe in patients
with HIV related thrombocytopenic purpura and that a specific interaction
between RBC and anti-Rh antibodies is required.
191
THURSDAY, JUNE 4
THP171 Mediastinoscopy and Mediastinal Lymphadenopathy in AIDS
Patients. JIHAD SLIM, G.E. TONNESSEN, G. PEREZ, E. PEREZ
E.S. JOHNSON. St. Michael's Medical Center, Newark, New Jersey.
A 16 month experience (8/8 5-12/86) involving mediastinoscopies
in AIDS patients led to the following review.
In this period 10 procedures were done and all yielded diagnoses.
Only one patient suffered any sequelae. All 10 patients had posi-
tive gallium scans prior to the procedure, 80% chest x-ray evidence
and 90% CT scan evidence of adenopathy.
All the patients had bone marrow biopsies with no diagnoses and
one non-diagnostic peripheral node biopsy.
All the results were infectious in origin with 20% showing cryp-
tococcus (both with + serum crypt antigen) and 80% showing acid-
fast bacilli. In the acid-fast group 3 of 8 were mycobacteria
scrof ulacium, 1 of 8 mycobacteria tuberculosis and 2 of 8 did not
grow.
Except for one post operative mortality all clinically improved
on therapy initially, but 6 of 9 eventually died with all still
showing evidence of their original disease at the time of death.
These results suggest that mediastinoscopy is a safe valuable
diagnostic procedure. Also infections are the primary causes of
mediastinal lymphadenopathy with malignancy conspiculously absent.
THP174 HIV Laboratory Reporting: The First 12 Months in Colorado
FREDERICK C. WOLF. C. RAEVSKY, N. SPENCER, S. VALWAY, Colorado
Department of Health, Denver, CO, U.S.A.
In November 1985, the Colorado State Board of Health required
laboratories which collect or process specimens in Colorado to report
individuals testing positive for HIV antigen or antibody to the Colorado
Department of Health (CDH) . The regulation was implemented in February
1986 by CDH staff visits to clinical laboratories. The controversial
regulation which is similar to those for syphilis and gonorrhea, has
been complied with.
In 1986, 391 reports were submitted (average 32.6 per month) by 38
laboratories (21 in Colorado and 17 in other states including
commercial, federal, military, hospital and plasma laboratories). The
number of reports by laboratory averaged 10.3 (range 1 to 75).
Compliance is illustrated by completion rates for patient data (name,
94.6*, date of birth 69.8*, sex 92.1*. race 51.9*, address 67.5*),
provider data (name 94.1*, address 70.9*), and laboratory data (name
98.0*. test date 79.0*, test type 93.1*, test result 91.6*).
Reported positives (391) were predominantly men (323, 82.6*), although
37 (9.5*) were women. Most (61.8*) reports were on persons between 20
and 34 years old. Patient name allows identification of repeat tests on
individuals (391 positives on 363 individuals). Although number of tests
processed is currently being collected, positive reports from these
laboratories accounted for approximately 24* of all newly identified HIV
Ab positive tests in Colorado during 1986. HIV laboratory reporting by
name is a practical and essential program to understand the full scope
of the HIV epidemic and trigger follow-up for prevention counseling.
THR172 ALTERNATIVE SITE COUNSELLING AND HIV SCREENING.
SM Burns, RP BRETTLE, C Bisset, J Davidson, S Davidson,
JMN Gray et al. City Screening Clinic, Edinburgh, Scotland.
Extensive infection with Human Immunodeficiency Virus (HIV)
amongst intravenous drug misusers (IDMs) ocurred in Edinburgh
between 1983 and 1985. With the introduction of routine HIV
screening of blood donations would current and ex IDM attend an
alternative counselling and screening clinic outwith the Blood
Transfusion Service and Sexually Transmitted Diseases service?
In one year from October 1985 - September 1986 441 individuals
attended the City Screening Clinic (CSC) for counselling. There
was a 35% default rate on the first appointment, a 21% post test
default rate and a test refusal rate of 7% which ranged from 2.5%
in IDMs, 3% in their sexual contacts, 7.5% in homosexuals, 9% in
heterosexual contacts to 20% in those with no identified risk
activity. Of those attending 43.5% were IDMs, 20% their sexual
contacts, 12% heterosexual contacts in general, 9% homosexuals/bi-
sexuals, 3% had been exposed to blood and 12.5% with no identified
high risk activities.
The overall HIV seropositivity rate was 26%, 52% in IDM, 10% in
homosexuals/bisexuals and 7% in sexual contacts of IDM. Despite
initial sceptism there is a place for an alternative counselling
and screening clinic on a site distinct from the Blood
Transfusion and Sexually Transmitted Diseases services directed
towards but not just for IDM.
THP175 "'^ Seropositivity in Newborns: A novel method for estimating
prevalence of infection in childbearing women.
GEORGE F. GRADY, V.P. Berardi, R. Hoff, M.L. Mitchell. Massachusetts
Department of Public Health, Boston, MA
As a prerequisite for designing programs to reduce perinatal transmission of
HIV, we determined the rate of seropositivity at birth among Massachusetts infants
of various demographic characteristics. Individual anonymity was assured by
removing identifiers from the PKU (filter paper-adsorbed) blood specimens that
were used for microassay of HIV antibody. Immunoblot was used to confirm an
IgG-speeific immunofluorescence assay that detected antibody primarily of mater-
nal origin. Births from Dec'86 through Jan'87 provided 4919 specimens in three
batches from groups of hospitals with the respective characteristics of "inner city",
mixed metropolitan, and suburban/rural, and which represent about 45% of state-
wide births.
Inner Mixed Suburban Not
City Metro and rural tested Totals
Annual births
Number tested
HIV Ab(+)
(Rate/1000)
5385
849
13
(15.3)
18,256
2,499
8
(3.2)
12,266
1,571
2
(1.3)
43,845
79,752
4,919
23
The concentration of seropositivity in inner city hospital births (15.3/1000) was
not unexpected but the widespread distribution of rates between 1/1000 and
3/1000, and the assumption that 1/1000 was the minimal rate among hospitals not
sampled, led us to a minimum estimate of 2.6/1000 as the state-wide average.
TUD17Q Lessons of History: How best can we buy time awaiting a vaccine
for HIV?
CHARLES F. CLARK, M.D., AUSTIN C. KUHN, MSW, SHAPE Hospital, Casteau, Belgium,
RAY MOEHRING, Boulder, CO, EDMUND C TRAMONT, M.D., Walter Reed Army Institute
of Research, Washington DC.
Recognizing that HIV is a sexually transmitted disease, we can gain some
insights into the probable dynamics of the HIV epidemic by looking at
syphilis information from the pre-antibiotic era.
In 1917, a survey using the Wasserman blood test in United States Army
personnel showed a 16.77% positive rate overall, a 16.08% rate in white
enlisted men, and a 36.0% rate in black enlisted men. Over the next 25
years, major efforts were made to reduce the prevalence of syphilis in the
United States. Educational programs were launched to teach the population
about human reproduction, the venereal diseases and how to avoid them.
Prostitution was suppressed, and the case finding technique with medical
treatment of positive contacts using Arsphenamine was developed. The
effectiveness of this multipronged attack is seen in the Wasserman Blood
Survey data of 2 million World War II recruits in 1941. The overall rate was
4.77%, with a white rate of 2.35% and a black rate of 27.2%. From this data
we would drawn several conclusions: (a) That multiple efforts, including a
modestly effective treatment, will reduce but not stop the spread of a
sexually transmitted disease, thereby buying time for the development of a
vaccine, (b) Minority groups require specialized programs with exceptional
allocation of resources, (c) Massive crash educational programs will alert
the general population to the danger of HIV, but a long term thoughtful
multifaceted program will be required to significantly slow- the spread of
HIV.
THP176 A Model for Assessing Statewide Needs for HIV Prevention and Risk
"" Reduction Education KAREN A. HECKERT, K.L. MACDONALD, R.N. DANILA,
M.T. 0STERH0LM. Minnesota Department of Health, Minneapolis, MN, U.S.A.
The Association of State and Territorial Health Officers and the Centers
for Disease Control have recommended the development of community education
and risk reduction efforts to prevent transmission of Human Immunodeficiency
Virus (HIV) in every state. The MN. Dept. of Health is implementing a
comprehensive statewide risk reduction and disease prevention plan to
identify, assess, and respond to professional, community, and client needs.
This plan applies L. Green's health education planning model, PRECEDE, for
determining appropriate educational strategies by collecting epidemiologic,
social, behavioral, and educational data. Ongoing AIDS surveillance, HIV
counseling and testing, and community programs serve to collect some of
these data. We have also developed eight survey tools designed to collect
information on knowledge, attitudes, risk behaviors, and availability of
community resources from health-care providers, public health professionals
and persons at high risk. These surveys include: 1,000 persons randomly
selected from the general population, 500 gay-identified men, 300 intravenous
drug users, 180 persons with hemophilia, 600 randomly selected family
practitioners and internists, all 75 infection control practitioners in
acute care facilities, 1,000 hospital nurses with potential exposure to
HIV and all 73 public health nursing directors at local health departments.
Implications for educational strategies for clinical providers, public health
professionals and at risk clients are drawn from survey results and may
have valuable application to other low prevalence states.
192
THURSDAY, JUNE 4
THP177 Evaluation of an AIDS Education Unit for High School Students.
LESLIE MILLER, University of Washington and A. Downer, Seattle-
King County Health Department, Seattle, Washington, U.S.A.
We conducted a survey to assess the effects of an AIDS curriculum on high
school students' knowledge and attitudes about AIDS. The survey contained
23 items and was administered to a population of 240 eleventh graders before
and after instruction.
When scores were compared for percentage correct responses on knowledge
items, scores following instruction were 16X higher. Significant changes
were observed on most questions; e.g. , students learned that kissing, giving
blood and food handling are not major risk for AIDS transmission. Prior to
instruction, 711 of students believed that sharing needles was a risky
behavior compared to 92X after the class.
Attitude questions were grouped and scored on the basis of restrictive and
fearful versus tolerant and compassionate beliefs about people with AIDS. A
15X increase in tolerance was observed following instruction, corresponding
to the 16X increase in knowledge about AIDS. When asked prior to
instruction where they learned about AIDS, only 30X of students mentioned
school. Schools become the major source of learning (721) after only one
hour of instruction.
In conclusion, apparently even one hour of AIDS instruction can positively
impact what young people know about AIDS. More importantly, knowledge
appears to influence attitudes. This may enable an adolescent to make
informed decisions about AIDS as a public health issue and to make safer
choices in risk-taking behavior.
THR180 Ana^ysis °f Variables Impacting on Safe Sexual Behavior Among
Homosexual Men in an Area of Low Incidence for AIDS
Leonard H . Calabrese* / Buck Harris** , Kirk Easley* , *Cleveland CI inic
Foundation, Cleveland/ OH, **Ohio Department of Health, Columbus, OH.
In an effort to assess the impact of risk reduction education targeted at
the male homosexual community in Northeastern Ohio, 303 men attending one of
two homosexual social outings were studied in the fall of 1986 by means of a
questionnaire describing their recent sexual practices as well as a number of
variables including basic demographics, sources of information of safe sex,
personal knowledge of their HIV serologic status, use of available medical
resources and others. Among the respondants only 28% (Group-I) were
practicing totally safe sex with 71% (Group-II) persisting in some activities
that have been clearly described as unsafe. Among Group-II the vast majority
admitted to some modification of their sexual behavior and 75% admitted to
feeling comfortable that they have taken adequate sexual precautions. In
addition, among those who had not been tested for HIV antibody (n=210) 95%
predicted that they would be seronegative. Univariant and multivariant
analysis comparing Group-I to the elicited variables revealed no association
between safe sexual behavior and any of the elicited variables including
knowledge of a friend with AIDS, personal knowledge of their serologic
status, or receiving advice on AIDS from a physician. We conclude that
educational efforts on safe sex education in our area have resulted in
clinically meaningful behavior modification in only a small segment of the
socially and sexually active homosexual community. Furthermore, additional
studies are urgently needed to define the barriers to change so that clear
and effective educational programs can be developed.
THP178 Ncedle cleaning knowledge among intravenous drug users in treatment and AIDS
prevention policy
JOL.SOTHERAN*. AS ABDUL-QUADER*, SR FRIEDMAN*, DC DES JARLAIS**,
M MARMOR***, S BARTELME***, et al., *Narcotic and Drug Research, Inc., **NY
State Division of Substance Abuse Services, ***New York University Medical Center,
N.Y., N.Y.
Proper sterilization of needles may be important in reducing HIV transmission among IV drug users.
In a 1986 survey, 164 patients in a large New .York City methadone maintenance program were asked
what they thought was the "best way to clean needles." While 43 subjects (26%) said only that one
should "always use new needles," 121 (73%) named at least one medically-accepted cleaning method.
Among the latter, alcohol (64%)-the traditional method among IV users-and boiling (43%) were named
most often; few (12%) knew about the recently promoted bleach method, and none knew about peroxide.
However, being able to name a method does not always mean that subjects know how to use it correctly.
Gender, education, and minority status had no relationship with knowledge of at least one
medically -recognized effective method (alcohol, boiling, bleach, peroxide). There were relationships with
subjects' drug use patterns. The most likely to show needle-cleaning knowledge were the
moderately -frequent injectors: those who, during the year preceding the interview, had continued to inject
but on a less-than-daily basis. Similarly, those who last injected more than a month but less than two
years before the interview were most likely to know how to sterilize needles. These moderately -frequent
and moderately-recent injectors participate in both street-drug and treatment worlds and, while still
injecting, may be particularly concerned with disease prevention.
Policy implications include: 1) the importance of needle-cleaning education efforts among frequent
injectors, who have both the highest infection risk and the least cleaning knowledge; 2) the untapped
educational outreach potential of the moderate injectors, who might be used as informal information
conduits from treatment programs to street users.
THP1A1 Needs Assessment and Development of Model Standards for AIDS
Primary Prevention in California
E. MICHAEL GORMAN*, D. FRANCIS**, D. KANOUSE*. B. DECKER***, *The RAND Corpora-
tion, **California Dept. of Health Services, ***California Health Policy
Research Foundation
Despite widespread discussion about AIDS prevention, no model standard or
masterplan for primary prevention exists. To remedy this situation, the
California Health Policy and Research Foundation and the Department of Health
Services have developed a set of model standards for prevention that are re-
sponsive to needs and resources at the community level. These are based on
recommendations of the 1986 Institute of Medicine Report and are informed by
relevant prevention literature and expertise of California's public health,
research and service provider communities. To establish a baseline of the
state's prevention needs, we undertook site visits in five counties representa-
tive of a diverse range of geographic and population characteristics.
Activities and information assessed included surveillance (case reporting for
AIDS and ARC), seroprevalence data on general and specific populations, screen-
ing activities, educational interventions, skill building programs, drug abuse
programs, special population activities, and program evaluations. In addition,
we ascertained size, political and socioeconomic characteristics and location
of at-risk populations and their accessibility for primary prevention interven-
tions. We identified gaps between the proposed model standards and ongoing pro-
grams and made recommendations to narrow the gap.
We believe that both the model standards and the process of assessing local
prevention needs are generalizeable to other state or regional prevention and
planning efforts.
THR179 Sexual Behavior Change among HIV Seropositive Individuals.
DAVID NYANJ0M*,w". GREAVES*, R.DELAPENHA*, S.BARNES*, F.BOYNES*, W.R.
FREDERICK*. *Howard University Cancer Center, Washington, DC.
Sexual behavior was assessed in 95 HIV seropositive subjects enrolled in a
prospective study of the natural history of AIDS to determine if there was sig-
nificant sexual behavior change as a result of supportive counselling and edu-
cation provided during the study. All 95 subjects (65 males, 30 females) were
seen by the same investigator during the 12 month evaluation period and receiv-
ed the same intense one-on-one counselling and education regarding safe sex
practices. The subjects were categorized into group (1) 46 homosexual men,
group (11) 36 intravenous drug abusers (IVDA) and group (111) 13 blood trans-
fusion recipients and heterosexual contacts. At entry and at each 3-monthly
visit subjects were asked whether they had adopted each of 3 modifications. Data
collected showed that 85% had fewer different sexual partners, 76% had adopted
safe sex practices and 73% began condom use during sexual activity. Since en-
rollment 23% had not adopted any consistent modifications in their behavior.
Overall sexual activity decreased significantly in all subgroups in terms of
number of partners, specific high risk activities and failure to use condoms.
The greatest change was seen in group 1 subjects and was more striking in males
than females in each of the other subgroups. The least change was among IVDA
prostitutes. Among 22 patients who failed to adopt any consistent modification,
7 developed STD's and 6 were involved in a pregnancy.
These findings suggest that ongoing counselling and education about AIDS
leads to changes in sexual behavior among HIV infected persons.
THP182 A ComParlson of Three Educational Models For Changing AIDS Risk-
Associated Behaviors
JOANNE MANTELL, ANTHONY DIVITTIS, LEE KOCHEMS, PETER MASTROIANNI, KEVIN MAHONY,
CHARLES MCKINNEY
A community-based risk reduction program was conducted to test the relative
effectiveness of three educational strategies in changing AIDS-related knowledge,
attitudes, behavioral intentions and behaviors among a sample of 515 gay and
bisexual men.
Men were randomly assigned to a cognitive-behavioral (CB), cognitive-affective
(CA) or cognitive only (C) condition. The CB and CA curricula were six-
session groups In which a didactic presentation about AIDS, its transmission
and modes of protection were given, followed by a group process. The CB group
process used skill-building behavioral techniques. The CA process focused on
participants' emotional responses to the information. The C group received
weekly mailings matched to the content of the other two strategies.
All groups completed a baseline screening Instrument, a pre-test, and a post-
test, at program completion and four- months later. The battery included self-
report measures of knowledge and attitudes about^AIDS, perceived susceptibility,
self-efficacy, self-esteem, personal control, adequacy of supports, and risk-
associated intentions and behaviors.
Preliminary analysis of the screening Instrument indicated that of those
participants who engage in anal sex, 363 rarely or never use a condom whether
the active or passive partner (n=281; n=231, respectively). Of the partici-
pants who engage In either active or passive oral sex, 80Z indicated that they
rarely or never use a condom. Data regarding the relative effectiveness of
each program based on pre-test and post-test 1 data are being analyzed, and
will be presented.
193
THURSDAY, JUNE 4
THR183 Statewide Free Condom Distribution Program
THERESE MCCLUSKEY, G. WUNDERLICH, A. WILEY, Maryland State Depart-
ment of Health and Mental Hygiene, Baltimore, MD.
Proper use of condoms are an effective method to prevent AIDS and other STD
infections.
In an effort to make condoms available, the concept of "Three-For-Free" was
developed by the Maryland State Department of Health and Mental Hygiene. The
purpose of "Three-For-Free" is to decrease the number of barriers to condom
use by making free condoms and instructions available for anonymous pick-up
at as many sites as possible in Maryland. At most sites, bags of condoms and
instructions are placed on tabletops in hallways, waiting rooms, bathrooms or
clinic examination rooms. As of December 1986, "Three-For-Free" sites have
been established in thirteen county health departments, five social service
agencies, three Maryland universities, and eight clinics in Baltimore City.
In less than one year, approximately 75,000 condoms with instructional pam-
phlets have been distributed through this program.
The State of Maryland also supplies free condoms to Baltimore City STD clin-
ics. In order to increase the availability of condoms to risk groups in Mary-
land, the State Health Department supplies condoms at cost to a non-profit
community agency for distribution to high risk groups.
An illustrated, wallet-sized pamphlet has been developed to be distributed
along with the condoms.
THR186 Voluntary Screening For HIV Infection In Patients Attending
A Sexually Transmitted Diseases Clinic
CARL J. BETTINGER*, H.F. HULL*, N.M. KELLER*, D.J. DUNNUM**, C. SCHAAB***,
and G.J. MERTZ***. *Health and Environment Department, Albuquerque and
Santa Fe, NM; **NM AIDS Services, Albuquerque, NM; ***UNH School of
Medicine, Albuquerque, NM
To determine the prevalence of HIV infection in persons attending a
Sexually Transmitted Diseases (STD) clinic and in order to offer
counselling and voluntary partner referral, we instituted a program
offering voluntary, anonymous serologic testing of all persons attending
the STD clinic. We continued serologic testing by request at the STD
clinic and at New Mexico AIDS Services (NMAS). Serum was screened by EIA,
and sera positive by EIA were confirmed by indirect flourescent antibody
testing. 693 of 1221 patients (52% of 155 gay males, 57% of 662
heterosexual males, and 58% of 404 females) seen from October 1 to
December 31, 1986 accepted the test, and 12 (1.7%) were positive. All 12
were gay males. In contrast, 16 (9.8%) of 163 screened by request at the
STD clinic, and 12 (11.7%) of 102 screened at NMAS were seropositive. Of
265 screened by request, 21 were screened for symptoms and 14 because of
exposure to a seropositive partner. Twelve (86%) of these 14 were
seronegative. We conclude that voluntary, anonymous HIV screening is
accepted by both heterosexual and homosexual patients attending a STD
clinic. Knowledge that a partner was seropositive led to screening and
counselling in 5.2% of persons requesting screening, and 86% of these were
seronegative at the time of counselling. Voluntary screening of persons
attending STD clinics and voluntary partner referral should be considered
in areas of low seroprevalence for HIV antibody.
THR184 street Outreach AIDS Prevention Program for IV Drug Users.
JACK STEIN. B. M. Branson, C. Hurd. Health Education Resource
Organization, Baltimore, MD, USA.
Estimates indicate only 10% of IV Drug users are in treatment at any one
time. In order to accomplish effective AIDS prevention among the 90% not in
treatment, a program was designed to assimilate peer AIDS education outreach
workers into known drug use communities in Baltimore City. Reformed IVDU's
who had successfully undergone treatment were recruited and trained about
AIDS, with specific emphasis on viral transmission, prevention guidelines, and
communication skills. The workers were well-received, and pre- and post-
intervention evaluations demonstrated a significantly increased awareness
among targeted IVDU's not in treatment programs.
Success of the program depended on careful selection of outreach workers.
Successful candidates were identifed by scores on a rating scale incorporating
factors such as drug abusing history, length of time in treatment, treatment
progress, reading and educational level, interpersonal skills and motivation
level. Team building and organizational support were identified as significant
components in outreach workers' abilities to cope with job-related stress,
including return to drug use.
THP187 Teaching AIDS: A Resource for High School AIDS Prevention Programs
MARCIA QUACKENBUSH*, P. Sargent**, *UCSF AIDS Health Project, San Francisco,
CA, **San Francisco General Hospital Department of Psychiatry, San Francisco,
CA.
The need for resources for high school AIDS prevention programs has been
noted by many policy experts. The first professionally published, nationally
distributed curriculum for high school students represents an important
contribution in this area. The curriculum includes rationales for teaching
AIDS to high school students, basic information about AIDS, suggestions for
and concerns of teachers, and seven teaching plans. The plans are appropriate
for a variety of classes, including family life, science, history, social
studies, civics or psychology.
THP185 Motivations and Consequences of AIDS Antibody Testing Among
■ill. uu Heterosexuals. SUSAN KEGELES, JOSEPH CATANIA, AND THOMAS J. COATES,
University of California, San Francisco, School of Medicine.
This study was designed to determine demographic characteristics of hetero-
sexuals seeking antibody testing, to assess why heterosexuals seek antibody
testing, to obtain data on measures of susceptibility and anxiety specific to
AIDS, and to determine consequences of antibody testing. Data on 232
respondents were collected at two antibody testing centers in Alameda County,
California; 40.5% (n=124) were heterosexuals. Respondents were administered
questionnaires when they arrived at the testing sites, and were followed
at 1 and 6 months post-testing. Approximately 65% of heterosexuals had sought
antibody testing because of concerns that they may have contracted HIV from
sexual contacts; approximately 20% had sought testing because of concerns
they were IV drug users, with the remainder being concerned because of trans-
fusions (10%) for miscellaneous reasons (5%). Approximately 26% of the males
and 32% of the females were continuing to engage in high risk sexual activities
in the month prior to obtaining antibody testing. Perception of increased
susceptibility for AIDS were associated with greater anxiety over the
possibility of developing AIDS. However, male heterosexuals (even when seeking
testing) perceived themselves as less susceptible to contracting HIV than male
homosexuals. Antibody postive status was associated with reductions in high
risk behavior than antibody negative status.
THP188 The Centers f°r Disease Control (CDC) Computerized Bibliography for
Information on the Acquired Immunodeficiency Syndrome (AIDS)
DEBORAH M. COLLIER, D.P. DROTMAN, T.A. LEONARD, J.W. CURRAN. Centers for
Disease Control, Atlanta, Georgia, U.S.A.
There has been an explosive increase in the number of requests for AIDS in-
formation received by CDC. In the last 2 months of 1986, the Technical Infor-
mation Activity office of the AIDS Program, Center for Infectious Diseases at
CDC filled 670 requests for journal reprints, responded to 362 letters, and
answered 17 telephone calls per day (average) . Many more such inquiries are
received by other CDC offices. Inquiries come from State and local health
agencies, infection control practitioners, clinicians, counselors, Federal and
State legislators, a multitude of grass-roots AIDS organizations, and many oth-
ers seeking to educate themselves or care for others. Quick access to relevant
information is necessary to assist these people in accomplishing their work.
One source used to assess what CDC personnel have written on AIDS is the
computerized bibliographic retrieval system. One of the databases maintained
on this system includes published articles written by CDC staff members on
prevention, public health policy, epidemiology, surveillance, and laboratory
research. The database also includes 94 AIDS-related articles published in the
Morbidity and Mortality Weekly Report. The bibliography can be requested
through the Information Resources Management Office, or it can be accessed
through any terminal linked to the main CDC computer. Searches can be
requested by various parameters (e.g. subject, author, time period, journal).
New software for this database will provide easier access and wider
application. The new system will be one of the most efficient mechanisms for
public health workers, clinicians, and others to document CDC AIDS-related
information and respond to important demands.
194
THURSDAY, JUNE 4
THP189 HIV Antibody Testing In British Columbia: An 18-month Report
MICHAEL L. REKART, Division of STD Control, British Columbia
Ministry of Health, Vancouver, B.C., Canada
HIV antibody testing has been available in British Columbia since October 7,
1985. An ELISA test is used initially with IFA and Western Blot confirmation.
Testing is available through any registered physician and through a government
testing, evaluation and counselling clinic in Vancouver. The laboratory requi-
sition notes age, sex, date, risk group, physician and geographic location.
Results of over 10,000 tests have shown the following prevalences: gay/bisexual
males 25%, intravenous drug users 3%, heterosexual contacts 1%, hemophiliacs
28%, blood transfusion recipients 1%, and prostitutes 2%. The overall reac-
tivity rate was 10%. Samples submitted per month were stable at 400-500 until
1987 when the number began to rise dramatically. Accompanying the rise in
samples submitted the monthly reactivity rate declined from 12-15% to less than
3%. Private physicians submit approximately 60% of all samples followed by
hospitals (16%) and the government clinic (15%). Samples from the government
clinic have a significantly lower reactivity rate than those from elsewhere,
perhaps reflecting a reluctance for those at greatest risk to use the
government facility.
This testing system has proven acceptable to the medical community, to high
risk groups and to the general public. The results have been useful to public
health officials.
THP192 Random-digit Telephone Survey for Knowledge and Attitude about AIDS
RICHARD L. VOGT, D. KUTZKO, S. KAPPEL, M. BRDZICEVTC, Vermont
Department of Health, Burlington, Vermont.
Trained interviewers, using a random-digit dialing system, called 3,650
Vermont phone numbers state-wide soliciting both knowledge and attitudes about
AIDS and HIV transmission. Interviews were completed on 602 Vermont residents
aged 18 and older. Responses were analyzed by demographic variables, including
age, sex and education. Thirty-one questions on the questionnaire which had
clear answers were chosen to test the knowledge of those surveyed.
Persons with greater education, those who were younger and the male gender
tended to answer more questions correctly. Questions answered more correctly
by all respondents included those concerned with risks associated with sharing
needles (96% correct) , male homosexual sex (96% correct) and heterosexual sex
(94% correct) . Ninety-five per cent of the respondents correctly stated that
persons can be infected with the AIDS virus without their knowledge.
Questions that tended to be answered incorrectly included those concerning
the lack of risk associated with female homosexual sex (10% correct) and
potential risk of virus transmission through breast milk (26% correct) . Only
75% of respondents stated that you could not catch AIDS from donating blood.
Those surveyed had inconsistent responses on the lack of risk of casual
transmission. Ninety-five per cent stated one could not catch AIDS by shaking
hands; but only 64% stated that AIDS could not be transmitted through sharing a
drinking glass or an eating utensil. Whereas 78% of respondents felt that it
was all right for children with the AIDS virus to attend school, only 60%
would not be worried about their child catching AIDS from a classmate.
Those surveyed seemed to be knowledgeable about the major risks for infec-
tion but less knowledgeable about the lack of risk of casual transmission.
TUpiOfl Strategies for Intervention in Minority Communities
inr. I3U [^lph j. DICLEHENTE, PhD and CHERRIE B. BOYER, PhD
University of California, School of Medicine , San Francisco, CA
The incidence of STDs among adolescents suggest that the future
rate of HIV infection may far exceed its present rate. Data on
Black adolescents strongly suggest that they may be at increased
risk of HIV infection. A survey of misconceptions about AIDS
indicates that Black and Hispanic adolescents were twice as
likely than White adolescents to believe that AIDS could be
contracted through casual contact, i.e., touching or being near
someone with AIDS (p<.01). Black and Hispanic adolescents were
also more likely to believe that "all gay men have AIDS" (p<.01)
and that "all gay women have AIDS" (p<.001). These findings
suggest that adolescents generalize from gay men to gay women
even though there is no evidence to suggest that this group is at
risk of HIV infection. These misconceptions may increase
adolescents, particularly Black and Hispanic adolescents' risk of
HIV infection by diverting attention from risk behaviors. To
dispel these misconceptions requires communicating factual
information about AIDS and sensitivity to the cultural and
emotional issues which the AIDS epidemic engenders. This
requires a systematic public health education effort including
school-based AIDS curricula as well as the support and
participation of the community-at-large . One strategy may be to
train indigenous community members/groups to serve as educational
resources, as they may be sensitive to potential barriers that
could inhibit receptivity to AIDS information and behavior
change. Interventions in minority communities will be discussed.
THP193 Anonymous Testing in Public Places: A Social Psychological
Examination of the Destigmitization of HIV Antibody Testing
RONN D. RUCKER*, D. TRIPP*, C. BROWN*, R. BOYER**, L. LANSKY**, P. OGG**,
*The Cincinnati Health Department, Cincinnati, Ohio, "Psychology Department,
The University of Cincinnati, Cincinnati, Ohio
A team of social psychologists and public health AIDS program staff designed
and implemented the first freely accessible and anonymous testing offered to
the general public apart from the alternate test sites. During a two day
health fair conducted in the busy lobby of the Federal Building in Cincinnati
and at the work site of an Environmental Protection Agency, 225 individuals
completed questionnaires examining attitudes about AIDS and 84 individuals
requested HIV testing. Destigmitization of the test was achieved by
positioning it between diabetes and blood pressure screening.
This presentation considers issues related to the social psychology of AIDS
antibody testing and the factors that need to be considered in the
destigmitization of the test.
AIDS hysteria is described as a form of collective behavior in which the
public finds itself in an ill defined normative setting. Routine, anonymous,
and wellness-oriented HTV screening is presented as a means of resolving
ambiguity and decreasing AIDS hysteria.
THR191 ^ne imPact °f information on AIDS: The blood donor perspective
A.P.M. LOS*, G. ROLSMA*, L. ACHTERHOF**, T J . TIJMSTRA*, T.B.P.M.
SUURMEYER*, C.TH. SMIT SIBINGA**, *Div. of Medical Sociology, University of Gro-
ningen, ** R.C. Blood Bank Groningen-Drenthe , Groningen, NL
Since 1983 all donors receive information on AIDS and risk factors by circu-
lar letter, and since May 1985 on anti-HIV testing. A study was set up to in-
vestigate: 1) Adequacy of information, 2) How donors associate with the infor-
mation and 3) Impact of information on motivation.
Methods : Analysis of donor population In period '83-'87, and a postal questi-
onnaire sent to a random sample (500) of the donor population (55,000).
Results: 133 persons (115m/18f) terminated blood donation indicating a risk
factor. Total donor population Increased 7%, without any change in demographic
composition. The increase did not differ from previous years. From the 133
'risk factor' donors, 18 (13.7%) enrolled as a first time donor. These 18 re-
present only 0.12% of all first time donors registered since April '83. Of over
97,000 donations tested since May '85 only 4 (0.004%) were confirmed positive
(WB +IF) . The results of the questionnaire showed positive attitude, good moti-
vation of the donor population and great concern with information on AIDS.
However, results show striking discrepancies between aspects of attitude, and
cognitive aspects.
Conclusion: Combining test results and results of the self-deferral programme
it seems that the given information was well received by those who recognise a
link with risk factors. In contrast, the results of the postal survey indicate
that to the majority of our donor population the right emphasis and meaning are
not adequately conveyed by the given information.
THP194 The Level °f knowledge and Attitudes Regarding AIDS and HIV
Infection in the Nashville, Tennessee Metropolitan Area
ANGELO GENE COPELLO, M.S. CURVIN, J.S. DYE, R.M. ZANER* , J. PERKINS**,
"Vanderbilt University School of Medicine, Nashville, TN, **Meharry Medical
College, Nashville, TN.
A survey was conducted of the adult Nashville, Tennessee Metropolitan
population during September, 1986 to establish the level of knowledge and
types of attitudes concerning AIDS and HIV infection. The instrument was
developed on the basis of previous studies; it included 6 demographic
questions, 22 knowledge-base questions, and 4 attitudinal questions.
Subjects were randomly chosen from the area phonebook and surveyed by
trained interviewers.
Four-hundred and five subjects participated. Comparison of demographics
with census reports indicated the sample to be representative; in particular
level of education and racial figures were highly representative.
Three results were considered significant both statistically and for
program development in AIDS education and prevention. First, demographic
variables statistically associated with the highest level of knowledge about
AIDS were general level of education and age. The more educated the
subject, the more he or she knew about AIDS; younger subjects knew more
about AIDS than older subjects. Second, the difference in level of know-
ledge about AIDS between blacks and whites was so slight statistically that
it posed no practical implications. And third, a strong statistical
association existed between higher levels of knowledge about AIDS and a
resistance to sanction employment and housing discrimination against persons
infected with HIV. This result supports the importance of general AIDS
education programs.
AIDS education and prevention programs in metropolitan areas with lower
caseloads can be assisted in their development by studies of existing local
attitudes and levels of knowledge concerning AIDS.
195
THURSDAY, JUNE 4
THR195 AIDS and Biomedical Research: A Comparative Analysis
E. I. CHATZIANDREOU, M.D., MPH, JOHN GRAHAM, Ph.D., Harvard School of Public
Health, Boston, MA.
The rapidly expanding AIDS research budget may be exacerbating political
pressures to reduce or slow the rate of growth in biomedical research funding
aimed at other health impairments. In this paper, we present a framework and
method for comparing the size of the AIDS research budget to the size of
research budget for Cancer, Coronary Heart Disease (CHD), and Accidents. The
framework utilizes information about several measures of the burden of health
impairments on society; deaths, early deaths, forgone life years, and medical
care costs. The calculations in the paper relate Fiscal Year 1986 budgetary
expenditures to projection of disease burden in 1991.
We show that these four health impairments are not given equal investment
priorities by the Federal Government. Accidents receive relatively little
priority; Cancer and AIDS are roughly comparable. The priority assigned to
CHD is sensitive to the index of disease burden selected by the analyst. The
paper relates these findings to the National Research Council's recent recom-
mendation of one billion dollars AIDS research budget for 1990. The authors of
the paper urge policy makers and scientific institutions to make explicit
decisions about the marginal productivity of research investments - against
health impairments - that claim limited resources.
THP1Q8 Beliefs and Behaviors Regarding AIDS: A Survey of Street
""• aw Intravenous Drug Users. PAULA H. KLEINMAN.' S.R FRIEDMAN,* C. E
MAUGE,* D S. GOLDSMITH
D. C. DES JARLAIS," & W. HOPKINS" 'Narcotic & Drug Research
Inc., N.Y..N.Y., USA "New York State Division of Substance Abuse
Services, N.Y..N.Y. USA
Effective work in helping addicts to engage in risk reduction behaviors will be
enhanced by understanding what addicts currently believe about AIDS, and what theii
relevant behaviors are. Data were collected by a "street survey" of addicts in one
high-drug-use area in each of three New York City boroughs. While most previous
reports have studied IV users in treatment programs, street users are particularly
important as a group that continues frequent IV drug use. The Street Research Unit
of the New York State Division of Substance Abuse Services asked open-ended
questions of 137 IV drug users who were unaware that they were being interviewed.
Three quarters of these "street addicts" knew that the spread of the AIDS virus is
related to IV drug use and four-fifths relate it to sexual activity. The proportion
aware of drug use as a factor is noticeably lower than that reported for a 1984
sample of methadone maintenance treatment clients (Friedman & Des Jarlais, I986).
Slightly over half of the street IV drug users engage in at least one valid protective
measure, very similar to Friedman & Des Jarlais1 comparable proportion. Two-fifths
have changed their drug taking practices to protect themselves, while measures
related to sex were mentioned by one fifth. These findings show that although there
is already considerable knowledge and risk reduction even by street addicts, there
are also large numbers who lack information and/or sufficient motivation to engage
in risk reduction behaviors. Efforts to disseminate accurate information about AIDS
to street IV users are likely to result in an increase in both knowedge and risk
reduction practices.
THP196 *° Ethnography of Needle Sharing
CLAIRE STERK, J.FRENCH, New Jersey Dept. of Health, Trenton,
NJ
The hypodermic set ( "works" ) has a meaning in the heroin subculture
beyond that of a mechanism to achieve a goal. It is a symbolic
representation of the world of dope.
Sharing and reusing works among IV drug users is a significant means for
transmission of the HIV. Street wisdom often dictates behaviors that
foster continued transmission. For example, addicts have learned that
boiling the works jams the plunger by removing the silicon lubricant.
However, much street wisdom has little factual foundation, rather serving
only socialization processes.
The care and maintenance of works serves to perpetuate reuse, as do
users' perceptions of statutes that restrict sale and possession. HIV is
transmitted at the shooting gallery, but users' perception of the latter is
complex. A few galleries provide only rental of works. More sell drugs,
only secondarily renting works. Still more provide free access to works
for drug purchasers. Many house dealers allow steady customers to borrow
works as a convenience. Finally, some users become known for their
willingness to allow friends to shoot up in their hemes.
Along this continuum, the risk for HIV transmission is a function of the
number of users involved in sharing and the looseness of the participant
network. An understanding of user perceptions and behavior is crucial to
the development of prevention efforts directed toward reducing the spread
of the virus through these sharing processes.
THP199 Accurate Determination of Risk Behavior in Persons with AIDS.
ANASTASIA M. LEKATSAS, R. O'DONNELL, J. WALKER, P. THOMAS, New York City
Department of Health AIDS Surveillance Unit, NYC, NY.
The New York City Department of Health AIDS Surveillance conducts sensitive
investigation of AIDS patients denying major risk factors of intravenous drug
use (IVDU), male homosexuality, transfusion and, for women, sex with a man at
risk. Of 270 cases reported monthly, 19 (7%) fail to identify a risk on ini-
tial interview. After investigation, 40% of these cases are found to have en-
gaged in IVDU or homosexuality. Of 204 women claiming sex with a man at risk,
all knew their sex partners were at risk and could identify them by name.
Sixty (29%) were married or common-law to the man. Nineteen (9%) were later
identified to be IVDU themselves. Only four (8%) of 53 males claiming female
contact were able to identify the women they believed infected them. Three
men claiming sex with Haitian women as a sole risk had engaged in homosexual
activity. Of 47 men claiming sex with female prostitutes, 31 (66%) had engaged
in IVDU or homosexuality. Seven of eight health care workers claiming occupa-
tional exposure were subsequently identified as IVDU or homosexuals. Our
statistics support the epidemiologic benefit of careful case investigation.
Interview of AIDS patients or close contacts is psychologically stressful
for interviewer and interviewee. Supportative elicitation of highly personal
information can represent a catharsis for the individual, who may have signi-
ficant motives for denial of risk behavior. This paper addresses issues en-
countered in undertaking investigations. Case material provides examples of
how to initiate, sustain, make transistions and close a non- identified risk
interview while maintaining the utmost concern for the patient's feelings,
rights and dignity.
THR197 Tfle e^^ect °f MDS diagnosis upon close personal interactions among
family members of AIDS patients.
GH FRIEDLAND, P KAHL, C FEINER, M ROGERS, M MAYERS, RS KLEIN, et al. Montef iore
Medical Center, Albert Einstein Coll. of Med., Bx, NY, CDC, Atlanta, Ga., USA
To explore the effect of AIDS diagnosis upon behavior, we evaluated the sharing of
household facilities and items and close personal interactions among household
contacts of AIDS patients before and after the diagnosis of AIDS and during two time
periods in which availability of information about risk of household transmission
differed.
199 household contacts of AIDS patients were evaluated with detailed standardized
interviews to determine the nature and amount of household interactions with the AIDS
patient. The first 104 (group 1) were evaluated from 10/84 to 5/85, the second 95
(group 2) from 6/85 to 11/86, after information about lack of transmission of HIV
infection was known and made available to study participants. The median age of the 2
groups was similar. Of the 199, 144 had household contact both before and after the
AIDS diagnosis (87 in group 1, 57 in group 2).
By McNemar's test for matched pairs, significant decreases in sharing of household
items occurred after diagnosis in both groups: combs, towels, eating utensils,
plates, glasses. In group 1 measures of close personal interaction decreased
significantly after diagnosis: (hugging 78-54%, kissing 86-67%). In the group 2 there
was no significant change in these close personal interactions after diagnosis
(hugging 70-63%, kissing 65-61%).
Despite information showing lack of risk of transmission arrong household members of
AIDS patients, significant reduction in sharing of household items and facilities
occurred. Close personal interactions were maintained, however, after information
about lack of risk became available. Therefore, Patients and family interactions may
be influenced by information about lack of transmission.
THP200 A Mode" °f Psychosocial Intervention in a Family Practice Center: forpersons
with Human Immunodeficiency Virus
JOYCE PERKINS, T. J. WOOLRIDGE, R.A. FRANCIS, MEHARRY School of Medicine,
Nashville, TN, Family Practice Center, Nashville, TN.
The Family Practice Center (FPC) of Meharry Medical College has developed a model
of psychosocial intervention for patients with Aquired Immune Deficiency Syndrome
(AIDS) and other Human Immunodeficiency Virus (HIV) related conditions.
The patients served by the center are typically socially and economically disadvantaged
with minimal social support -and limited access to medical care.
All patients diagnosed or suspected being at high risk for AIDS are evaluated by a train-
ed AIDS counselor usingftwenty-two page Inventory Assessment Form. Individualized
comprehensive treatment plans are then developed to provide patients with emotional,
social, medical and economic assistance.
In evaluating these patients, it has been found that they and their lovers, family mem-
bers and friends are severely stressed. Even persons who are antibody-negative but athigh
risk for infection are found to exhibit symptoms indicative of stress.
Recurrent psychological themes found are depression, conflict associated with a life
threatening illness, feelings of isolation from friends, family and medical personnel, guilt,
diminished self-esteem, preoccupation with economic problems and suicidal thoughts.
Our experience, following one year of intervention, suggests that individual and group
counseling enhances the quality of life for these patients and augments the effectiveness
of the medical care delivered.
196
THURSDAY, JUNE 4
HP.2U1 Homelessness
Syndrome (AIDS).
in Patients with the Acquired Immune Deficiency
THR204
Catherine Butkus Small, G. Laper, L. Ricci, North Central Bronx-Montefiore
Hospitals, Albert Einstein. College of Medicine, Bronx, New York.
The number of homeless individuals in New York City (NYC) increased
from approximately 7,500 to 10,000 from 1/85 to 12/86. Since North Central Bronx
Hospital(NCB) serves one of NYC's poorest boroughs, we tried to determine if
homelessness was a major problem among our AIDS patients and, if so, how it
affected their discharge planning.
From 9/85 to 9/86, 87 patients with full-blown AIDS were hospitalized
at NCB. Seventy-seven were intravenous drug abusers (IVDA) or their sexual
partners; 10 were homosexual. Seventy-eight were members of minority groups.
Seventy-two (83%) either lived with relatives (68) or had their own homes (4).
Fifteen (17%) were homeless; 14/15 were IVDA; 10/15 (66%) were homeless prior to
the diagnosis of AIDS. Of the 15 homeless patients^ 4 were accepted home by
relatives or friends; k went to hotel rooms provided by the municipal social
services department; 3 went to hospices; 3 died; 1 left against medical advice.
Although largely IVDAs from indigent minority groups, the majority
(83%) of our AIDS patients had family or friends who accepted them within their
homes despite their diagnosis. Homelessness is still a problem for a significant
number of our AIDS patients (17%) who often have severe social problems unrelated
to their diagnosis of AIDS. Discharge planning thus becomes more difficult.
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
THR202 Attitudes of Female Prostitutes in London to Barrier Protection.
SOPHIE DAY, H Ward, J Wadsworth, JRW Harris. St Mary's Hospital
London, UK.
Fifty-two female prostitutes were recruited tc the anthropological com-
ponent of a prospective study of STD and lifestyle at the Praed Street Clinic
between 7.86 and 1 .87.
Female prostitutes are placed in a high risk category for HIV infection
but condoms are thought to offer significant protection. Research on the
epidemiology and the effectiveness of condoms will have tc be considered in
terms of their use. Data collected so far suggest :-
1. London prostitutes are predisposed tc use barrier protection in order
to avoid contamination with semen itself, as well as pcssible
infection. The entire sample used ccndoms some of the time with clients at
the time of their first visit.
2. This population is also predisposed not to use barrier protection with
non-paying partners, including pimps. The discrimination provides a critical
means of demarcating work from pleasure, and 'punters ' from 'partners'.
3. The women in this group are worried about affecting, other prcstitutes.
This anxiety is related to corr.iron ideas about prostitutes as individual
sources of infection and a collective pool of infection.
Health education has been able tc capitalise on two of these conclusions
and the amount of condcrr. use with clients has risen. However, there has been
little change in pstterns of use with non-paying partners. As this latter
group is said tc have contact with many other women, this may be a critical
avenue for infection.
THP2n*i Tne Right -to-Know: AIDS -Free International Certificates .
1 JOHN R. SEALE, Private Practice, London, England.
HIV infection has presented modern medicine with novel chall-
enges and e thical dilemmas demanding innovation if its spread is
to be controlled within the framework of a free and responsible
society. Infected people usually remain infectious , unknowingly,
for several years before illness ensues , and they are particularly
likely to infect wives , husbands , fiances and infants . People who
are not infected with HIV have a Right-to-Know. They also have a
Right-to-Know that another person with whom they are proposing to
start, or continue, a sexual relationship - whether within or out-
side marriage - is also not infected. All "safe sex" techniques
are inconsistent with procreation.
The serological tests used to screen blood prior to trans-
fusion provide very good evidence of freedom from infection with
HIV. This information on a certificate would satisfy the Right-
to-Know of individuals and their sexual partners. The certificate
must be unf orgeable , up-datable , internationally recognisable
and clearly identifyable as belonging to the owner. Only
laboratories approved by public health authorities and WHO
should be licensed to test . Active encouragement by governments ,
WHO, medical , scientific and religious leaders for people to
obtain certificates on a voluntary basis will benefit
individuals and slow transmission of the virus in the community.
The need for the certificates to be regularly up-dated will
provide a powerful incentive for responsible behaviour -
particularly by young people.
THP203 Psychological Interventions for Persons With AIDS and Their Part*
ners: A Group Approach.
JUDY MACKS, MSW, LCSW, University of California San Francisco AIDS Health
Project, San Francisco, CA, United States.
In this report from the University of California AIDS Health Project, the
author will present a group model for working with homosexual and heterosexual
couples in which at least one of the partners is diagnosed with AIDS. The
author will present case material based upon eight completed groups involving
a total of 33 couples. Couples were either self-referred or referred by
mental health practitioners. The primary psychological themes presented by
each individual and the impact of these issues on the couple will be addressed.
The goals of the group include: 1. increasing coping and adaptive skills,
2. increasing independent functioning of the individual and couple ,
3. improving communication skills and 4. augmenting social support. Group
interventions for medically ill populations including patients with coronary
disease, cancer and other life-threatening Illnesses have been extensively
documented in the literature, as has the Impact of the illness on the family.
The author will discuss the relevance of this literature in work with this
population.
THP206 Medicine in Plague Time: Duty or Virtue? ABIGAIL ZUCER and S.H.
MILES, Center for Clinical Medical Ethics, Department of Medicine,
University of Chicago Hospitals and Clinics, Chicago, Illinois.
The profound reluctance of some physicians to care for patients with AIDS
prompted us to review medical responses to analogous historical plagues. No
consistent professional tradition emerged. Many historical physicians,
including Galen and Sydenham, fled from patients with contagious epidemic
diseases. Many of their colleagues remained behind to care for plague
victims at considerable personal risk. No formal statement of this duty,
however, was enunciated until 1847. This historical ambivalence suggests
that an ethic stressing traditional professional duties may not be ideal for
defining the optimal relation of the medical profession to patients with
AIDS.
A new statement to guide the profession in the AIDS pandemic cannot invoke
punitive sanctions against physicians refusing to treat HIV-infected persons,
for these would violate physicians' civil liberties and personal autonomy.
Nor can it be derived from these patients' right to health care, for that is
a claim against society rather than individual practitioners. Civil and
professional proscriptions against negligence or abandonment apply only to
therapeutic liaisons after they are contracted. However, a professional duty
to treat HIV-infected persons could be based on the understanding of medicine
as a moral enterprise. In this context, treating HIV-infected persons is a
virtuous act, that meets both patients' and society's health needs and
confirms the moral mission of health care.
197
THURSDAY, JUNE 4
THR207 Mar»agement of Confidentiality by a Cohort of Gay and Bisexual Men
Who have Learned their Antibody Status.
JANE S. ZONES*, D.R. BEESON**, D.F.ECHENBERG***, G. W.RUTHERFORD***, P. O'MALLEY***
*University of California, San Francisco; **California State University, Hay-
ward; ***San Francisco Department of Public Health, California, U.S.A.
While much attention has been given to the issue of confidentiality within
the research process, there has been little recognition of the difficulties
those who are undergoing HIV antibody testing may have in maintaining their
own privacy once they leave the research setting. We followed, for an average
10 months, 116 gay and bisexual men who were tested for HIV antibody as part
of ongoing epidemiologic studies conducted by the Health Department and the
Centers for Disease Control. Of those who chose to learn their antibody
status, both seropositives (N=51) and seronegatives (N=36) told an average of
19 of their acquaintances their serostatus. Those who chose not to learn their
antibody status (N=29) told fewer acquaintances (X=14) about their having been
tested and their decision not to find out the results. Several of those inter-
viewed noted changes in relationships, either for the better or for the worse,
that they attribute to risk status disclosure. Few, however, would change whom
they told about their risk status had they the opportunity to reconsider these
past decisions. Likewise, if they could choose anew, nearly all stated that
they would consent to being tested again as part of the research process.
Study participants found disclosure of antibody or risk status to others to
be either helpful or neither helpful or harmful. In general, these men have
not encountered damaging reactions to disclosure of antibody status in the
relatively supportive environment of San Francisco.
THP210 American Corporate Policy on AIDS and Employment
BENJAMIN SCHATZ, ESQ., Director, AIDS Civil Rights
Project, National Gay Rights Advocates, San Francisco, CA.
Survey was sent to "Fortune 1000" companies in October and again
in November, 1986 in order to learn approaches of America' s major
corporations towards employees with AIDS and related conditions.
Of 16 5 companies which responded non-anonymously , 165 ( 100% )
indicated they provide health insurance benefits to employees with
AIDS or ARC, 164 (99.5%) indicated that they do not test employees
or job applicants for HIV antibodies, 109 ( 66% ) declared that it
is their official policy to forbid employment discrimination
against employees with AIDS or related conditions, and 38 ( 23% )
had developed or are developing written policies on AIDS. In
addition, several companies indicated that they have provided
educational materials and programs about AIDS to their employees.
Results are significant because they reveal higher-than-
previously-estimated degree of proactive response by major
employers to the AIDS epidemic . It is hoped that survey findings
will encourage other employers, as well as government agencies,
to develop compassionate, legally sound policies towards employees
and applicants with AIDS and related conditions without fearing
that they will be going out on a limb to do so.
TUDOnQ Continuous Variables* Discrete Decisions: Determination of Ethically
inr.lUO AccepCable Risks of False Laboratory Results in Blood Donor Screen-
ing. CELSO BIANCO. The New York Blood Center, New York, N.Y. 10021
The establishment of appropriate "cut-offs" for screening assays in blood
banks raises issues that go beyond the technical, medical and scientific
community and require the resolution of ethical issues. The problem occurs
because: (1) sophisticated assays produce continuous results, e.g. the
ELISA for antibodies to HIV produces results from zero to maximum, may miss
specific antibodies and detects non-specific antibodies; the cut-off value
that separates reactives from non-reactives is arbitrarily defined as the
best possible discriminator between populations and presumably normal
individuals, and (2) assay results have to be applied without the benefit
of clinical evaluations combining medical history, physical examination
and laboratory studies. The problem is further complicated by unrealistic
expectations of no risk of disease transmission by transfusion, goal that
can only be achieved by eliminating transfusions.
Risk-benefit assessment can be used In the determination of screening
assay cut-offs. Committees comprised of experts, ethicists and recipients
could, at regular intervals, determine the maximum acceptable risk for a
transmissible disease based on epidemiologic studies, clinical trials,
assay characteristics, and curves of risk probability of various cut-offs.
Recipients of transfusion would be able to make their own decision based on
this information. Insurance' carriers would have guidelines for coverage,
and the legal system would have means for dealing with litigation and
compensation of victims.
THR211
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
TUpOflQ Issues of Foster Care and HIV Infection in Infants of Drug
Addicted Mothers. ANN SUNDERLAND*, H. MENDEZ*, S. HOLMAN*,
M. BERTHAUD*, G. MOROSO* , S. LANDESMAN* , et al . SUNY Health Science Center
at Brooklyn**, Brooklyn, N.Y., U.S. A. and National Institutes of Health**,
Bethesda, M.D., U.S.A.
A cohort of 43 babies born to HIV seropositive <SP) and seronegative ( SN)
drug addicted (DA) women are being followed in a prospective perinatal
HIV transmission study. Sixteen of 43 (36.1%) of these are in foster care
{FO. There is no difference in incidence of placement between SP(9/16)
and SN(7/16) groups. Where results are known to the FC system, 3/4 SP
babies are in group settings as foster homes are unavailable, including
1 "boarder baby" awaiting placement out of the hospital and 1 child who
was abandoned by the caretaker after learning results.
Placement of babies tested for HIV raises ethical dilemmas involving
confidentiality. A mothers right of confidentiality conflicts with a
caretakers right to know results. The latter is needed for proper
precautions and appropriate delivery of health care. Informing a FC agency
of the serological status of a child born to a SP mother may jeopardize
or limit placement possibilities. As fear of AIDS may hinder placement
of all babies born to DA women, telling results may enhance SN baby's
chance of placement. Informed consent obtained when testing the mother
should allow for informing the FC system of the baby's status.
Our experience and the estimate of 800-1000 SP infants born in N.Y.C.
per year points to the need for the FC agencies and their governmental
overseers to (1) develop a coherent policy for educating case workers,
and potential foster care parents and (2) increase recruitment efforts
for foster parents of SP infants.
THP212 HIV Seroprevalence Among Nurses Caring for Children with AIDS/ARC
MARY 80LAND, J. KERESZTES, P. EVANS, J. 0LESKE, E. CONNOR
Children's Hospital of New Jersey (CHNJ) & UMD-NJ Medical School, Newark, NJ
Sera from 45 female nurses caring for children with AIDS/ARC at CHNJ was
tested for HIV antibody. The nurses were volunteers who anonymously completed
a questionnaire designed to define type of patient contact and to identify HIV
infection risk factors. Nurses worked in the following areas: ICU (14);
medical-surgical units (26); ambulatory service (2), and AIDS program (3).
26 (56%) of the nurses cared for patients for over 12 months for an average
of 8-12 hour shifts/month (0-15 shifts). Nurses reported the following types
of contact: bathing (41/45), feeding (41/45), care of central venous catheters
(42/45), administration of oral and intravenous medication (40/45), obtaining
and handling specimens (e.g. blood, urine, stool) (45/45), contact with blood
and secretions (eg diaper changes) (43/45) and touching and comforting a child
(43/45).
The nurses reported following standard hospital infection control procedures
sometimes 4 (958), usually 25 (25%), and always 15 (32%). 3/45 nurses reported
needlesticks and 2/45 reported mucous membrane or broken skin contact with a
child's blood. 43/45 nurses were healthy. 1/45 had the diagnosis of chronic
Esptein Barr Virus infection; 1/45 had contact dermatitis of the hand that re-
quired periodic use of steroid cream. 3/45 had received blood transfusions
within the past 5 years. All denied nonprescription drug use and all were
heterosexual. 1/45 had a sexual partner who since developed AIDS, and 1/45
reported a present partner who is HIV positive.
100% (45/45) nurses were HIV negative by ELISA and Western Blot. Annual
re-testing is ongoing. Data from this study suggests that risk of transmission
of HIV during nursing care of children with AIDS/ARC appears to be small.
198
THURSDAY, JUNE 4
THP213 Attitudes Concerning AIDS: Relationship to Behaviors of Dental Health
Professionals
BARBARA GERBERT*. V. BADNER', B. MAGUIRE*, •UCSF School of Dentistry, San
Francisco, CA.
To determine AIDS patients' access to dental care, a randomized survey of dental
health professionals in California was conducted. Respondents' attitudes, knowledge,
and behaviors regarding patients with AIDS and at-risk for AIDS were assessed, as well
as the number of patients they perceived to be at-risk for AIDS in their practice.
Usable responses were obtained from 297 dentists, 128 hygienists, and 177 dental
assistants. Use of infection control was more closely related to attitudes than to
knowledge in all three professional groups. When compared with practitioners who
thought few of their patients were at-risk for AIDS, those who perceived more of their
patients to be at risk had more positive attitudes (p<.004) and were more likely to
practice infection control (p<.000l) and to screen patients for AIDS by taking a
thorough medical history (p<.02) and sexual history (p<.04). The authors conclude that
attitudes toward AIDS, particularly perception of the number of patients at risk in
one's practice, affect the screening and infection control procedures used by dental
health professionals. Attitudes, rather than knowledge, should be targeted in education
programs designed to improve AIDS patients' access to dental care.
THP216 Hepatitis Delta Antigenemia in Intravenous Drug Abusers with AIDS:
Potential Risk for Health Care Workers
MARY JEANNE KREEK*, D. DES JARLAIS**, C. TREPO***, D. NOVICK*"*, A.
QUADER»*,J. RAGHUNATH*, 'Rockefeller University, **NY state Division of
Substance Abuse Services, ****Beth Israel Medical Center, New York City, USA,
•"Faculte Alexis Carrell, Lyons, FRANCE
Intravenous drug abusers (DA) are the second largest group at risk for
infection with HIV and developing AIDS (25% of U.S. cases) . DA are also a
major risk group for infection with hepatitis B virus (HBV) ; over 80% of
heroin addicts have some marker of HBV infection. Hepatitis delta virus (HDV)
is a defective RNA virus which can replicate only in the presence of repli-
cating HBV. The prevalence of HDV infection, which can cause fulminant
hepatitis and death, or rapid progression to cirrhosis, has been increasing
in DA. This study was conducted to determine the prevalance of markers of HDV
infection along with HBV markers in a group of unselected DA entering or in
treatment and, in a group of DA with AIDS disease and to examine the
relationship of immunosuppression in AIDS on the expression of HDV infection.
Subjects (N) Positive Test: HB Ag HDAg anti-HDV
PDA 347 18 (S5.2%) 2 (0.6%) 104 (30.0%)
PDA with AIDS 53 8 (15.1%) 3 (5.7%) 0 ( 0%)
The overall prevalence of HDV markers was 27.3% in DA subjects. Delta
antigenemia, associated with infectivity, and usually detected only in the
first 2 weeks of delta infection, was found in a significantly increased
number of DA with AIDS, probably due to either a persistence or reappearance
of antigen in the setting of AIDS related immunosuppression. HBV vaccination
to protect against HBV and HDV infection is recommended for all persons
working with blood from patients with HIV disease.
THR214 Creation of a Dedicated Unit for AIDS S HIV-Related Illness (HIV
Patients) at Bellevue Hospital- Impact on ICU Utilization, Care
Patterns of Critical Patients & Mortality
LOIS BRAUNSTEIN, R. HOLZMAN, J. RIVERA, M. SEIDLIN, Bellevue Hospital Center,
New York, N.Y.
A designated unit (12E) for HIV patients with 10 private rooms was created in
January, 1986 to concentrate nursing care for acutely ill, non-intubated patients and
provide an alternative to ICU for these patients. We studied the 278 admissions
during the 6 months prior to the opening of 12E ('Pre') and the 298 admissions during
the 6 months following it's opening ('Post'). During this period the average daily
census of HIV patients was 46.6 (range 37-55). 133 admissions were excluded because
they spanned the transition period.
The proportion of HIV admissions who spent time in ICU, 15%, and the mean length
of stay (LOS) in ICU, 7.5 days, did not differ significantly between the two periods.
Mortality of ICU admissions was 53.5% during both periods compared to 30% for 12E
admissions and 20% for all HIV admissions. Mean LOS in the ICU for patients who
died was 10 days in contrast to 4.7 days for those who survived. Mean LOS on 12E
was 8.6 for patients who died and 12.4 for those who survived. It is notable that the
LOS of patients in ICU who died is longer than that of those who lived while the
reverse is true for 12E. This may be attributable to the fact that patients in
respiratory distress who elected not to be intubated were often admitted to 12E
where their deaths were not prolonged by mechanical ventilation.
We conclude that the creation of a dedicated unit did not alter ICU utilization or
overall mortality for HIV patients. Instead, it offered a setting in which acutely ill,
non-intubated patients could receive a higher level of nursing care. This relieved
the burden experienced by the general medical wards and provided a humane
alternative for critically ill patients who chose not to undergo intensive care.
TrlKZli Coming Home Hospice: A Model Residential Hospice Alternative
JEANNEE PARKER MARTIN, Director, AIDS Home Care and Hospice Program, San Fran-
cisco, CA.
In 1984, Hospice of San Francisco developed the first AIDS Home Care and Hos-
pice Program in the country. This program has provided care for more than 500
AIDS/ARC patients at home.
Increasingly, needs for 24-hour attendant care and supervision have been
identified. Consolidated housing alternatives were established to help meet
this need but were inadequate.
In March 1987, Hospice of San Francisco will open Coming Home Hospice, a res-
idential board and care facility for terminally ill persons with AIDS and ARC.
This facility will allow 15 patients to receive comprehensive hospice services
24 hours a day. These services will be provided by Licensed Vocational Nurses,
attendants, volunteers, Registered Nurses, and Social Workers.
This presentation will highlight the unique characteristics of Coming Home
Hospice, its Advisory Board, community support, and public and private funding
sources.
THP215 AD3ence °f HIV Antibody Among Dental Professionals, Surgeons, and
Household Contacts Exposed to Persons with HIV Infection.
SCOTT HARPER, N. FLYNN, J. VAN H0RNE, S. JAIN, J. CARLSON, S. P0LLET, et al.
Univ. of California, Davis, Sacramento, CA.
Dental professionals and surgeons have increased risk of acquiring
hepatitis B through professional contact with this virus, raising the
question of transmission (T) of HIV in the same manner. Close household
contacts of HIV-infected individuals (HIV-I) have not been shown to be at
risk for T of HIV.
To examine these hypotheses we tested 300 Sacramento and L.A., CA
dentists, hygienists, and chairside assistants (who experienced approxi-
mately 200 or more exposures to HIV-I), 25 surgeons who operated on HIV-I
(usually unaware of HIV Infection) and 20 household contacts of HIV-I, for
antibodies to HIV by ELISA and Western blot techniques. An additional 700
dentists from major U.S. cities will be tested prior to presentation of this
data. Subjects were asked not to participate if they had any other recog-
nized ri3k factor(s) for HIV exposure. We also questioned dental profes-
sionals regarding gloving practices and frequency of accidental puncture
wounds. Dentists and chairsides seldom wore gloves, whereas hygienists wore
them for the majority of procedures. 12$ reported >2 puncture wounds per
month, 25$ had ^6 per month.
No subject had antibody to HIV by Western blot analysis. We conclude that
risk of T of HIV to dental professionals in Sacramento is small. Our small
numbers of surgeons and household contacts provide additional evidence that
T of HIV in these settings is rare.
THP.218
A Model for AIDS Professional Education
JEFFREY S^ MANDEL, PHD, MPH , M. GRADE PHD, L.S. ZEGANS, MD,
H. BARTNOF, MD, B. FALTZ , RN, J.L. ZIEGLER, MD, et al.,
UCSF School of Medicine, San Francisco, CA, USA
A model has been developed specific to the education of
physicians and nurses, in practice and in-training, at the
University of California, San Francisco. Over a 3-year period,
under federal contract, 5000 health practitioners will be
comprehensively educated via this model.
Curricula have been fashioned with sensitivity for HIV-
related diseases as medical illnesses, as the topic of extensive
research, and as diseases of unprecedented psychosocial and
legal /ethical complexities. The model extends beyond traditional
educational frameworks; it addresses the dilemma of how to impart
both technical and provocative information in such a way that it
is not only assimilated but applied. An emphasis on diagnosis and
treatment is matched by that placed upon prevention and health
education.
The numerous organizational challenges of AIDS professional
education are reflected in this model; attention has been paid to
interdisciplinary issues and related concerns about professional
domain, interagency cooperation, and the integration of community
issues into the academic arena. In keeping with epidemiologic
trends, both curricula and core faculty reflect the special
concerns of third world persons, substance abusers, recipients of
blood products, women and children.
199
THURSDAY, JUNE 4
THR219 Identifying Major Concerns of Patients with AIDS
CHRISTINE GRADY, J. JACOB, B. BAIRD, J. SPROSS*, Y. OSTCHEGA.
National Institutes 6T Real th , Bethesda, Maryland, Massachusetts General
Hospital .
A descriptive study was conducted to identify and categorize major concerns
of individuals with AIDS. Thirty adults were interviewed. The majority were
male homosexuals with Kaposi sarcoma undergoing experimental therapies. In-
formation gathered included impact of the diagnosis, major concerns, support
networks, and persons and actions perceived most helpful.
The majority (66%) were told the diagnosis by a physician in person, and
(30%) were told over the telephone. The most common reaction was shock or
disbelief but 13% expressed relief and 7% expressed feeling "empty" or "dead".
Eighty-three percent initially discussed their diagnosis with a lover or
friend, while 10% first told a family member(s) with 77% responding in a
manner perceived to be helpful. Helpfulness was described most frequently as
keeping the relationship intact without significant change. The predominant
concern expressed was personal health and continued functioning followed by
uncertainty about the future, fear of death and completing research require-
ments. At the time of the interview 47% reported feeling always hopeful and
10% never hopeful. Ninety-seven percent reported some uncertainty, 90% fear,
90% fatigue, 97% sadness and 83% anger. Seventy-seven percent of the patients
reported never feeling abandoned. From participation in research 23% hoped
for a cure, 23% a treatment or experimental drug, and 23% maintenance or
prolongation of function. Twenty percent expected no help for themselves but
participated to help others.
Study information also provides understanding that gives direction to the
planning and provision of quality care to this patient population.
THP222 The Nurse Ro3e in an HIV Diagnosis and Management Centre
Patrick M. Turbitt, Andrew Morlet, Julian Gold, Albion Street
(AIDS) Centre, Sydney Hospital, N.S.W., Australia.
The Sydney AIDS clinic was established by the state government in March
1985 to provide free, confidential testing and management for persons infected
with HIV. Over 6,000 people have presented for testing of whom 750 were HIV
antibody positive. All HIV antibody positive persons are offered ongoing
medical management, receive psychological assessment and counselling and
return to the clinic for further T-cell testing and review every three to
six months after initial diagnosis.
The nurse ro]e in this context has developed to include the assessment of
new clients to triage them into medium/high and low risk categories
according to their likelihood of infection. The nurse collects demographic
and extensive lifestyle data from those in the moderate/high risk group
before referring for medical examination and counselling. The low risk
persons are managed by nurses without referral .
Nursing staff are the first line contact for all clients entering the
clinic, thus providing an important role in imparting factual,
comprehensible information to allay fears and educate those who perceive
themselves to be at risk. Nurses are also called upon to provide information
to other health care professionals and to conduct in-service training.
Whilst the majority of HIV antibody positive clients are at the early
stages of infection and require minimal clinical management, the nursing
staff offer advice on maximising health, prevention of concurrent infection
and reinforce safe sex practices.
THP220 MULTIDISCIPLINARY APPROACH TO AIDS PATIENTS, POLICIES AND
PROCEDURES IN A COMMUNITY HOSPITAL. L. Andrews, R.N., S. Patronik,
R.N., K. Hryb, B. Cooper, M.D., J.J. Klimek, M.D., Hartford Hospital, Hartford,
CT, USA.
Ours is a 1,000 bed community teaching hospital in central CT where 1 to 4 new
AIDS cases are treated each month. In response to increasing needs within our
hospital, a Multidisciplinary Committee (MC) was formed to address patient care
and staff issues.
MC is comprised of representatives from Epidemiology, Social Service, Nursing,
Home Care, Pastoral Services, Microbiology, and Rehabilitation. MC functions
as an educational resource, and attempts to identify and anticipate problems
and share solutions. Members are notified of the admission of an AIDS patient,
confidentially, in writing by the Section of Epidemiology. Bimonthly meetings
are held during which issues are discussed, policies are established, and
individual patient cases are reviewed. Specific patient problems and their
solutions are addressed by a team with representatives from each discipline.
Educational needs within the hospital are met through inservices to all
departments on a regular basis.
The MC functions in conjunction with the Infection Control Committee and the
Hospital Administration to anticipate and identify the needs of our institution.
Collaboration with other state hospitals allows further sharing of problems
and solutions.
As our number of AIDS admissions increases, this collaborative approach utiliz-
ing a variety of departments has worked well. This committee was comprised
solely of representatives from within our institution and did not require ad-
ditional funds or outside resources. The MC model may be useful for handling
small to moderate numbers of AIDS admissions in a community setting, where
resources are limited.
THP223 Update: Prospective Evaluation of Health-Care Workers
Parenterally Exposed to Blood of Patients Infected with Human
Immunodeficiency Virus. RUTHANNE MARCUS AND THE COOPERATIVE NEEDLESTICK
SURVEILLANCE GROUP, Centers for Disease Control, Atlanta, GA, USA.
As of September 15, 1986, 1,116 health-care workers (HCWs) with documented
exposures to blood of human immunodeficiency virus (HlV)-infected patients
were enrolled in a surveillance project to determine the risk of occupa-
tionally acquiring HIV infection. HCWs have been followed for a mean of 20.7
months. Percutaneous exposures to blood accounted for 77% (n=856) of the
incidents. Exposed HCWs Included 679 nurses, 186 physicians, 111 laboratory
workers, 68 phlebotomists, and 72 others. Exposures occurred in patient-care
wards (59%), intensive-care units (20%), operating rooms and morgues (10%),
laboratories (7%), and emergency rooms (4%). Exposures judged preventable
included recapping used needles (17%), improperly disposing of used needles
(13%), and contaminating open wounds (10%). HIV-antibody testing has been
performed on serum samples from 716 (64%) exposed HCWs. Two hundred five
HCWs with both acute- (<30 days postexposure) and convalescent- phase (>90
days postexposure) serum samples tested for antibody to HIV were exposed to
patients who meet the Centers for Disease Control's surveillance definition
of AIDS; one (0.5%) has shown evidence of seroconversion. An additional 47
HCWs with paired serum samples were exposed to HIV-infected patients that
did not meet the CDC definition of AIDS; none of these have seroconverted.
We conclude that 1) at least 40% of injuries in this project might have been
prevented by use of recommended infection control measures; 2) the risk
(0.5%) of occupational transmission of HIV infection from patients with AIDS
(CDC surveillance definition) is low (95% CI 0.00-2.30); and 3) the risk of
infection from other HIV-infected patients warrants further examination.
THR221
Costs of AIDS to a Public Hosp
GERI R BROWN*. T BRANDES*-*
HALEY*. R ANDERSON***. *Univ Tx HSC-Dal
Health De»pt, ***Parkland Mem Hosp ( PMH )
Since all AIDS cost studies have been
rather than true hospital costs, and
f i xed budgets, this study intends to de
costs of AIDS to PMH. From 1982-86, 168
admitted to PMH , accounti ng for a total
number of admissions increased from 5 i
The total charges were $37,312 in 1982
in 1 986 . Marginal costs were deter mi ned
components for labor C nur s i ng , housesta
ancillary services, dietary, pharmaceut
laboratory. Estimates for nursing labor
patient care units ass igned to each pat
labor on progress note frequency. Total
from 415,000 in 1982 to 41.03 million i
admission peaked in 1984 and then dec 1 i
length of stay: the mean stay was 22 da
1986. The mean daily charge decli ned f r
in 1986. However the mean dai ly cost ro
$719 in 1986. 1 V/. of charges to AIDS pa
compared to 31'/. of charges to other pat
substant ial imp ac t on the economics of
requires major efforts at economic and
idap t the tax base to increasing case 1
*l°B6 data are estimates pending final
ital .
HALEY**, GB SE
las , **Dal las
, Dal las, TX
based on pati
nee pub lie hos
term i ne the ma
per sorts with
of 252 adm iss
n 1982 to 134
and rose to 41
by add i ng the
f f , and soc ial
ica 1 s . supp 1 ie
were based on
ient and for h
i npat ient cos
n 1986. The
ned due to a s
ys in 1984 -and
41 , 109 in 1
se from 4579 l
t i ents were pa
ients. AIDS ha
pub lie hosp i ta
epidemic forec
oads .
ana 1 ys i s .#
IBERT*. R
County
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rg inal
AIDS were
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in 1986.
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cost
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standard
ausestaf f
ose
sts per
hor ter mean
12 days in
96^ to 4872
n 1984 to
id.
s a
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THP224 A|0S-HIV Educa
at the UCSF Sc
HARVEY S. BARTNOF MO, UCSF
Health care provider stu
with HIV-infected patients
This may lead to unecessar
patients with AIDS and ARC
San Francisco has the high
order to obviate this prob
was de signed and named, "A
was modeled after a slmlla
In the Spring quarter of I
course evaluation forms fr
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The Course Is thirteen h
and 2 hours of panel dlscu
researchers and clinicians
Introduction;" "Epidemic P
Lab Tests, and Autolmmunlt
Manifestations of AIDS;
"Transfusion and Blood Ban
and AIDS;" "Psych I atr I c/Ps
Minorities and AIDS;" "Inf
"Legal Issues;" "Public Po
"Persons with AIDS and ARC
Pre- and post-course know I
to assess the success of t
phobias and Increased know
tlon for Med
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dents may be
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200
THURSDAY, JUNE 4
THR225
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
THR228 Ansamycin (Ri
Blood-Brain B
BRUCE P. DAVIDSON*, F.P.
WEISER-'"", R. ANAND***, *
**SUNY/Stony Brook, Ston
Current data indicate
progressive encephalomye
complication of late HIV
virustatic agents will p
bra i n barrier. Ansamyc i n
a semisynthetic derivati
trations greater than 5-
clinical trial involving
mine toxicities and pote
treatment of M. avium-in
fabutin), an Inhibitor of H
arrier
SIEGAL*, R.A. REIFE*, K. G
Long Island Jewish Medical
y Brook, NY and ***CDC, Atl
early involvement of the ce
lopathy (HIV-EM) appears to
infections. The ultimate
robably depend on their abi
(ANSA) (Rifabutin, LMA27,
ve of rifamycin S, inhibits
10 micrograms/ml . ANSA was
subjects with case-defined
ntial utility at doses grea
tracellulare infections. Se
its major 25"desacetylat
(56°C, 20-30 min) wi thou
chromatography (HPLC) .
weeks' oral dosing (300-
HPLC method established
present in sera, but onl
in serum. These studies
across clinically uninfl
drugs considered for the
ed metabolite, LM565, were
t affecting drug detectabil
Sera collected serially and
600 mg/day) were assayed us
by Adrta Laboratories. Both
y ANSA was found in CSF, at
ndicate that ANSA travers
amed meninges, fulfilling an
treatment of HIV infection
IV in vi tro, Crosses the
EHAN*( H. BURGER-----'-', B.
Center, New Hyde Park, NY,
anta, GA, USA.
ntral nervous system by HIV;
be an exceedingly frequent
ut i 1 i ty of cand i date
1 i ty to traverse the blood-
spi ropi per idyl r i famyc t n) ,
""'^ 'n vi t ro at concen-
employed in an open- I abel
AIDS or HIV-EM, to deter-
ter than those employed for
ra "spiked" with ANSA and
heated to inactivate HIV
ity by high-pressure liquid
CSF obtained after several
ing a modification of an
ANSA and LM565 were
levels 30-*t0% of those
es the blood-brain barrier,
essential requirement for
THR226 Immunologic Reconstitution in AIDS Employing 3'-azido-3'
deoxythymidine and Syngeneic Bone Marrow Transplantation
H. CLIFFORD LANE, H. MASUR, J. KOVACS, R. STEIS, M. MEGILL, A.S. FAUCI,
et al . , National Institutes of Health, Bethesda, MD.
The immunologic defect in AIDS is characterized by a decrease in the absolute
number of helper/inducer T lymphocytes and an inability of the remaining cells
to proliferate in vitro in response to soluble protein antigens. Bone marrow
transplantation and the adoptive transfer of syngeneic lymphocytes employing
identical twin pairs where one has AIDS and the other is HIV negative have
accomplished only a transient improvement in immunologic function, presumably
due to the destruction of the new immune system by HIV. The present study was
designed to determine the effects of combining anti-retroviral therapy with
3'azido-3'deoxythymidine (AZT) with adoptive immunotherapy and bone marrow
transplantation. Patients were selected for the study if they were culture
positive for HIV (with or without clinical illness), demonstrated immunologic
defects characteristic of HIV infection and had an identical twin with a
normal immunologic profile and no evidence of HIV infection. Patients were
treated with 500mg AZT q4h for the 12 weeks prior to bone marrow
transplantation. At week 10 of AZT they received 4 infusions of peripheral
blood lymphocytes from their identical twin, at week 12 of AZT they received 2
infusions of peripheral blood lymphocytes from their twin and at the end of
week 12 they received the bone marrow transplant without conditioning.
Following transplantation patients were randomized to receive either lOOmg AZT
or placebo q4h. At the present time 12 patients have entered the study and 4
bone marrow transplants have been performed. While it is still too early to
assess the effects of this therapy it is hoped that the data generated over
the next 4 months will allow an evaluation of the efficacy of anti-retroviral
therapy with bone marrow transplantation in patients with HIV infection.
THP229 0pen Trial of Azidothymidine (AZT) in AIDS Patients at Parkland
Memorial Hospital (PMH) , Dallas, Texas
DANIEL J. BARBARO*, T. EMANUELE**, L. FREDENBURG**, J. P. LUBY*. *University
of Texas Health Science Center at Dallas, Southwestern Medical School,
Dallas, TX, **Parkland Memorial Hospital, Dallas, TX.
Forty patients have been enrolled In an open, uncontrolled trial of AZT at
the AIDS Clinic (PMH). Of the 40 enrolled, there have been 7 deaths. Two
deaths occurred during the week treatment was to have begun and 5 died during
the first 3 weeks of therapy. Deaths were due to opportunistic infection or
neurological deterioration. Six patients developed opportunistic infections
diagnosed after at least 6 weeks on AZT. Three patients developed Pneumo-
cystis carinii pneumonia and the other 3 have been diagnosed with Mycobacte-
rium avium- in tracellulare infection. One patient dropped out of the study
because of intractable nausea and vomiting and another was lost to follow-up.
The remaining 25 patients taking AZT are either clinically stable or improved.
Of 20 patients taking AZT for a least 1 month, there has been an average
weight gain of 4 lbs.
Side effects have been numerous and include nausea and vomiting in seven.
Six of these seven improved after lowering the dose. Maculopapular/f ollicular
skin reashes were seen in 5 patients. Two patients developed convulsions on
the drug. Laboratory abnormalities have included unexplained, significant
drops in the hemoglobin level of 4 patients who have required intermittent
transfusions . Six patients had decreases in granulocyte counts requiring
dosage adjustment, including one patient whose count fell soon after the
initiation of acyclovir therapy. AZT represents a significant advance in AIDS
therapy , but its administration is not without problems .
THR227 Suromin-Imuthiol Combination Therapy of Patients with AIDS-
-Related Complsx (ARC) Results in 6 casec, . .
H. TAELMAN, S. SPRECHER, 0.TEIRLYNCK,"5 M.BOGAERTS, P.GIGASE, P.PIOT1.
1. Institute of Tropical Medicine, Antwerp, Belgium. 2 Institut Pasteur,
Brussels, Belgium. 3 C.Heymans Institute, Ghent, Belgium.
Previous studies hove shown us that suramin, despite its effectiveness as
a HIV inhibitor, is unable to improve the immune and clinical status of
patients with AIDS or ARC. We therefore started with a clinical trial com-
bining suramin with diethyldithiocarbamate (Imuthiol) a drug with immuno-
regulatory properties in 6 patients with ARC. They oil had initially
lymphocyte cultures positive for HIV markers (HIV antigens and/or RT activity).
Once the cultures became negative, suramin Ig IV every 2 weeks together with
Imuthiol 10 mg/kg per os once weekly were administered for at least 16 weeks.
Each patient was examined clinically and questioned for side-effects of drugs.
Plasma suramin levels were determined by HPLC before each new administration
of suramin.
The immune status of the patients was screened every 2 months for lymphocyte
subsets and for cutaneous delayed hypersensitivity with 7 recall antigens
(Multitest).
After 16 weeks of treatment, despite maintenance of plasma suramin levels
> lOOyg/ml, there was no change of the clinical status of the patients and
no improvement of % or absolute nb of T4 cells or skin tests score was
observed.
One patient develop ed adrenal insufficiency.
TUpOOn Progressive His topatho logy and Prognostic Value of Sequential
Lymph Node Biopsies in Patients with AIDS and ARC.
AMY CHADBURN*. C. Metroka**, J. Mouradian*. *The New York Hospital-Cornell
Medical Center, New York, New York and **St. Luke's/Rooaeve 1 t Hoepital
Center, New York, New York.
The prognostic value of progressive 1 ymph node his topatho logy was
studied in 66 sequential lymph node biopsies (bxs) from 27 male patients (2
to 6 bxs per patient) with the Acquired Immunodef icieocy Syndrome (AIDS) or
AIDS-related complex (ARC). Initial bxs revealed four patterns: explosive
follicular hyperplasia (EFH) in 17; mixed EFH and follicular involution (M)
in 5; follicular involution (FI) in 4; and lymphoid depletion (LD) in 1.
Lymph node histology showed a progressive loss of follicles and lymphocytes
corresponding to a temporal pattern of change; EFH to M to FI to LD.
Overall 18 of 27 patients (671) progressed to different histologies on repeat
biopsy. On second bx of those 5 initially with H, 3 progressed; 2 to FI and
1 to LD. On the second bx of those 4 initially with FI, 3 progressed; 1 to
LD and 2 to lymphoma. This progressive histologic pattern of change
correlated with a deteriorating clinical course; there was an increased
incidence of developing opportunistic infections (01), Kaposi's sarcoma (KS),
and lymphoma (L) and decreaeed mean time of survival. Of the 18 patients
with progressive lymph node histology 15 died (83Z). Of patients with FI or
LD on first or second bx, 92* had or developed 01, KS, or L and died with a
mean survival or 11.5 months. However, only 501 of those with EFH or K on
first or second bx had these diseases and died, mean survival of 29.8 months
(p-0.01). Sequential lymph node biopsies may be prognostic of the clinical
course in AIDS and ARC.
201
THURSDAY, JUNE 4
TUDOQI Successful Chemoprophylaxis for Pneumocystis carinii pneumonia
with Dapsone in Patients with AIDS and ARC
CRAIG E. METROKA. M. Lange, N. Braun, M. O'Sullivan, H. Josefberg, D. Jacobus.
St. Luke's/Roosevelt Hospital Center, New York, New York.
In an open study to evaluate the efficacy of dapsone for the prevention of
Pneumocystis carinii pneumonia (PCP), we studied 156 patients who were at high
risk for PCP from 4/85 to 1/87. The groups included patients with a prior
history of PCP, other life-threatening opportunistic infections (01), AIDS-
related Kaposi's sarcoma (KS), generalized lymphadenopathy, ITP, and malignant
lymphomas. All patients initially had less than 200 T4+ cells/mm . Only 1
patient receiving 25 mg po qid of dapsone developed PCP. This patient was also
receiving ansamycin for disseminated MAI. Since ansamycin is a derivative of
rifamycin and rifamycin lowers serum dapsone levels 7 to 10 fold, it is
possible that ansamycin may have similarly affected dapsone levels. In
contrast, 14 of 19 patients who refused treatment with dapsone and who were
clinically matched with patients in this study developed PCP. Dapsone
administration led to a decline in red cell mass, a rise in serum LDH, and the
development of methemoglobinemia. 39 patients required one or more transfusions
of packed red blood cells. However, temporary discontinuation of dapsone in 11
patients decreased the transfusion requirement but did not eliminate the need
for repeated transfusions. Complications included nausea (2) and skin rash
(6). Eight patients with ARC or AIDS developed KS while receiving dapsone. By
itself, dapsone did not cause significant regression of any skin lesions and
did not prevent the development of new lesions. 55 patients developed other
life-threatening OI's or malignant complications; 36 of these patients have
died* In summary, dapsone is well tolerated and highly effective in the
prevention of PCP.
THR234 Effects of 3'-Azido13'-deoxythymidine (AZT) in Patients with Acquir-
ed Immune Deficiency Syndrome (AIDS) post-pneumocystis carinii
pneumonia infection.
DELIA F. CHIUTEN* **, P. MANSELL* **, L. McCRORY**, P. KUROWSKI**, M. HERNAN-
DEZ* **, S. RODRIGUEZ* **. *U.T.S.C.C. M.D. Anderson Hospital and Tumor
Institute, Houston, Texas, **Institute for Immunological Disorders, Houston,
Texas.
AZT has been shown to limit multiplication of HIV through inhibition of
reverse transcriptase. A clinical trial using AZT 200 mg every 4 hours p.o.
was initiated in 43 evaluable patients with AIDS post-pneumocystis carinii
pneumonia (PCP) infection. Twelve concurrent opportunistic infections or tumor,
i.e. CMV retinitis, Kaposi's sarcoma, cryptosporidiosis, Candida esophagitis,
mycobacterium avium intracellular and Burkitt's lymphoma were present in some
cases but did not require treatment while patients were receiving AZT. Median
age was 33 years with median performance status of Karnofsky scale 90. All
patients had 1 episode of PCP except 4 who had 2 episodes of PCP prior to
starting treatment. The main side-effect was anemia which occurred in 30% of
the patients and 26% required blood transfusion. Other side-effects included
nausea, headache, fatigue, anxiety, confusion and skin rash. Treatment was
interrupted in 19 patients due to hematologic toxicity, opportunistic infection,
other infection and other medical problems. Twelve patients were treated for
recurrent or possible recurrent PCP. Four patients refused further treatment
due to intolerable gastrointestinal symptoms and fatigue. Clinical improvements
were observed in the form of weight gain, decrease in abnormal liver function
tests, increase in Hb and increased energy after taking AZT from 2 to 10 weeks.
AZT may have a role in the treatment of AIDS patients with PCP.
THR232 Long-terra Follow-up of Fansidar Prophylaxis for
Pneumocystis carinii Pneumonia (PCP) in Patients With
AIDS.
DAVID HARDY, P.R. WOLFE, M.S. GOTTLIEB, S. KNIGHT, R. MITSUYASU,
L.S. YOUNG, UCLA School of Medicine, Los Angeles, CA.
PCP continues to be the most common opportunistic infection
diagnosed in AIDS patients. While therapy with either
trimethoprim-sulfamethoxazole (T/S) or pentamidine is successful
in 80 to 90% of episodes of PCP, recurrence rates without
prophylaxis remain between 30-50%/year. An increased prevalence
of adverse reactions to T/S among AIDS patients often complicate
use of this agent as prophylaxis for PCP.
We report 11 month (range 2.5-27) follow-up of 60 patients
recovered from an initial episode of PCP given Fansidar (20:1
sulfadoxine+pyrimethamine) dosed 1 tablet/week. While 50/60
patients experienced adverse reactions to T/S (rash, leukopenia
or GI disturbance) only 6/50 developed rash on Fansidar. No
episodes of Stevens-Johnson syndrome were observed. Bronchoscopy
with TB biopsy was done in 12/60 patients due to respiratory
symptoms. PCP was diagnosed in 5/12 but not found in 7/12 (2 KS,
2 bacterial, 2 CMV, 1 no etiology) . Plasma sulfonamide levels
done in 3/5 patients with recurrent PCP were undetectable. No
hematologic, hepatic or renal toxicity was noted in any patients.
We conclude that Fansidar prophylaxis significantly reduces
the recurrence of PCP in AIDS patients and appears to be well-
tolerated in the majority of patients with previous adverse
reactions to T/S.
THP235 Improvement of Lymphoid Interstitial Pneumonitis in a Child Treated
with Azidothmidine
STEPHEN C. EPPES*. CM. WILFERT*, K.J. WEINHOLD*, M.A. MAHA**, and S.N.
LEHRMAN**, *Duke Univ. Med. Center, Durham, NC, **Burroughs-wellcome, Research
Triangle Park, NC
A seven year old girl with ALL in prolonged remission developed generalized
lymphadenopathy, Strep, pneumoniae septicemia, and bilateral pulmonary infil-
trates three years after she had received blood products from 23 donors. Anti-
body to HIV was present by ELISA and Western blot. She had hypergammaglobulin-
emia, cutaneous anergy, markedly low T4/T8 ratio and low total T4 number. IgG
antibody to EBV capsid antigen was extremely high (1:4096) as was EBV early
antigen (1:512). Her chest x-ray showed diffuse fine nodular opacities through-
out both lungs and bilateral hilar adenopathy. Pulmonary function testing
showed marked restrictive changes, however, blood gases were within normal
limits. Open lung biopsy demonstrated severe chronic inflammation, mainly
lymphocytes, in the perivascular, peribronchial, and interstitial regions and
lympnoid follicles with germinal centers. No pathogens were demonstrated by
routine or special stains. The child received 7 1/2 weeks of azidothymidine in-
travenously; at no point did she receive other antiviral or immunomodulator
therapy .Physical examination, chest x-ray and pulmonary function tests all
showed marked improvement in her lung disease. Her lymphadenopathy and spleno-
megaly also improved during IV therapy. Blood and CSF cultures for HIV, both
initially positive, showed distinctly less RT activity during IV AZT; immuno-
logic parameters did not change significantly during the initial study period.
There were no reductions in the EBV titers. The patient was continued on oral
azidothymidine.
TKP233 *" Antiviral Trial of Rifabutin in Patients with ARC.
H. BURGER*, B. WEISER* , S. NEFF* , K. GEHAN** , R. ANAND***,
F.p. SIEGAL**, *SUNY, stony Brook, NY; **Long Island Jewish Medical Center,
New Hyde Park, NY; ***CDC, Atlanta, GA.
We are evaluating rifabutin (ansamycin, Adria Labs), a rifamycin S deriv-
ative's a therapeutic agent for HIV infection in patients with ARC. Rifabu-
tin was selected as a candidate drug for this phase I-II study because it in-
hibits HIV replication in vitro, enters the central nervous system (B. P.
Davidson et al abstract this meeting) , has minimal toxicity in AIDS patients
treated with low doses for M. avium complex, and is taken orally.
We are treating HIV culture positive ARC patients with escalating doses of
rifabutin. Virologic response is measured by monthly co-cultivation of
patient peripheral mononuclear cells (PMCs) with normal donor PMCs. A signi-
ficant increase in the time interval to positive reverse transcriptase activ-
ity post-treatment compared to pre-treatment is interpreted as a decrease in
circulating HIV titer. We have treated 5 patients with a low daily dose of
450 mg and have followed them for 6-12 weeks clinically, immunologically and
virologically. None of the patients treated at this initial dose showed any
toxicity or change in clinical, immunologic or virologic status, but the serum
levels at 450 mg are below the in vitro effective doses. We have therefore
recently increased the dose to 600 mg daily on the 2 patients who showed no
antiviral effects at 8 weeks (patients were cultured at 4 and 8 weeks) . We
have entered 5 new patients at 600 mg and are continuing the study. Groups of
5 new patients will be entered at escalating doses. The dose for each group
of 5 new patients will be raised by 150 mg until antiviral or toxic effects
are seen. In addition, if no antiviral effect is seen after a patient re-
ceives 8 weeks of therapy at a given dose, the dose will be escalated in the
came manner.
THP236 Phase I study of the use of Lymphoblastoid interferon
HuIFNo<(Ly) and Dif luormethyl-ornithine (DFMO) in the
treatment of Acquired Immune Deficiency Syndrome (AIDS) related
Kaposi's sarcoma.
ADAN RIPS, J. REUBEN, G. BREWTON, AND P.W.A. MANSELL, Univ. of
Texas System Cancer Center/Institute for Immunological Disorders.
HuIFN«(Ly) is active against AIDS-related Kaposi's sarcoma.
(JCO, 1985:506). DFMO augments the in vitro antitumor activity
of interferon. In addition, DFMO may be protective against the
development of Pneumocystis carinii pneumonitis. We therefore
are conducting a phase I study aimed at defining the maximum
tolerated dose (MTD) of the combination of HuIFNoC(Ly) and DFMO
in patients with AIDS-related K.S. The treatment plan, consists,
of the administration of HuIFNei-(Ly) at a dose of 20x10 units/m
intramuscularly (IM) daily x 30 days followed by the administra-
tion of HuIFN<K(Ly) and DFMO in combination. The dose of HuIFNoc
(Ly) remains the same and DFMO was initiated at a dose of 6 grams
/m by continuous infusion every day x 60 days.
Nine patients with AIDS-KS have been treated and major toxici-
ties have been thrombocytopenia and proteinuria. One patient
has had a partial remission. ,
It is anticipated that 20x10 units IM daily x 21 days every 28
days (8 days of rest period) with daily continuous intravenous
administration of DFMO at a dose of 3 grams/m will be the MTD
for this combination. Phase II studies will then be conducted to
determine the therapeutic efficacy of this combination in the
treatment of AIDS-related K.S.
202
THURSDAY, JUNE 4
THP237 Treatment of cytomegalovirus pneumonitis with foscarnet
(trisodium phosphonoformate) in patients with AIDS tr
MICHAEL G. ANDERSON*, C. FARTHING**, M.E. ELLIS1", B.G. GAZZARD**, A. CHANAS
**St Stephens and Westminster Hospitals London UK;"*"Monsall Hospital,
Manchester UK; and^Astra Clinical Research Unit, Edinburgh UK.
Cytomegalovirus (CMV) is a frequent opportunistic infection in patients with
AIDS and is associated with both high morbidity and mortality. CMV
pneumonia has proved particularly difficult to treat with other experimental
agents including 9-( l-3-Dihydroxy-2-propoxymethyl) guanine (DHPG). Foscarnet
(trisodium phosphonoformate) has shown probable benefits when used for
serious CMV infections in other immunosuppressed patients and we therefore
undertook an initial study of this agent in AIDS patients with CMV
pneumonia.
Eight patients were included. Diagnosis of CMV pneumonia was based on
the typical clinical features together with viral culture and the detection
of early antigen fluorescent foci (DEAFF) with monoclonal antibodies in
bronchoalveolar lavage specimens obtained prior to treatment. Following
an initial bolus of 20mg/kg, foscarnet was administered as a continuous
intravenous infusion via a peripheral vein for between 8 and 26 days. The
infusion aimed at keeping the plasma foscarnet level at 150ug/ml. Four
patients had co-existing Pneumocystis carinii (PCP) which had been treated
for at least 3 days without clinical improvement prior to foscarnet
therapy. Therapy for PCP was continued in all patients. All 8 patients
improved following treatment, and 7 left hospital.
Side effects included minor thrombophlebitis, reversible rises in serum
creatinine and reversible anaemia. These results suggest clinical benefit
of foscarnet in CMV pneumonia and a controlled trial is being undertaken.
THP240 imrnune Parameters of Patients with Acquired Immune Deficiency
Syndrome (AIDS) /Kaposi vs Sarcoma (KS) during Human Lymphoblastoid
Interferon Treatment
GEORGEANN C. BARON, N.G. KLIMAS, M.R. ASHMAN, M.A. FISCHL, and M.A. FLETCHER,
Univ. of Miami School of Medicine, Miami, FL, USA,
Immune parameters were assessed for 35 patients with AIDS/KS before and
longitudinally during treatment with human lymphoblastoid interferon (IFN)
(Wellferon). IFN was given intramuscularly at a dose of 20mg/m2 daily for 8
weeks, and patients without progressive disease continued receiving interferon
3 times per week. Immunologic parameters assessed included mononuclear cell
surface marker analysis; natural killer cell activity (%CYT) determined on an
effector cell (CD16+) rtarget cell (K562) ratio of 1:1; proliferative responses
to mitogens and antigen; and serum immunoglobulin levels. Upon enrollment to
therapy protocol, patients had significantly decreased leukocytes, numbers of
lymphocytes, %CD4+ cells; increased %CD8+ cells, %CD16+ cells and %CD14+
cells; decreased %CYT; decreased proliferation to mitogen and antigen
stimulation; increased IgG and IgA compared to normal values. After 12 weeks of
therapy, the patients remaining on protocol showed significant decrease in
leukocyte count, in lymphocyte count, and in proliferative responses to
phytohemagglutinin. There was a significant increase in %CD4+ cells and
increase in %CYT to K56 2 cell line (p=.0 5 repeated measures analysis of
variance). A second group of 22 AIDS patients with more extensive KS received
vinblastine administered intravenously at a dose of 5mg/m2 every 2 weeks
concurrently with IFN therapy. These patients did not show increase in %CD4+
cells or increase in %CYT after 12 weeks on therapy. These data suggest some
degree of immunomodulation in these patients as a result of jri vivo INF therapy
which was not seen in patients with more extensive disease who recived INF plus
chemotherapy.
THR238 Foscarnet-treatment in HIV-infected homosexual men.
Susanne Bergdahl MD, Gunnel Biberfeld MD,Inger Julander MD,Jan-01of
Lernestedt dent, Linda Morfeldt-Manson MD,Birgitta Asjd MD,Clin.depts Inf. Dis.
Immunol, and Virol. ,Karolinska Institute, Stockholm, ASTRA Pharm. , Sweden.
Phosphonoformic acid (Foscarnet) is an antiviral agent with in vitro activity
against some retroviruses including HIV, all human herpes viruses and Hepatit B
virus. Foscarnet selectively inhibits DNA-polymerases and reverse transcrip-
tases. April -85 - April -86 U men aged 20-42 with PGL or ARC and positive HIV-
cultures were treated with continuous infusion of Foscarnet solution in penfe-
ral veins. Treatment period was 2-3 weeks with a dosage of 0.14-0.16 mg/kg/min.
Pharmacokinetics and clinical effects were studied.
Results: Side effects. In 4 pats treatment was discontinued due to nausea.
Nausea, heaBache an3 fatiqe were most frequent and correlated to Foscarnet plas-
ma levels. All pats had a slight to moderate rise in their Se-Krea. levels.
All side effects were rapidly reversible.
Clinical symptoms such as nights sweats, bowel disturbances, fever periods tem-
porarily disappeared or improved in about 80 %. The placebo effect must however
be regarded as high. Follow up period was 3-4 months.
Viral isolations. HIV was isolated in 20/25 cultures taken 6 months - 2 days be-
Fore treatment and in 14/39 cultures from the last day of treatment - 4 months
after. T and T„ cells and immunoglobulins remained unchanged. Lymphocyte
stimulation tests showed no significant changes.
Conclusions: In view of Foscarnets broad antiviral spectrum, the encouraging
clinical and virological results of this study and the reversibility of side-
effects, further and controlled studies are important. Intermittent administra-
tion of Foscarnet for longer periods but with lower doses may be one way.
In vivo antiviral effect against HIV remains to be proven for Foscarnet as well
as for other antiviral drugs against HIV.
THP241 Clinical and Immunologic Improvement in AIDS/ARC Patients Treated
with IMREG -1 , an Immunosupportive Agent
A. ARTHUR GOTTLIEB, M.S. Gottlieb, C.H. Kern. Imreg, Inc. and Tulane Medical
School, New Orleans, LA and Cambridge, MA, USA.
IMREG -1, a potent Immunosupportive agent, isolated from normal human leuko-
cytes by a series of HPLC separations, contains an active small peptide whose
composition indicates that it may be an important link between the neuro-
endocrine and immune systems. IMREG -1 augments delayed hypersensitivity (DTH)
to recall antigens, and enhances the production of MIF, LIF and IL-2 by stimu-
lated T4+ helper cells.
50 patients with AIDS/ARC have been repeatedly treated with IMREG -1 in
protocols lasting several months. Such treatment results in return of DTH in
anergic patients, which is associated with enhanced mitogen induced prolifer-
ative responses and IL-2 production. Such responses have been noted in over
60% of patients, and are associated with sustained stabilization of hematocrit,
platelet and total lymphocyte counts. T4+ helper cell numbers increased or did
not fall in 23 of 48 patients who were followed for three months. Weight gain,
clearing of refractory oral Candida and a decline in serum hyperglobulinemia
and uric acid levels were noted in some patients. IMREG -1 has a peak action
at 7 to 10 days. The most beneficial results were observed in patients having
a minimum residual of 100 T4+ cells/mm . There has been no observable toxicity
following prolonged administration of IMREG -1 for up to three years.
The ability of IMREG -1 to reconstitute the ability of AIDS/ARC patients to
mount antigen-specific immune responses is a fundamental indication of the
effect of this agent on HIV-induced immunodeficiency. These important effects
on the immune system coupled with the beneficial clinical effects observed
suggest that IMREG -1 appears to be useful in ameliorating the immunodeficiency
seen in AIDS/ARC patients.
THP239 Immunological and clinical response
sevoposi tive patients.
JEAN MARIE ANDRIEQ. PHILIPPE EVEN.
STERN, WILLIAM LOWENSTEIN. et al., Lae
Cyclosporin 7.5 my/Ay daily wa s
patients. Their characteristics were
Cyclosporin m 25 HIV
ALAIN VENET, JEAN MAR
nnec HIV study group,
given to 25 HIV seropo
in age: 36 years
sex; males Ji females *, stages II (T4 cells/ul :■ 300. C
/// (Ti/ul ^300); 10. 8 were a symptuma tic . U had persi
lymphadenopathies and 3 had constitutional symptoms . The d
) 6 months with the hypothesis that it CQUld inhibit Lot
and the potential auto-immune component of HIV disease.
significant increase over 600 Ti/ul occurred in ? stages
111. A transient Ti cell peak was only observed in the uth
cells/ul which were > 800 in 16 cases sharply decreased in
lymphadenopathies disappeared m tl/16. After cyclosporin wi
T8 cells as well as lympha-denopathies returned to pre-t
within 2 months. The evolution of treated patients was comp
a matched control group of 56 subjects. After a mean
months, 0/U control and 3/10 treated stage. 111 ewl
oesophageal candidiasis. J reversible Kaposi s sarcoma)
* 1 1,2 and 0/15 for stages II. Cyclosporin side eft
c re j timne increase and anaemia ) were moderate and
results might stimulate biological research as well as dim
Cyclosporin in selected groups of HIV seropositive subjects
delaying or preventing AIDS occurrence. Updated results wi
at the time of the Conference.
C 70URANI
iris, Fr
itive ni«
(range :
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ant gener
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A sustain
II and J
er patien
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ared to
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towards A
he figure
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al trial
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II be pre
. MARC
in-: e ,
n AIDS
0-56) .
stages
alued
en foi
c a t J o i -
ed and
stage
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status
h,,t. ol
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THP242 Variable Serologic Status in Children with Hypogammaglobulinemia (HG)
and Transfusion (TX) Induced HIV Disease
NLC LUBAN*, A. WILLIAMS**, S. JOSEPHS*, V. CRISS*, G. REAMAN*. Children's
Hospital National Medical Center, Jerome H. Holland Laboratory, American Red Cross,
Washington, D.C. and Rockville, M.D.
As part of a prospective study of highly transfused infants and children, we have
identified two children with EIA positive, Western blot (WB) confirmed HIV disease and
subsequently identified HIV infected donors in both. Both children had profound HG at
the time of receipt of the implicated tx and for a time subsequent to its receipt. They
had received units of fresh frozen plasma (FFP) from different donors at 2 days of age
for treatment of severe hyaline membrane disease and at 5 years of age during
therapeutic plasmapheresis for immune thrombocytopenia, from which both recovered.
Both patients remain EIA/WB positive; one has oxygen dependent bronchopulmonary
dysplasia, is now normoglobulinemic, with normal T4/T8 ratio and has positive HIV
cultures, now 2 1/2 years post receipt of the FFP. The other has biopsy proven lymphoid
interstitial pneumonitis, has normal immunoglobulins but reversed T4/T8 ratio. Two
additional children were identified as recipients of blood from HIV infected donors but
were EIA, RIP and WB negative repeatedly despite clinical presentation and symptoms of
AIDS/ARC in both. One received washed packed red blood cells (PRBC) at 25 days of
age and the other FFP at 34 days of age. Both were 26 week gestation premature infants
who had multiple episodes of fungal & bacterial sepsis, Pneumocystis pneumonia,
monoliasis and thrombocytopenia culminating in death at age 49 months and 10 months,
respectively. One had normal immunoglobulins for age prior to receipt of the implicated
unit. Both developed profound HG. One of the two was cultured for HIV and had positive
reverse transcriptase activity on day 21 of culture. Autopsies on both were consistent
with HIV disease. These data suggest that post-transfusion HIV infections result in
variable serological manifestations and that EIA/WB tests alone may be inadequate
diagnostic tools to document HIV disease in some children with HG.
203
THURSDAY, JUNE 4
THR243 EVALUATION OF A SYNTHETIC PEPTIDE BASED HIV-EIA. Barbara Hosein,
William Ying, Louis Baker, William R. Oleszko, Beverley Lightbourne,
and Celso Bianco. The New York Blood Center, NY, NY.
Our center has evaluated a synthetic peptide based ELISA assay for antibody
to HIV developed by UBI-Olympus. The solid-phase antigenic adsorbent employs
polypeptides synthesized chemically with sequences corresponding to highly
antigenic segments of both envelope (gp41) (PNAS 83, 6159-63, 1986) and core
(P24) proteins of HIV.
The initial reactive rate in 2000 random donors who designated their units
for transfusion is 0.85% and the repeat reactive rate is 0.25%. Of the repeat
reactive samples, 40% are positive by Western Blot (WB) analysis. The
specificity if this assay is 99.85%.
Samples (n=505) found to be repeat reactive in other licensed HIV antibody
assays at our center were retested with the synthetic peptide-based assay. All
of the 419 WB positive samples tested were reactive, whereas only 2 of the 86
WB negative samples were reactive.
Sequential samples (n=90) collected at short intervals from 13 individuals
who seroconverted during the period were tested by this assay, by those of six
other manufacturers, and by WB. The peptide based assay detected HIV anti-
bodies earlier than did all other ELISAs in 2 individuals and earlier than or
equal to all other ELISAs in ten other individuals. It detected HIV antibody
two to five weeks prior to detection by WB in 5 of the 13 individuals.
The synthetic peptide based assay has the potential to eliminate
non-specificity associated with host cell antigens. Its detection of antibody
in all WB positive samples studied and its high sensitivity in seroconversion
samples suggest that all individuals exposed to HIV make antibodies against a
restricted set of amino acid sequences of HIV.
THR246 Assessment of the Demographic and Motivational Characteristics of
HIV Seropositive Blood Donors
ALAN ti. WILLIAMS*. S.KLEINMAN**, H. LAMBERSON***, M. P0P0VSKY****, K.
WILLIAMS*, R.D0DD*, et al . Merome H. Holland Laboratory, American Red Cross,
Rockville, MD. **American Red Cross Los Angeles-Orange Counties, ***Syracuse,
N.Y., and ****Northeast Blood Services Regions.
Seventy five male and 14 female blood donors found to be confirmably HIV
seropositive during routine blood donor screening, together with age and sex
matched controls, have been enrolled into a five year multi-center prospective
study. For 59 males (78%), the primary hierarchical risk for HIV infection was
sexual contact with other males; the mean number of partners was 25.5 (range 1-
250). Of 14 males whose primary risk was parenteral, 8 had a history of IV drug
use, and 6 had a history of prior transfusion. No established AIDS risk factors
were found during interviews with 8 seropositive males. Of the 14 HIV+ females
enrolled, the primary hierarchical risk of HIV exposure was sexual contact with
bisexual or IV drug abusing males (50%). Parenteral exposure via drug use or
transfusion was the primary risk for 4 seropositive females. No AIDS risk
factors could be determined for 5 females. Prior STDs were reported in 52% of
index donors vs. 9% of controls.
Forty five percent of index donors suspected that they were in an AIDS risk
group at the time of donation. These individuals reported the following
motivations for blood donation despite self-deferral measures: peer pressure to
proceed with donation (29%), desire to learn HIV status (29%), self-denial of
risk status, or impression that their blood was of particular value (61%),
appeal for self-deferral not taken seriously (6%). Additional interview data
indicated that 65% of donations from subjects with self-recognized AIDS risk
would not have been excluded by a confidential designation that their blood
donation should not be used for transfusion.
THR244 IMPAIRED CELL MEDIATED IMMUNITY (CHI) IN HAEHOPILIA
R_HADHOK_JA GRACIE E FOLLETT A BURNETT GDO LOWE CD FORBES
GLASGOW ROYAL INF UNI DEPT MED GLASGOW SCOTLAND
We and subsequently others have shown that lyophilised factor concentrates
are in immunosupressive in vitro.The aim of this study was to determine if
haemophiliacs treated with factor concentrate show immunosupression.The CMI
response was evaluated in 29 haemophiliacs by means of the DNCB skin test. All
patients had a response below the lower limit of the normal range. No differe
nee was seen in the skin response between pts positive and negative for HIV
In the whole grp.&in seronegative pts . (N=17) there was an inverse correlation
between clotting factor concentrate exposure &the skin response .In HIV posi
tive pts no such association was apparent.
The T-4 count showed a correlation (r=.49)with the skin response in HIV ne
gative patients but not in HIV positive pts. In positive pts. a correlation was
seen with T-8 cnt ■ ( r= ■ 45 ) ■
This study shows that clotting factor concentrate impairs the CMI response
to a new antigen in the absence of HIV infection .Future studies may show
a lower response in positive patients as HIV immunosupression may take years
to devlop.
THP247 Comparative HIV Antibody Testing in Blood Donors
CHERYL A. MCMAHON, N.L. DOCK, H.V. LAMBERSON, American Red Cross
Blood Services, byracuse, NT, USA
We have screened 164,7/5 blood donations for antibody to HIV by two
ELISA's: 120,229 samples were tested by Abbott EIA from Mar. '85 - June '86;
44,546 samples were screened by the DuPont ELISA from July '86 - Dec. '86.
The Abbott initial reactive rate (IR) ranged from 0.2 - 5.8% per week; the
repeat reactive rate (RR) was .44% (range: 0 - 1.5%). Abbott Western blots
(WB) on 531 RR samples were: 488 (.41%) negative. 12 (.01%) positive and 31
(.03%) atypical. The DuPont IR rate was .4 - 1.1%; the RR rate was .57%
(range .2 -.8%). WB performed at Biotech Research Labs (BTRL) on 255 repeat
reactive samples were: 114 (.26%) negative, 3 (.007%) positive and 138
(.31%) atypical. Samples found to be WB positive or atypical were submitted
to both labs for comparison. The same 15 samples were identified as WB(+)
by both labs but there was a wide variation in the reporting of atypical WB.
"ly reported as Abbott WB atypical, 27 (87%) were
DuPont ELISA (-) BTRL WB (-). Subsequent samples on 17/31 have remained
DuPont ELISA(-) BTRL WB(-), 4 others remain BTRL WB atypical. Of the 138
BTRL WB atypical samples, 128 (93%) were Abbott WB(-) and 10 (7%) were
atypical. Eleven of the Abbott (-) DuPont (+) BTRL WB atypical donors have
returned for subsequent donations. Seven of il remain BTRL WB atypical,
Abbott EIA(-) WB(-); 2/11 are now negative on all assays. Two remaining
Abbott EIA(-) DuPont ELISA(+) donors with p24 on both WB's, returned within
2 months, were reactive on both screening assays and were fully positive on
both WB. The original samples from these donors are reactive on the
recently licensed modification of the Abbott EIA. These results suggest
that sensitivity and specificity of screening tests are evolving and that
there is considerable variation in WB procedures. Ongoing comparative
testing of blood donors is essential to assess assay performance and develop
donor notification strategies.
THP245 Characterization of HTLV-III (HIV) and HTLV-I Antibody Reactive
Sera by Specific Western Blot Assays. STEVE S. ALEXANDER, A.J.
BODNER, A.J. CORRIGAN, T. CLEMENT AND W.R. FREDERICK*, Biotech Research
Laboratories, Inc., Rockville, MD and *Howard University Cancer Center,
Washington, D.C.
Western Blot assays have been developed to identify the antibody specificity
of HTLV-III (HIV) and HTLV-I ELISA reactive samples. Most strongly reactive
HTLV-III samples contain antibodies to all major viral proteins: ENV (gp41/160),
GAG (pl7, p24/55) and POL (p31, p51/66). HTLV-I reactivity is primarily
directed against the major gag proteins pl9, p24 and their intermediates.
Both Western Blot assays were carried out on a large group of predominantly
black IV drug users. More than half of the positive sera were reactive in
both assays. The majority of these samples contained antibodies to the major
viral proteins of both viruses indicating co-reactivity rather than cross
reactivity. Previous analysis of another group of HIV positive on HTLV-I and
a HTLV-I group on HIV demonstrated minimal cross reactivity. Concomitant
infection with HTLV-I and HIV has been reported (Harper et al. (1986) New Eng.
J. Med. 315, 1073-1078). Our results indicate a significantly high frequency
of dual exposure/infection among this particular at-risk population.
THP?48 HIV Seroconversions after Heated Clotting Factor Concentrates in
Hemophiliacs .
P. VERANI" F. MANDELLI* G.B. ROSSI*, P.M.
of Rome, Italy;
A. Bianchi
GUGLIELMO MARIANI*
GHIRARDINI*
*Dept. Hematology,
MANNUCCI*" et. al. "Dept. Hematology, "La Sapienza" Univ.
*ffDept. Virology, Istituto Superiore Sanita, Rome, Italy;
Bonomi Hemophilia & Thrombosis Center, Univ. of Milano, Italy.
In Italy, heated concentrates became the only source of hemophilia therapy
since July 1985. Since then 63 anti-HIV seronegative hemophiliacs treated
with heated concentrates were followed-up prospectively, focusing on
seroconversions. Anti-HIV (documented by ELISA and WB) occurred in 6 patients
without other risk factors for HIV infection. For 3, anti-HIV was first found
in Sept., Oct. or Nov. 1985. Another patient seroconverted in Sept. 1986, but
no sample was available after the last negative test (Nov. 1985). For these 4
cases we cannot exclude that seroconversions are due to nonheated
concentrates. The remaining 2 patients seroconverted in July 1986. For both,
a hemophilia A patient (treated only with a concentrate dry-heated for 72 hr
at 68°C) and a hemophilia B patient (treated with both a steam-heated and a
dry-heated concentrate for 72 hr at 68°C) the last seronegativities were found
in March 1986, i.e. 7.0 and 7.5 months after commencing the use of heated
concentrates or 3.5 and 4.0 months before the first seropositivity . In
conclusion, two seroconversions occurred in previously seronegative patients
treated exclusively with heated concentrates. Intensity and duration of
concentrate exposure to heating were greater than those for dry-heated
concentrates (60°C for 30 hr) that induced two reported seroconversions.
204
THURSDAY, JUNE 4
THP9AQ Experience with a Competitive ELISA for HIV Antibody in Blood
inr.£H3 nonors in the USA
JAMES F. KELLY, R.P. ELKINS, B.J. ROSENBERG,
Laboratories, Research Triangle Park, NC USA
The Wellcome Research
Sera and plasma from 12150 blood donors at 4 different geographic
locations were tested with a competitive ELISA for anti-HIV antibody
(Wellcozyroe, Wellcome Diagnostics; Dartford, England) . Samples were tested
in parallel at each site with a noncompetitive assay for HIV antibody. All
samples initially reactive by either HIV ELISA were retested by Wellcome and
examined by western blot. The Wellcome ELISA results obtained by the 4
laboratories are given below:
INITIAL REACTIVES
REPEAT REACTIVES
# Samples
Laboratory
Tested
No.
%
No.
%
A
3,137
6
0.19
2
0.06
B
3,018
7
0.23
1
0.03
C
3,001
6
0.20
1
0.03
D
2,994
1
0.03
0
0
TOTALS
12,150
20
0.16
4
0.03
Only 1 of the 65 initially reactive specimens was reactive on repeat test
in both HIV assays. This sample was also reactive by western blot.
THR250
ABSTRACT NOT AVAILABLE AT TIME OF PRINTING
205
FRIDAY, JUNE 5
Epidemiology— HTV- AIDS Cofactors
p 4 4 U.S. Department of Defense HIV Testing Programs: An Overview.
DONALD S. BURKE*, J.F. BRUNDAGE*, R.R. REDFIELD*. P.W. KELLEY* ,
J.R. HERBOLD**, et al., *Ualter Reed Army Institute of Research, Washington,
D.C., **Offlce of the Assistant Secretary of Defense (Health Affairs),
Washington, D.C.
In 1985 and 1986 the US Department of Defense instituted programs for
routine HIV testing of the following populations: civilian applicants for
military service, active duty personnel, National Guard, and Reserves.
Separate programs are conducted by the Army, the Air Force, and the Navy and
Marines. In all programs, sera are screened by ELISA, and repeatably
positive specimens are tested by Western blot. Through December 1986 over
1.9 million persons have been tested. The mean prevalence rate of positive
Western blots among civilian applicants for military service is 1.5 per 1000
and among active duty personnel it is 1.6 per 1000. Age, male gender, and
black racial group are independent risk factors for seropositlvity. The
ratio of male:female prevalence rates is 2.5:1. A summary of prevalence
data and of demographic factors associated with HIV seropositlvity is
presented.
F.1.4 *ge an<' Cum"latlve Incidence of AIDS among Seropositive Homosexual
Men in High Incidence Areas of San Francisco.
JAMES A. WILEY*, GEORGE W. RUTHERFORD**, ANDREW R. MOSS***, WARREN WINKELSTEIN,
JR.*, *U.C. Berkeley, CA, **San Francisco Department of Health, San Francisco,
CA, ***Unlversity of London, England.
From a probability sample of homosexual men living in 19 census tracts of San
Francisco where AIDS was most prevalent, we estimated the age-specific
prevalence of infection by HIV. By March 31, 1986, 805 cases of AIDS were
diagnosed among an estimated 8,346 seropositive men, aged 25-54, in this area,
yielding a rate of 96.5 cases per 1,000 seropositives (95% confidence interval,
86.6 to 108.8 per 1,000). Cumulative Incidence was more than twice as high
among older (aged 35-54) than among younger (aged 25-34) men (144.5 vs. 67.8
per 1,000, p<.001).
To investigate whether or not the association between age and cumulative
incidence was due to earlier infection of older men, we examined the relation
between current age and serostatus in 1978 in a sample of 394 homosexual men
from the San Francisco City Clinic Cohort. There was no relation between age
and early infection in this sample. Moreover, age was Inversely related to
the rate of seroconversion from 1978 to 1984 (chi-square test for trend - 11.4,
ldf, p<.0001).
We conclude that the higher cumulative incidence of AIDS among older men
cannot be explained by the hypothesis that older infected men seroconverted
earlier than younger infected men. Other hypotheses, including the possible
effects of age-related co-factors of disease progression and of biological
aging, need to be examined.
p "| 2 HLA Phenotypes are Possible Risk Factors for Development of AIDS.
PL MANN*, C_Murray**, JJ Goedert*, WA Blattner*, M Robert-
Guroff*,* National Cancer Institute, Bethesda, MD and Braton
**Biotech, Inc, Rockville, MD
To evaluate a possible immunogenetic role for developing AIDS, we HLA
typed 226 white homosexual males, 91 who were HIV seronegative, 135
seropositive of whom 56 had AIDS (28-Kaposi's (KS), 28-opportunistic
infections (0I)or subsequently developed AIDS. The frequency of individual
HLA antigens in the HIV negative population was similar to North American
Caucasians. HLA-DQ1 was higher in frequency in all AIDS patients (77%)
compared to HIV+ non-AIDS individuals (56%). HLA-DR1 was higher in frequency
in 01 patients (39%) compared to KS (25%) and HIV non-AIDS (16%) HLA-DR3
frequency was 36% in 01 patients, M in KS and 28% of the at risk group.
HLA-DR7 was found in 29% of KS compared to 4% in 01 (HIV+ non-AIDS, 19%).
HLA-DRw53 was also higher in frequency in KS (60%) compared to 01 (15%)
(HIV+ non-AIDS, 44%). In 106 HIV+ individuals enrolled in the study in 1982,
44%+14% DR1 individuals developed AIDS during this 4 year period while AIDS
occurred in only 19%+5% DR1 neg. individuals. Total numbers of CD4+, CD8+
cells were virtually identical in 1982. These data demonstrate that the HLA-
DR phenotype may be associated with an increased risk for developing AIDS
after exposure to HIV and that certain phenotypes may be associated with KS
or 01. The mechanism whereby this risk is conferred is not demonstrable.
However since HLA-D. region molecules are recognition elements in the immune
response, specific molecules may tend to promote or protect in development
of AIDS.
C 1 R Hepatitis B virus coinfection in homosexual men seropositive for
human immunodeficiency virus antibody
DENNIS OSMOND, R.CHAISSON, P.BEASLEY, P.BACCHETTI, A. MOSS. UCSF and SF General
Hospital, San Francisco, California, USA
Among subjects positive for anti-HIV in a cohort of initially healthy homo-
sexual men under prospective study for risk of AIDS, we examined the associa-
tion of HBsAg with impairment of cellular immunity and progression to AIDS. At
baseline 62% (292/469) were seropositive for anti-HIV and 87% (410/469) had one
or more serological markers for HBV. Of HBV seropositives, 10% (39/410) were
seropositive for HBsAg and of HBsAg seropositives 74% (29/39) were also posi-
tive for anti-HIV. Among the 29 HBsAg carriers who are anti-HIV positive, 1
developed AIDS (3%) over 2 years of followup compared to 40 of 258 (16%) anti-
HIV positives who are not HBsAg carriers (OR=0.19,p=0.057) . Comparing anti-HIV
positive subjects with any HBV antibody marker with subjects with no HBV mar-
ker, 38 of 240 (16%) HBV Ab positives developed AIDS versus 2 of 15 (13%) with-
out HBV markers (p=0.78). Among anti-HIV seropositives, HBsAg carriers were
significantly less likely at baseline to have an H/S ratio below 0.6 (OR=0.29,
p=0.025). At 1-year followup HBsAg carriers were again less likely to have an
H/S ratio below 0.6 (OR=0.31 ,p=0.08) . These observations suggest coinfection
with HBsAg may be associated with reduced pathology of HIV infection.
Supported by a grant from the Universitywide Task Force on AIDS.
p 1 Q Familial Tendency to Serious Sequelae of HIV Infection^
N.J. MEROPOL , P.R, K.RAUSE , M.M. LEDERMAN , P.H. LEVINE , M.E.
f.YSTER+, G.C. WHITE++, et al. Case Western Reserve Univ., Cleveland OH,
Univ. Mass., Worcester MA, "'T'enn State Univ., Hershey PA, ++Univ. N. Carolina,
Chapel Hill NC.
Cofactors for the development of serious complications of HIV infection are not well
recognized. To ascertain if genetic factors might contribute to the outcome of HIV
infection, we examined 34 sibships wherein at least two siblings with classic
hemophilia had serologic and/or clinical evidence of HIV infection.
HIV-infected subjects were classified as having a) no symptoms (with or without
generalized lymph node enlargement) b) AIDS related complex (ARC), c) AIDS, d)
thrombocytopenia (T) (< 1 50,000 platelets/uL on at least 2 occasions) e) leukopenia (L)
(<3,000 WBC/uL) or combinations of clinical and hematologic manifestations.
As of December 1986, 31 of 52 patients for whom complete information was available
were asymptomatic. 5 of 52 had developed ARC. 5 of 52 had developed AIDS. 8 of 68 had
L. 13 of 68 had T. Siblings of patients with AIDS or ARC had a 75% chance of having
AIDS, ARC, L or T as opposed to an 11% risk of these complications among sibs of
asymptomatic hemophiliacs (p - 0.003, Fisher Exact). The risk of AIDS or ARC among sibs
of patients with AIDS or ARC was 33% vs. a 10% risk among sibs of patients without AIDS
or ARC (p = 0.22) Siblings of patients with T or L had a 44% chance of also having T or
L as opposed to a 12% chance among sibs of patients without T or L. This concordance
was almost significant (p ■ 0.06). These data suggest that there is a familial
tendency to certain serious complications of HIV infection or that other factors common
to sibs may contribute to the outcome of HIV infection. These observations warrant
longitudinal follow-up of sib pairs and expansion of the study to identify factors that
affect the outcome of HIV infection.
F 1 R Association of Anogenital Ulcer Disease with Human Immunodeficiency Virus
Infection in Homosexual Men
HUNTER HANDSFIELD1'2
HANDSFIELD'^. R. L. ASHLEY^, A. M. ROMPALCT, W. E. STAMM^
R. W. WOOD1'2 and L. COREY2, Seattle-King County Department of Public Health1
and University of Washington School of Medicine , Seattle, Washington, USA
To test the hypothesis that genital or anorectal ulcer disease predisposes to acquisition
of HIV, 2 groups of homosexual men (HM) were studied. Type-specific herpes simplex
virus (HSV) antibody (Ab) was measured by Western blot (WB); HIV Ab was analyzed
by ELISA (Genetic Systems) and WB; the hemagglutination treponemal test for syphilis
(HATTS) was performed. Of 176 HM with acute proctitis or enteritis, all of whom
participated in receptive anal intercourse, 103 (59%) had HIV Ab and 145/167 (87%) had
Ab to HSV-1 and/or HSV-2. HSV-2 Ab was present in 77% of subjects with HIV Ab,
compared with 37% of those without HIV Ab (P<0.0001). By logistic regression, control-
ling for numbers of sex partners in the preceding 1 mo, 6 mo and lifetime and years of
sexual activity, the following were significantly associated with HIV Ab: HSV-2 Ab
(odds ratio [OR)) 4.0, P=0.0005), past history of genital or anorectal herpes (OR 2.7,
P=0.018)), past oral herpes (OR 4.0, P=0.02), and past syphilis (OR 4.8, P=0.0007). In a
separate group of 109 HM seeking AIDS counseling, HSV WB was performed in 99;
HSV-2 Ab was present in 31 (74%) of 42 HIV-positive and 15 (26%) of 57 HIV-
negative subjects (P<0.000l). HATTS was reactive in 9 (18%) of 49 HIV-positive and 3
(5%) of 60 HIV-negative subjects (P=0.047). These associations also persisted when
controlling for number of sex partners. Past HSV infections and syphilis are significant
risk factors for HIV infection in HM, perhaps because they cause mucocutaneous ulcers
that facilitate HIV acquisition.
206
FRIDAY, JUNE 5
Virology — Diagnostics
p 2 1 Correlation between Antibody Response to HIV Antigens, Neutralizing
Antibody Titers and Clinical Status.
FRANC01SE BARRE-SIN0USS1*. F. REY*, S. GHARAKHANIAN**, F. OLLIVIER-HENRY*.
W. ROZENBAUM** and J.C. CHERMANN*, Institut Pasteur, Viral Oncology Unit,
Paris, France, **Piti6-Salp§trieYe Hospital , Paris, France.
The antigen specific antibody response in 159 sera from HIV seropositive
patients has been analysed by Western blot. The samples were including two
sequentiel sera from two groups of individuals. Group 1 was corresponding to
individuals with no evolution in the disease (5 asymptomatic carriers, 28 lym-
phadenopathy and 4 ARC patients). Group 2 was corresponding to patients who
developed AIDS (3 asymptomatic carriers, 15 lymphadenopathy and 6 ARC patients)
In the first group, the mean time between the 2 serum samples was about 30
months whereas in the second group, the mean was approximatively 17 months and
the second serum sample was at the time of the disease. A lower antibody res-
ponse to viral antigens was observed mainly in group 2. Neutralizing antibody
activity of 18 sera from group 1 and of 22 sera from group 2 was also studied.
In group 1, 4 out of 9 patients presenting high antigen antibody response have
increasing neutralizing titers with no changes in Western Blot patterns. In
group 2, 9 out of 11 patients have constant or decreased neutralizing titers
and antibody response. The decrease of neutralizing antibody titers seems to
correlate with the lower antibody response observed in the second serum sample.
The lower reactivity of this sample by Western Blot was concerning mainly the
one to HIV core antigens. Such prospective studies might be important for pre-
dictive status of the disease outcome.
E O A Double HIV-1 and HIV-2 seropositivity in four patients in Paris.
M.HARZIC? Franchise BRUN-VEZINET1 A.G.SAIMOT1 F.COURTOIS^
Y.DOMART? S.WAIN-OBSONl,et al, Hopital Claude Bernard1, Bichat? Louis Mourier?
Institut Pasteur, Paris. France.
The presence of antibodies to both HIV-1 and HIV-2 has already been described
in sera from AIDS patients in Central African Republic and Ivory Coast. This double
seropositivity is probably not a recombinent event but rather a double infection.
We report here four cases of double HIV-1/HIV-2 seropositivity in patients (pts)
who have been living in France for several years. Two originated from West Africa:
pt1 (21 years) born in Ivory Coast has been living in France since 1984, he is a
heterosexual single male with numerous partners, one beeing an intravenous drug
abuser. Pt2 is a 37 years old female from Ghana, having had 2 Ghanaian partners
and living in France since 1978. Pt3 (37 years) and 4 (33 years) are white homo-
sexual males, pt3 having multiple West African partners since 1980. All the 4 pts
presented with AIDS-related complex (group III, subgroup A) diagnosed in 1986.
In the 4 pts IgG antibodies to HIV-1 and HIV-2 were detected by Elisa and
Western blot (Diagnostics Pasteur). Double HIV-1/HIV-2 seropositivity was demons-
trated on the presence of antibodies to HIV-1 (gp160-gp110 and gp41) and HIV-2
(gp130-gp105 and gp 41) envelope glycoproteins. In pts 2, 3 and 4 immunoblot
analysis showed variable reactivities against the gag and pol gene products of HIV-1
and HIV-2. A similar banding pattern for HIV-1 and HIV-2 was observed in sera
collected in 1985 for pt3 and in 1984 for pt4. Retroviral isolates were performed
from the peripheral blood lymphocytes of the 4 pts. Isolates were caracterized by
Southern blot analysis. Neutralizing antibodies to HIV-1 and HIV-2 were evaluated.
These data showed that HIV-2 infection was present in the trench gay community
in 1984. To diagnose HIV-1/HIV-2 double infection HIV-1 and/or HIV-2 Elisa posi-
tive sera should be checked by HIV-1 and HIV-2 Western blot. Evaluation of the
pathogenicity and the extent of this double HIV-1/HIV-2 infection is needed.
C O 9 Virologic Studies in the Diagnosis of Pediatric AIDS
r ■*■* WADE P. PARKS*. E.S. PARKS*, C. HUTTO*, G.B. SCOTT*, J. P.
ALLAIN**, 'Department or" Pediatrics, University of Miami School of
Medicine, Miami, Ft., **Abbott Laboratories, North Chicago, IL.
The diagnosis of AIDS virus infection in infants during the first 12
months postpartum is complicated by the presence of maternal anti-viral
antibody. Virus isolation in infants who present with or subsequently
develop AIDS-associated clinical disease was positive in 78/94 (83%) cases
on the first isolation attempt. All virus positive infants were
seropositive in immunoassays with virion p24 and bacterially synthesized
components of gp41 protein. Two approaches have been utilized to provide
surrogate tests for virus isolation which is currently the definitive
laboratory measure of infection. First, decline of maternal antibody was
evaluated in 6 infants who were born to seropositive mothers but were
themselves not infected as evidenced by normal clinical, immunologic and
virologic findings in a follow-up averaging 36 months (range 26-50 months).
Both p24 antibody and gp41E antibody declined to baseline by 12 months from
high levels immediately post-partum. Conversely, by 12 months of age, all
infected infants had easily detected antiviral antibodies. The second
approach was to utilize a p24 antigen detection ELISA on serum and plasma
from virus positive infants. Antigen positive plasma from 18 infants was
virus positive in 17 instances; 15 patients were antigen negative but virus
positive; all antigen negative virus positive patients had high levels of
anti-p24 antibody. No antigen negative, antibody negative, virus-positive
infants have been detected in over 125 infants that have been
tested. Thus, it is possible to utilize a combination of p24 antigen
detection and anti-p24 antibody determination in pediatric patients to
achieve objective laboratory diagnosis of AIDS virus infection.
C 9 C Efficacy of five HIV enzyme immunoassays (EIA) in detecting
' antibody to HTLV-IV.
F.A. Denis , G. Leonard , M. Mounier , A. Sangare , G. Gershy-Daraet , F.
Barin , et al., C.H.U. Dupuytren, Limoges, France, Institut Pasteur,
Abidjan, Cote d'lvoire, CHRU Bretonneau, Tours, France.
Recent seroepidemiological studies show that STLV-III related human
retroviruses (HTLV-IV, LAV-II) are widely present in West-Africa. Moreover
HTLV-IV- or LAV-II- seropositive subjects have been found occasionally in
Europe. Since no type specific ELISA is yet available we have compared the
performance of 5 HIV commercial EIAs in detecting cross-reactive antibodies
to HTLV-IV. The assays evaluated were from Abbott, Organon, Pasteur (two
wells) and Wellcome. A fifth EIA, from Abbott, was also evaluated. This
EIA is a competitive immunoassay employing as antigen recombinant DNA-
produced HIV proteins (ENVACORE*) . In this assay every sample is tested for
the presence of antibody to either core proteins or envelope proteins.
Preliminary results on 26 sera from healthy West-African residents positive
for antibody to HTLV-IV (serotype specificity assessed by western-blot
and/or radioimraunoprec ipitat ion) indicate that the HIV test kits are not
equally efficient in detecting HTLV-IV antibody positive sera. The Wellcome
test was the less sensitive (42 X posltivity) whereas the ENVAC0RER kit was
the more sensitive (96 X positivity). The Organon, Pasteur, and Abbot first
generation EIA kits detected 73 X, 81 X, and 92 X of HTLV-IV antibody
positive sera, respectively. Futhermore, approximately 50 X of people
exposed to HTLV-IV develop antibodies that cross-react with a recombinant
DNA derived HIV antigen from the env region containing all amino acids of
gp 41 as well as a portion of gp 120. These results indicate that the env
gene products of HIV and HTLV-IV are conserved to the degree that they are
serologically cross-reactive. Results on larger series will be presented.
This data must be considered when regarding African seroepidemiological
studies as well as screening of blood donors.
C 2 3 Identification of HIV Sequence in DNA Extracted Directly from Peripheral
Blood Lymphocytes and Bone Marrow Using In Vitro DNA Amplification.
3QHN 3, SNINSKY1, S. KWOK1, D. MACK1, G. EHRLICTPTP. ULLRICH3, B.
POIESZ2, et al. 'Cetus Corporation, Emeryville, CA, SUNY Upstate Medical
Center, Syracuse, NY, University of California, San Francisco, CA.
While serological tests have significant sensitivity and specificity for the
identification of antibodies against HIV, they do not provide direct identification
of the virus. The identification of virus generally requires co-cultivation of patient
specimen with permissive cells, followed by either assays for reverse transcriptase
activity, immunofluorescence using antibodies to the structural components of the
virus, or Southern blot analysis. Because the number of infected cells is generally
low and due to transcriptional domancy, these procedures are often inadequate for
detection of virus.
We have used the polymerase chain reaction (PCR) and oligomer restriction
(OR) procedures to amplify and detect HIV viral sequences. These procedures are
both sensitive and specific for HIV and can detect as few as 25 genome copies in
200,000 cells. Previously, we reported the successful identification of HIV
sequences in cell lines established from AIDS and ARC patients. These included
cell lines that were devoid of reverse transcriptase activity and/or negative by
Southern blot analysis. We report here that PCR-OR can identify HIV viral
sequences in DNA extracted from mononuclear cells of fresh blood and bone
marrow, thereby eliminating the lengthy process required for cell culturing.
Notably, these procedures have also made possible the identification of HIV viral
sequences in asymptomatic, seropositive individuals as well as in seronegative,
culture positive individuals who are at risk for AIDS. Optimization of the
amplification procedure and overall sensitivity and specificity of the assay will be
presented.
C 2 K Diagnosis of HIV Infection: Utility of Radioimmunoassays for
the Major Internal Antigen (p24) and Transmembrane Envelope
Glycoprotein (gp41) of Human T-Cell Lymphotropic Virus, Type III (HTLV III).
SUSHIL G. DEVARE, J. H. CASEY, D. A. PAUL, H. 0. LEUTHER, J. S. HELLER, G.
J. DAWSON, et al., Abbott Laboratories, North Chicago, IL.
The radioimmunologic techniques have provided invaluable avenues in
epidemiologic studies of retroviruses. In the present studies we have
developed specific and sensitive immunoassays for the major internal antigen
(p24) and the transmembrane envelope glycoprotein (gp41) of HTLV III
purified from the density gradient banded virus preparations. In an attempt
to evaluate their utility In diagnosis, sera from patients with acquired
immunodeficiency syndrome (AIDS), AIDS related complex (ARC), clinically
asymptomatic as well as normal individuals were tested for antibodies to p24
and gp41. High titered antibodies to gp41 could be readily detected 1n 1001
of the sera from AIDS patients, whereas, only 70% of these patients
exhibited antibodies to p24. These data, along with the analysis of sera
obtained from sequential bleeds of patients throughout the course of
Infection and the disease. Indicated that antibodies to gp41 persist, while
the antibodies to p24 are either not detected or have much lower titers
during late stages of infection. The sera from the individuals which lacked
detectable levels of antibodies to p24 were subjected to an enzyme linked
Immunoassay which detects presence of HIV antigens (predominantly p24) in
the body fluids. These analyses revealed that in a large number of cases,
the lack of antibodies to p24 in the sera correlated with the presence of
HIV antigen. Based on these observations, the antibodies to gp41 are the
most consistent marker for evaluation of HTLV III exposure, whereas,
antibody titers to p24 may indicate various stages of the disease.
207
FRIDAY, JUNE 5
Clinical Management — Infections II
C O -J Cross-Allergy to Sulf onamides/Sul f ones (Sulfa), and
folic antagonists in AIDS
ILEANA MEDINA, FEIGEL D, WOFSY C. UCSF School of Medicine, San
Francisco General Hospital, San Francisco, CA , USA.
Thirty AIDS patients who showed sulfa allergy following
Pneumocystis carinii pneumonia (PCP) treatment were rechallenged
with another sulfa. 21 pts received Trimethoprim-sulfamethoxazole
(TS) for first episode PCP and developed a major allergy (9 rash,
10 fever, 5 ^ WBC , 1 1" LFT ' s ) . when they received dapsone/TMP
(DT) for the second PCP, 6/21 showed side effects (4 rash/fever,
1 VwBC, i Opiates) 7-10 d after the initial dose. Four of these
21 pts also received Pyrimethamine (Pyr) and Sulfadiazine (Sdz)
for toxoplasmosis; 2 showed severe rash 2 and 6 wks later. Two
of 21 also received Pyr-Sulf adoxine (Fansidar) for PC?
prophylaxis; 1 developed a rash after 4 wks.
Nine pts were allergic to DT for the 1st episode of PCP (7
rash/fever, 1 ^ WBC 1 -1/ plates); ail 9 received TS for 2nd
episode PCP w/o side effects; 3 received Pyr/Sdz (1 developed
rasn at 10 days; 2 had no side effects); another received
Fansidar w/o incidents. Of the 21 pts with initial TS allergy 3
were rechallenged with TS during a subsequent episode of PCP; 2
pts who received >8 d of TS developed the same- side effect
(rash/ fever) 7 & 10 days after the initial dose. The 3rd received
4 d of TS IV w/o side effect; all finished 21 d of total therapy.
There is no cross-allergy between TS and DT ; often no cross-
allergy between different sulfonamides, sulfones, & folic
antagonists. Rechalienge with the identical agent (TS) is often
well tolerated and may be undertaken in selected circumstances.
F.3.4
Infectious Causes of Diarrhea in Patients (pts) with AIDS.
MA ANTONY, LJ BRANDT, ROBERT S KLEIN, LH BERNSTEIN. Montefiore
Medical Center, Albert Einstein College of Medicine, Bronx, New York, U.S.A.
We retrospectively reviewed the records of 100 pts with AIDS to determine the
rate and spectrum of microorganisms producing diarrhea in this syndrome. 64
pts had diarrhea documented. Diarrhea occurred in 28/35 homosexual or bisexual
men (80%) compared to 37/64 heterosexual subjects (58%) (p< .05).
An infectious cause of diarrhea was found in 36/64 (56%). 11/36 (31%) were
found on ova & parasite examination, 8 by stool culture, 4 by acid fast smear
of stool, 4 by histological examination of a colon biopsy specimen, and 9 by
any combination of these methods. Simultaneous enteric infections occurred in 9
pts. Enteric pathogens identified included Mycobacterium avium- intracellular
(MAI) in 9 pts, cytomegalovirus (6), Cryptosporidium (5), salmonella sp. (5),
Herpes simplex (3), Candida (2), Isospora belli (2), Strongyloides stercoralis
(2) , and 1 each of Giardia lamblia, Schistosoma mansoni, Entamoeba histolytica,
hookworm, Blastocystis hominis, Aeromonas hydrophila, Clostridium difficile,
Campylobacter jejeuni, and adenovirus.
Blood cultures were positive in 19 pts. Isolates included MAI (10), salmonel-
la sp. (5), Campylobacter jejeuni (2), and shigella (2). In 4/5 pts with sal-
monella and all with Campylobacter or shigella, stool cultures were negative.
In 16 pts with a microorganism identified in stool, tissue, or blood, initial
evaluation for the diarrhea led to the diagnosis of AIDS. In the remainder of
those with infectious diarrhea, the diarrhea occurred at a mean of 7.7 months
(range 1-27) after the diagnosis of AIDS.
This study demonstrates that infectious diarrhea is common in pts with AIDS.
Gastrointestinal infections associated with diarrhea are often multiple (25%).
MAI is the most commonly identified cause of diarrhea in our pts. Diarrhea in
AIDS occurs more commonly in homosexual or bisexual men than In heterosexuals.
F3 2 Diminished Sulf a-Trimethoprim ( ST ) Toxicity in Black
Treated for Pneumocystis carinii Pneumonia(PCP).
E. HAZEL, N. SETHI, G. JACQUETTE, J. DOBKIN. Harlem Hospital a
Columbia U. College of Physicians and Surgeons, New York, N. Y
ST therapy of PCP has been reported to produce frequent and
severe toxicity in mainly white AIDS patients(pts). In 54 pts
blacks) with AIDS treated for PCP no ST rashes occurred. One
white pt had mild rash due to oxacillin. Neutropenia < NP ) was
frequent and milder and began later than reported previously
despite the normally lower white blood counts(WBC) of blacks.
54 pts (table) 23 had NP (drop of 1000 to WBC below 2500) but
only 13 had to have ST stopped (D/C). Male homosexuals (MH)(7
blacks, 1 white) had no NP. Median onset of NP was 9 days on
Treatment failures (ST f ail) , pentamidine ( Pent ) use and deat
paralell other reports, but toxicity is strikingly less.
GROUP #CASES #NP #D/C Onset #ST Fail #Pent #Death
nd
(53
less
Of
ST.
hs
Females
12
6
2
14
2
3
1
Male IVDA
33
17
11
8
7
13
7
HH
8
0
0
-
5
5
1
Total»« 54 23 13 9
( IVDA=iv drug abuser; *»one MH/
Thirteen patients had WBC<4000
WBC drops while on ST (mean loves
only 5 required ST discont inuatio
in black AIDS pts. Low WBC does
therapy and most blacks even with
course. Use of ST prophylaxis for
15 22 10
IVDA patient added to total)
before ST therapy: 10 had slight
WBC=1.9; range: 1. 4-3. 2) but
ST toxicity is markedly lower
ot contraindicate ST as initial
low wbc can tolerate a full ST
PCP in blacks may be feasible.
F 3 5 AIDS and AIDS Related Complex: Oral Manifestations and Treatment
MARIO ANDRI0LO, JR., St. Clare's Hospital and Health Center, New York, NY, USA
Fifty (50) people with AIDS/ARC, undergoing dental treatment, were evaluated
for AIDS related infections and malignancies in the oral cavity. Candidiasis
was the most common manifestation (53%), with the lateral borders of the
tongue usually involved. Other sites were the floor of the mouth, palate,
buccal mucosa and pharynx. Treatment consisted of several anti-fungal drugs,
depending on severity and longevity of infection. Oral Kaposi's sarcoma
lesions (32%) showed the palate and gingiva as the most common sites, while
tongue and tonsillar involvement was seen. Lesions that interfere with
patient comfort and function may require chemotherapy, radiation, laser or
surgical treatments. Hairy leukoplakia (23%) was seen almost exclusively on
the lateral borders of the tongue, with one case on the buccal mucosa. All
but one patient had superimposed candidal infections or a history of
candidiasis. Treatment could include anti-fungal and/or anti-herpetic drugs,
although lesions seem to regress and recur independently. Gingival and
periodontal problems (20%) included gingival pain resembling acute necrotizing
ulcerative gingivitis (ANUG) and accelerated deterioration of pre-existing
periodontal conditions. Acute infections required antibiotic therapy, but
gentle debridement and careful scaling and root planing eliminated most
problems. Stomatitis (12%), seen here as a chronic infection, can be painful
and debilitating. Herpetic gingivostomatitis, on the keratinizing and
non-keratinizing mucosa, was treated with anti-herpetic drugs and major
apthous ulcerations responded to topical antibiotics. No oral manifestations
were seen in 12% of the patients.
F 3 3 Oral Therapy for Pneumocystis carinii Pneumonia (PCP) in
AIDS. A Randomized Double Blind Trial of Trimethoprim
Sulfamethoxazole (S) Versus Dapsone Trimethoprim (D) for First
Episode Pneumocystis carinii Pneumonia in AIDS.
ILEANA MEDINA, G LE0UNG , J MILLS, P HOPEWELL, D FEIGEL, C WOFSY,
UCSF School of Medicine, San Francisco General Hospital, SF, USA.
Fifty-eight AIDS pts with first episode PCP and a p02 >60 on
room air were randomized to S (TMP/SMX 20/100 mg/kg/d) or D
(dapsone 100 mg + TM? 20 mg/kg/d divided by 4) for 21 days (14
days inpt; 1 wk outpt). At entry, groups were equally matched.
Patients with clinical failure (severe decline by day 4 or no
improvement at day 7) or severe toxicity were switched to IV
pentamidine. Clinical failure occurred in 4 pts (2 S, 2D); 2
failed at 4 days; 2 at < 24 hrs . Major toxicity occurred in 24
pts (see table); 19 additional pts had minor rash. 29 pts (34.4
as) required hospitalization for at ieast 4 days due to symptoms;
38 pts (65.4%) could have avoided all hospitalization. Daily
monitoring for toxicity was needed in 27 (13 S, 14 D) between
55 have been followed greater than 3 months with
days 9 and 14
7 relapses in
Toxicity
Sash >48 hrs
WBC <750
LFT's 5X nl
and 4
n=29
2
5
6
in D.
D n=29
3
1
1
Toxicity
Platelets <40X
MethemagloDin >20
Nausea & Vomiting
S n=29
D n=2<
1
1
2
In 1st episode PCP, oral D and S are equally effective. S showed
higher incidence of major toxicities (JW3C , +LFT ' s ) p=.0049.
Outpt therapy is appropriate for pts with p02 >60. Frequent
laboratory monitoring is required in the 2nd week of therapy.
F 3 6 ^ne Value °f Liver Biopsy in the Diagnosis of Mycobacterial
Infection in AIDS Patients
DAVID S. RUBIN, G.S. SIDHU, W. EL-SADR, M.S. SIMBERKOFF, NYVAMC, New York, NY
Sixty-five liver biopsies(Lvbx) from patients with AIDS were reviewed. We
analyzed pathological (path) , microbiologic culture (Cx) and liver function tests
(LFTs) . Biopsies were divided into 3 groups: Group(Gp) A(23 pts) had positive
path and/or Cx for acid fast bacteria(AFB) in the Lvbx(all M. avium- intracellul-
are[MAI]); 13/26(56%) had granulomata(10 were poorly formed), 7/23(30%) had
hepatitis, both portal and lobular. Gp B(18 pts) having negative AFB on path
and Cx in liver but Cx positive in bronchial fluid(13) ,blood(3) , lymph nodes(3),
bone marrow(2) ,urine(l) ,spleen(l) and colon(l). Fourteen pts had MAI,3MTb,
1 M.gordonae and 1 M.kansasii. Poorly formed granulomata were seen in 2 and
hepatitis in 16. Gp C(23 pts) had no evidence of AFB from any site(13 Lvbx with
hepatitis, 4 with granulomata, 1 with lymphoma and 5 normal). The meantS.D. for
alkaline phosphatase was 643±711 , 195+239 and 241+190 mU/ml for Gp A,B and C,
respectively. There was a significant difference between alk. phos. in Gp A and
Gp B(pC.02) and Gp A and Gp C(p=.0148). There was a significant association
between granulomata and AFB in Lvbx(p^.OOl) . Mycobacteremia was associated with
AFB in Lvbx(pC.Ol), but in 5/17(29%) in Gp A blood Cxs were negative and thus
would not have indicated the presence of AFB disease. The yield of AFB was
15/30(50%) in blood, 23/41(56%) in Lvbx and 26/31(83%) in bronchial secretions.
Lvbx was helpful in the management in 32/65(49%) of pts.
We conclude that Lvbx may speed the diagnosis of disseminated AFB(in 13/23
the diagnosis was rapidly evident on path). Granulomata on Lvbx, albeit poorly
formed, and elevated alkaline phosphatase were both strongly associated with
AFB in the liver.
208
FRIDAY, JUNE 5
Immunology — Immunopathogenesis
P 4 1 Influences of Related Retroviruses on Human Lymphocyte Functions
SAVTTA PAHWA*. R. PAHWA**, R.A. GOOD**, C. SAXINGER***, *North
Shore University Hospital, Cornell University Medical College, Manhasset, NY,
"All Children's Hospital, University of S. Florida, St. Petersburg, FL,
♦"National Cancer Institute, Bethesda, MD.
Infection with the human immunodeficiency virus (HIV) can lead to profound
perturbations of the immune system as well as to clinical disease. In
contrast, two related retroviruses, the human lymphotropic virus type IV
(HTLV-IV) and the Simian lymphotropic virus type III (STLV-III) have not been
associated with clinical disease in their infected hosts. In this study,
these viruses were grown up in the Hut-78 cell line, concentrated,
band-purified and disrupted. Protein-rich preparations of these viruses were
compared for their influences on functions of B- and T lymphocytes of
healthy, HIV-uninfected donors. As described previously, the HIV protein
preparation could induce a T-dependent, polyclonal response in B lymphocyte
cultures resulting in immunoglobulin secretion. In contrast, the other two
viral preparations did not cause either proliferation or differentiation of
normal B lymphocytes. Pokeweed mitogen-induced B cell differentiation
responses were inhibited in a dose-dependent manner with HIV but minimally
with HTLV-IV or STLV-III. None of the viral preparations induced a blasto-
genic response in peripheral blood lymphocyte cultures. T lymphoproliferative
responses to mitogens, antigens and allo-antigens were inhibited somewhat
inconsistently and to varying degrees by these viral preparations, but most
regularly with HIV. These findings suggest that these viruses differ in their
capacity for causing immunologic dysfunction.
p A A Altered IL-2 Gene Expression in HIV Infected Peripheral Blood
CD4+ Lymphocytes: Possible Mechanism for Virus Induced T Cell
Death for the Immunopathogenesis of AIDS
H. CLIFFORD LANE*, M. DUKOVICH**, S. MCCARTHY*, A.S. FAUCI*, w. GREENE**.
♦National Institutes of Health, Bethesda, MD, **Howard Hughes Medical
Institute, Duke University School of Medicine, Durham, NC.
The peripheral blood lymphocytes of patients infected with HIV exhibit a
variety of immunologic abnormalities the most consistent being a decrease in
the number and function of CD4+ T lymphocytes. Several mechanism have been
postulated to account for this defect HIV envelope protein induced cell
fusion, and the intracellular accumulation of non-integrated viral DNA. The
present study was designed to determine the effects of HIV infection on IL-2
gene expression in CD4+ peripheral blood lymphocytes. IL-2 production, a
protein since this protein plays a central role in T cell growth and
differentiation. Purified peripheral blood CD4+ lymphocytes were infected with
HIV and maintained in culture for 14 days. Non-infected cells were maintained
in culture as a control. On various days following infection cells were
removed and stimulated for 12-18 hours with PHA/PMA. These cell cultures were
assayed by FACS analysis, in situ hybridization and northern blot
hybridization. CD4+ cells infected with HIV progressively lost the CD4
antigen, while retaining CD3 reactivity with virtually all cells being
CD3+/CD4- by day 14. Northern blot analysis revealed that cells infected with
HIV underwent a progressive and marked reduction in IL-2 gene expression. In
contrast the expression of the IL-2 receptor on several other cellular genes
was not altered by HIV infection. This pronounced inhibition of IL-2 gene
expression induced by HIV infection may contribute to the death of CD4+, the
lymphocytes in patients with AIDS.
C A 9 Homologous Peptides From HIV P41 and HLA CLASS II Bind CD4 on
Human T Cells
HANA COLDING, FRANK A. ROBEY, FREDERICK T. GATES, III, WOLFGANG LINDNER and
BASIL GOLDING, NCI, NIH; DBP and DBBP, FDA; Bethesda, MD 20892.
The CD4 molecule has been identified as the receptor for HIV envelope protein.
Recently, the possible natural ligand for CD4 on antigen presenting cells has
been localized to the (3-1 domain of MHC class II. It was postulated that the
MHC class II and HIV bind the non-polymorphic CD4 via similar conserved regions .
A hydrophilic septamer was identified displaying a high degree of homology be-
tween p41 of HIV and the 8-1 domain of HLA-DR and -DQ . Both the HIV and MHC
class II derived septamers were synthesized. Incubation of these peptides, but
not control peptides, with CD4 positive cells at 37°C for 45 min resulted in
reduced binding of anti-CD4 antibodies ( 0KT4 , 0KT4a, Leu3) to the cells. This
reduction of binding to CD4 could be blocked in the presence of chloroquin.
Binding of antibodies directed against other surface antigens, were unaffected
by pre-incubation with the peptides. The temperature requirement and sensi-
tivity to chloroquin suggest that the peptides induced partial modulation of
the CD4 molecules via receptor mediated endocytosis. In addition, flow cyto-
metry showed that blotinylated chicken albumin conjugates of the peptides can
bind directly to CD4 bearing CEM cells, but not to a CD4 negative CEM mutant
or to B cell lines. This binding could be partially inhibited in the presence
of mouse monoclonal anti-CD4 antibodies. In addition, solubilized CEM mem-
branes were passed over a column of immobilized HIV-derived peptide. The
bound material which was eluted with the soluble peptide contained a 57,000
dalton material which was positively stained with 0KT4 + 0KT4a reagents using
Western blot analysis. These findings suggest that, the homologous regions
of HIV and MHC class II, which we have identified, may be the sites involved
in binding of AIDS virus and MHC class II antigens to CD4 on human T cells.
P 4 5 A Synthetic Peptide Homologous To HIV gpl20 Envelope Glycoprotein
Inhibits IL-2 Production. T. C. CHANH, B. E. ALDERETE, G. D.
FRENZEL, G. R. DREESMAN, R. C. KENNEDY, P.
Biomedical Research, San Antonio, Texas.
KANDA. Southwest Foundation for
We have chemically synthesized a peptide homologous to sequence 304-321
of the HIV gpl20 envelope glycoprotein. Peptide 304-321 was found to
decrease the production of IL-2 of a gibbon cell line MLA-144,
Phytohemagglutinin-Induced IL-2 production by normal human peripheral blood
mononuclear cells was also reduced in the presence of peptide 304-321.
Incubation of the IL-2 dependent murine CTLL-2 with peptide 304-321
resulted in a decrease in the uptake of H-thymidine, whereas control
peptides have no effect. HIV peptide-lnduced inhibition of CTLL-2
proliferation could be partially restored by addition of exogenous IL-2.
Peptide 304-321 had no effect on the expression of IL-2 receptor (IL-2r)
since peptide-treated and -untreated cells express comparable amount of IL-
2r as detected by immunofluorescence using a monoclonal antibody to IL-2r.
These data together with recently published results on viral Induced-
immunosuppresion support further studies in the role of HIV envelope
glycoprotein In the Immunodeficiency observed in AIDS.
p 4 3 HLA-DR is Involved in the HIV Receptor
DEAN L. MANN, F LESANE.WA BLATTNER, M POPOVIC, National Cancer
Institute, Bethesda, MD.
Cells procured from human tissues that can be infected with HIV express
both the CD4 molecule and major histocompatibility class (MHC) class II
antigens. We therefore, investigated the interaction of HIV with cell
surface CD4 molecules and (MHC) II antigens. Exposing whole virus
preparations for 15 min to a cultured T lymphocyte line and
phytohemagglutinin (PHA) stimulated peripheral blood lymphocytes (PBL)
resulted in a decrease in the CD4a epitope and in HLA-DR cell surface
antigens while HLA-DP and HLA-DQ increased or remained unchanged. After 120
min of virus exposure, the CD4a epitope remained diminished while HLA-DR
returned to the levels of detection found on cells not exposed to virus.
The specific portion of HIV that binds the CD4 molecule has been shown to be
the large envelope protein, gpl20. When immunopuri fied gpl20 was added to
PHA stimulated and unstimulated PBL, the CD4 epitope decreased in the same
manner as was observed with whole virus preparations. However, in contrast
to the binding of whole virus preparation, HLA-DR expression increased after
15 min of exposure to gpl20. These studies show that HLA-DR and the CD4
molecule are involved in the receptor for HIV binding and suggest a dynamic
role for a CD4-HLA-DR complex in HIV attachment to target cells.
p 4 K PERIPHERAL BLOOD ADHERENT CELLS FROM AIDS PATIENTS INHIBIT NORMAL
T-CELL COLONY GROWTH THROUGH DECREASED EXPRESSION OF INTERLEUKIN
2-RECEPTORS AND PRODUCTION OF INTERLEUKIN 2.
Y. LUNARDI-ISKANDAR*. V. GEORGOULIAS*, D. VITTECOQ**, F. BARRE-SINOUSSI***,
J.C. CHERMANN***, C. JASMIN* et al., *INSERM U 268, Hop. Paul Brousse, B.P.
200, 94804 VillejuTf Ce'dex, France ; Service des maladies infectieuses.
Hop. Saint Louis, PARIS and ***Dpt of Virology, Institut Pasteur, PARIS,
France.
Colony formation in semi-solid media from peripheral blood T-cell colony-
forming cells (T-CFC) of AIDS patients is extremely impaired. To define whether
the low plating efficiency is due to inhibition mechanisms or/and to decreased
clonogenici ty of T-CFC, patients' peripheral blood mononuclear cells (PBMC)
were fractionated into T-cell enriched and T-cell depleted subpopulations.
Both cell fractions failed to generate T cell colonies although colony growth
could be obtained from unfractionated PBMC. In 5 out of 12 AIDS patients,
adherent cell-depletion of PBMC enhanced the plating efficiency. Moreover,
patients' but not normal adherent cells could inhibit normal T-cell colony
growth in a dose-dependent manner. Media conditiosed by patients' unstimulated
adherent cells (LCM-A+p) also inhibit normal T-cell colony formation. In
addition, LCM-A+p could inhibit interleukin 2-receptor (IL2-R) expression
and Interleukin 2 (IL2) production by normal mitogen-stimulated T cells.
These LCM-A+p did not contain detectable reverse transcriptase activity or
could not infect the Human Immunodeficiency Virus (HlV)-permissive T-cell
line CEM. Conversely, this adherent-cell-derived inhibitory activity could
be abrogated by both heating and treatment with proteolytic enzymes. These
findings indicate that the low T-cell colony formation in some AIDS patients
could be due to inhibitory adherent cell-derived activities.
209
FRIDAY, JUNE 5
F 5.1 Confidentiality and the Duty to Protect: The Limits of Autonomy
in the Case of AIDS
RONALD BAYER, CAROL LEVINE and SUSAN M. WOLF, The Hastings Center, Hastings-
on-Hudson, N.Y., USA.
Autonomy — the right to control one's own life, including the right to
privacy — is a basic ethical principle. In the case of HIV infection, which
can be transmitted through sex and blood to others, autonomy comes into
conflict with the harm principle — the obligation to prevent harm to others.
There are both legal duties to protect third parties placed at risk by a
person with HIV infection and moral duties, and the two are not necessarily
coextensive. This paper explores the moral duties, in comparison to the
legal ones. It presents an ethical framework for guiding physicians and
health care providers, public health officials, and others who have knowledge
of a person's HIV infection. The paper considers clinical, residential or
institutional, and public settings. It addresses such questions as: How
ought physicians and health care providers respond when HIV-infected
individuals refuse to notify their sexual or drug-using partners? What are
the moral, professional, and social costs of breaches of confidentiality,
compared to the possible benefits of notification? What kinds of public
health program can protect the interests of those already infected, those
who may be infected, and those currently at risk?
F 5 4 Anti-Discrimination Legislation and the Reduction of
Social Disruption Caused by AIDS
GREGORY J. TILLETT, New South Wales Anti-Discrimination Board,
Sydney, Australia
Extensive community fear of AIDS has led to widespread
discrimination against people who have or who are perceived to
have AIDS, especially in the area of employment, but also in
service provision (including health and welfare services) ,
accommodation and education. Breaches of confidentiality,
invasion of privacy and violation of duty of care have also
been reported.
Anti-discrimination and human rights legislation has been
used in an attempt to protect the rights of those who have
been subjected to AIDS-related discrimination. In some cases,
pre-existing legislation has been used, in others, AIDS-
specific legislation has been introduced.
Ten cases of AIDS-related discrimination are surveyed, and
four cases analyzed in detail to assess the effectiveness
of such legislation. By itself, legislation does not enable
problems based on fear of a terminal illness or prejudice
against a traditionally stigmatized minority to be resolved.
Legislation, however, provides an important symbolic and
statutary support for attitudinal change through education.
F.5.2
Ethical Dilemmas Inherent in HIV Antibody Testing Legislation: A One Year Retro-
spective
NANCY J. KAUFMAN, J. VERGERONT, H. FRISBY, Wisconsin Division of Health, Madison, Wisconsin
In November, 1985, the Wisconsin Legislature enacted unique legislation, protecting the confi-
dentiality and rights of persons with HIV infections while protecting the public's health by re-
quiring HIV antibody-positive case reporting. Provisions include HIV testing informed written con-
sent procedures, a specific listing of persons to whom test results may be disclosed, reporting of
positive, validated test results to the state epidemiologist, restrictions on the use of antibody
test results for insurance underwriting and employment, and civil and criminal penalties for un-
lawful disclosure.
Ethical dilemmas faced by the bill's drafters were the following: 1) Would confidentiality/con-
sent procedures and reporting requirements deter physicians from testing? 2) Would reporting of
antibody-positives deter individuals from seeking testing? 3) Would physicians comply with re-
porting requ i rements?
Data collected from alternate sites and Wisconsin's public health laboratory were analyzed one
year post implementation to determine antibody testing practices, patterns, and reporting effica-
cy. Of the 4,487 antibody tests performed, 57S were from private physicians, indicating their
willingness to participate in the program and the willingness of at-risk individuals to be tested
without anonymity. Of persons tested by private practitioners, 4.62 were western-blot positive,
compared to 7.5J positivity for those tested at alternate sites. The reporting requirement of the
new law may have encouraged higher risk individuals to seek anonymous testing. Use of alternate
sites and private physicians has increased steadily, irrespective of the legislation. Of the 117
positives tested by private physicians, 712 (83) were reported to the state epidemiologist. Com-
pliance is adequate for first year implementation.
Public policy makers need to consider the effect that HIV antibody testing legislation will have
on encouraging at-risk individuals to seek testing, counseling, and medical supervision. Wiscon-
sin data indicate that such legislation did not deter individuals from seeking assistance.
F 5 5 Legal and Ethical Analysis of Insurance Underwriting for
AIDS
BENJAMIN SCHATZ, ESQ., Director, AIDS Civil Rights Project, Nat-
ional Gay Rights Advocates, San Francisco, CA.
Presents results of article which will appear in June '87 Har-
vard Law Review. Reviews approaches used by insurance companies to
eliminate applicants at high risk for AIDS, and evaluates their le-
gal and social impact. Concludes that insurers have legal right to
exclude applicants diagnosed with AIDS or ARC. Attempts by insurers
to eliminate all gay male applicants are also documented, and are
shown to violate state insurance laws, recommended policy of Nat-
oinal Association of Insurance Commissioners, and state and local
law prohibiting discrimination in public accomodations. Such eff-
orts also increase employment discrimination, decrease candor of
gay and bisexual males towards physicians and sexual partners, and
increase financial burden on govt, programs such as Medicare, Medi-
caid and public hospitals.
Use of HIV antibody test results by insurers is shown to violate
laws or insurance department policies in 13 jurisdictions. Legal
precedent for such laws exists in 11 states which prohibit genetic
testing by insurers. HIV antibody testing by insurers is demonstra-
ted to discourage voluntary testing, deter participation in res-
earch studies, and impede vaccine trials. Such testing also viol-
ates F.D.A. labeling of the test, omits the crucial component of
counseling, and cannot be guaranteed to be confidential. Financial
argument used by insurers to justify testing is shown to be "exagg-
erated.
F.5.3
AIDS: Transfusion and Litigation
BARR, DUNCAN.
J.D.
LISA T. UNGERER, J.D., SUSAN J. RIEFEL, J.D.,
O'CONNOR, COHN, DILLON & BARR, San Francisco, California
Concurrent with the medical disaster presented by the spread of AIDS is
the filing of lawsuits by individuals who have been exposed to or have
contracted AIDS through blood transfusions or use of Antihemophilic Factor
VIII. The authors are currently defending approximately fifty such lawsuits.
In some instances, hemophiliacs have brought lawsuits in the form of class
action, wherein the class action representative claims to represent the
interest of all hemophiliacs claiming similar injuries. No Court to date has
allowed this type of action; if this occurs, it would have a detrimental
effect on all AIDS patients because of the invasion of privacy and
interference with the physician/patient relationship.
While HIV antibody tests are now used by all blood banks and plasma
centers, the number of transfusion related AIDS cases will continue to
increase because of the incubation t ime between exposure and onset of
symptoms.
Litigation is growing in tandem with reported cases of AIDS. The very
future existence of non-profit volunteer blood banks is in question as
insurance for AIDS lawsuits is now unavailable. The authors address the
future of TAA litigation and the future question of the obligation and
ethics of blood banks in contacting the recipients of blood obtained from
individuals who, subsequent to blood donation, test positive for HIV anti-
body.
F.5.6
DAVID I.
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1 AIDS Discrimination Laws as Public Health Ed-
Tools for Preventing HIV Transmission
*, M. KARP**, N. NICKENS***, Los Angeles City
**New York City Commission on Human Rights,
Human Rights Commission.
the Los Angeles City Council passed the na-
discrimination law, receiving national media
ter created a special AIDS Discrimination Unit,
e since been created in San Francisco and New
, heads of these three units, have handled
discrimination complaints in the employment,
n, government, business, dental and medical
e vast majority have been handled without
their philosophy of early intervention and
e disputes.
ines the nature of AIDS discrimination disputes
te to attitudinal change about AIDS. It addres-
hich the public's desire to obey local AIDS
ws can be used as effective public health
or compelling citizens to learn about HIV
role of stigma and taboo are discussed as they
rvention and mediation of disputes. Specific
funeral societies in New York and the dental
Angeles, as well as related San Francisco
died to reveal the importance of locally-based,
ent attorneys experienced in community organi-
n successfully conducting such intervention.
210
FRIDAY, JUNE 5
Epidemiology — Other Retroviruses
F fi 1 Lymphadenopathy Associated Virus Type 2 (LAV2) - Seroepidemiological
' Study in Cape Verde islands.
FRANCOISE BRUN-VEZINET*. C. KATLAMA' , D. CEUNINCK**, D. ANDRADE* , D. DARIO",
M.A. REY, et al.'Hopital Claude-Bernard, Paris, France, "Delegado da Saude,
Santiago, Cape Verde.
A new human retrovirus (LAV2/HIV2) was isolated from an AIDS patient from
Cape Verde Islands; therefore we designed a seroepidemiological study to
evaluate the presence of HIV2 infection in this country. In the main island,
Praia-Santiago, 236 subjects (217 males, 19 females) were tested : 93 soldiers,
110 prisoners, 13 blood-donors and 20 hospitalized patients. In the second
island, Sal, sera were taken from 144 subjects (67 males, 77 females). All sera
were tested for antibodies to HIV1 (HIVl-Ab) and HIV2 (HIV2-Ab) by Elisa and
confirmed by Western blot. In Sal, all sera were negative for both HIVl-Ab and
HIV2-Ab; in Praia, all were HIVl-Ab 9 and 15/236 were HIV2-Ab 9 : 13 were
healthy subjects (2 soldiers, 9 prisoners and 2 blood-donors) and 2 women had
clinical symptoms consistent with AIDS. None were homosexual men nor drug
addicts. 7/15 had previous history of sexually transmitted diseases (STD) (7
patients) or transfusion (1 patient). No significant difference was found
between the 9 HIV2-Ab 9 and the 101 HIV2-Ab 9 prisoners considering mean age
(29.6 years vs 27.6), previous transfusion (1/9 vs 4/101), STD (5/9 vs 40/101)
or travel to other African countries (1/9 vs 3/101). 4/15 HIV2-Ab 9 sera were
completely negative by HIV1 Elisa.
This study assessed the presence of HIV2 infection in Cape Verde islands;
heterosexual contacts seem to be the predominant route of HIV2 transmission.
Moreover HIV1 Elisa can miss HIV2 antibodies. Therefore blood-bank screening
as seroepidemiological surveys must include, at least in Western Africa, both
HIV1 and HIV2 assays.
F 6 4 Transmission of HTLV-I and HIV Among Homosexual Men in Trinidad.
' ' WILLIAM A BLATTNER*, F CLEGHORN", WC SAXINGER*, 8 MAHABIR*",
B HULL-DRYSDALE"", C BARTHOLOMEW**. *Natl Cancer Institute, Bethesda, MO
20892, "The General Hospital, and ***Caribbean Medical Centre, and ****Pan
American Health Organization, Port-of-Spain, Trinidad.
Risk factors for HTLV-I and HIV infection were evaluated among a cohort of
100 homosexual /bisexual men in Trinidad. The high seropositivity for HTLV-I
(15%, a six-fold increase compared to general population rates) and the finding
that duration of homosexuality and number of sexual partners were associated
with increased seropositivity suggested that HTLV-I like HIV can be transmitted
by homosexual sex. Forty percent of homosexuals compared to 0.19% of a general
population comparison group were seropositive for HIV, and sexual contact with
U.S. men was the major risk factor. Prior history of gonorrhea, a marker of
sexual promiscuity, was associated with HIV seropositivity as well. HIV
seroprevalence was three times higher than that for HTLV-I, suggesting that HIV
is more efficiently transmitted, especially since HIV appears to be recently
introduced into Trinidad while HTLV-I is endemic. Markers of altered immune
status were most perturbed in 6 study subjects coinfected with HTLV-I and -III.
One case of HTLV-I-associated adult T-cell leukemia (ATL) in an HIV infected
homosexual raises the possibility that HIV coinfection accelerated the
pathogenesis of clinical ATL. Interactions between human retroviruses may
amplify their clinical effects, a hypothesis that will require further
consideration in populations and in areas where multiple human retroviruses
occur.
/
F.6.2
Prevalence of HIV and STLV- III related human T-lymphotropic retrovirus (HTLV-
IV) 1n several populations of Ivory-Coast, West-Africa.
G. LEONARD*, F. BAR1N**. A. SANGARE***, G. GERSHV-DAHET***, J.L. REV***, F.
DENIS*, et al . , *CHU Dupuytren, Limoges, France, ** CHU Bretonneau, Tours, *** Institut Pasteur
and INSP, Abidjan, Ivory-Coast.
The sera from 2900 individuals were collected from January to December 1986 in six geographic
areas of Ivory Coast. Sera were tested for antibody to HIV by a commercially available ELISA
(Abbott). All the sera which gave a ratio sample absorbance /cut-off value over 0.80 were
subsequently tested by two western-blots using either HTLV-IIIg or HTLV-IVp289 as antigenic
probes. The results indicate that both viruses, HIV and STLV- III related human retrovirus-
HTLV-IV-, are widely present in Ivory-Coast. Briefly the results are as follows :
- In control populations (without any risk factor) including 300 children and 850 adults,
the adult prevalences were 2.7 J for HIV and 0.4 » for HTLV-IV.
- In populations with risk factors were included :
. 350 patients receiving multiple injections. The prevalences were 6.1 % for HIV and 1.8
* for HTLV-IV
. 1200 individuals having multiple sexual partners (prostitutes, prisoners, ...). The
prevalences were 8.9 * for HIV and 9.9 I for HTLV-IV. 2.9 I had serological evidence of
exposure to both viruses.
. 200 inpatients presenting with pulmonary infections associated with asthenia and weight
loss (considered as AIDS related symptoms). The prevalences were 19 I for HIV and 8 %
for HTLV-IV. 13 % had antibodies to both serotypes evidenced by reactivities to envelope
glycoproteins of HTLV-IIIB and HTLV-IV.
The coexistence of both HIV and STLV-III related retrovirus -HTLV-IV- In Ivory Coast will
allow prospective studies providing important informations on the natural history of diseases
associated with these two viruses in Africa.
p 6 5 Emerging High Rates of Human T-Cell Lymphotropic Virus Type I
(HTLV-I) and HIV Infection Among U.S. Drug Abusers (DA).
STANLEY H. WEISS*, H.M. GINZBURG*. W.C. SAXINGER*, K.P. CANTOR*, F.K. MUND0N**,
D.H. ZIMMERMAN**, W.A. BLATTNER*. *National Cancer Institute, Bethesda MD,
**Electro-Nucleonics, Inc., Columbia MD.
HTLV-I is associated with adult T-cell leukemia (ATL) in Japan and in
populations of African ancestry in the Caribbean basin and bordering areas
including southern U.S. blacks. Endemic virus infection is observed in areas
where ATL may account for >50% of adult non-Hodgkin's lymphoma. Surveys of U.S.
populations document low or absent HTLV-I seroprevalence in most study groups.
Following-up our finding of 16% seropositivity for HTLV-I among Queens, NY DA
(JAMA 255:3133), we surveyed 963 New Jersey (N.J.) and 214 New Orleans, LA
(N.0.) DA. Sera were screened for HTLV-I antibodies by ELISA and confirmed
by immunofluorescence, competition and/or immunoblot.
SEROPREVALENCE BY LOCATION AND RACE
BLACK DA NON-BLACK DA
SITE (year) HTLV-I HIV BOTH HTLV-I HIV BOTH
N.0. (1985) 49.3% 0.0% 0.0% 6.6% 2.6% 1.3%
N.J. (1984) 30.2% 45.0% 15.5% 8.5% 31.0% 3.2%
Black DA were significantly more likely to be HTLV-I seropositive than
whites or Hispanics. Almost 50% of black N.0. DA were HTLV-I positive but HIV
was absent suggesting that HTLV-I is an older endemic virus in this population.
The elevated HTLV-I infection rates in the non-black DA raise the possibility
that new spread of HTLV-I is emerging as a consequence of paraphernalia
sharing. There are potential public health implications of this trend
including long term sequelae such as lymphomas/leukemias and neurologic
diseases, heightened risk to the blood supply, and potential for adverse
modification of HIV natural history from retroviral co-infection.
p C 3 LAV2/HTLV IV INFECTION AMONG BLOOD DONORS. HULTITRANSFUSED
PATIENTS AND DIFFERENT AIDS RISK GROUPS. IN FRANCE.
A.M. C0UR0UCE - Ch. R0UZI0UX - F. BAR IN - S. CHAMARET and the RETROVIRUS
study group of the french society of blood transfusion - Paris FRANCE -
Since the discovery of a 2nd virus responsible for AIDS in West-Africa,
5 blood donors have been found LAV2/HTLV IV seropositive in different french
blood banks during 1986 :
- A man from Senegal with multiple heterosexual partners
- A french man living with a LAV2 positive woman from Ivory Coast
- A french heterosexual man and I.V. drug user, having stayed in Ivory Coast.
- An heterosexual man from Ivory Coast living in France for 4 years,
- The french wife of a LAV2 positive man from Ivory Coast.
All of them have been detected thanRs to a positive reaction by LAV1 Elisa.
They gave unusual pattern by Western-Blot analysis (WB)= clear bands on
p25 and p34 only. They were strongly positive by WB-LAV2 (Diagnostics Pasteur)
and RIPA-LAV2.
In addition, a multi-Centre study has been made by Elisa LAV2 (Diagnostics
Pasteur) on 1145 sera : 210 polytransfused patients, 167 hemophiliacs, 452
IV drug users, 123 subjects from Africa and 193 sera which recognized only
core proteins (pl8 or p25) by WB. None of them have been found LAV2
seropositive.
These results suggest a West African localisation for this second AIDS
virus and a very low prevalence of this virus among blood donors collected
in France.
Further studies on over 9000 blood donors are in progress.
F 6 6 HTLV-IV and HTLV-I I I/HIV in West Africa
PHYLLIS KANKI*. S. M'BOUP**, F. BARIN***, D. RICARD*. F. DENIS****,
M. ESSEX*, et al ., *Harvard School of Public Health, Boston, MA, "University
of Dakar, Dakar, SENEGAL, *"University of Tours, Tours, FRANCE, ""Univer-
sity of Limoges, Limoges, FRANCE.
A new human T-lymphotropic virus has been recently described from healthy
West Africans. A unique feature of preliminary studies with HTLV-IV indicated
that in contrast to HTLV-I I I/HIV it was not associated with classic AIDS or
related disorders. We present data on 4,248 serum samples from Senegal,
Guinea, Guinea Bissau, Mauritania, Burkino Faso, and Ivory Coast. Control,
sexually active risk and disease populations including AIDS were sampled from
1985 to 1987 and analyzed for reactivity to HTLV-IV and HTLV-III/HIV by radio-
immunoprecipitation and SDS/PAGE and immunoblotting. Evidence for HTLV-IV
infection was found in 5 of 6 countries, however the seroprevalence rates
varied markedly (l%-32% overall). Healthy sexually active risk groups demon-
strated higher levels of HTLV-IV infection compared to healthy control and
disease groups including AIDS. The seroprevalence of HTLV-III/HIV infection
also varied from country to country and highly correlated with the rare cases
of AIDS diagnosed; seroprevalence for HTLV-III/HIV was uniformly lower than
that of HTLV-IV. It is not clear if HTLV-IV is a completely non-pathogenic
HTLV, however the biology of this virus infection shows marked differences
from that of HTLV-III/HIV and the pathogenesis of AIDS. The existence of at
least two cross-reactive HTLVs in many countries of West Africa indicates the
necessity for distinguishing serologic assays such as RIP-SDS/PAGE and immuno-
blot analysis. Present data indicates HTLV-IV is not correlated with AIDS or
other related disorders. This points out the need for health policy that will
address issues of prevention and control for T-lymphotropic viruses of
differing Dathoge inicity.
211
FRIDAY, JUNE 5
Virology — Animal Models
C ~1 •% Infection of Rhesus Macaques with HIV-2 .
PATRICIA N. FULTZ*, WILLIAM M. SWITZER*. and LUC MONTAGNIER**, *AIDS
Program, Centers for Disease Control, Atlanta, GA, **Institut Pasteur, Paris,
France.
We have attempted to infect rhesus macaques with four different isolates of
human immunodeficiency virus type 2 (HIV-2, originally called LAV-2). Eight
macaques, ranging in age from 18 months to 5 years, were given intravenous in-
jections of cell-free virus using the ROD and MIR isolates. Fourteen weeks
after inoculation, three animals received a second injection of virus. At time
of rechallenge, one rhesus had serum antibodies to env gene products, gp!40 and
gp34, which we detected by immunoblot and radioimmunoprecipitation assays.
Within 7 weeks of the second inoculation, two other macaques had seroconverted
with antibodies to gp34 and gpl40; however, virus had not been isolated up to
9 months after the initial injection of virus. More recently, two additional
HIV-2 isolates, EHO and DIA, were each injected into one rhesus 3 days after
xenogeneic stimulation of the animals with 10' human lymphocytes. Virus was
isolated from peripheral blood mononuclear cells of the rhesus that received
EHO at both 2 and 4 weeks after inoculation, but serum was antibody negative
both times. These data suggest that the EHO strain of HIV-2 may be more infec-
tious for macaques than other isolates tested. We have injected EHO recovered
from rhesus PBMC into additional animals to determine whether infections can be
established readily with this strain of HIV-2. A model system using macaques
and the human virus HIV-2 would be extremely important in developing a vaccine
against HIV, since a wider range of experimental vaccines could be tested than
is feasible with the more limited chimpanzee-HIV system.
C 1 A Expression of Human Immunodeficiency Virus Long Terminal Repeat
in Transgenic Mice.
JOHN M. LEONARD*, HOWARD E. GENDELMAN* , JASPAL KHILLAN**, ADIO ADACHI*,
MONTE MELTZER***, HEINER WESTPHAL**, and MALCOLM A. MARTIN*.
*LMM, NIAID* **LMG, NIAID; National Institutes of Health, Bethesda, MD 20892;
and ***Walter Reed Army Institute of Research, Washington, DC.
Transgenic mice were constructed that contain the human immunodeficiency
virus (HIV) long terminal repeat (LTR) driving the bacterial enzyme
chloramphenicol acetyl transferase (CAT) . Independently derived transgenic
animals showed a consistent tissue pattern of high CAT expression in thymus,
heart, tail, and lens epithelium; intermediate CAT levels in spleen; and no
CAT activity in brain, liver, lymph nodes, monocytes, and peripheral blood
lymphocytes (PBL) . Peritoneal macrophages, stimulated in vitro by
supernatants from activated murine lymphocytes, showed an 8-fold increase in
CAT expression when compared to unactivated cells. When T-lymphocytes from
transgenic animals were propagated in the presence of IL-2, a 10-fold increase
of CAT activity over unstimulated T-cells was seen. In addition, the
stimulated T-cells exhibited an approximately 5-fold further augementation of
CAT activity when infected with human adenovirus type-5 or herpes simplex virus
type-1. These results show that tissue, immunologic, and virologic factors
influence expression of the HIV LTR in these animals. This transgenic mouse
system represents a safe and potentially valuable method of evaluate the
effects of cellular and viral transactivators on dormant HIV proviruses.
C 7 O Response of Pig-tailed Macaques to SIV/SMM Infection
HAROLD M. MCCLURE*, D.C. ANDERSON*, R.B. SWENSON*, J. ORKIN*,
E.A. STROBERT*, AND P.N. FULTZ**, *Yerkes Primate Research Center, Emory
University, Atlanta, GA, **AIDS Program, Centers for Disease Control, Atlanta,
GA.
A pig-tailed macaque, inoculated IV with SIV/SMM, developed a viremia that
persisted until death 14 months post-inoculation (PI) . The animal had chronic
diarrhea, lymphadenopathy , lymphopenia and thrombocytopenia and terminally was
anemic and ataxic. Autopsy revealed emaciation (22% wt. loss) and generalized
lymphadenopathy and splenomegaly. Histology revealed lymphoid depletion and
multinucleated giant cells in lymph nodes, spleen, intestine, brain and most
other tissues. The animal also had cryptosporidiosis, and retrovirus was
isolated from multiple tissues, including the brain. Blood transfusions from
this animal to 3 other macaques resulted in acute disease in all 3 recipients.
Two of these died at 7 and 9 days PI and the third is recovering from a clini-
cal disease that included diarrhea, weight loss , anemia, thrombocytopenia and
oral candidiasis. Animals which died had generalized lymphadenopathy, spleno-
megaly and hyperplasia, hemorrhage and necrosis of lymphoid tissue of the in-
testine. Histologically, lymphoid tissues were reactive and contained foci of
necrosis and multinucleated giant cells. Bacterial organisms were not isolated
or demonstrated by special stains in tissue sections. Three additional
macaques were inoculated with a retrovirus isolated from either the initial
case or a transfusion recipient. All 3 developed acute disease within 5 days
and died within 7-8 days PI. Lesions in all 3 animals were identical to those
seen in the transfusion recipients. These observations suggest that SIV/SMM is
more pathogenic in the pig-tailed macaque or that the virus has become more
virulent after passage in one animal (supported by NIH grant no. RR-00165) .
F.7.5
The Isolation of a T-lymphotropic Lentivlrus from
Cats with an Immunodeficiency Syndrome
E.W.HO , R.MUNN
Davis, CA.
UCD School
NIELS C. PEDERSEN", J.K.YAMAM0T0", E.E. SPA&GER'
of Veterinary Medicine, UCD School of Medicine
A lentivirus, highly tropic for T-lymphocytes, has been isolated from FeLV
negative cats with an immunodeficiency-like syndrome. A lentivirus present in
the blood or plasma of 3 affected cats was passaged into specific pathogen free
(SPF) kittens and then into cultures of ConA and 11-2 stimulated cat lymphocytes.
Virus from infected SPF kittens or cultures has been injected into a larger
number of SPF kittens, some having been now observed for more than 10 months.
Infected kittens developed a transient fever and leukopenia several weeks after
inoculation. This was followed by a generalized lymphadenopathy persisting for
months.
Disease seen In naturally infected cats appeared 1/2 to 4 years or more after
infection. At this stage, generalized lymphadenopathy was not as pronounced,
but chronic infections of the nasal cavity, conjunctiva, gums, intestines, skin,
ears, and sometimes nervous system, were prevalent. Affected animals survived
in ill-health for months or years before dying. Anemia was seen terminally in
some naturally and experimentally Infected cats.
The virus is widespread among cats but is Infectious only after prolonged and
intimate contact. The feline lentivirus appears antigenically and genetically
distinct, but structurally and morphologically similar, to HIV and other animal
lentiviruses. Serologic tests confirmed a strong relationship between this
virus infection and acquired immunodeficiency. This is the first animal lenti-
virus other than those of Old-world primates that has been T-lymphotropic and
associated with acquired immunodeficiency-like syndromes.
F 7 3 Natural and Experimental Infection of Macaques With the Simian
Immunodeficiency Virus
RONALD C. DESROSIERS, M.D. DANIEL, M. KANNAGI, P.K. SEHGAL, N.W. KING, N.L.
LETVIN, et al., Harvard Medical School, New England Regional Primate Research
Center, 1 Pine Hill Drive, Southborough, MA.
Three of 848 macaques (0.35%) of the NERPRC colony had antibodies to simian
immunodeficiency virus (SIV); SIV has now been isolated from these three
macaques (two Macaca mulatta and one Macaca f ascicularis ) . Analysis of stored
sera and earlier studies have revealed six additional macaques, now dead, who
previously were infected naturally with SIV while at NERPRC. Three of these
six had lymphoprolif erative syndromes /lymphomas. SIV was also isolated from
two of these macaques. In one case, in utero transmission was documented. A
total of 16 juvenile rhesus macaques have been inoculated with SIV grown in
human peripheral blood lymphocytes or in HUT-78 cells. Eight of the macaques
died 129-352 days post-inoculation with a variety of clinical and pathologic
findings paralleling those of AIDS in humans. The other eight macaques became
persistently infected for prolonged periods; these eight macaques remain alive
537-820 days post inoculation despite the continued ability to isolate SIV and
persistent lymphadenopathy. The ability to survive infection correlated
directly with the strength of the antibody response. There was no correlation
of the dose of virus inoculum with either the strength of the antibody
response or clinical outcome. Antibodies readily detected by ELISA and by
immunofluorescence have been induced in macaques by ISC0M and inactivated
virus vaccines; these antibodies recognized the 160/120 kd presumed envelope
protein. Vaccinated macaques were not protected against persistent infection
by intravenous inoculation of SIV. Additional vaccinations using larger
amounts of column purified SIV are in progress in order to define conditions
needed to achieve protective immunity.
F 7 fi Evaluation of an HTLV-III gpl20 Prototype Vaccine in Chimpanzees
U LARRY 0. ARTHUR*, W.G. ROBEY**, S.W. PYLE* , J.W. BESS, JR.*, P.
NARA**, J. KELLIHER***, D. BOLOGNESI, R.V. GILDEN, AND P.J. FISCHINGER,
♦Program Resources, Inc., NCI-Frederick Cancer Research Facility (FCRF),
Frederick, MD 21701, **0ffice of the Director, Virus Control Unit, NCI-FCRF,
Frederick, MD 21701, Primate Research Institute, Alamogordo, NM 88330, USA.
Currently, the only known experimental animal reproducably infectable with
human immunodeficiency virus (HIV) is the chimpanzee. We have inoculated
chimpanzees with a prototype subunit vaccine consisting of the 120,000-dalton
external outer envelope protein of HTLV-IIIb. The gpl20 was purified from
detergent extracts of membranes of HTLV-IIIb-infected H9 cells by immunoaffin-
ity chromatography as previously described (Robey, et al. PNAS 83: 7023,
1986). Experimental animals inoculated with the gpl20 prototype vaccine
developed antibodies which precipitated the gpl20 and neutralized HTLV-IIIb in
in vitro infectivity assays. The chimpanzees received 4 inoculations, 50 ug
each, of gpl20 prototype vaccine. All chimpanzees were found to have anti-
bodies to gpl20 as detected by 125I~gpl20 radioimmune precipitation assays and
neutralizations of HTLV-IIIb in vitro infections. Antibody to the major core
antigen, p24, was not detected in the vaccinated chimpanzees indicating the
purity of the gpl20 vaccine preparation. HTLV-IIIb viral stocks have been
prepared and titered in vitro and, after in vivo infectivity titration in
chimpanzees, will be used to challenge the vaccinated animals. If the vaccin-
ated animals can resist challenge with the homologous virus, challenge with a
heterologous virus will be evaluated.
Research sponsored, at least in part, by the National Cancer Institute,
DHHS, under Contract Number N01-CO-23910 with Program Resources, Inc.
212
FRIDAY, JUNE 5
Prevention/Public Health — Monitoring
Changes in Sexual Behavior
F.8.1 Self-Reported Behavioral Change In Homosexual Men in the San
Francisco City Clinic Cohort
LYNDA S. DOLL*, W. DARRUW* , P. O'MALLEY**, T. BODECKER**, H. JAFFE*; *AIDS
Program, Center for Infectious Diseases, CDC, Atlanta, GA, **San Francisco
Department of Public Health, San Francisco, CA.
Although studies have documented recent declines in high-risk sexual
behaviors in homosexual men , none have used information collected before the
AIDS epidemic as a baseline for assessing behavioral change. Of 125 men who
answered questions regarding their sexual practices in iy78, 1984, and 1985,
90% had reduced their number of nonsteady partners between 1978 and 1985. The
number of nonsteady partners decreased from a median of 16 in the previous 4
months in 1978 to 1 in 1985. Comparison of men who decreased their number of
nonsteady partners between 1978 and 1984 with those who did not showed no
demographic differences between the groups. Exposure risk from insertive and
receptive anogenital and orogenital contact declined significantly between
1978 and 1984, although anogenital contact failed to decline further in 1985.
Overall decline for orogenital contacts , while significant , was not as
dramatic. Comparison of long-term negatives (52% of sample) with men who
serocon verted between ly 78 and 1984 (41% of sample) showed that sero convert or s
were younger (mean=28 years) than long-term negatives (mean=33 years). Both
groups significantly decreased their number of nonsteady partners and their
participation in high-risk sexual practices. The groups did not differ in
their decrease in these activities over the 7 -year period. While these
dramatic declines provide an indirect and positive evaluation of risk-
reduction educational programming, in 1985, some men continued to engage in
high-risk behaviors. These data emphasize the need to characterize men who
have and have not changed their behavior in response to the AIDS epidemic .
F 8 4 Changes in Sexual Activities Among Participants in the Multicenter
AIDS Cohort Study
ROBIN FOX, D. Ostrow, R. Valdisseri, M. Van Raden, B. Visscher, B.F. Polk, for
the Multicenter AIDS Cohort Study, NIH, Bethesda, MD
4,955 gay/bisexual men were enrolled in a prospective study of the natural
history of HIV infection. Data on self-reported sexual activities were
collected at four 6-month intervals beginning in April, 1984. We observed a
study increase in celibacy [2% - 12%) and monogamy (12% - 27%) and a decrease
in number of partners. In general, there was a reduction in all high risk
behaviors; the proportion not practicing receptive anal intercourse increased
from 26% to 49%. Fisting was uncommon at baseline and has become a rare prac-
tice. Use of douches/enemas has declined markedly. At baseline, 66% of MACS
participants reported use of nitrite inhalants; this proportion had declined
to 44% at the fourth visit.
The use of condoms with anal sex (either receptive on insertive) doubled
over the course of 4 visits, but still less than one-third reported using con-
doms with anal sex. The direction and magnitude of reported changes in activi-
ties varied modestly when stratified by race, age, city, education or HIV
antibody status. We do not now have data to determine whether our participants
are becoming more selective in choosing partners who have similar serologic
status. We will present information on behavior changes through five visits.
These data demonstrate a marked and continued decrease in sexual practices
that increase risk of HIV infection. However, further reductions are clearly
warranted. Safe sex education programs must be improved, expanded and
sustained.
F 8 2 Prevention of HIV Infection Among Gay and Bisexual Men: Two
' Longitudinal Studies. Co-Authors: L. MCKUSICK, THOMAS J. COATES,
J. A. WILEY, S.F. MORIN, R. STALL, University of California, San Francisco,
School of Medicine. This presentation will focus on levels of high risk
sexual behavior and predictors of compliance to safe sex guidelines among gay
and bisexual men in San Francisco. The first cohort is a sample of 700 men
recruited for participation in 1983 and 1984 as the epidemic was just beginning
in San Francisco. The San Francisco Men's Health Study is a population-based
sample of 843 single men from the 19 census tracts in San Francisco with the
highest cumulative incidence of AIDS in 1984. They have also lowered
significantly rates of participation in dangerous sexual activity. As of May,
1985, approximately 25% of the cohort were still engaged in at least one high
risk sexual act per month which involved sex outside of a primary relationship.
Our most recent analyses of predictors of levels of high risk sexual activity,
cross-validated in both cohorts, identified 8 variables to be significantly
related (R= .47, p is less than .001) to sustained low risk activity in a
multiple regression analysis. Personal efficacy (the belief that one is capable
of making recommended changes), was most powerfully associated with level of
risk activity. Men in relationships were also found to be engaged more
frequently in behavior that might transmit HIV than men not in relationships.
Depression was greater in those who subsequently reduced risk. Younger men
were more likely to be engaged in high risk activity and level of agreement
with risk reduction guidelines was related to low risk activity. Denial of the
virulance of the epidemic was related to continued high risk activity.
Holding a visual image of AIDS deterioration was related to low risk activity.
Finally, levels of both drug and alcohol use during sexual activity was related
to non-compliance with safe sex practices.
F.8.5
Declining incidence of sexually transmitted diseases as a result of
an AIDS-prevention campaign.
B.D.P. EIJROND*. J.A.R. VAN DEN HOEK**, J. A. EMSBROEK**, F. JANSEN SCHOONHOVEN
**, R.A. COUTINHO**; * AIDS policy co-ordination of the Netherlands; ** Muni-
cipal Health Service Amsterdam.
An AIDS-prevention campaign especially directed towards homosexual men started
in the Netherlands in 1983. This campaign was nationwide but a special effort
was made in Amsterdam. To see what influence this campaign had on the lifestyle
of homosexual men, we studied rectal (RG) and homosexually acquired (HAG) male
cases of gonorrhoea treated at the STD-clinics of the Municipal Health Service:
1981 1982 1983 1984 1985
year
male cases total
of RG (%)
gonorrhoea HAG (%)
3,407 3,139 2,837 2,380 2,051
451 (13.2) 502 (16.0) 471 (16.6) 271(11.4) 218 (10.6)
1,060(31.1) 1,137(36.2) 1,013(35.7) 570(23.9) 435 (21.2)
The incidence of syphilis among men in Amsterdam was in 1981 108, in 1982 110,
in 1983 101, in 1984 91,5 and in 1985 53 per 100,000.
From these data we conclude that homosexual men in Amsterdam changed their
sexual lifestyle since 1984.
Data from 1986 will be presented at the conference.
F 8 3 Condom Use in a Cohort of Gay & Bisexual Men
RONALD 0. VALDISERRI, D. LYTER, C. CALLAHAN, L. KINGSLEY , C. RINALD0,
AIDS Prevention Project & Pitt Men's Study, University of Pittsburgh, Pgh. , PA
Between 5/1/86 and 12/1/86 503 gay and bisexual men enrolled in a prospective
study of HIV Infection were surveyed concerning their attitudes and use of con-
doms. 328 (65%) reported at least one episode of anal intercourse during the 6
months prior to the survey and constitute the study population. Most men were
non-monogamous with 72% reporting 2-100 sexual partners in the last 6 months.
24% reported half or more of their sexual partners were anonymous. Although a
majority (90%) endorsed the belief that condoms can "reduce the spread of AIDS,"
62% stated that they "never" or "hardly ever" wore a condom during anal Inter-
course in the last 6 months and 64% stated that their partners "never" or "hard-
ly ever" wore condoms during anal intercourse. 8% of the men reported a past
experience of condom breakage but the majority indicated this happened only
once. 5% reported a past experience of condom slippage, usually before ejacu-
lation; but again most (60%) related that this was rare or happened only once.
Factors involved in the underutilization of condoms in this population may re-
late- to the following surveyed perceptions: condoms spoil sex (22%); purchas-
ing condoms is embarrassing (18%); using condoms "turns off" partners (16%);
condoms are not readily available (22%); or condoms are only used by "straights"
(26%). Their underutilization is probably not related to deficits in knowledge
since 91% identified receptive anal intercourse as the highest risk sexual ac-
tivity vis-a-vis AIDS transmission. Also, the fact that 35% reported that they
were "high" on alcohol/drugs with half or more of their partners may contribute
to this underutilization. Finally, this underutilization may relate to the re-
latively low incidence of AIDS in Pittsburgh, and the fact that 60% of our
group did not personally know someone with AIDS.
F 8 6 ^se °^ an AIDS Hotline as an Educational Tool as well as a Measure
of Effectiveness of Outreach Efforts.
INDIRA KOTVAL, B.M. Branson, T. Widmark, W. Hansen-Sparks. Health Edu-
cation Resource Organization, Baltimore, MO, USA
HERO has conducted an AIDS information and referral hotline since 1983. A
record of each call was kept, and analysed to identify trends, to characterize
the different types of caller, and to categorize the type of information asked
or advice sought.
This analysis demonstrated that the hotline was primarily an information tool,
rather than a crisis or counseling service. In order of frequency, callers were
gay white males (33.7%|, straight white females (28.3%), gay black males (10.5%)
and straight black females (8.5%). The majority of calls (53.3%) were for gen-
eral information on AIDS; 14.3% of calls were for referrals to antibody testing
sites, 8.1% asked symptoms of AIDS, and only 2.1% of callers were seeking
counseling.
Analysis of calls after subsequent targeted outreach efforts by HERO to
specific groups (minorities, IV drug users) indicated an increase of calls from
these groups. This suggests that tracking of hotline calls can be used to help
evaluate the effectiveness of outreach efforts.
213
FRIDAY, JUNE 5
Immunology — Viral Replication
C Q 1 Mononuclear Phagocytes and Accessory Cells in the Pathogenesis
of AIDS
MIKULAS POPOVIC, S. GARTNER AND R.C. GALLO, Laboratory of Tumor Cell
Biology, NCI/NIH, Bethesda, MD.
Several lines of evidence indicate that, ^n vivo, cells other than T4+
lymphocytes harbor HTLV-I II/LAV. Using a number of different methods,
extensive studies of brain, lung, lymph node and skin tissues from HTLV-
III/LAV-positive individuals clearly established that the virus-positive
cells belong to the mononuclear phagocyte lineage. In brain tissue the
virus-positive cells exhibited characteristics of monocyte/macrophages, in
the lung they were mainly alveolar macrophages, in the lymph nodes they
were the follicular dendritic cells and, in the epidermis, the Langerhans
cells were HTLV-III/LAV positive. I_n vitro virological studies using
monocyte/macrophages as targets demonstrated that these cells are highly
susceptible to and permissive for the virus, particularly those isolates
which were recovered from cells of the mononuclear phagocyte lineage. The
longevity of virus production, the cytopathic effect and the presence of
infectious virus particles within vacuoles indicates that these types of
cells represent not only targets for HTLV-III/LAV, but perhaps more
importantly, they are the primary source of virus persistence Jji vivo.
Moreover, the normal physiological role of mononuclear phagocytes strongly
suggests that these virus-infected cells are responsible for virus
dissemination. The biological properties as well as the nucleic acid
analysis of several isolates recovered from various types of cells from the
mononuclear phagocyte lineage will be discussed.
P Q 4 INFECTION OF HUMAN BONE HARROW CELLS BY THE HUMAN IMMUNODEFICIENCY
VIRUS (HIV).
Y. LUNARDI-ISKANDAR*, M.T. NUGEYRE**, V. GEORGOULIAS*, F. BARRE-SINOUSSI**,
CLAUDE JASMIN*, J.C. CHERMANN** et al., *INSERM U268, Hop. Paul Brousse,
B.P. 200, 94804 Villejuif Ce'dex, France and ^Department of Virology, Institut
Pasteur, 25, rue du Dr. Roux, 75015 PARIS, France.
In order to examine whether immature T cell precursors are infectable by
HIV, normal bone marrow cells were infected in vitro, before and after deple-
tion of mature T cells with 0KT3 or Til plus complement. The culture was
performed in the presence of phytohemagglutinin (PHA) and recombinant IL2
(rIL2). Five to 105! of unfractionated or T-cell depleted bone marrow cells
were specifically labelled with a fluorescein-conjugated HIV preparation.
The peak of reverse transcriptase activity was detected at day 15 in all
cases. At this time, infected cultures of T-cell depleted bone marrow were
composed of T3+(50-55%), T8+(50-55%) but not T4+ (less than 2%) cells whereas
non-infected cultures were composed of T3+(70-78%), T8+(15-20X) and T4+(50-55X)
cells. Non-infected bone marrow cells generated a relatively high number
of T-cell colonies in methyl eel lulose (more than 100 colonies/5xl04 cells
at day 15) whereas for infected cells, both unfractionated and cell fractions,
displayed a time-dependent impaired T-cell colony growth capacity (less than
20 colonies/5xl04 cells). Phenotypic characterization of T-cell colonies
obtained from infected bone marrow cells revealed the presence of
T3+,T4+,T6+,T8+ cells whereas colonies derived from non-infected cells were
composed of T3+,T4+ and T3+, T8+ but not T6+ cells.
This model thus seems to mimic the abnormal proliferation and differentiation
of T-CFC observed in patients with AIDS and Persistent Lymphadenopathy Syn-
drome.
F 9 2 Cytokine Regulated Control of HIV Expression in Chronically
Infected Promonocyte Clones
THOMAS M. FOLKS*, 0. JUSTEMENT*, K. CL0USE***, C.A. DINARELLO**, M. DUK0VITCH,
A.S. FAUCI*, et al., *National Institutes of Health, Bethesda, MD, **Tufts
University, Boston, MA, ***Georgetown Univ., Washington, D.C.
Cells of the monocyte/macrophage lineage have been implicated as major
targets of HIV infection. In order to further study this phenomenon, the
promonocyte cell line, U937, has been used as a model for monocyte infection.
Following HIV infection of U937 cells, chronic low-level virus-producing
clones can be isolated which do not manifest a cytopathic effect and which
contain integrated HIV proviral DNA copies. Clones such as these permit the
detailed study of factors which might regulate or influence HIV expression.
Our findings have shown that T cell and monocyte derived factors can control
virus expression in these chronic HIV-producing clones. The T cell lymphokine,
granulocyte-macrophage colony stimulating factor, can increase HIV production
in one clone, Ul, by 3 to 4 fold. Another lymphokine, gamma interferon,
produces the opposite effect by inhibiting virus production. Monokines derived
from LPS induced macrophages were shown to strongly up-regulate HIV production
in these clones. The purified monokine, IL-lB, has been tested for viral
regulatory properties in Ul. Even though recombinant IL-lB had no effect on
HIV expression, antibody to IL-lB inhibited the enhanced expression of HIV in
Ul by other factors. Interestingly, following factor induction IL-lB mRNA
was up-regulated 20 fold in Ul over uninfected U937 cells. This implies a
regulatory role for IL-lB in controlling HIV expression in this chronic
HIV-producing clone and suggests that the inductive signals for virus
expression by other external factors involve IL-lB in the final common pathway.
F 9 5 ^ow Numbers of Cytotoxic/Suppressor CD8+ Lymphocytes Prevent HIV
Replication in Autologous Purified CD4+ Lymphocytes
CHRISTOPHER M. WALKER, D.J. MOODY, D.P. STITES, and J. A. LEVY, Cancer Research
Institute and Department of Laboratory Medicine, University of California,
School of Medicine, San Francisco, CA.
Our studies have focused on the role of cytotoxic/suppressor T lymphocytes in
the control of human immunodeficiency virus (HIV) replication in cultures of
peripheral blood mononuclear cells (PMC) from HIV seropositive subjects. Prev-
iously published results demonstrated that when this T cell subset, which ex-
presses the CD8 (OKT8/Leu2) surface antigen, is removed from PMC by cellular
immunoaff inity chromatography and anti-CD8 antibodies, HIV replication is
detected. Reconstitution of these cultures with the recovered CD8+cells abro-
gated HIV replication.
Some individuals have been identified whose PMC fail to release HIV even after
CD8+ cell depletion. Analysis of this cell population revealed that It con-
tained 10-15% contaminating CD8+ cells. To determine if these cells were suf-
ficient to interfere with HIV replication in the PMC, we specifically
enriched for CD4+ cells using anti-CD4 antibodies. The resulting population,
which contained greater than 90% CD4+ and less than 5% CD8+ cells, routinely
yielded high titers of HIV, while PMC depleted of CD8+ cells by negative sel-
ection as described above did not produce virus. Readdition of CD8+ cells
inhibited replication of HIV, and prevented the appearance of HIV-induced cyto-
pathology which was often evident in cultures of purified CD4+ cells.
These results suggest that most HIV seropositive individuals harbour HIV in
their peripheral blood CD4+ cells, and that the efficiency of CD8+ cell con-
trol of HIV replication within this subset varies from individual to
individual.
F.9.3
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C Q C Immunologic Profiles of Mothers in Perinatal Transmission of HIV
Infection
HENRY FRANCIS M.D.*,N. LUBAKI*, M.P.DUMA*, RW RYDER*, J MANN***, T.C. QUINN**,
et al., * Project SIDA, Kinshasa, Zaire, **NIAID, Johns Hopkins Univ,*** WHO
Geneva, Switerland.
HIV infection is known to infect T-helper lymphocytes and many
other cells important to the function of the cellular immune system. To
assess if these effects are associated with perinatal transmission of HIV,
we used a fluorescent automatic cell counter to evaluate the levels of
Leu 2,3,4,7,11,2H4 and 4B4 positive lymphocytes in HIV seropositive mothers
who gave birth to IgM western blot positive infants, HIV seropositive mothers
of HIV IgM seronegative children and seronegative control mothers who were
matched for age and parity. Of the 234 mothers who delivered babies in
the study group in Kinshasa, Zaire, 25 were HIV seropositive. Six of the
25 mothers had HIV IgM seropostive infants. The mothers of the IgM positive
babies had a significantly lower T-helper/T-suppressor ratio ( . 57±. 12) than
the mothersof IgM negative babies (3.3± .68) pCOOl. The mothers of IgM
positive children also had significantly more T-suppressors (820+257 cell/mm3)
than mothers of IgM negative babies (375+58 cells/mm3) but no differences in
Leu3+2H4+ or Leu3+4B4+ cells. HIV positive mothers of IgM negative infants
and seronegative control mother! had similar T-helper ,T-suppressor, 2H4 and 4B4
population, but the HIV positive women had slghficantly lower numbers of
Leu 11+ (NK) cells (33+5 cells/mm3 vs 130+14 cells/mm3) p<.001. HIV positive
motherswho transmit AIDS to their children have inversed T-helper/T-suppressor
ratio and elevated suppressor cells which are signficantly different from
what is seen in HIV positive mothers who do not transmit the infection to
their infants. With further study, these lymphocyte parameters may be used
to judge the risk of perinatally transmitted HIV infection.
214
FRIDAY, JUNE 5
Closing Plenary Session
F.10
Chairmen : Jean-Claude Gluckraan
Chairman, II International Conference on AIDS
Paris , France
Lars Olaf Railings
Chairman, IV International Conference on AIDS
Stockholm, Sweden
Summary and Current Status of AIDS Research
June Osborn, Dean, School of Public Health, University of Michigan,
Ann Arbor, Michigan.
Lars Olaf Kallings, Director, National Bacteriological Laboratories,
Stockholm, Sweden .
Edward N. Brandt, Jr., Chancellor, University of Maryland,
Baltimore, Maryland.
Introduction of the Secretary
Robert E. Windom, Assistant Secretary for Health, U.S. Department of
Health and Human Services, Washington, D.C.
Concluding Address: AIDS — Charge for the Future
The Honorable Otis R. Bowen, Secretary, U.S. Department of Health and
Human Services, Washington, D.C.
215
INDEX
-A-
Abdul-Ouader, A, MP.201 (45); THR 178 (193)
Abel, C, WP.10 (112)
Ablashi, D, MP.146 (34); TP.20 (65); THP.3
(164)
Abrams, D, M.11.2 (9); M.11.3 (9); TP.44 (69);
TP.197 (95); WP47 (118); WR58 (120);
WP.207 (744); THP57 (173)
Abrams, E, WP.62 (120); TH.11.3 (162)
Achterhof, L, TP.193 (94); THP.191 (195)
Acra, J, TP.187 (93)
Acuna, G, TP.184 (93)
Adachi, A, F.7.4 (212)
Adachi, N, WP.209 (745)
Adams, L, WP.40 (117); WR133 (132)
Adelsberg, B, WP145 (134)
Ades, A, MP.47 (18)
Adler, W, WP.119 (130); WP.123 (750)
Adrien, A, TP.175 (91)
Ahearne, P, M.10.3 (8); TP128 (83)
Ahlgren, D, WP.90 (125)
Aime, F, M.5.4 (4)
Aiuti, F, TP.117 (82)
Aizawa, H, MP.235 (49)
Ajdukovic, D, MP.102 (27)
Albert, J, MP.ll (12); THP.13 (165); THP.29
(168)
Albrecht, P, TP.245 (103)
Alcami, J, THP.116 (182)
Alderette, B, F.4.5 (209)
Alderman, M, TH.11.2 (161); THP.41 (170)
Alessi, E, TP.164 (89); WP.161 (137)
Alexander, S, MP.85 (24); MP.95 (26); TP.242
(102); WP.226 (148); THP.71 (275;; THP.245
(204)
Alger, L, MP.85 f24J
Alizon, M, TH.2.1 (153)
Allain, J, MP. 45 (17); MP.87 (24); MP.119 (30);
T.8.1 (5#); TP.38 (68); TP.69 (74); THP.9
(•765); F.2.2 (207)
Allaire, J, MP. 80 (23)
Allan, J, MP.29 (75); TP.7 (63); WR17 (7/5)
Allegra, C, TH.4.1 (155)
Allen, J, M.3.5 (2); MP.169 (5S); TP.133 (84);
WP.130 (732); THP.102 (/SO)
Allen, R, WP.242 (750)
Allen, S, T.10.1 (60)
Allouche, M, MP.112 (28)
Alter, H, TP.74 (74); WP.107 (128); WP.249 (757)
Alter, M, W.45 (7/7); TH.5.3 (756)
Amadori, A, MP.153 (35); TP.104 (79)
Ambinder, R, MP. 10 (77)
Amiel, C, MP. 118 (29)
Amitai, H, T.5.1 (55); WP.148 (735); H, THP.153
(189)
Amoroso, W, M.6.2 (4)
Anand, R, TP.36 (68); WP.29 (775); THR228
(207); THR233 (202)
Ancelle, R, WP.87 (724); THP.74 (775); THP.81
(777)
Anderson, D, M.11.6 (9); MP.27 (14); WP.168
(758); F.7.2 (272)
Anderson, M, MP.141 (35); WP.131 (752);
THP.237 (203)
Anderson, R, M.3.2 (7); TP.184 (93); THP.221
(200)
Anderson, V, WP.170 (138)
Andiman, W, TP.150 (87)
Andrade, D, F.6.1 (277)
Andreev, S, MP. 97 (26)
Andrews, C, M.11.4 (9); TP.144 (86)
Andrews, L, THP.220 (200)
Andreyev, S, WP.98 (726)
Andrieu, J, THP.239 (203)
Andriolo, M, F.3.5 (208)
Andron, L, MP.140 (33)
Andrulis, D, WP.211 (745)
Andzhaparidze, O, THP.40 (770)
Angeloni, R WP.122 (750); WP.248 (757)
Anns, M, WP.188 (747)
Anselmo, M, WP.134 (752)
Antonen, J, M.10.4 (8); MP.119 (30)
Antony, M, F.3.4 (208)
Antunes, E, MP. 42 (77)
Antunes, F, THP.88 (178)
Aoussi, E, TP.165 (90)
Appleman, M, T.7.2 (57); WR156 (756); THP.149
(188)
Aquilante, R, WR152 (755)
Arakaki, D, TH.4.1 (755)
Archer, G, WR243 (750)
Archibald, D, WR84 (724)
Arcidiacono, I, WP.250 (752)
Arendrup, M, TP.81 (76)
Argelagues, E, MP.165 (37)
Arnaiz-Villena, A, THP.116 (182)
Arnow, R TP.212 (97)
Aronstam, A, MP. 54 (19)
Arrizabalaga, J, TR 118 (82)
Arthur, L, M.10.2 (8); TRIO (64); TP.13 (64);
WP.3 (770); TH.2.5 (754); F.7.6 (272)
Arya, S, MP.25 (74); TH.2.3 (755); THP.15
(766); THP.23 (767)
Asher, D, TP.29 (67); WP.3 (770)
Ashley, R, F.1.6 (206)
Ashman, M, THP.240 (203)
Asjo, B, MP.ll (72); THP.13 (765); THP.238
(203)
Assogba, U, WP.87 (724)
Atherton, S, MP.146 (34)
Atkinson, J, MP.145 (34); MP.200 (43)
Atkinson, W, MP. 184 (40)
Aubry, J, WR126 (757)
Autran, B, MP.123 (30); MP.149 (35); WP.126
(757); WP.216 (746); THP.76 (776)
Avrunin, J, TP.174 (91); WP.172 (759)
Axel, R, M.4.3 (5); WP.2 (770)
Axthelm, M, WP.34 (776)
Ayehunie, S, MP. 214 (45)
-B-
Baba, M, MP.4 (70); T.4.2 (54); TP.l (62)
Bacchetti, R TP.53 (77); THP.43 (770); F.1.5
(206)
Bach, M. MP.10 (77)
Bacheler, L, TP.35 (68); Wp.28 (775); THP.27
(168)
Bachi, T, THP.14 (765)
Badamchian, M, THP.107 (181)
Badner, V, THP.213 (799)
Baffoni, L, TP.112 (81)
Bailey, S, TP.154 (88)
Bailey, V, MP.191 (42); TP.184 (93); WP.175 (759)
Baillou, A, WP.27 (774)
Bain, B, T.48 (70)
Baird, B, WP.205 (744); THR219 (200)
Baird, K, WR168 (138)
Baker, J, TH.3.6 (755)
Baker, L, THP.243 (204)
Baker, S, MP.86 (24)
Balfour, Jr., H, TP.231 (707)
Balzarini, J, MR4 (70); T.4.2 (54); TP.l (62)
Bandemer, C, MR188 (47)
Barbara, D, THP.229 (207)
Barbier, M, MP.80 (23)
Barin, F, TP.7 (63); WR27 (774); F.2.5 (207);
F.6.2 (277); F.6.3 (277); F.6.6 (277)
Baringtang, D, TH.4.2 (755)
Barlow, J, TH.4.2 (755)
Barnes, S, THP.179 (795)
Barnes, T, MP.63 (20)
Barnett, J, TH.8.5 (759)
Barnhart, J, T.49 (70); TR51 (77); W46 (118)
Baroldi, G, THP.165 (797)
Baron, G, WP.105 (727); THP.240 (203)
Barr, D, F.5.3 (270)
Barre-Sinoussi, F, MP.37 (76); WP.37 (776);
WP.77 (725); THP.37 (769); F.2.1 (207);
F.4.6 (209); F.9.4 (214);
Barrera, J, MP.165 (37)
Barry, A, MP.89 (25); WP.210 (745)
Barry, M, TP.47 (70)
Bartczak, S, THP.161 (790)
Bartelme, S, MP.201 (43); WP.72 (722); THP.178
(795)
Bartholomew, C, TP.96 (78); F.6.4 (277)
Bartlett, E, MP.188 (47)
Bartnof, H, MP.194 (42); TP.203 (96); WP.193
(742); THP.218 (799); THP.224 (200)
Baruchel, S, MP.117 (29)
Basiripour, L, M.4.6 (5)
Baskin, G, WP.19 (775); THP.21 (767); THP.30
(76£);THR113 (182)
Bassett, M, M.8.3 (6)
Basten, A, MP.168 (38)
Bates, J, WR69(727)
Baum, B, MP.152 (35)
Baum, G, TP.168 (90)
Bausell, B, TP.172 (97)
Baxter, R, MP.210 (45)
Bayende, E, TH.7.6 (158)
Bayer, R. F.5.1 (270)
Beall.G,THR16O(/90)
Beasley, R F.1.5 (206)
Beaton, D. MP.59 (20)
Beatrice. S. TP.69 (74)
Beatson, D. TP.124 (83); TP.238 (702)
Beaver, B, THP.15 (766); THP.23 (767)
Beavers. B, MP.25 (74)
Bebenroth. D. WP.141 (755); THP.103 (180)
111
INDEX
Becherer, P, MP.78 (23)
Bechtel, G, TP.202 (96)
Becker, J, MP.37 (16)
Beckham, D, MP.197 (43)
Beckstead, J, TP.115 (81)
Bedarida, G, WP.250 (152)
Bednarik, D, WP.38 (116)
Bedos, J, MP.158 (36)
Beers, V, WP.211 (145)
Beeson, D, THP.207 (198)
Behets, F, TH.7.6 (158)
Beil, J, TP.57 (72)
Bekesi, G, WP.115 (729)
Bekesi, J, MP.132 (32); TP.131 (84); WP.114
(129); THP.117 (183)
Bellanti, J, MP.18 (13)
Bellin, E, TP150 (87)
Bellobuono, A, MP.249 (51)
Bellonti, J, MP.188 (41)
Belloso, L, TP.118 (82)
Belman, A, TP.146 (86); W5.3 (109)
Belongia, E, MP.182 (40)
Bender, B, WP.123 (130)
Bene, M, MP.118 (29)
Benjers, B, THP.12 (165)
Bensch, K, MP.12 (12)
Benson, C, TP.225 (100)
Benter, T, M.9.6 (7)
Bentley, J, WP.211 (145)
Benveniste, R, MP.13 (12); MP.15 (12); THP.30
(168)
Berardi, V, THP.175 (192)
Beresford, H, WP.159 (136)
Beresford, R, WP.158 (136)
Beretta, A, WP.124 (131)
Berg, G, WP.223 (147)
Berg, K, WP.229 (148)
Berg, S, TP.135 (85); TP156 (88)
Bergdahl, S, THP.13 (165); THP.238 (203)
Berger, J, MP.139 (33); MP.143 (34); T.8.3 (58);
TP.136 (85); THP.155 (189)
Berggren, I, THP78 (176)
Bergman, T, MP.39 (16)
Berlin, F, MP.198 (43)
Berman, M, TP.ll (64); TP.119 (82)
Berman, P, M.4.4 (3); WP.25 (114); WP.107
(128); THP.20 (166); THP.125 (184)
Bernard, J, T.16.5 (62)
Bernstein, D, TP.116 (81)
Bernstein, L, F.3.4 (208)
Bernstein-Singer, M, THP.144 (187)
Berry, A, TP.208 (97)
Berry, C, T.10.5 (60)
Berry, G, WP.86 (124)
Berthaud, M, THP.209 (198)
Berti, E, WP.161 (137)
Bertram, J, MP. 231 (48)
Bertrand, W, T.7.6 (57)
Bess, J, TP.10 (64); TP.13 (64); F.7.6 (212)
Beth-Giraldo, E, TP.244 (103)
Bellinger, C, THP.186 (194)
Beverley, P, TP.4 (63); TH.9.4 (160); TH.9.6
(160)
Bhan, A, TP.129 (84)
Bianchi, F, TP.112 (81)
Bianco, C, TP.240 (102); WP.236 (149); THP.208
(198); THP.243 (204)
Biberfeld, G, M.10.6 (8); MP.93 (25); TP.86
(76); WP.128 (131); THP.78 (176); THP.238
(203)
Biberfeld, P, TP.125 (83); WP.5 (111); WP.128
(131)
Biel, J, WP.88 (125)
Bierling, P, WP.228 (148); THP.170 (191)
Biernacki, P, TP.176 (91); WP.197 (143)
Biesert, L, WP.24 (114)
Biggar, R, MP.65 (21); TP.28 (67); TP.56 (77);
W.2.6 (706); WP.68 (121)
Bigger, B, THP.71 (175)
Biglieri, E, TP.197 (95); WP.207 (144)
Bihari, B, WP.227 (148); THP.124 (7S4)
Bilello, J, THP.12 (165)
Bircher, J, THP.77 (176)
Birriel, J, THP.167 (797)
Birx, D, WP.110 (128); THP.105 (7S7)
Bishburg, E, MP.160 (36); E, TP.57 (72)
Bishop, P, THP.129 (185)
Bisset, C, THP.172 (792;
Black, I, WP.180 (140)
Black, P, WP.198 (745)
Blackwelder, W, WP.67 (727;,- THP.64 (774)
Blain, N, WP.8 (777)
Blanche, S, TH.7.4 (158)
Blasco, E, TP.118 (82)
Blattner, W, T.3.3 (53); T.48 (70); F.1.2 (206);
F.4.3 (209); F.6.4 (277); F.6.5 (277)
Bloch, A, TP.42 (69); THP.86 (777)
Bloom, J, TH.11.2 (767)
Blough, H, TP.23 (66)
Blumberg, R, WP.104 (727)
Blumenfeld, W, THP.163 (190)
Boccon-Gibod, L, MP.117 (29)
Bockelman, M, WP.22 (114)
Bodecker, T, F.8.1 (275)
Bodner, A, TP.242 (102); WP.21 (775); WP.128
(757); THR245 (204)
Bofill, M, WP.137 (755)
Bogaerts, M, THP.227 (207)
Bogner, J, WP.165 (757)
Bohan, C, MP.26 (14)
Boix, J, TP.167 (90)
Bolan, G, TP.51 (77)
Boland, M, MP.162 (37); MP.213 (45); TP.215
(98); WP.213 (745); THP.212 (198)
Bolgiano, D, WP.49 (118)
Bolognesi, D, T.16.4 (62); T.9.4 (59); TP.128
(83); TP.132 (84); F.7.6 (272)
Bolton, W, WP.243 (750)
Bonapour, B, TP.114 (81)
Bonavida, B, TP.127 (83); WP.103 (727)
Bond, G, TP.194 (94)
Bond, W, MP.229 (48); WP.233 (749)
Bonhomme, M, T.6.3 (56)
Bonk, S, THP.145 (757)
Bonner, R, TP245 (705)
Bonneux, L, MP.82 (23); W.2.4 (706)
Bonney, D, WP.179 (140)
Boo, T, MP.74 (22)
Boone, D, WP.245 (757); THP.129 (185)
Borek, E, WP.55 (779)
Borkowsky, W, W.5.2 (108); WP.141 (755);
THP.103 (180); THP.145 (187)
Borucki, M, TP.159 (89)
Bosch, D, MP.237 (49)
Bosio, R, WP.95 (726)
Bosire, M, TH.5.5 (757)
Boswell, R, T.7.2 (57); WP.107 (128); WP.156
(136)
Bosworth, C, WP.113 (729); THP.114 (752)
Bottiger, B, M.10.6 (8); WP.83 (124); THP.29
(168); THP.78 (776)
Bottiger, M, M.6.5 (5)
Bouhasin, J, THP.127 (184)
Boulos, C, THP.63 (174)
Boulos, R, THP.63 (774)
Bouramoue, C, WP.79 (725)
Bourguignon, L, WP.105 (727)
Bouscary, D, THP.123 (184)
Boussin, F, TP.27 (67)
Bouvet, E, TP.180 (92)
Bowles, C, TP.210 (97)
Bowman, R, MP.250 (57); WP.235 (749)
Bowry, T, TP.41 (69); TP.249 (704)
Boyd, V, THP.34 (769)
Boyer, C, THP.190 (795)
Boyer, R, THP.193 (795)
Boyko, W, M.3.3 (2); M.6.3 (5); MP.lll (28);
TP.99 (79)
Boyle, R, MP.43 (77)
Boylen, C, THP.151 (188)
Boynes, F, THP.179 (795)
Bracco, M, MP.134 (32)
Brackmann, H, TH.10.4 (767); THP.168 (797)
Braddick, M, WP.50 (118); TH.7.5 (158)
Brahic, M, MP.2 (70)
Brandes, T, THP.221 (200)
Brandt, L, F.3.4 (208)
Branson, B, MP.181 (40); TP.191 (94); WP.185
(747); THP.184 (794); F.8.6 (275)
Brasfield, T, MP.174 (39)
Bratt, G, MP.93 (25); THP.130 (785)
Braun, B, MP.244 (50); TP.235 (707)
Braun, D, THP.101 (180)
Braun, M, WP.74 (722); TH.2.5 (754)
Braun, N, THP.231 (202)
Braunstein, L, THP.214 (799)
Bredberg-Raden, U, TP.86 (76); THP.29 (168)
Brede, H, WP.24 (774)
Breer, P, MP.181 (40)
Brenner, M, W.5.4 (709)
Brettle, R, MP.137 (33); TP.205 (96); WP.204
(744); THP.172 (792)
Brettler, D, M.11.4 (9); MR86 (24); MP.240
(50); TP.144 (86)
Brew, B, WR149 (755)
Brewster, F, M.11.4 (9); TP.144 (86)
Brewton, G, TP.134 (84); TP.218 (98); THP.135
(186); THP.236 (202)
Brey, R, MP.115 (29); WP.156 (756)
Bricaire, F, WP.138 (755); THP.141 (187)
Bridge, P, M.5.3 (4)
Brink, B, M.8.2 (6)
Brisker, J, WP.152 (755)
Britton, S, MP.214 (45)
Britz, J, MP.107 (28)
Broaddus, R, WP.74 (722); THP.70 (775)
Brockmeyer, N, THP.131 (185)
Broder, S, T.2.3 (52); T.4.1 (54); T.4.4 (54); TP.l
(62); WP.223 (747); THP.10 (765)
Brodie, B, MP.206 (44)
Brodie, H, MP.221 (47); WP.231 (148)
218
INDEX
Bron, C, THP.14 (165)
Brondum, J, MP.185 (41); TP.179 (92)
Brossard, Y, THP.170 (191)
Brousse, N, MP.2 (10)
Brouwers, P, THP.146 (187)
Brown, C, WP.155 (136); THP193 (195)
Brown, D, MP.90 (25)
Brown, G, THP.221 (200)
Brown, L, MP.203 (44); TH.11.6 (162)
Brown, M, MP.114 (29)
Brown, R, WP.139 (133)
Browning, R, WP.53 (119)
Brozicevic, M, THP.192 (195)
Brucker, G, TP.229 (100); THP.24 (167)
Brtihwiler, J, WP.81 (123)
Brun-Vezinet, F, MP.148 (34); MP.189 (41); TP.27
(67); TP.37 (68); TP.153 (88); WP.32 (115);
THP.24 (767J; THP.33 (169); THP75 (776;,-
F.2.4 (207); F.6.1 (277;
Brunda, M, TP.17 (65)
Brundage, J, MP.81 (23); T.7.1 (57); TP.237
(702;,- WP.110 (128); Fl.l (206;
Brunei, J, TP180 (92); THP.74 (775J; THP.81
(177)
Brutus, J, THP.63 (174)
Bubiey, G, WP.224 (747;
Buchner, B, TP.45 (70); TP.243 (103)
Buchow, H, T.120 (S2;
Bucknall, A, TP.195 (95)
Bucquet, D, MP.79 (23)
Buimovici-Klein, E, THP.124 (181); WP.227
(148)
Biiki, B, MP.21 (13)
Bulkin, W, TH.11.6 (162)
Buller, M, WP.100 (727;
Bunin, J, MP.81 (23); TP.237 (702;
Buning, E, MP.183 (40)
Burcham, J, MP.63 (20); WR86 (124)
Burger, D, THP.128 (184)
Burger, H, THP.228 (201); THP.233 (202)
Burgess, M, THP.137 (186)
Burke, D, MP.81 (23); T.7.1 (57); TP166 (90,);
W.3.5 (707;; WP.17 (113); WP.110 (728;;
THP.99 (180); THP.105 (787;; Fl.l (206)
Burnell, R, TH.8.3 (759)
Burnett, A, THP.244 (204)
Burnett, W, WP.68 (727;
Burns, S, THP.172 (792;
Busch, K, MP.152 (35)
Busch, M, W.4.3 (708j; W.4.5 (108); WP.237
(749)
Buschman, F, WP.55 (779;
Bushar, G, TP.16 (65)
Buttner, W, TP.157 (88)
Byers, R, WP.42 (777); TH.7.1 (757;
Bygbjerg, I, MP.62 (20); WP.229 (148)
Bykovsky, A, TP.2 (62)
Byron, K, THP.2 (163)
-c-
Cabbad, M, WP.157 (136)
Cadeo, G, MP.153 (35)
Cai, Q, WP.106 (727)
Cain, C, THR3 (764;
Cairns, M, T.9.4 (59)
Calabrese, L, TR182 (92); THP.180 (793;
Calderone, R, THP.134 (185)
Calisher, C, W.2.3 (706;,- F.8.3 (275;
Callan, M, TH.11.5 (762;
Callegari, F MP.8 (77;
Calvelli, T, THP.156 (189)
Calzavara, L, MP. 49 (18); MP.50 (18)
Cambie, G, WP.250 (752;
Cameron, C, THP.138 (186)
Cameron, D, M.8.4 (6); MP.91 (25); TH.5.5
(157)
Campos, A, WP.137 (133)
Camus, F, TP.165 (90)
Candido, K, WP.135 (732;
Canessa, A, WP.134 (732;
Cano, J, MP.165 (37;,TR167 (90)
Canton, P, MP.118 (29); THP.164 (790;
Cantor, K, F.6.5 (277;
Cao, Y, THP.9 (765;
Caouette, S, THP.128 (184)
Capobianchi, M, TP.117 (82)
Capon, D, M.4.5 (3); MP.19 (73;; TP.31 (67)
Caralis, P, WP.196 (743;
Caraux, J, MR227 (48)
Carcassonne, Y, T.5.6 (55)
Card, R, WP.163 (737;
Cardell, N, TR59 (72)
Carden, J, TP.227 (700;
Carey, J, MP.105 (27)
Carey, V, MP.92 (25)
Carleton, S, T.8.2 (58)
Carlson, J, MP.151 (35); MP.191 (42); TP.28 (67);
TP.53 (77;; WP.53 (779;,- THP.215 (799;
Carminati, G, TP.164 (89)
Carpenter, S, TH.2.6 (754;
Carr, G, MP.206 (44)
Carron, W, THP.150 (188)
Carsley, J, TP.175 (97;
Cartel, J, TP.95 (78)
Carter, S, M.10.2 (8); TH.2.5 (754;
Carter, W, MP.5 (77;; MP.216 (46)
Carwein, V, TP.210 (97)
Casareale, D, MP.108 (28); TP.103 (79)
Casasnova, S, TP.187 (93)
Casavant, C, TP.53 (77;
Casertano, M, TP.113 (81)
Casey, J, F.2.6 (207)
Casini, M, THP.89 (178)
Cassani, F, TP.112 (81)
Cassuto, J, T.10.3 (60)
Castagna, A, WP.89 (725;
Castano, R, WP.88 (725;
Castello, G, TP.244 (703;
Castro, K, TP.84 (76); W.2.3 (706;
Catalini, M, TP.112 (81)
Catania, J, THP.185 (794;
Causey, D, TP.160 (89); WP.221 (747;; THP.149
(188)
Cauthen, G, TP.42 (69)
Cavicchini, S, WP.161 (737;
Cederberg, D, WP.231 (148)
Cenzuales, S, TP.230 (700;
Ceparano, S, TP.244 (703;
Cereb, N, MP. 18 (73;
Ceroni, M, THP.108 (181)
Ceuninck, D, F.6.1 (277;
Chabner, B, TH.4.1 (755;
Chace, B, TP.231 (707;
Chachoua, A, TH.4.5 (756;
Chadburn, A, THP.230 (207;
Chaisson, R, MP.87 (24); T.8.1 (58); WP.112
(729;; F.1.5 (206)
Chakrabarti, S, T.9.1 (59); T.9.2 (59); W.3.1
(706;;
Chamaret, S, MP.80 (23); F.6.3 (277;
Chamberland, M, T.7.3 (57)
Chambers, L, MP.242 (50)
Chan, E, MP.102 (27); WP.242 (750;
Chan, H, THP.17 (766;
Chan, Y, TP.90 (77)
Chanas, A, THP.237 (203)
Chandra, P, MP.24 (74;,- TR^O (99) «-»- ""
Chandwanl, S, W.5.2 (708;,%P.l4l (733;;
THP.103 (180); THP.145 (187)
Chang, K, MP.95 (26)
Chang, M, MP.71 (22); TP.135 (85)
Chang, N, M.10.3 (8); TP.ll (64)
Chang, W, TP.90 (77)
Chanh, T, TP.3 (63); WR113 (729;; TH.9.5
(760;; THP.102 (180); F.4.5 (209)
Chanock, S, MR242 (50)
Chanteau, S, TP.95 (78)
Chapman, S, MR223 (47)
Charap, M, TH.3.3 (754;
Chase, M, WP.54 (779;
Chase, R, MP.147 (34)
Chatziandreou, E, THP.195 (796;
Cheinsong-Popov, R, T.3.4 (53)
Chemtai, A, TP.41 (69)
Chen, C, WP.35 (776;
Chen, J, T.10.2 (60); TP.171 (97;,- THP.39 (770;
Chen, R THP.lll (182)
Cheng-Mayer, C, WP.7 (777;; WP.14 (772;
Cher Mann, J, MP.149 (35)
Cherchi, M, TP.117 (82)
Chermann, J, MR37 (76;; TP.53 (77;,- WP.37
(776;; WP.216 (746;; THP.37 (769;,- F.2.1 (207);
F.4.6 (209); F.9.4 (274;
Cherry, N, WP.215 (746;
Chesebro, B, TH.2.6 (754;
Cheung, T, WP.29 (775;,- WP.109 (128)
Chew, E, TH.8.1 (158)
Chiasson, M, MP.83 (24); TP.75 (75); WP.70
(722;; THP.66 (774;
Chieco-Bianchi, L, TP.104 (79)
Chinnock, B, TR231 (707;
Chiodi, F, MRU (72;,- TP.132 (84); THP.29 (765;
Chiuten, D, THP.234 (202)
Chmiel, J, T.3.6 (53); WP.63 (720;,- THP.60
(173)
Cho, E, THP.21 (767;
Chollet-Martin, S, TP.126 (83)
Chotard, J, TP.52 (77;
Chou, D, TP.62 (72)
Chou, M, WP.17 (773;
Chou, T, TP.30 (67)
Choutet, R WP.27 (774;
Christ, G, MR197 (43); T.10.2 (60); TP.171 (97;
Christensen, L, MP.113 (29)
Christonikos, N. THP.55 (772;
Chuang, M, W.5.6 (709;
Chungue, E, TP.95 (78)
Church, J, MR110 (28); TP.137 (85)
Ciantia, F. THP.84 (777;
Civeira, M, MP.24 (74;
Clapham, P. M.10.5 (8); T.3.4 (53); TP.3 (63)
219
INDEX
Clark, C, TP.183 (93); WP.195 (142); THP.173
(192)
Clark, E, MP.15 (12)
Clark, J, MP212 (45)
Clark, S, TP.122 (82)
Clark, V, WP.64 (121)
Clause, K, THP.53 (172)
Clausen, L, M.8.2 (6)
Clauvel, J, MP.148 (34); TP.216 (98); WP.228
(148); THP.170 (797;
Clavel, F, TH.2.1 (153)
Clayton, A, THP.72 (775)
Clayton, <W, MP.140 tt?)
Cleghorn, F, TP.96 (TO); F.6.4 (277)
Cleland, J, MP.204 (44)
Clement, M, TH.3.1 (154); THR154 (189)
Clement, T, THP.245 (204); TP242 (702)
Clements, M, WP116 (729)
Clivio, A, WP124 (757)
Clotet, B, MP.165 (37); TP.167 (90)
Clouse, K, M.9.4 (7); MP.22 (75); F.9.2 (214)
Clumeck, N, TP.82 (76); WP.59 (720); WP.80
(725); THP.61 (775)
Coates, R, MP. 49 (18); MP.50 (18); TH.4.3 (755)
Coates, T, T.10.1 (60); WP.184 (747); WR186
(747); WP.232 (749); THP.185 (794); F.8.2 (275)
Cobb, E, WP.231 (748)
Cochi, S, WP.122 (750)
Cochran, M, MP.16 (72); W.3.4 (707)
Cochran, S, MR202 (43)
Cockerill, F, MP.147 (34)
Cogniaux, J, MR124 (30); TP.23 (66)
Cohen, B, MP.142 (33)
Cohen, H, TP.146 (86); WR72 (722)
Cohen, J, T.4.4 (54); W.2.1 (705); WR57 (779);
WP.126 (757); WR208 (745); TH.3.1 (754);
THP.151 (188)
Cohen, W, WP.147 (754)
Cohn, D, TP.70 (74); TR71 (74); TP.239 (702);
WP.182 (740); THP.58 (775)
Cohn, J, WP.147 (754)
Cohn, M, TP.141 (86)
Cohn, S, WP.116 (729); THP.119 (785)
Cole, C, THP.86 (777)
Cole, R WP.196 (745)
Colebunders, R, M.8.5 (6); T.7.6 (57); TP.139
(85); TP.145 (86); W.4.6 (708); WP.136 (755);
THP.139 (786)
Collalti, E, MP. 33 (75)
Collier, A, T.5.3 (55); WP.54 (779); WP.76 (725);
THP.73 (775)
Collier, D, THP.188 (794)
Colman, L, TP.30 (67)
Colombe, B, WP.112 (729)
Colombini, S, MP. 25 (74)
Colombo, S, MP. 41 (77); WP.58 (720); Conant,
M, WP.112 (729); WP.219 (746); TH.8.5 (759);
THP.57 (775)
Cone, L, MP.108 (28); TP.103 (79)
Conklin, R, MP.217 (46)
Connor, D, WP.168 (758)
Connor, E, MP.162 (37); MP.170 (38); MP.213
(45); TP.170 (90); TP.215 (98); TP.226 (700);
W.5.1 (708); WP.169 (758); WP.213 (745);
THP.212 (798)
Conte, J, TP.217 (98); WP.222 (747)
Conviser, R, MP.208 (44); WP.174 (759)
Cook, D, MP.196 (42)
Cook, L, WP.243 (750)
Cooke, M, TH.3.2 (754)
Coombs, R, T.5.3 (55); WP.54 (779)
Cooney, D, THP.10 (765)
Cooper, B, THP.220 (200)
Cooper, D, MP.63 (20); MP.64 (20); MP.186 (47);
TP.101 (79); WP.86 (724); WP.149 (755)
Cooper, L, WP.65 (727)
Cooper, R, T.4.6 (54)
Copeland, T, M.9.3 (7); TP.21 (66)
Copello, A, THP.194 (795)
Corallo, S, THP.165 (797)
Cordoba, S, T.7.4 (57)
Corey, L, T.5.3 (55); WP.54 (779); F.1.6 (206)
Corless, I, TP.197 (95); WP.207 (744)
Cornblath, D, MP.66 (27); TP.140 (85)
Cornet, R MP. 82 (23); W.2.4 (706)
Corrigan, A, TP.242 (702); WP.21 (775);
THP.245 (204)
Cort, S, TP.108 (80)
Cortes, E, TP.227 (700)
Cosand, W, TP.32 (67)
Cossaboom, M, WP.200 (745)
Costa, C, THP.88 (778)
Costin, C, MP.51 (78)
Cottenot, F, MP.98 (26)
Cottone, J, MP.187 (47)
Cottrell, M, WP.198 (745)
Couderc, L, MP.148 (34); TP.216 (98); WP.228
(748)
Coulaud, J, THP.169 (797)
Coulits, T, WP.243 (750)
Counihan, C, TP.156 (88)
Coupal, L, MP.215 (46)
Courouce, A, F.6.3 (277)
Courtois, F, F.2.4 (207)
Cousineau, E, WP.206 (744)
Coutinho, R, M.6.1 (4); MP.53 (79); MP.74 (22);
TP.40 (69); F.8.5 (275)
Cowan, M, MP.163 (37)
Cox, D, WP.28 (775)
Crabb, E, THP.121 (785)
Craib, K, M.6.3 (5); MP.lll (28)
Crane, C, WP.4 (777)
Crapper, R, WP.92 (725)
Craske, J, TP.250 (704)
Crawford, J, WP.69 (727)
Crawford, L, WP.212 (745)
Creech, R WP.70 (722)
Criss, V, THP.242 (203)
Critchley, S, MP.241 (50)
Critchlow, C, THP.68 (774)
Crocchiolo, R TP.230 (700); WP.250 (752)
Cronin, W, MP.106 (27); THP.110 (787); THP.152
(188)
Cross, G, TP.108 (80)
Crotti, D, WP.95 (726)
Crovari, R TP.83 (76); WP.134 (752)
Crowe, S, F.9.3 (274)
Crumpacker, C, WP.224 (747); TH.4.6 (756)
Crush-Stanton, S, TP.119 (82)
Cuadrado, E, TP. 118 (82)
Cumming, C, WP.22 (774)
Cumming, S, TP.18 (65); WP.6 (777)
Cunillera, C, TP.187 (93)
Curran, J, Tl.l (52); TP.84 (76); W.4.6 (708);
WP.56 (779); WP.190 (742); THP.188 (794)
Curvin, M, THP.194 (795)
Cusano, A, TP.148 (87)
Cushion, M, MP.219 (46)
Cusini, M, TP.164 (89); WP.161 (757)
Cuthbert, R, MP.245 (57); TP.124 (83); TP.238
(702); WP.102 (727)
Cutler, K, WP.150 (755); THP.56 (772)
-D-
Daffos, F, MP.189 (47)
Daguillard, F, T.9.2 (59); WP.85 (724)
D'Agustino, F, WP.250 (752)
Dahl Christensen, L, WP.229 (748)
Dalakas, M, MP.144 (34); TP.151 (87); WP.223
(147)
Dal Conte, I, MP.41 (77)
Dalgleish, A, M.4.3 (5); MP.20 (75); MP.122
(30); TP.3 (63)
Damrosch, S, TP.172 (97)
Dandekar, S, TP.36 (68)
Daniel, M, F.7.3 (272)
Danila, R, MP.193 (42); T.7.5 (57); WP.235
(749); THP.176 (792)
Danner, S, MP.220 (46)
D'Aquila, R, THP.44 (770)
Darby, G, THP.22 (767)
Dario, D, F.6.1 (277)
Darr, F, TP.74 (74)
Darragh, J, MP.225 (47)
Darrow, W, M.3.1 (7); W.2.1 (705); F.8.1 (275)
Daugherty, D, M.9.4 (7)
Davenny, K, MP.156 (36); WP.41 (777); TH.7.2
(757); THP.140 (786)
Davey, M, TP.243 (705); WP.240 (750)
Davidson, A, TP.70 (74); TP.71 (74)
Davidson, B, THP.228 (207)
Davidson, J, THP.172 (792)
Davidson, S, TP.205 (96); THP.172 (792)
Davis, G, TP.9 (64)
Davis, J, MP.182 (40); TH.4.4 (756)
Davis, T, TH.11.2 (767)
Davis, W, TH.5.1 (756)
Dawson, G, WP.242 (750); F.2.6 (207)
Dax, E, WP.119 (750)
Day, J, TP.47 (70); WP.88 (725)
Day, S, THP.202 (797)
Dayton, A, M.4.6 (5); T.16.2 (62); THP.6 (764)
Dazza, M, T.5.4 (55); TP.37 (68); WP.32 (775);
THP.33 (769); THP.75 (776)
D'Costa, L, MP.91 (25); THP.68 (774)
Dean, L, THP.79 (776)
de Andres, R, TP.102 (79)
De Biasi, R, TP.244 (705)
Debouck, C, TP.100 (79)
Debre, R MP.123 (30)
Debuono, B, MP.185 (47); TP.179 (92)
De Castro, L, TP.187 (93)
Decazes, J, THP.141 (787)
Decker, B, THP.181 (795)
Decker, R, WP.242 (750)
De Clercq, E, MP.4 (70); T.4.2 (54); TP.l (62);
TP.23 (66)
De Cock, K, MP.84 (24); TP.145 (86); WR43
(117)
De Goede, R, TP.33 (68); WP.125 (757)
de Gruttola, V, THP.76 (776)
Dehovitz, J, MP.136 (32)
220
INDEX
Deinhardt, F, T.46 (70); TH.10.6 (161); THP.93
(179)
Deitch, D, WP.237 (149)
De Jong, W, WP.180 (140)
de la Barrera, S, MP.134 (32)
Delagneau, J, MP.79 (23)
De Lalla, F, THR84 (177)
de la Macorra, L, MP.173 (39)
De La Monte, S, TP.129 (84)
Delapenha, R, THP.179 (193)
Delaporte, E, M.8.1 (5); WP.32 (115)
Del Bono, V, WP.134 (132)
De Leeuw, H, TP.212 (97)
DeLeo, M, MP.222 (47)
Delfin, M, MP.168 (38)
Delorme, N, THP.164 (190)
De Maria, A, TP.83 (76)
Demeulemeester, R, MP. 96 (26)
de Miranda, P, WP.231 (148)
Denis, F, F.2.5 (207); F.6.2 (211); F.6.6 (211)
Denis, M, MP.123 (30)
Denny, T, TP.226 (100); WP.169 (138)
De Paoli, P, WP.95 (126)
Deppe, D, M.3.5 (2)
De Rossi, A, MP.153 (35); TR104 (79)
Derrick, J, TP.243 (103); WP.240 (150)
Deschamps, M, M.8.6 (6); MP.68 (21); MP.69
(21); MP.136 (32); TP.43 (69)
Des Jarlais, D, MP.201 (43); TP.69 f74;,- W.1.4
(105); WP.180 (740); THP.67 (174); THP.178
(793); THP.198 (796); THP.216 (199)
Desmyter, J, MP.4 (10); TP.23 (66)
De Souza, Y, MP.223 (47); TP.138 f55;
Desrosiers, R, MP.72 (22); F.7.3 (212)
Detels, R, TP.72 C74J; TP.73 (74); WP.63 (720);
WP.64 (121); THP.60 (773)
de The, G, MP.117 (29); TP.153 fSSJ
Dettke, T, TP155 (88)
Deutsch, M, MP.114 (29)
Devare, S, F.2.6 (207)
De Vathaire, F, THP.76 (176)
DeVico, A, THP.97 (179)
De Vinatea, M, TP.169 (90); WP.168 (138)
De Wit, S, TP.82 (76); WP.59 (720;
De Wolf, F, M.6.1 (4); MP.53 (19); TP.100 (79;,-
THP.136 (756;
De Wolff, F, THP126 (184)
Diamond, G, TP.146 (86); W.5.3 (109)
Dickinson, G, T.8.5 (58); W.2.2 (105); WP.91
(725); WP.167 (138); THP.92 (178)
Dickson, D, W.5.3 (709;
Diclemente, R, T.6.5 (56); WP.192 (142);
THP.190 (795;
Diecidue, R, MP.41 (17)
Dierich, M, MP.99 (26)
Dieterich, D, TH.4.5 (156)
Dietrich, M, TP.155 (88)
Dietrich, S, WP.245 (151)
Difini, J, MP.139 (33)
Digiovanni, C, MP.142 (33)
Dijkgraaf, M, MP.177 (39)
Dillon, B, MP.192 (42); TP.185 (93); TP.239 (702)
Di Lorenzo, A, WP.122 (750;
di Marzo Veronese, F, THP.97 (179)
Dinarello, C, F.9.2 (274)
Diodato, S, WP.95 (726;
Dittel, B, WP.9 (777)
Divittis, A, THP.182 (793;
Dix, R, TP.136 (85)
Dobkin, J, F.3.2 (208)
Dobson, A, MP.64 (20)
Dock, N, WP.226 (148); THP.247 (204)
Dodd, M, TP.197 (95); WP.207 (144)
Dodd, R, MP.234 (49); THP.77 (776); THP.246
(204)
Dodds, S, WP.196 (143)
Doering, S, MP.181 (40)
D'Offizi, G, TP.117 (82)
Doherty, R, TP.18 (65); WP.6 (777)
Doinel, C, THP.132 (185)
Dolan, K, MP.186 (41)
Doll, L, M.3.1 (1); F.8.1 (275;
Domart, Y, F.2.4 (207)
Donahue, R, MP.222 (47); TR122 (82)
Dondero, T, T.7.3 (57); TP.84 (76); TP.179 (92);
WP.56 (779;; THR77 (776)
Dondero, Jr., T, WP.190 (742;
Donegan, E, W.4.5 (108)
Donovan, B, MP. 63 (20)
Dorfman, T, THP.6 (764;
Dormont, D, TP.27 (67)
Dorner, D, THP.59 (773)
Dorsett, B, MP.106 (27); THP.110 (181)
Dorsey, B, WP.119 (730;
Dosik, M, THP.16 (766;
Douglas, B, M.3.3 (2); M.6.3 (5); MP.lll (28);
TP.99 (79)
Douglas, D, W.4.1 (707;; WP.241 (750;
Dove, S, MP.187 (41)
Dowbenko, D, WP.12 (772;,- WP.35 (776)
Dowling, H, MP.182 (40)
Downer, A, TP.186 (93); TP.190 (94)
Downs, A, THP.74 (775); THP.81 (777)
Dreesman, G, TP.3 (63); WP.107 (128); TH.9.5
(760); THP.102 (180); F.4.5 (209)
Dreis, M, W.4.4 (108)
Drew, H, TP.228 (700)
Driscoll, J, T.4.1 (54)
Drotman, D, THP.188 (794)
Drouet, L, MP.98 (26)
Drucker, E, TP.66 (73); WP.52 (779); TH.11.2
(767); TH.11.5 (762)
Drury, F, WP.227 (748); THP.124 (184)
Dudley, J, TH.5.6 (757)
Duflo, B, TP.229 (700)
Dugan, M, WP.230 (148)
Duginski, T, MP.115 (29)
Dukovich, M, F.4.4 (209)
Dukovitch, M, F.9.2 (274;
Duma, M, THP.18 (766;, THP.19 (766), THP.139
(786); THP.159 (790); F.9.6 (274)
Duncanson, F, TP.154 (88)
Dunlop, N, MP.31 (75)
Dunnum, D, THP.186 (794)
Durack, D, T.9.4 (59)
Durand, J, M.8.1 (5); WP.78 (723)
Durand, S, TP.142 (86)
Durda. P, TH.9.1 (759)
Dwyer, B, THP.31 (768)
Dwyer, J, WP.225 (747); THP.115 (782)
Dye, J, THP194 (795)
Dzwillo, G, WP.132 (732)
-E-
Eales, L, TP.lll (87)
Earl, P, T.9.3 (59); W.3.1 (706)
/
Earle, S, MP.244 (50); TP.235 (707)
Easley, K, THP.180 (793)
Eaton, D, MP.150 (35)
Eberle, J, TH.10.6 (767)
Echaniz, P, TP.118 (82)
Echenberg, D, THP.207 (798)
Edson, R, MP.147 (34)
Edwards, M, THP.87 (778)
Edwards, V, MP.84 (24)
Eeftinck Schattenkerk, J, MP.220 (46); THP.126
(784;; THP.136 (786)
Ehrlich, G, WP.23 (774); F.2.3 (207)
Eichberg, J, T.9.5 (59); WP.10J (728); THP.20
(766); THP.102 (780) *
Eichnelaub, D, TP.157 (88)
Eijrond, B, F.8.5 (273)
Einck, L, MP.216 (46)
Eisdorfer, C, MP.116 (29); THP.155 (789)
Eisele, J, THP.82 (777)
El-Beik, T, W.4.5 (708)
El-Sadr, W, TP.163 (89); THP.69 (775); F.3.6
(208)
Elder, G, MP.159 (36)
Eldred, L, THP.119 (783)
Elkin, C, WP.154 (736)
Elkins, R, THP.249 (205)
Ellis, M, THP.237 (203)
Elmslie, K, THP.72 (775)
Emanuele, T, THP.229 (207)
Embree, J, WP.50 (778)
Emerman, M, TH.2.1 (753)
Emmanuel, J, M.8.3 (6); TP.68 (73)
Emmons, C, T.10.6 (60)
Emsbroek, J, F.8.5 (273)
Eng, R, MP.160 (36)
Englard, A, TP.223 (99); WP.218 (746)
Engleman, E, MP.12 (72)
Ensoli, B, M.9.5 (7); MP.32 (75); TP.125 (83);
THP.15 (766); THP.23 (767)
Eppes, S, THP.235 (202)
Epstein, A, WP.210 (745)
Epstein, J, WP.129 (737); THP.52 (772)
Epstein, L, MP.162 (37); THP.21 (767)
Ercilla, C, MP.165 (37)
Erfle, V, MP.104 (27); MP.166 (37)
Ericson, B, W.3.4 (707)
Eron, L, MP.13 (72)
Eskenazi, B, MP.75 (22)
Eskin, T, TP.149 (87)
Essex, M, MP.29 (75); TP.7 (63); WP.17 (113);
WP.84 (724;; TH.1.2 (753;,- TH.5.1 (756);
TH.10.5 (767); TH.P.7 (764); F.6.6 (277)
Esteban, J, WP.249 (757)
Etchebes, S, TP.79 (75)
Evans, D, THP.143 (787)
Evans, L, TP.130 (84); TH.2.6 (754)
Evans, M, T.7.2 (57)
Evans. P. MP.213 (45); TP.51 (77); TP.215 (98);
WP.213 (745); THP.212 (798)
Evans, W, TP.224 (99)
Evatt, B, WP.82 (724)
Even. P. THP.239 (203)
Ewing. W TP.247 (703)
Eymard. D. THP.96 (779)
Eyster. E. MP 65 (27)
Eyster. M, MP. 70 (27); TP.56 (77); W.2.6 (706);
F.1.3 (206)
221
INDEX
-F-
Faber, V, MP.113 (29); MP.224 (47); WP.229
(148)
Fahey, J, MP.92 (25); T.3.1 (53); T.9.6 (59);
WP.64 (121); WP.118 (730); WP.129 (737);
THP.121 (183)
Fahrner, R, WP.208 (745); TH.3.1 (154)
Fainboim, L, MP.134 (32)
Falcke, H, MP. 42 (17)
Falk, L, TP.225 (100); WP.9 (111); THP.101 (780)
Falkner-Gunter, F, W.3.1 (106)
Faltz, B, TP.203 (96); THP.218 (799)
Falutz, J.THR133 (185)
Fang, C, MP.234 (4$)
Fannin, S, THP.51 (172)
Fanning, M, MP. 49 (18); MP.50 (18); MP.209
(45); TP.224 (99); TH.4.3 (155); TH.8.1 (758);
Faraone, N, MP.185 (41)
Farber, B, WP.158 (136); THP.16 (766)
Farber, C, MP.124 (30)
Farthing, C, M.6.4 (5); THP.237 (203)
Farzadegan, H, MP.66 (21); T.3.1 (53); WP.66
(121)
Fauci, A, MP.103 (27); MP.228 (48); T.2.2 C52;;
T.8.2 (58); T.9.3 (59); TP.96 (78J; TP.106 (80);
W.5.4 (709); THP.109 (787); THP.226 (207);
F.4.4 (209); F.9.2 (214)
Faulkner- Valle, G, TP.104 (79)
Faure, G, MP.118 (29); THP.164 (190)
Fearns, M, MP.55 (19)
Feck, J, THP.70 (775;
Fehniger, T, MP.214 (45)
Feigal, D, TP.44 (69); WP.47 (118); WP.58 (720);
WP.150 (135); THP.56 (772); THP.57 (773);
THP.154 (189); F.3.1 (208); F.3.3 (20S)
Feigal, E, TP.115 (81)
Feinberg, J, MP.228 (48)
Feiner, C, TP.67 (73); W2.5 (706); THP.197
(796)
Feingold, A, MP.156 (36); TH.3.3 (754); TH.7.2
(757); THP.41 (770); THP.140 (186)
Feldman, H, TP.176 (97); WP.197 (143)
Feldman, I, TP.209 (97)
Felgenhauer, K, TP.157 (88)
Fennie, C, M.4.4 (3)
Fenyo, E, M.10.6 (8); MRU (72); THP.13 (765);
THP.29 (168); Fenyo, E, TP.132 (84)
Feorino, P, WP.181 (140); THP.28 (168); THP.42
(770)
Ferchal, F, MP.149 (35)
Ferguson, B, TP.35 (68); WP.28 (775); THP.26
(767); THP.27 (168)
Fermosel, J, MP.167 (58)
Fernandez, A, WP.96 (726); WP.120 (730)
Fernandez-Cruz, E, WP.96 (726); WP.120 (730)
Fernando, L, WP.175 (739)
Ferris, S, MP.80 (23)
Fertel, D, TP.168 (90)
Fiala, M, MP.108 (28); TP.103 (79)
Fields, H, THP.119 (783)
Figueroa, P, T.48 (70)
Fikrig, S, WP.169 (738); WP.170 (738)
Finaud, M, T.5.6 (55)
Fior, R, THP.123 (784)
Fioravanti, D, WP.122 (730)
Fischel, M, T.8.3 (58)
Fischer, A, MP.166 (37)
Fischinger, P, M.10.2 (8); MP.31 (75); TRIO (64);
W.3.6 (707); WP.3 (770); F.7.6 (272)
Fischl, M, MP.38 (76); TP.38 (68); TP.136 (85);
TP.232 (707); W.2.2 (705); WP.91 (725);
WR105 (727); WP.167 (738); WP.223 (747);
THP.92 (778); THP.240 (203)
Fishbach, R, THP.150 (788)
Fishbein, D, THP.42 (770)
Fisher, A, M.9.5 (7); MP.23 (74); W3.5 (707);
WR20 (773)
Fishinger, R MP.17 (73)
Fitzgerald, R, MP.248 (57); WP.246 (757)
Fitzgerald-Bocarsly, R WP.109 (728)
Fitzhugh, Z, TH.3.4 (755)
Flack, S, TP.198 (95)
Flageul, B, MP.98 (26)
Flanagan, S, W.2.2 (705); THP.92 (778)
Flaviano, A, MP. 46 (77)
Fleisher, E, WP.70 (722); THP.66 (774)
Fleming, A, MP.77 (23); WP.145 (734)
Fletcher, C, TR231 (707)
Fletcher, M, MP.116 (29); MP.246 (57); W.2.2
(705); WP.105 (727); WP.196 (743); THP.240
(203)
Fletcher, W, WP.202 (744)
Flexner, C, W.3.1 (706)
Flodby, R MP.39 (76)
Flye Sainte Marie, F, TP.95 (78)
Flynn, N, MP.191 (42); TP.184 (93); WP.175
(739); THP.215 (799)
Flynn, T, WP.158 (736)
Foeste, W, WP.227 (748)
Folks, T, M.9.4 (7); MP.22 (73); TP.106 (80);
TP.133 (84); W.3.4 (707); THP.109 (787); F.9.2
(274)
Follett, E, THP.244 (204)
Fonina, L, MP.97 (26)
Forbes, C, TP.241 (702); WP.238 (750); THP.244
(204)
Ford, R, MP.34 (75)
Fordycebaum, M, MP.116 (29)
Forestier, F, MP.189 (41)
Forlenza, S, WP.29 (775)
Formany, A, WP.179 (740)
Forrest, K, WP.192 (742)
Forsberg, A, M.11.4 (9); MP.240 (50); TP.144
(86)
Forstein, M, TP.178 (92)
Forster, S, TP.lll (87)
Forthal, D, WP.43 (777)
Foss, B, TH.5.1 (756)
Foster, C, TP.195 (95)
Foucault, C, WP.87 (724)
Foult, J, TP.165 (90)
Fouret, R MP.158 (36)
Fox, R MP.152 (35)
Fox, R, TP.72 (74); TP.73 (74); WP.67 (727);
TH.5.6 (757); THP.64 (774); F.8.4 (273)
Foy, J, MP.219 (46); TP.74 (74)
Francavilla, E, TP.104 (79)
France, A, MP.137 (33)
Franchini, G, MP.33 (75); TP.15 (65)
Francis, D, TP.152 (87); W.45 (777); TH.5.3
(756); THP.181 (793)
Francis, H, M.3.6 (2); MP.61 (20); MP.73 (22);
T.7.6 (57); TP.145 (86); W.4.6 (708); WP.84
(724); WP.136 (733); TH.7.6 (758); THP.18
(766); THP.19 (766); THP.139 (786); F.9.6 (274)
Francis, R, THP.200 (796)
Frank, B, MP.146 (34)
Fratantoni, J, TP.245 (703); W4.4 (708)
Fraulino, L, TP.150 (87)
Frazer, I, WP.92 (725)
Fredenburg, L, THP.229 (207)
Frederick, W, TP.242 (702); THP.179 (793);
THP.245 (204)
Frederiksen, B, MP.62 (20)
Freeman, A, WP.187 (747)
Freeman, K, MP.155 (36); TH.3.3 (754); TH.3.5
(755)
Freeman, W, TR160 (89)
Freese, U, TP.138 (85)
French, J, W.2.1 (705); THP.196 (796); TP.57
(72)
Frenkl, T, MP. 238 (49)
Frenzel, B, TP.25 (66)
Frenzel, G, F.4.5 (209)
Freudenberg, N, MR176 (39)
Friedland, G, M.3.4 (2); MP.155 (36); TP.67
(73); TP.143 (86); WP.41 (777); TH.3.5 (755);
TH.4.6 (756); TH.11.6 (762); THP.41 (770);
THP.197 (796)
Friedman, E, MP.157 (36)
Friedman, S, MP.201 (43); TP.69 (74); WP.180
(740); THP.67 (774); THP.178 (793); THP.198
(796)
Friedman-Kien, A, WP.133 (732); THP.9 (765)
Frisby, H, F.5.2 (270)
Frosner, G, MP.166 (37); THP.93 (779)
Fuchs, D, TP.87 (77); MP.99 (26); THP.166 (797)
Fuerst, T, W.3.1 (706)
Fulilove, M, WP.178 (740)
Fultz, R MP.27 (74); MP.72 (22); F.7.1 (272);
F.7.2 (272)
Fung, M, TP.ll (64)
Fung, S, TP.ll (64)
Fusillo, C, MP.90 (25)
Fust, G, MP.21 (73); MP.236 (49)
-G-
Gabuzda, D, TP.129 (84); WP.139 (733)
Gadelle, S, TP.37 (68); THP.33 (769)
Gadol, C, TP.170 (90)
Gadow, A, TP.25 (66)
Gage, L, WP.211 (745)
Gage, R TP.17 (65)
Gajdusek, D, TP.29 (67)
Galbraith, N, WP.94 (726)
Galibert, F, WP.37 (776)
Gallagher, K, MP.168 (38)
Galli, M, TP.230 (700); WP.89 (725); THP.84
(777)
Gallo, R, M.2.1 (7); MP.17 (73); MR23 (74);
MP.25 (74); MP.32 (75); MP.33 (75); MP.34
(75); MR131 (32); T.3.3 (53); T.16.4 (62);
T.120 (82); TP.19 (65); TP.20 (65); TP.21 (66);
TP.125 (83); TP.132 (84); W.3.3 (707); W.3.5
(707); W.3.6 (707); WP.5 (777); WP.20 (773);
WP.128 (737); TH.2.3 (753); TH.2.4 (754);
TH9.1 (759); THP.3 (764); THP.15 (766);
THP.23 (767); THP.97 (779); F.9.1 (274)
Galloway, W, TP.195 (95)
Ganfield, M, MP. 36 (76)
Gangadharam, R WP.69 (727); THP.147 (788);
THP.157 (789)
222
INDEX
Ganjei, P, THP.143 (187)
Gantz, N, WP.171 (138)
Garcia, N, WP.70 (122); WP.71 (122)
Garcia Montes, M, WP.120 (130); WP.96 (126)
Garcia-Pons, F, WP.127 (131)
Gard, E, TP.19 (65)
Gardner, L, MP.81 (23); T.7.1 (57); T.50 (70)
Gardner, M, MP.230 (48); TP.6 (63); TP28 (67)
Gardner, T, MP.141 (33)
Garfinkle, J, TP.169 (90)
Garner, J, WP.237 (149); THP.53 (172)
Garovoy, M, WP.112 (129)
Garrigue, G, WP.78 (123)
Garry, R, THP.112 (182)
Garsia, R, MP.168 (38)
Gartner, S, MP.104 (27); MP.131 (32); TP.107
(80); T.120 (82); F.9.1 f2/4;
Garvey, M, TP.224 (99)
Garzon, S, MP.102 (27)
Gastaut, J, T.5.6 (55)
Gaston, I, TP.130 (84)
Gatenby, P, MP.168 (38)
Gates, F, F.4.2 (209)
Gaub, J, MP. 224 (47)
Gaynor, S, MP. 247 (51)
Gazengel, C, MP. 45 (17)
Gazit, E, TH.10.5 (161)
Gazzard, B, M.6.4 (5); MP.141 (33); THP.237
(203)
Geary, J, TP.196 (95)
Gehan, K, THP.228 (201); THP.233 (202)
Gelderblom, H, TP.24 (66)
Geltosky, J, MP.107 (28)
Gendelman, H, MP.19 (13); MR22 (13); F.7.4
(212)
Genesca, J, WP.249 (151)
Gentilini, M, TP.229 (100); WP.79 (123); THP.24
(167)
George, A, MP.171 (38)
George-Nascimento, C, T.121 (82)
Georges, A, M.8.1 (5); MP.37 (16); MP.164 (37);
TP.79 (75); WP.77 (123)
Georges-Courbot, M, MP.164 (37); TP.79 (75);
WP.77 (123)
Georgoulias, V, MP.112 (28); F.4.6 (209); F.9.4
(214)
Gerard, H, THP.164 (190)
Gerard, J, MP. 154 (35)
Gerber, M, WP.189 (141)
Gerbert, B, THP.213 (199)
Gershy-Dimet, G, F.2.5 (207); F.6.2 (211)
Gerstoft, J, T.3.5 (53); TP.123 (83)
Gervais, F, TP.89 (77)
Gesemann, M, THR131 (185)
Geurts, J, MP.177 (39)
Gharakhanian, C, M.5.4 (4)
Gharakhanian, S, TP.229 (100); F.2.1 (207)
Ghazzouli, I, THP.8 (164)
Ghirardini, A, THP.248 (204)
Ghrayeb, J, TP.28 (67); TP.132 (84)
Gianakakos, V, TP.110 (80)
Giaquinto, C, MP.47 (18); MP.153 (35); TP.104
(79)
Gibbons, J, W.3.3 (107); WP.ll (112)
Gibbs, C, TP.29 (67); WP.18 (113)
Gibbs, W, T.48 (70)
Gibson, P, WP.178 (140)
Gibson, S, MP. 217 (46)
Gigase, P, THP.227 (201)
Gilden, R, TRIO (64); THP.34 (169); F.7.6 (212)
Giles, M, THP.51 (172)
Gill, R W.2.1 (105); WP.146 (134); WP.215 (146);
THR49 (171); THP.96 ^79>; THP.144 (757)
Gilman, T, THP.151 (188)
Gilmore, N, MP.215 (46); WP.215 (146); THP.96
(179)
Gilson, I, TH.8.5 (159)
Gindi, E, MP.90 (25;
Gindo, A, MP. 80 (23)
Gingeras, T, TP.9 (64)
Ginzburg, H, TP.87 (77); F.6.5 (211)
Giorgi, J, T.9.6 (59); WP.117 (129); WP.118
(130); THP.60 (773); THP.121 (183)
Giovanni, C, MP.198 (43)
Giraldo, G, TP.244 (103)
Girard, M, THP.32 (168)
Girard, R MP.161 (37); TR165 (90); TP.216 (98);
WP.160 (737); WR228 (748); THP.169 (191);
THP.170 (797;
Giri, C, TP.16 (65)
Giuliani, G, MP.41 (17)
Gjerset, G, WP.54 (119); THP.50 (777)
Glover, L, T.6.4 (56)
Gluckman, J, M.10.1 (7); TP.105 (80); TH.9.6
(160)
Gluckmann, J, WP.87 (124)
Goebel, F, MR166 (37); TR213 (98); WP.165
(137)
Goeddel, D, T.4.5 (54)
Goedert, J, MP.65 (21); MP.70 (21); T.3.3 (53);
TP.56 (71); TP.87 (77); W.2.6 (706); TH.7.3
(158); THP.71 (775); F.1.2 (206)
Goh, W T.4.3 f54j
Gold, J, MP.64 (20); MP.186 (41); THP.222 (200)
Gold, R TP.89 (77); WP.163 (737); THP.133 (185)
Goldberg, E, THP.96 (779)
Golde, D, MP. 222 (47)
Golden, J, TP.217 (98)
Goldfinger, D, MP. 169 (38)
Goldfinger, S, THP.167 (797)
Golding, B, F.4.2 (209)
Golding, H, F.4.2 (209)
Goldman, E, MP.76 (22)
Goldsmith, D, WP.180 (140); THP.198 (796)
Goldstein, A, MP.24 (14); TP.134 (84); WP.18
(773); THP.107 (181); THP.128 (184)
Goldstein, D, MP.248 (51); WP.246 (757)
Goldstein, L, WP.65 (727); THP.52 (772)
Goldwater, R MP. 204 (44)
Gomperts, E, MP.138 (33)
Gonda, M, M.10.2 (8); MP.13 (72); TH.2.5
(154); Gonda, M, THP.34 (769)
Gonzalez, J, TP.79 (75); WP.77 (725); WP.93
(725); THP.59 (773)
Gonzalez-Porque, R TP.118 (82)
Good, R, F.4.1 (209)
Gootenberg, J, MP.126 (37)
Gordon, L, TP.199 (95); TH.11.5 (762)
Gorman, E, TP.59 (72); THR181 (793) .
Gorman, R, MP.225 (47)
Gornitsky, M, MP.102 (27)
Gottleb, M, THP.241 (203)
Gottlieb, A, MP.218 (46); TR228 (100); THP.241
(203)
Gottlieb, M, MP.109 (28); MP.218 (46); TP.127
(83); TR228 (700); WP.103 (727); THP.232
(202)
Gotzsche, R WP.229 (148)
Goudeau, A, WP.27 (114)
Goudsmit, J, M.6.1 (4); MP.9 (77); MP.53 (79);
TP.33 (68); TP.40 (69); TR100 (79)
Gougerot-Pocidalo, M, TP.126 (83)
Gourley, R WP.182 (740)
Gowan, L, TR248 (703)
Gowda, S, MP.12 (72)
Grabau, J, TP.177 (92)
Gracie, J, TP.241 (702); WP.238 (750); THP.244
(204) *
Grade, M, TP.203 (96); THP.218 (799)
Grady, C, THP.219 (200)
Grady, G, THP.175 (792)
Graham, D, W.4.4 (108)
Graham, J, THP.195 (796)
Graham, V, WP.200 (143)
Grant, I, MP.145 (34); MP.200 (43)
Grape, R, MP.140 (33)
Grassi, F, WP.124 (737)
Grassi, M, WP.143 (734)
Grassi, R WP.144 (134)
Gravell, M, MP.144 (34)
Gray, J, THR172 (792)
Greaves, W, THP.179 (793)
Green, J, MP.205 (44); T.6.2 (56); THP.162 (790)
Green, L, MP.185 (41)
Greenberg, A, M.8.5 (6); MR73 (22); TR139
(85)
Greenberg, R, MP.199 (43)
Greenblatt, R, THP.47 (777); THP.68 (174)
Greene, W, F.4.4 (209)
Greenspan, D, MP.223 (47); TP.138 (85); WP.58
(720)
Greenspan, J, MP.223 (47); TP.138 (85); WP.58
(720); WP.112 (729)
Gregg, R, WR129 (737)
Gregory, T, M.4.4 (3); WP.12 (772); THP.20
(766)
Grieco, M, MP.90 (25); TP.223 (99); WP.218
(746); THP.62 (773)
Grieve, W THR142 (757)
Griffin, D, MP.66 (27)
Griffin, J, TP.140 (85)
Griffiss, J.THR163 (790)
Griffiths, C, MP.171 (38)
Griffiths, R MP.76 (22); TP.233 (707)
Grifol, M, MP.165 (37); TP.167 (90)
Grigoriu, A. WP.60 (720)
Grimaila, R, WP.33 (775)
Grimes, J, WR53 (779)
Grimfeld, A. MP.117 (29)
Grindon, A, MR241 (50); W.4.1 (707)
Grim, R MP.67 (27)
Griscelli, C, TH.7.4 (158)
Gritti, F, TP.113 (81)
Groen. G, TP.63 (73)
Groh, V TP.107 (80)
Groopman, J, MP.89 (25); MP.222 (47); TP.17
(65); TP.64 (73); TR122 (82); TH.5.1 (756);
THP.20 (766)
Grosch-Worner, I, MP.47 (78); THP.94 (779)
Gross. M, TP.178 (92)
Gross, S, WR178 (740)
223
INDEX
Gross, W, MP.100 (26); MP.101 (27)
Grossman, R, MP.65 (21)
Grover, S, MP.215 (46)
Growe, G, WP.163 (137)
Gruttola, V, MP.52 (18)
Gschwind, C, WP.131 (132)
Guerois, G, WP.27 (114)
Guerra, C, THP.85 (777)
Guigli, P, WP.155 (136)
Guillon, J, MP.123 (30)
Guinan, M, THP.54 (772)
Gunnel, B, THP.29 (168)
Gunson, H, MP.233/49)
Guo, C, WP.20 (IB)
Guo, H, MP.33 (75)
Gupta, P, WP.106 (128)
Gurbindo, D, WP.96 (726)
Gurbindo, M, MP167 (38)
Gurgo, C, MP.33 (75); MP.34 (75)
Giirtler, L, T.46 (70); TH.10.6 (767); THP.93
(779)
Gust, I, THP31 (765)
Gutierrez, C, WP.120 (130)
Gutzwiller, F, MP.179 (40)
Guyader, M, TH.2.1 (753)
Guyton, R, TP.22 (66)
Gyenes, A, T.121 (82)
-H-
Habermehl, K, TP.34 (68); WP.26 (774); THP.25
(167)
Haburchak, D, MP140 (33)
Haddadian, A, WP.103 (727)
Hadley, W, TP.219 (99); THP.163 (790)
Haffar, O, WP.25 (774)
Hahn, B, WP.ll (772); TH.2.3 (753)
Halabi, F, TH.9.6 (760)
Haley, C, TP.77 (75); WP.187 (747); THP.221
(200)
Haley, R, THP.221 (200)
Hallberg, P, M.5.1 (3)
Hallick, L, WP.34 (776)
Halloran, P, TH.4.3 (755)
Halsey, N, THP.63 (774)
Hamamoto, Y, MP.235 (49)
Hamerschlack, N, THP85 (777)
Hamilton, P, MP. 55 (79)
Hammarskjold, M, MP.30 (75)
Hampe, A, WP.37 (776)
Hampl, H, WP.26 (774)
Handsfield, H, T.5.3 (55); TH.4.6 (756); WP.76
(723); THP.73 (775); F.1.6 (206)
Hankins, C, WP.179 (140)
Hannon, R, MP.140 (33)
Hanrahan, J, THP.70 (775)
Hansen, J, THP.36 (769)
Hansen-Sparks, W, F.8.6 (273)
Hanson, M, MP.237 (49)
Harada, S, M.4.2 (2); MP.235 (49)
Harding, R, TP.45 (70)
Hardy, A, MP. 89 (25); THP.54 (772)
Hardy, D, THP.232 (202)
Harmon, T, MP.209 (45)
Harper, M, WP.241 (750)
Harper, S, MP.191 (42); TP.184 (93); WP.175
(739); THP.215 (799)
Harris, B, THP.180 (793)
Harris, C, W.2.5 (706)
Harris, J, THP.101 (180); THP.202 (797)
Harrison, S, MP.140 (33)
Harrison, W, TP.135 (85); TP.156 (88)
Hartel, D, M.3.4 (2); WP.41 (777); THP41 (770)
Hartshorn, K, TP.30 (67); WP.104 (727)
Hartzman, R, THP.109 (181)
Harvey, E, MP.150 (35)
Harzic, M, MP.149 (35); TP.37 (68); WP.138
(733); THP.33 (769); THP.75 (776); F.2.4 (207)
Haschke, F, TH.10.4 (767)
Haseltine, W, M.4.6 (3); M.9.2 (7); T.4.3 (54);
T.16.2 (62); WP.16 (773); WP.38 (776); THP.6
(764)
Haskin, J, T.6.5 (56)
Hassig, S, MP.184 (40)
Hatch, W, MP. 31 (15)
Hattori, T, W3.2 (706)
Hauer, L, WP.57 (779)
Hausen, A, MP.99 (26)
Hausler, W, MP.129 (37)
Hausmann, E, TP.24 (66)
Hawkins, J, THP.53 (772)
Hayami, M, MP.28 (74); MP.94 (25); THP.65
(774)
Hayward, G, WP.38 (776)
Hazan, U, MP.37 (76)
Hazel, E, F.3.2 (208)
Hazell, E, T.6.1 (56)
Heagarty, M, TH.11.3 (762)
Hearn, J, TP.4 (63)
Hearst, N, WR150 (735); THP.56 (772)
Heckert, K, TP.189 (94); THP.176 (792)
Hedderman, M, TH.11.1 (767)
Hedley-Whyte, E, TP.129 (84); WP.139 (733)
Hegarty, J, TH.11.3 (762)
Hehlmann, R, MP.166 (37)
Heimer, E, MP.238 (49)
Heisterkamp, S, MR74 (22)
Hejjas, M, MP.236 (49)
Helgerson, S, TP.181 (92)
Heller, J, F.2.6 (207)
Henco, K, WP.24 (774)
Henderly, D, TP.160 (89)
Henderson, L, M.9.3 (7); THP.112 (182)
Hendrickson, E, WP.28 (775)
Hendrix, H, MP.219 (46)
Hendry, R, MP.125 (37); THP.122 T7&3)
Hengy, C, M.8.1 (5)
Henin, Y, THP.37 (769)
Henriques, H, MP.216 (46)
Henry, K, MP.193 (42)
Herbold, J, T.7.1 (57); THP.77 (776); Fl.l (206)
Herbst, J, MP.146 (34); TP.141 (86)
Herdewijn, P, MP.4 (70)
Hermans, P, TP.82 (76); WP.59 (720); THP.61
(773)
Hernandez, J, WP.249 (757)
Hernandez, M, TP.147 (87); THP.234 (202)
Hernandez Sampelayo, T, MP.167 (38)
Herndon, K, TP.77 (75)
Herpin, B, MP.228 (48); WP.205 (744)
Herrera, M, TP.102 (79)
Hersh, E, MP.225 (47); TP.218 (98); WP.131
(732)
Herve, P, MP.148 (34)
Heseltine, P, T.8.5 (58); WP.221 (747); TH.11.1
(767); THP.149 (188); THR151 (188)
Hess, E, WP.133 (732)
Hesselink, J, T.8.3 (58); TP.158 (88)
Hessol, N, M.3.1 (7)
Heutink, P, TP.100 (79)
Higgins, B, MP.199 (43)
Higgins, J, MP.151 (35)
Hildebrandt, D, MP. 83 (24)
Hill, J, M.5.1 (3)
Hill, T, MP.107 (28)
Hingson, R, T.6.6 (56)
Hinuma, Y, M.4.2 (2)
Hirsch, A, TP.142 (86)
Hirsch, D, T.10.5 (60)
Hirsch, M, T.9.1 (59); TP.30 (67); TP.129 (84);
WP.104 (727); WP.139 (733); TH.4.6 (756)
Hirsch, V, TH.2.2 (753); WP.15 (772); THP.5
(764)
Hirschmann, M, WP.152 (735)
Hittelman, J, THP.158 (189)
Hitzeman, R, WP.35 (776)
Ho, D, TP.129 (84); WP.139 (733)
Ho, E, F.7.5 (272)
Ho, M, THP.60 (773)
Hoban, M, THP.146 (187)
Hobusch, G, MP.101 (27)
Hodge, J, TP.179 (92)
Hodges, R, THP.128 (184)
Hoff, C, WP.50 (118)
Hoff, R, THP.175 (792)
Hoffken, G, WP.132 (732)
Hoffman, P, THP.12 (765)
Hoffman, R, TP.58 (72)
Hofmann, B, TP.123 (83); WP.101 (727); WP.162
(737)
Hojvat, S, WP.44 (777); THP.9 (765)
Hollan, S, MP.21 (73); MP.236 (49)
Holland, B, W.5.1 (705)
Holland, J, T.10.5 (60); W.5.6 (709); WP.115
(729)
Holland, P, M.3.5 (2); WP.175 (739); MP.120
(30); MP.151 (35); T.5.5 (55); TP.121 (82);
TP.217 (98); WP.58 (720); TH.8.4 (759);
TH.9.2 (759); THP.57 (773)
Hollinger, F, THP.114 (182)
Holman, S, TP.78 (75); WP.157 (736); TH.7.3
(758); THP.158 (189); THP.209 (198);
Holmberg, S, MR241 (50); W.4.1 (707); TH.10.1
(160)
Holt, E, THP.63 (774)
Holtzman, D, THP.45 (777); THP.83 (777)
Holzemer, W, TP.207 (97)
Holzman, B, THP.167 (797)
Holzman, R, WP.147 (734); THP.214 (799)
Homsy, J, TP.130 (84); WP.14 (772)
Honey, E, WP.200 (743)
Hong, T, TP.68 (73)
Honnen, W, TP.110 (80)
Hood, H, MP.174 (39); MP.196 (42)
Hooykaas, C, MP.53 (79)
Hopewell, P, F.3.3 (208)
Hopkins, D, Wl.l (705)
Hopkins, S, TP.186 (93); WP.49 (118); WP.88
(725)
Hopkins, W, THP.198 (796)
Hording, M, WP.229 (148)
Horsburgh, C, TP.70 (74)
Horvath, A, MP.21 (73)
224
INDEX
Horwitz, S, TP.77 (75)
Hosein, B, TP.240 (102); WP.236 (149); THP.243
(204)
Hoshino, H, WP.31 (115)
Hoshino, T, WP.103 (127)
Houff, S, MP.159 (36)
Houghton, R, MP.35 (16); TP.32 (67)
Houk, R, MP.115 (29); WP.156 (136)
Hovanessian, A, TP.5 (63)
Howard, J, MP.175 (39)
Howard, L, WP173 (139)
Howard, T, TP.246 (103)
Hryb, K, THP.220 (200)
Hsu, A, MP.18 (13)
Hu, S, T.9.5 (59); WP.39 (116)
Huhtala, M, TH.9.3 (160)
Huisman, H, THP.90 (178)
Huisman, J, TP.33 (68); TP.92 (77); WP.36 (116)
Hull, H, THP.186 (194)
Hull-Drysdale, B, F.6.4 (211)
Hulley, S, T.10.1 (60)
Hummel, R, TP.209 (97)
Humphreys, P, TP.243 (103)
Hunsmann, G, MP.28 (14)
Hunt, J, WP.242 (150)
Huprikar, J, T.3.6 (53)
Hurd, G, THP.184 (194)
Hurzeller, R, WP.214 (146)
Hussey, S, WP.224 (147)
Hutchinson, V, TH.11.3 (162)
Hutto, C, MP.38 (16); F.2.2 (207)
Hutto, S, WP.166 (138); THP91 (178)
Huyghen, K, MP.124 (30)
Hyldig-Nielsen, J, WP.101 (127)
-I-
Icardi, G, WP.134 (132)
Iijima, H, MP.235 (49)
Illeman, M, WP.219 (146)
Imagawa, D, MP.8 (11); THP.160 (190)
Imam, F, THP.3 (164)
Imperato, D, TP.68 (73)
Imrie, A, MR186 (41)
Inada, Y, THP.62 (173)
Intrator, L, THP.123 (184)
Ioachim, H, MP.106 (27); THP.110 (181);
THP.152 (188)
Ioannou, S, TP.175 (91)
Ippolito, G, TP.93 (78); WP.248 (151)
Ischenko, A, WP.98 (126)
Iseman, M, THP.147 (188)
Ishikawa, Y, MP.94 (25); THP.65 (774)
Itoua-Ngaporo, A, Wp.79 (123)
Ivanoff, L, M.9.5 (7)
-J-
Jackson, J, MP.210 (45); TH.5.2 (156); TH.11.4
(162)
Jacob, J, WP.147 (134); THP.219 (200)
Jacobs, R, WP.183 (140); TH.8.4 (159)
Jacobsen, P, MP.195 (42)
Jacobson, D, TP.61 (72); WP.234 (149)
Jacobson, M, MP.221 (47); WP.231 (148)
Jacobus, D, THP.231 (202)
Jacquette, G, F.3.2 (208)
Jaeger, H, T.46 (70); THP.166 (191)
Jaenisch, R, TP.62 (72)
Jaffe, H, M.3.1 (I); MP.83 (24); MP.127
(57);W.2.3 (106); F.8.1 (213)
Jaffe, J, MP.74 (22); TP.54 (71); WP.119 (130);
THP.74 (175); THP.95 (179)
Jagodzinski, L, MP.25 (14)
Jain, S, MP.191 (42); TP.184 (93); WP.175 (139);
THP.215 (199)
Jairam, B, THP.157 (189)
Jakobovitz, A, TP31 (67)
Janett, A, MP.56 (19)
Janier, M, MP.98 (26); TR216 (98)
Janossy, G, WP.137 (133)
Jansen Schoonhoven, F, F.8.5 (213)
Janssen, R, T.5.2 (55)
Jarrett, W, T.2.1 (52); TP.19 (65)
Jarry, A, MP. 2 (10)
Jarvik, J, TP.158 (88)
Jasmin, C, MP.112 (28); F.4.6 (209); F.9.4 (214)
Jason, J, WR82 (724)
Jayle, D, THP.106 (181)
Jean-Charles, M, TP.43 (69)
Jeannequin, O, TP.5 (63)
Jeffries, D, TH.4.4 (156); TH.8.3 (159)
Jelesoff, N, M.5.1 (3)
Jellis, C, THP.35 (169)
Jendis, J, THP.14 (765)
Jennings, A, T.3.3 (53)
Jennings, M, TP.6 (63); TP.28 (67)
Jensen, F, MP. 34 (15)
Jesson, W, M.6.4 (5)
Jett, K, MP.85 (24)
Joffe, R, THP.146 (787)
Johl, S, MP.18 (13)
Johns, D, T.4.2 (54); TP.l (62)
Johnson, A, TP.179 (92)
Johnson, D, TP.188 (93)
Johnson, E, MP.160 (36); THP.171 (792)
Johnson, J, MP. 49 (18); MP.50 (78); MP.85 (24);
WR123 (130)
Johnson, M, TP.122 (82)
Johnson, R, MP. 66 (27)
Johnson, S, MP.58 (19); THP.31 (168)
Johnson, W, M.8.6 (6); MP.68 (27); MR69 (27);
MP.136 (32); TP.43 (69)
Joist, J, THP.127 (184)
Jondal, M, M.10.6 (8)
Jones, B, THR100 (180)
Jones, F, MP.231 (48)
Jones, M, MP.137 (33)
Jones, R MP.55 (19); TH.8.5 (759)
Jones, T, TP.182 (92)
Jones-Mangione, E, TP.58 (72)
Jornvall, H, MP.39 (76)
Josefberg, H, THP.231 (202)
Joseph, J, T. 10. 6 (60)
Josephs, S, MP.23 (14); TP.ll (64); TH.2.4 (754);
THP.242 (203)
Josephson, S, MP.129 (31)
Joshi, V, MP.162 (37); MP.170 (38); TR170 (90);
W.5.1 (108); WP.169 (138)
Josse, R, M.8.1 (5); WP.78 (123)
Jothy, S, WR215 (746); THP.96 (779)
Jouvin, M, WP.126 (131)
Jubran, A, WP.140 (133)
Judkins, K, MP.125 (31)
Judson, F. TP.70 (74); TP.71 (74); WP.181 (740);
WP.182 (740); THP.58 (773)
Julander, I, THP.238 (203)
Junca, J, TP.167 (90)
Jung, M, MP.46 (77)
Jupp, R MP. 40 (76)
Jurkiewicz, E, MP.28 (74)
Justement, J, TP.106 (80); F.9.2 (274)
-K-
Kabote, N, M.8.5 (6); MP.73 (22)
Kahl, P, TP.67 (73); THP.197 (796)
Kahn, A, WP.195 (742)
Kahn, D, TP.169 (90)
Kain, S, WP.61 (720)
Kamani, N, THP.122 (183)
Kamradt, T, THP.168 (797)
Kanda, R THP.102 (180); F.4.5 (209)
Kang, E, MP.243 (50)
Kanki, R MP.29 (75); TP.7 (63); THP.7 (764);;
F.6.6 (277)
Kannagi, M, THP.104 (180); F.7.3 (272)
Kanouse, D, TP.59 (72); THP.181 (793)
Kapila, R, MP.160 (36); WP.60 (720)
Kapita, B, M.3.6 (2); T.7.6 (57)
Kaplan, C, WR180 (740)
Kaplan, J, T.5.2 (55); THP.42 (770)
Kaplan, L, M.11.2 (9); M.11.3 (9); TR115 (81)
Kaplan, M, WP.158 (756); WP.159 (756); THP.3
(764); THP.16 (766)
Kaplowitz, L, TP.208 (97)
Kappatos, D, W.5.6 (709)
Kappel, S, THP.192 (795)
Karaffa-Myles, C, TP.162 (89); WR222 (747)
Karamov, E, WP.98 (726)
Karlsson, A, MP.93 (25); WP.83 (724); THP.130
(185)
Karp, M, F.5.6 (270)
Karty, R, WP.34 (776)
Kasali, M, THP.18 (766)
Kashkin, J, TP.146 (86)
Kasili, E, TP.249 (704)
Kaslow, R, TP.72 (74); TP.73 (74); WR67 (727);
TH.5.6 (757); THP.64 (774)
Katlama, C, T.5.4 (55); WP.160 (757); THP.24
(767); THP.75 (776); F.6.1 (277)
Katoff, L, WP.203 (744)
Katona, I, MP.133 (32)
Katz, D, MP.159 (36)
Katz, J, TP.127 (83); Katz, J, WP.103 (727)
Katz, S, THP.16 (766)
Katzenstein, D. M.8.3 (6)
Katzmann, J, MP.147 (34)
Kauffman, S, WP.169 (758); WP.170 (758)
Kaufman, F, MR138 (33)
Kaufman. J, TP.16 (65)
Kaufman, N, F.5.2 (270)
Kaufmann, M. MP.56 (79)
Kay, J. WP.247 (757)
Kayembe. K, MP.61 (20)
Keddie. E. MP.191 (42)
Kegeles, S. THP.185 (794)
Keiser, J, WP.152 (755)
Keith. D, T.9.6 (59)
Kekow, J, MP.100 (26); MP.101 (27)
Kelen. G, TH.3.6 (755)
Keller, A, MP.46 (77)
Keller, G. WR21 (775); WP.22 (774)
Keller, N. THP.186 (794)
225
INDEX
Keller, S, WP.165 (137)
Kelley, P, T.50 (70); F.l.l (206)
Kellie, S, MP.68 (21)
Kelliher, J, F.7.6 (212)
Kelly, J, MP.174 (39); MP.196 (42); WP.199 (143);
THP.249 (205)
Kemp, B, TP.18 (65); WP.6 (777,)
Kenealy, W, MP.36 (16); TP.23 (66)
Kennedy, C, MP145 (34); MP.200 (43); T.8.3
(58); TR61 (72); TP.158 (88); WP.234 (749)
Kennedy, M, MP.127 (31); TP.3 (63); TP.108 (80);
WP.113 (729); TH.9.5 (760); THP.102 (780);
F.4.5 (209)
Kenny, D, MP.168 (38)
Kenrick, K, WP.243 (750)
Keresztes, J, TP.215 (98); TP.226 (700); WP.213
(145); THP.212 (798)
Kern, C, MP.218 (46); THP.241 (203)
Kern, P, MP.100 (26); MR101 (27); TP.155 (88)
Kernoff, P, MP.76 (22); TP.233 (707); WP.137
(133); Kessler, H, TP.225 (700); WP.9 (777);
THP.101 (780)
Kessler, R, T.10.6 (60)
Ketlinsky, S, WP.98 (726)
Keur, W, TP.63 (73)
Keys, T, TP.162 (89)
Khaitov, R, MP.97 (26)
Khan, N, THP.99 (780)
Khillan, J, F.7.4 (272)
Khoury, E, WP.112 (729)
Kiango, J, TP.86 (76)
Kienny, M, M.10.1 (7)
Kieny, M, THR32 (768)
Kim, C, MP.219 (46)
Kim, H, THP.82 (777)
Kinder, B, WP.225 (147)
King, N, THP.104 (780); F.7.3 (272)
Kingsley, L, M.6.2 (4); MR92 (25); MP.121 (30);
WP.63 (720); TH.5.6 (757); THP.60 (775);
F.8.3 (275)
Kinney-Thomas, E, THR8 (164)
Kinter, A, TP.106 (80)
Kirk, R, WP.227 (748)
Kirn, D, WP.47 (778)
Kissinger, R, MP.107 (28)
Kitchen, L, MP.3 (70)
Kitonyi, G, TP.249 (704)
Kittur, D, WP.123 (750)
Klanieki, J, MP.35 (76)
Klatzman, D, TH.9.6 (760)
Klatzmann, D, M.10.1 (7); TP.105 (80)
Klauber, M, TP.61 (72); WP.234 (749)
Klauber, S, WP.234 (749)
Klein, E, MP.90 (25); TP.223 (99); WR65 (727);
WP.218 (746); THP.62 (775)
Klein, H, TP.74 (74)
Klein, M, MP. 49 (78); MP.50 (78); TH.4.3 (755)
Klein, N, TP.154 (88)
Klein, R, M.3.4 (2); MP.155 (36); TP.143 (86);
W.2.5 (706); WP.41 (777); WP.209 (745);
TH.3.5 (755); THP.197 (796); F.3.4 (208)
Klein, S, WP.202 (744)
Kleinman, P, THP.198 (796)
Kleinman, S, M.3.5 (2); MP.232 (48); TP.234
(707); W.4.1 (707); W.4.2 (707); THP.246 (204)
Klimas, N, MP.116 (29); WP.105 (727); THP.240
(203)
Klimek, J, THP.220 (200)
Klimenko, S, THP.40 (770)
Kline, A, TH.3.1 (754)
Kline, M, TP.224 (99)
Kline, R, THP.19 (766)
Klock, J, WP.10 (772)
Kloser, P, WP.60 (720)
Kluge, J, MP.230 (48)
Knight, S, THP.232 (202)
Knowles, D, WP.230 (748)
Knutsen, A, THR127 (784)
Koch, M, TP.24 (66); WP.48 (778); WP.93 (725);
THP.4 (764)
Koch, S, THP.94 (779)
Kochems, L, THP.182 (795)
Kochen, J, THP.16 (766)
Kock, M, THP.59 (775)
Kodama, C, TP.173 (97)
Koenig, B, TH.3.2 (754)
Koenig, R, TP.187 (93)
Koenig, S, MP.10 (77); MP.103 (27); T.9.3 (59);
THP.109 (787)
Koerper, M, MP.163 (37); TH.10.3 (767)
Kohler, C, THP.164 (790)
Kohmescher, R, T.6.3 (56)
Koito, A, W.3.2 (706)
Kong, L, TH.2.3 (755)
Kontio, S, TH.9.3 (760)
Korkolainen, M, TH.9.3 (760)
Kornfeld, H, WP.15 (772); TH.2.2 (755); THP.5
(164)
Kosowski, S, WP.39 (776)
Koss, L, TP.143 (86)
Kost, T, TH.2.5 (754)
Kotler, D, THP.148 (788)
Kotval, I, F.8.6 (275)
Kouri, Y, THP.138 (786)
Kourouma, K, THP.75 (776)
Kovacs, J, MP.228 (48); T.8.2 (58); THP.226
(207)
Kowalski, M, M.4.6 (5); T.4.3 (54)
Krailo, M, THP.49 (777); THP.144 (787)
Krall, G, MP. 21 (75)
Kramer, A, WP.132 (752)
Krampf, W, THP.43 (770)
Krasinski, K, W5.2 (708); WP.72 (722); WP.141
(755); WP.142 (754); THP.103 (780); THP.145
(187)
Kraus, B, TH.10.4 (767)
Krause, P, F.1.3 (206)
Krebs, J, WP.181 (740)
Kreek, M, THP.216 (799)
Kreiss, J, TH.7.5 (758)
Kreuz, W, TH.10.4 (767)
Kreuzfelder, E, THR131 (785)
Krilov, L, THP.122 (785)
Kristal, A, WP.189 (747)
Krogh, G, MP.93 (25); WR83 (724)
Krogsgaard, K, T.3.5 (53); TP.41 (69); TP.81
(76)
Krohn, K, M.10.4 (8); MP.17 (75); MP.119 (50);
W.3.6 (707); TH.9.1 (759); THP.35 (769)
Kronawitter, U, WP.165 (757)
Krone, W, TP.100 (79)
Krowka, J, T.121 (82); T.4.5 (54); TH.9.2 (759)
Krust, B, TP.5 (63)
Ktsanes, V, MP.184 (40)
Kuenssberg, B, WP.40 (777)
Kufta, C, MP.159 (36)
Kuhn, A, TP.183 (93); THP.173 (792)
Kuhnel, H, WP.24 (774)
Kumar, M, THP.155 (789)
Kumar, R TH.2.3 (755)
Kumari, S, TP.94 (78)
Kunches, L, MP.242 (50); TP.47 (70)
Kunze, R, TP.25 (66); THP.4 (764)
Kuo, A, MP.95 (26)
Kuritsky, J, W4.4 (708)
Kurowski, R THR234 (202)
Kurth, R, TP.132 (84)
Kushi, L, WP.198 (745)
Kutzko, D, THR192 (795)
Kuzma, R, TH.4.2 (755)
Kvinesdal, B, MP.57 (79)
Kvitash, V, TP.200 (95)
Kwoh, D, TR9 (64)
Kwok, S, WR23 (774); THP.28 (768); F.2.3 (207)
Kyle, G, WP.189 (747)
-L-
Lack, E, W.5.4 (709)
Lafleur, F, TH.4.5 (756)
L'age-Stehr, J, WP.48 (778); THP.59 (775)
La Grenade, L, T.48 (70)
Lainson, F, MP.245 (57); TP.238 (702)
Lamb, B, MP. 89 (25)
Lamb, G, WP.210 (745)
Lamberson, H, WP.226 (748); THP.246 (204);
THP.247 (204)
Lambert, T, M.11.5 (9)
Lamon, K, MP.240 (50)
Lamotte, G, MR248 (57); WP.246 (757)
Landay, A, WP.9 (777); THP.101 (780)
Landers, S, WR210 (745)
Landesman, S, TP.56 (77); TP.78 (75); TP.228
(700); WP.75 (722); WP.157 (756); WP.194
(742); WP.200 (745); TH.4.6 (756); TH.7.3
(758); THP.71 (775); THP.209 (798)
Lane, C, WP.85 (724); WR151 (755); THP.71
(775)
Lane, H, MP.103 (27); MR125 (57); MP.228 (48);
T.8.2 (58); T.9.3 (59); W.5.4 (709); TH.4.1
(755); THP.226 (207); F.4.4 (209)
Lang, W, M.3.2 (7)
Lange, J, MR9 (77); MP.53 (79); TP.33 (68);
TP.100 (79); THP.90 (778); THP.136 (786)
Lange, M, TP.223 (99); WP.218 (746); THP.62
(775); THP.231 (202)
Lange, W, TP.54 (77); THP.95 (779)
Langhoff, E, WP.101 (727)
Langlade-Demoyen, R WR127 (757)
Langlois, A, Tp.128 (83)
Lansky, L, THP.193 (795)
Lantos, G, W.5.3 (709)
Laper, G, THP.201 (797)
Larder, B, THP.22 (767)
Laroche, A, MP.69 (27)
Larouze, B, WP.32 (775)
Larson, D, TP.248 (705)
Laskin, O, TH.8.5 (759)
Lasky, L, M.4.4 (5); WP.12 (772); THP.20 (766)
Latif, A, M.8.3 (6)
Lau, A, WP.121 (750)
Laurent, A, TP.5 (63)
226
INDEX
Laurian, Y, MP. 45 (17)
Lauritzen, E, MP.57 (19)
Laursen, I, MP.62 (20)
Law, R, MP.204 (44)
Lawrence, A, M.6.4 (5)
Lawrence, D, M.11.5 (9)
Lawrence, J, MP.196 (42)
Lawrence, R, W.5.2 (108); WP.141 (133);
THP.145 (187)
Lazarowicz, R, T.6.3 (56)
Lazzarin, A, TP.230 (100); WP.89 (125); WP.151
(135); THP.89 (178); THP.118 (183); THP.165
(191)
Le, S, THP.39 (170)
Learmont, J, WP.243 (150)
LeBlanc, R, THP.96 (179)
Lebow, L, TP.127 (83)
Lebughe, I, TP.139 (85)
Lecocq, J, THP.32 (168)
Le Deist, F, TH.7.4 (158)
Ledergerber, B, WP81 (123)
Lederman, M, MP.105 (27); TP.97 (78); F.1.3
(206)
Lee, C, WP.137 (133)
Lee, F, THP.61 (173)
Lee, H, WP.170 (138)
Lee, J, MP.176 (39); WP.155 (136)
Lee, M, MP.8 (11)
Lee, N, TP.150 (87)
Lee, S, TP.90 (77); TH.2.3 (153)
Lee, T, T.3.1 (53); WR17 (113); WP.66 (121)
Leece, B, TH.9.1 (159)
Leedom, J, MP.175 (39); T.8.5 C5Sj; TP.160 (89);
WP.221 (747); TH.11.1 (161); THP.149 (788)
Legg, H, WP.13 (112)
Le Guern, A, TP.5 (63)
Lehrman, S, T.8.1 (58); THP.235 (202)
Leibowitch, J, THP.106 (181)
Leiderman, I, WP.145 (134)
Leite Da Costa, J, THP.78 (176)
Leitman, S, TP74 (74)
Lejeune, B, M.6.6 (5)
Lekas, P, TR115 (81)
Lekatsas, A, TP.75 (75); WP.71 (122); THP.199
(196)
Lelie, N, TP92 (77); WR73 (122); THP.90 (178)
Lemp, G, T.49 (70); TP.51 (71); W.46 (118)
Lennette, E, MR223 (47)
Lenoir, G, TP.8 (63)
Lenox, T, TP.154 (88)
Leonard, G, F.2.5 (207); F.6.2 (2/7)
Leonard, J, MP.19 (13); F.7.4 (212)
Leonard, P, T.6.4 (56)
Leonard, R, T.16.5 (62)
Leonard, T, THP.188 (794)
Leoung, G, THP.154 (189); F.3.3 (208)
Leport, C, MP.161 (37); WP.138 (133)
Lerche, N, TP.6 (63)
Lernestedt, J, THP.238 (203)
Lesane, F, F.4.3 (209)
Leslie, J, TP.185 (93)
Lessner, L, TP.76 (75)
Letvin, N, THP.104 (780); F.7.3 (272)
Leuther, M, MP. 45 (17); MP.87 (24); T.8.1 (58);
TP.38 (68); TP.69 (74); WP.44 (777); F.2.6
(207)
Levacher, M, TP.126 (83)
Levine, A, WP.146 (134); THP.49 (777); THP.144
(787)
Levine, C, F.5.1 (210)
Levine, J, TH.11.5 (762)
Levine, P, M.11.4 (9); MP.86 (24); MP.240 (50);
TP.144 (86); F.1.3 (206)
Levy, E, WP.198 (143)
Levy, J, M.4.1 (2); MP.163 (37); T.121 («2);
TP.130 (84); TP.187 (95); TP.44 (69); WP.7
(777); WP.13 (772); WP.14 (772); WP.80 (723);
WP.107 (728); WP.lll (728); TH.10.3 (767);
THP.47 (777); F.9.5 (214)
Lewis, D, WP.113 (729); THP.114 (782)
Lewis, J, TP.236 (707)
Li, P, TP.90 (77)
Liautaud, B, MP.69 (27); MP.136 (32)
Lieb, L, TP.91 (77); THP.51 (772)
Lieb, S, W.2.3 (706); THP.83 (777)
Liesnard, C, MP.124 (30); MP.154 (35)
Lifson, A, MP.83 (24); T.7.3 (57); TP.84 (76)
Lifson, J, MP.12 (72); MP.130 (31); TP.114 (87)
Lightbourne, B, THP.243 (204)
Lillehoj, E, THP.17 (766)
Lilley, P, TP.233 (707)
Lillo, F, WP.151 (135)
Lin, R, WP.135 (752)
Lin, T, THP.8 (164)
Lindhardt, B, MP.57 (79); MP.62 (20); MP.224
(47); TP.41 (69); TP.81 (76); WP.101 (727);
WP.162 (737)
Lindner, W, F.4.2 (209)
Lindstrom, E, MP.30 (15)
Linette, G, THP.109 (787)
Link, R, TH.3.3 (154)
Linke, M, MP.219 (46)
Linnan, M, THP.159 (790)
Liozner, A, MP.97 (26)
Lippa, A, M.5.6 (4)
Livartowski, J, THP.76 (776)
Ljunggren, K, M.10.6 (8)
Llena, J, WP.154 (756)
Lloyd, A, THP.115 (782)
Lode, H, WP.132 (732)
Lodynski, A, THP.162 (790)
Loeb, L, MP.169 (38)
Loftus, J, WP.224 (147)
Log, T, MP.95 (26); WP.85 (124)
Lombard-Cannan, M, WP.44 (777)
Longworth, D, TP.162 (89)
Looney, D, W.3.5 (707)
Lopez, C, WP.109 (728)
Los, A, TP.193 (94); THP.191 (795)
Loskoski, S, MP.229 (48); MP.239 (50); WP.233
(149)
Loureiro, C, THP.49 (777); THP.144 (787)
Lourenco, M, THP.88 (778)
Loveless, M, THP.128 (184)
Low, B, WP.50 (778)
Lowe, G, TP.241 (702); WP.238 (750); THP.244
(204)
Lowen, N, TP.245 (705)
Lowenstein, W THP.239 (203)
Lowenstine, L, TP.6 (63)
Lowy, M, TP.240 (702)
Lu, H, MP.84 (24)
Lubaki, M, T.7.6 (57)
Lubaki, N, F.9.6 (214)
Luban, N, WP.239 (750); THP.242 (203)
Luby, J, THP.229 (207)
Lucas, C, TP.246 (705)
Lucchini, A, MP. 41 (77)
Luciw, P, M.9.1 (6); MP.26 (14); TP.36 (68)
Ludlam, C, MP.245 (57); TP.124 (83); TP.238
(702); WP.102 (727)
Liier, W, TP.157 (88)
Luft, B, TH.8.6 (759)
Lugo, S, MP.134 (32)
Lui, K, TH.10.1 (760)
Lukehart, S, THP.68 (774)
Lunardi-Iskandar, Y, MP.112 (28); F.4.6 (209);
F.9.4 (214)
Lundin, K, MP. 39 (76)
Luney, C, TP.54 (77); THP.95 (779)
Lurhuma, Z, T.16.5 (62)
Luthy, R, WP.81 (725)
Luzia, L, THP.78 (776)
Lwegaba, A, TH.5.4 (757)
Lyerly, H, T.9.4 (59); TP.128 (83)
Lyndall, P, TP.85 (76)
Lynn, D, WP.33 (775)
Lyons, C, WP.75 (722); WP.200 (745)
Lyons, P, WP.90 (725)
Lyons, S, MP.40 (76); MP.58 (79)
Lyter, D, M.6.2 (4); MP.121 (30); WP.67 (727);
WP.106 (728); THP.64 (774); F.8.3 (275)
-M-
Maayan, S, MP.51 (78)
MacDonald, K, MP.193 (42); T.7.5 (57); WP.235
(749); THP.176 (792)
Macher, A, M.11.6 (9); TP.169 (90); WP.168
(758); WP.170 (758)
Macik, G, MP.78 (23)
Mack, D, F.2.3 (207)
Mackay, I, WP.92 (725)
Macks, J, THP.203 (797)
Madden, D, THP.108 (787)
Maddon, P, M.4.3 (5)
Madhok, R, TP.241 (702); WP.238 (750);
THP.244 (204)
Madjar, J. TP.37 (68); THP.33 (769)
Maesaka, J, TP.148 (87)
Maganu, E, MP. 60 (20)
Maguire, B, WP.74 (722); THP.213 (799)
Maha, M, THP.235 (202)
Mahabir, B, TP.96 (78); F.6.4 (277)
Mahloane, L, MP.60 (20)
Mahon, R, MP.175 (39)
Mahony, K, THP.182 (795)
Maillard. M, WP.89 (725)
Maino. V, TH.9.2 (759)
Maizel, J, THP.39 (770)
Major, E, MP. 159 (36)
Makuch. R, TP.38 (68)
Makuwa, M, TP.52 (77)
Malavade. V, WP.236 (749)
Males, B, MP.238 (49)
Malkovsky. M, M.4.3 (5); MP.122 (30); TP.3 (63)
Malone. G, TH.10.5 (767)
Manabe. S, MP. 235 (49)
Manak, M, WP.21 (775). WP.22 (114)
Mandel. J, TP.203 (96); THP.218 (799)
Mandelli. F, THP.248 (204)
Manikar. S, WP.240 (750)
227
INDEX
Mankikar, S, TP.243 (103)
Mann, D, T.9.2 (59); F.1.2 (206); F.4.3 (209)
Mann, J, M.3.6 (2); M.8.5 (6); MP.61 (20);
MP.73 (22); T.1.3 (52); W.4.6 (108); WP.55
(779); WP.84 (124); WP.136 Ci3J>; TH.7.6
(758); THP.55 (172); F.9.6 (274)
Mannella, E, WP.122 (130); WP.248 (757)
Mannucci, P, THP248 (204)
Manoff, S, TP42 (69); TH.7.1 (757)
Mansell, P, T.8.5 (58); TP.134 (30; TP.218 f98j;
THP.135 (786;; THP.234 (202); THP.236 (202)
Mantell, J, THP.182 (795)
Mantovani, A, THP.118 (183)
Manyeneng, W, MP. 60 (20)
Marcel, A, TP.228 (100); WP.75 (722)
Marche, C, MP.161 (37); WP.160 (137); THP.141
(787); THP.161 (190)
Marcus, R, THP.223 (200)
Marcus, S, TP.227 (100)
Marechal, V, THP.37 (769)
Marennikova, S, THP.40 (170)
Margolick, J, WP.117 (729)
Margolis, I, TP.87 (77)
Mariani, G, THP.248 (204)
Marin-Garcia, J, MP.170 (38); TP.170 (90)
Marion, R, WR153 (135)
Markham, P, MP.34 (75); TP.19 (65); TP.20 (65)
Marlene, M, THP.78 (776)
Marlink, R, TH.5.1 (756); THP.7 (764)
Marmor, M, MP.201 (43); TP.69 (74); WP.72
(722); THP.69 (775); THP.178 (193)
Marquis, J, W5.1 (108)
Marquis, L, WP.53 (779)
Marsh, J, MR130 (31)
Marsh, M, MP. 20 (13)
Marshall, D, WP.156 (756)
Martin, J, TP65 (73); WP177 (759); THR79
(776); THP.217 (799)
Martin, L, MP.229 (48); MP.239 (50); TP.109
(80); WP.19 (775); WP.233 (149); THP.113
(182)
Martin, M, M.4.5 (5); M.9.4 (7); MP.19 (75);
W.3.4 (707); F.7.4 (272)
Martinez-Maza, O, THP.121 (785)
Martini, E, THR132 (785)
Martini, M, THR168 (797)
Martiniwitz, U, TH.10.5 (767)
Martuzzi,M,TP113 (87)
Marx, R MR230 (48)
Mascaretti, L, MP.249 (57)
Mascola, L, THP.51 (772)
Masdeu, J, WP.154 (756)
Masinovsky, R, MP.35 (76)
Masison, V, TR17 (65)
Maskill, W, TP.246 (705); THR31 (768)
Maslansky, R, MP.201 (43)
Mason, R WP.115 (729)
Massari, V, TP.180 (92)
Massey, J, TP.57 (72)
Massuet, L, WP.249 (757)
Mastroianni, R THP.182 (795)
Mastrucci, M, WP.166 (758); THP.91 (778);
THP.167 (797)
Masur, H, MP.228 (48); T.8.2 (58); W.5.4 (709);
TH.4.1 (755); THP.226 (207)
Matheron, S, MP.148 (34); TR27 (67); TR165
(90); TP.216 (98); THP.161 (790); THP.169
(797)
Mathez, D, THP.106 (787)
Mathiot, C, MP.164 (37); TR79 (75)
Matsevich, G, THP.40 (770)
Matsukura, M, T.4.1 (54); T.4.4 (54)
Matsushita, S, T.4.1 (54); W3.2 (706)
Matthews, T, M.10.3 (8); MP.36 (76); MP.78
(23); 1.9.4 (59); T.16.4 (62); TP.128 (83);
WR33 (775); THR35 (769)
Mattinen, S, M.10.4 (8)
Matts, L, THP.82 (777)
Matuschke, A, MR166 (37)
Matzk, D, TP.159 (89)
Matzke, D, WP.140 (755)
Maude, D, TP.143 (86); W.2.5 (706)
Mauge, C, THP.198 (796)
Mauser-Bunschoten, E, M.11.5 (9)
Mawle, A, TP.108 (80); WP.99 (726)
May, T, MR118 (29); THP.164 (790)
Mayaud, C, MR123 (30); MP.158 (36); WP.164
(757)
Mayaux, M, TH.7.4 (758)
Mayer, K, MP.52 (78); MR89 (25); MP.244 (50);
TP.64 (73); TP.174 (97); WP.172 (759)
Mayers, D, TP.135 (85)
Mayers, M, TP.67 (73); TH.7.2 (757); THP.197
(796)
Mayr, C, T.46 (70)
Mazeron, M, TP.142 (86)
Mbayo, K, T.16.5 (62)
Mbena, E, TP.86 (76)
Mbesa, H, MP.61 (20)
M'Boup, S, THR7 (164); F.6.6 (277)
McAllister, D, THP.51 (772)
McArthur, J, MP.66 (27); MP.142 (33); TR140
(85)
McAuliffe, W, MP.181 (40)
McBride, L, MP.55 (79)
McCabe, D, THP.26 (767)
McCalla, S, TP.78 (75)
McCallum, D, MP.212 (45)
McCarthy, R TH.3.4 (755)
McCarthy, S, F.4.4 (209)
McCartney-Francis, N, TP.133 (84)
McClure, H, MP.27 (14), ¥.1.2 (212)
McClure, J, MP.35 (76), T.9.5 (59), TP.32 (67)
McClure, M, MP.20 (75), TP.4 (63)
McCluskey, T, THP.183 (794)
McCormick, J, MP.72 (22); TP.145 (86); WP.43
(U7)
McCrory, L, THP.234 (202)
McCusker, J, TP.64 (73); TP.174 (97); WP.172
(139)
McCutchan, A, WP.234 (749)
McCutchan, J, MP.145 (34); MP.200 (43); TP.61
(72); TP.158 (88)
McDonald, J, WP.215 (746)
McDonald, L, WP.40 (777)
McDougal, J, MP.127 (57); TR108 (80); TP.109
(80); WP.99 (726); THP.100 (780)
McEvoy, M, MP. 67 (27)
McFarlane, R, MP.197 (43)
McGhee, B, MP.238 (49)
McGillivray, G, MP.58 (79)
McGrath, H, TP.188 (93)
McGrath, K, TP.246 (705)
McGrath, M, MP.130 (57); TP.115 (87); F.9.3
(274)
McGuire, G, TH.11.6 (762)
McHenry, M, TP.162 (89)
McKinley, G, TP.223 (99); WP.218 (746); THP.62
(173)
McKinney, C, THP.182 (795)
McKusick, L, WP.184 (747); WP.186 (747);
WP.232 (749); F.8.2 (275)
McLane, M, MP.29 (75)
McLees, B, TH.4.2 (755)
McLeod, A, MR111 (28); TR99 (79)
McLeod, W, M.3.3 (2)
McMahon, C, THP.247 (204)
McManus, T, THP.137 (786)
McMaster, R TH.11.2 (767)
McMeeking, A, WP.147 (754)
McNally, L, TH.11.6 (762)
McNamara, G, WP.225 (747)
McNeil, J, TP.166 (90); TP.237 (702)
McNulty, W, WP.34 (776)
McPhee, D, TP.18 (65); WR6 (777)
Medina, I, W5.5 (709); F.3.1 (208); F.3.3 (208)
Megill, M, WP.205 (744); THP.226 (207)
Meidema, F, THP.126 (784)
Meigel, W, TP.155 (88)
Meignan, M, WP.164 (757)
Melbye, M, MP. 65 (27)
Melcher, G, T.7.2 (57)
Melica, G, TP.83 (76)
Mellert, W, MP.104 (27)
Mellor, A, M.4.3 (5)
Melpolder, J, TP.74 (74)
Meltzer, M, F.7.4 (272)
Mendelson, J, TP.170 (90)
Mendes, N, THR85 (777)
Mendez, H, WR157 (756); TH.7.3 (758); THP.71
(775); THP.158 (789); THP.209 (798)
Meon, M, TP.189 (94)
Merigan, T, THP.125 (784)
Merlin, M, M.8.1 (5); WP.77 (725); WP.78 (725)
Meropol, N, F.1.3 (206)
Merritt, R, MP.190 (47)
Mertens, S, TP.28 (67)
Mertz, G, THP.186 (794)
Mervis, R, THP.17 (766)
Mesa-Tejadar, R, WP.154 (756)
Mesagno, F, T.10.2 (60); TP.171 (97)
Mess, T, TP.219 (99); WP.217 (746)
Messiah, A, MP.79 (23)
Metellus, G, THP.45 (777); THP.83 (777)
Metroka, C, WP.220 (747); THP.230 (207);
THP.231 (202)
Mettetal, J, MR79 (23)
Meyer, R, THP.150 (788)
Mezzaroma, I, TP.117 (82)
Mhalu, F, TP.86 (76)
Mian, A, WP.l (770)
Michaeli, D, MP. 51 (78)
Michaelis, B, WP.13 (772)
Michel, F, WP.127 (757)
Michon, C, MP.148 (34); MP.161 (37); THP.169
(191)
Miedema, F, TP.33 (68); WP.36 (776); WR125
(757); THR90 (778); THP.136 (786)
Miehakanda, J, TR52 (77)
Mielke, C, WR10 (772)
Mijch, A, TP.246 (705)
Milberg, J, TP.42 (69); THR67 (774)
228
INDEX
Mildvan, D, TP.69 (74); W.5.6 (109)
Miles, S, TP.227 (100); THP.206 (197)
Miller, B, THP.66 (174)
Miller, D, T.6.4 (56); TP.201 (96)
Miller, E, MP.76 (22); TP.233 (101); TP.39 (69);
WP.137 (755)
Miller, J, WP.88 (125)
Miller, K, TR168 (90)
Miller, L, TP.186 r^J;,- TP.190 (94); THP.177
Miller, R, MP.76 (22); MP.81 (2J); T.50 (70)
Mills, J, MP.221 (47); T.121 <tf2j; W.5.5 (709);
WP.231 (148); F.3.3 (20Sj; F.9.3 (214)
Mimms, L, MP.244 (50); TP.235 (101)
Mingle, J, MP.94 (25); THR65 (774;
Minkoff, H, TP.78 (75); WP.157 (756); TH.7.3
(158)
Minnefor, A, TR226 (100)
Minnick, S, MP.209 (45)
Miotti, P, WP.116 (729)
Miraglia, E, TP.244 (103)
Mitchell, M, THP.175 (792)
Mitchell, N, T.6.1 (56)
Mitchell, S, THP.28 (768)
Mitchell, W, MP.5 (77); MP.6 (77); TP.98 (78);
WP.97 (726); THP.l (765)
Mitsuya, H, MP.103 (27); T.4.1 (54); T.4.4 (54);
THP.10 (765)
Mitsuyasu, R, MP.109 (28); MP.222 (47); TP.127
(83); TP.227 (700); WP.103 (727); THP.121
(183); THP.232 (202)
Mizel, D, TP.133 (84)
Mizuma, H, TP.110 (80)
Mizuochi, T, WP.100 (727)
Moas, C, THP.143 (187)
Moberg, L, MP.93 (25); WP.83 (124); THP.130
(185)
Moehring, R, TP.183 (93); THP.173 (792)
Moelling, K, THP.36 (769)
Moerkerk, H, MP.178 (39)
Mok, J, MP.47 (78); TP.205 (96); WP.204 (744)
Moller, J, TP.123 (83)
Monplaisir, N, MP. 96 (26)
Monroe, J, TP.8 (63)
Montagna, R, WP.23 (774)
Montagnier, J, TH.9.6 (760)
Montagnier, L, M.10.1 (7); M.10.5 (8); MP.2
(70); MP.80 (23); TP.5 (63); TH.1.1 (755);
TH.2.1 (755); THP.32 (168); F.7.1 (272)
Montefiori, D, MP.5 (77); MP.6 (77); TP.98 (78);
WP.97 (726); THP.l (765)
Montgomery, S, T.10.6 (60)
Moody, D, MP.120 (30); WP.lll (128); F.9.5
(274)
Moon, M.TP.64 (73)
Moore, J, TP.36 (68); WP.29 (775)
Moore, P, MP.211 (45)
Moore, T, W.5.2 (108); WP.141 (755); THP.103
(180)
Moran, P, T.9.5 (59)
Morfeldt-Mannson, L, WP.83 (724); THP.13
(765); THP.238 (203)
Morin, S, WP.184 (747); WP.186 (747); F.8.2 (275)
Morisky, D, WP.189 (747)
Morlet, A, WP.188 (747); THP.222 (200)
Moroni, M, WP.151 (755); THP.165 (797)
Moroso, G, THP.209 (198)
Morris, J, TP.246 (705)
Morrisey, E, WP.44 (777)
Morrison, C, WP.172 (759); TH.3.4 (755)
Morrison, M, WP.40 (777)
Morrison, S, MP.162 (37); MP.170 (38); TP.215
(98); TP.226 (700); W.5.1 (108)
Morrow, J, TP.130 (84)
Morse, D, TP.177 (92); WP.61 (720); WP.74
(722); THP.70 (775)
Mortimer, P, MR9 (77)
Morton, W, MP.15 (72)
Mosca, J, WP.38 (776)
Moser, S, MP.180 (40)
Mosimann, J, MP. 46 (77)
Moskovitz, B, TP.222 (99)
Mosley, J, MP.84 (24); TH.10.2 (760)
Moss, A, MP.87 (24); TP.53 (77); WP.199 (745);
THP.43 (770); THP.47 (777); F.1.4 (206); F.1.5
(206)
Moss, B, T.9.1 (59); T.9.2 (59); T.9.3 (59); W.3.1
(706)
Motley, L, MP.248 (57); WP.246 (757)
Motyl, M, MP.155 (36)
Moulton, J, WP.199 (745); WP.201 (745)
Mounier, M, F.2.5 (207)
Mouradian, J, THP.230 (207)
Moynihan, R, MP.197 (43)
Moyorga, R, WP.160 (757)
Mozzi, F, MP.249 (57)
M'Pania, M, WP.136 (755)
M'Pele, P, WP.79 (725)
Muchinik, G, MP.134 (32)
Mucke, L, MP.143 (34)
Muesing, M, TP.31 (67)
Mulder, C, TP.8 (63)
Mulhall, B, WP.92 (725)
Muller, J, THP.132 (785)
Miiller, W, MP.l (70)
Mullins, J, WR15 (772); TH.2.2 (755); THP.5
(764)
Mundon, F, TP.248 (705); F.6.5 (277)
Mundy, T, MP.169 (38)
Munjal, D, WP.247 (757)
Munn, R, F.7.5 (272)
Munoz, A, MP.92 (25); TP.73 (74); WP.64 (727);
THP.119 (183)
Munoz, L, TP.102 (79)
Murali, M, TP.228 (700)
Murhpey-Corb, M, THP.113 (182)
Murithii, J, WP.50 (778)
Murphey-Corb, M, THP.21 (767)
Murphy, D, MP.203 (44)
Murphy, E, T.48 (70)
Murphy, V, WP.76 (725); THP.73 (775)
Murphy-Corb, M, WP.19 (775)
Murray, C, F.1.2 (206)
Murray, P, WP.143 (754); WP.144 (754); THP.142
(787)
Mussa, M, WP.136 (755)
Mutinelli, M, THP.165 (797)
Mwendapole, R, MP. 77 (23)
Myers, C, WP.223 (747)
Myers, G, MP.14 (72)
Myers, P, TP.208 (97)
Myrtveit, M, THP.59 (775)
-N-
Nachman, S, TP.55 (77)
Nadelman. R, TP.211 (97)
Nagashima, K, MP.13 (72)
Nagel, J, WP.119 (750); WP.123 (750)
Nahmias, A, THP.61 (775)
Nair, P, MP. 85 (24)
Najera, R, TP.102 (79)
Nakamura, G, M.4.4 (5); WP.12 (772)
Nakamura, S, MP.32 (75); TP.125 (83); WP.5
(777)
Nara, P, MP.31 (75); WP.3 (770); F.7.6 (272)
Narvanen, A, TH.9.3 (760)
Nasca, P, WP.68 (727)
Nason, M, W4.3 (708)
Nath, N, MP.234 (49)
Nay, K, TP.141 (86)
Naylor, C, THP.107 (787)
Naylor, P, TP.134 (84); WP.18 (775); THP.107
(787)
Ndinya-Achola, J, M.8.4 (6); MP.91 (25); WP.50
(778); TH.5.5 (757); TH.7.5 (758)
Ndoko, K, TP.139 (85)
Ndongala, L, THP.18 (766)
Neequaye, A, MP.94 (25); THP.65 (774)
Neff, S, THP.233 (202)
Negre, M, T.10.3 (60)
Negri, C, TP.230 (700)
Neil, G, MP.137 (33)
Neisson-Vernant, C, MP.96 (26)
Nelson, A, WP.168 (758); TH.7.6 (758)
Nelson, K, WP.116 (729); WP.208 (145)
Nelson, L, WP.53 (779)
Nelson, W, TP.207 (97)
Nencioni, L, THP.118 (785)
Neshin, S, MP.210 (45)
Nettey, V, MP.94 (25); THP.65 (774)
Neumeyer, D, TP.30 (67)
Newlin, B, WP.219 (746)
Newman, C, MP.10 (77)
Newstetter, A, MP. 75 (22)
Ng, V, MP.130 (57)
N'Galy, B, MP.61 (20); WP.136 (755)
Ngaly, B, M.3.6 (2)
Ngovan, P, T.5.4 (55)
Ngugi, E, M.8.4 (6); TH.5.5 (757)
Nguyen-Dinh, P. M.8.5 (6); MP.73 (22); TP.139
(85)
Nicholas, H, T.6.4 (56)
Nicholas, S. TH.11.3 (762)
Nichols, M, TP.198 (95)
Nicholson. J, MP.127 (57); TP.108 (80); THP.100
(780)
Nickens, N, F.5.6 (270)
Nielsen, C. MP.224 (47); T.3.5 (53)
Nielsen, J, T.3.5 (53); TP.81 (76)
Nielsen, M, T.7.5 (57)
Nienaltow, M, MP. 150 (35)
Niese, D, THP.168 (797)
Nigra, E. MP.41 (77)
Nikora, B, T.5.3 (55); WP.54 (779)
Niland. J. MP.84 (24); MP.88 (24)
Nishanian. P, T.3.2 (53); T.9.6 (59)
Nixon, A, MP.204 (44)
Noa. M, WP.190 (142)
Noche. L, WP.78 (725)
Noel. L. TP.80 (75)
Norcross, M, TP.16 (65)
Norman. G, WP.146 (754)
Norman, S. TP.141 (86)
229
INDEX
Norrby, E, M.2.2 (1); THP.29 (168)
Norris, H, MP.199 (43)
Novick, D, THP.216 (199)
Nseka, K, W.4.6 (108)
Nugeyre, M, F.9.4 (214)
Nunes, A, THP.85 (177)
Nunes, W, WP.25 (114)
Nyamuryekunge, K, TP.86 (76)
Nyanjom, D, THP.179 (193)
Nyarango, P, TP.41 (69)
Nye, K, TP111 (81)
Nygren, A, MP.30 (15); MP.39 (16)
Nzila, N, THP.159 (190)
Nzilambi, N, TP145 (86); W.4.6 (108); WP.43
(117); TH.7.6 (158)
-o-
O'Brien, T, TP.236 (101); TP.242 (102); WP.226
(148)
Ochs, H, MP.15 (12)
Ocuno, L, WP.30 (115)
Odajnyk, C, WR230 (148)
Odaka, N, WP.66 (121); WP.116 (129); THP.119
(183)
Odete Santos Ferreira, M, THP88 (178)
O'Donnell, J, MP.221 (47)
O'Donnell, M, TP.173 (91)
O'Donnell, R, TP.76 (75); WP.71 (122); WR155
(136); THP.199 (196)
O'Dowd, M, WP.209 (145)
Odum, N, TP.123 (83)
Oette, D, MP.222 (47)
Officer, J, MP.204 (44)
Offutt, S, TP.211 (97)
Ogg, P, THP.193 (195)
Ognibene, F, W.5.4 (109)
O'Hearn, P, WP196 (143)
Ohta, Y, MP.28 (14)
Ojo-Amaize, E, T.9.6 (59)
Oksenhendler, E, WP.228 (148)
O'Leary, T, M.11.6 (9); THP.30 (168)
Oleske, J, MP.162 (37); MP.170 (38); MP.213
(45); TP.170 (90); TP.215 (98); TP.226 (700);
W.5.1 (108); WP.169 (758); WP.213 (745);
THP.212 (198)
Oleszko, W, THP.243 (204)
Oliva, G, T.6.5 (56)
Olivier, R, M.10.1 (7)
Ollivier-Henry, F, F.2.1 (207)
O'Malley, R M.3.1 (1); THP.207 (198); F.8.1
(213)
Ong, K, TP.223 (99); WR65 (121); WP.218 (146)
Operskalski, E, TP.60 (72)
Oppermann, A, WR70 (122)
Orbe, M, WP.227 (148)
O'Reilly, K, WR182 (140)
Orenstein, J, TP.106 (80)
Orgad, S, TH.10.5 (161)
Orkin, J, MP.27 (14); ¥.1.2 (212)
Ornitz, D, T.5.1 (55); WP.148 (135); THP.153
1789)
Oroszlan, S, M.9.3 (7); TP.21 (66)
O'Rourke, M, TP.207 (97)
Osborne, M, MP.108 (28); MP.109 (28)
Osei, W, MP. 60 (20)
Osei-Kwasi, M, MP.94 (25); THP.65 (174)
O'Shaughnessy, M, MP.16 (12); W.3.4 (107);
WP.215 (146); THP.96 (779)
Osmond, D, MP.87 (24); TP.53 (71); WP.199
(143); THP.43 (170); THP.47 (171); F.1.5 (206)
Ostchega, Y, THP.219 (200)
Ostergaard, L, W1.2 (105)
Osterholm, M, MP.193 (42); T.7.5 (57); WP.235
(149); THP.176 (192)
Ostrove, J, MP.19 (13); MP.22 (13)
Ostrow, D., MP.142 (33); T.10.6 (60); TH.5.6
(757); THP.80, (176); F.8.4 (275)
O'Sullivan, M, THP.231 (202)
Ottomanelli, G, WP.227 (148); THP.124 (184)
Ou, C, THP.28 (168)
Outuki, N, WP.30 (775)
Oxtoby, M, TH.7.1 (157)
Ozel, M, TP.24 (66)
-P-
Padian, N, WP.53 (119); THP.48 (171)
Paganelli, R, TP.117 (82)
Pahwa, R, F.4.1 (209)
Pahwa, S, F.4.1 (209)
Palangie, A, MP.98 (26)
Pallis, K, MP.248 (51); WP.246 (757)
Palmer, C, THP.162 (190)
Pamphile, M, M.8.6 (6)
Panavelil, T, W.3.6 (107)
Pantarotto, F, TP.83 (76)
Pape, J, M.8.6 (6); MP.68 (21); MP.69 (27);
MP.136 (32); TP.43 (69)
Papouin, G, TP.95 (78)
Papsidero, L, WP.23 (114)
Paradis, T, T.9.1 (59); WP.104 (727)
Parekh, B, MP.248 (51)
Parenti, D, TP.220 (99)
Parikh, K, THP.147 (188); THP.157 (189)
Parker, D, T.3.4 (53)
Parkin, J, TP.lll (81); WP.245 (757); TP.lll (81);
TH.8.3 (159)
Parks, E, MP.38 (16); TP.38 f68); W.3.3 (707);
WP.ll (112); ¥.1.2 (207)
Parks, P, TP.172 (97)
Parks, W, MP.38 (16); T.8.1 (58); TP.38 (68);
TP.136 (85); W.3.3 (107); WP.ll (772); WR166
(758); THP.91 (778); F.2.2 (207)
Parquin, F, MP.158 (36)
Parr, D, T.6.4 (56)
Parravicini, C, WP.124 (757)
Parry, J, MP.9 (77)
Partanen, P, TH.9.3 (760)
Pasechnik, V, WP.98 (726)
Pasquali, M, WP.250 (752)
Pastore, L, TR169 (90)
Patarca, R, T.16.2 (62)
Patel, P, MP.115 (29)
Patronik, S, THP.220 (200)
Patten, E, MR128 (57)
Patzer, E, WP.12 (772)
Paul, D, MR45 (77); MP.53 (79); TR225 (100);
W.5.2 (108); WP.9 (777); THP.101 (780);
THP.103 (780); THP.106 (787)
Paul, L, TR235 (707)
Paul, N, WP.108 (728)
Pauli, G, TP.24 (66)
Paulson, Y, THP.151 (788)
Pauwels, R, MP.4 (70); T.4.2 (54); TP.l (62);
TP.23 (66)
Pawel, B, MP.170 (38)
Payte, J, TP.54 (77); THR95 (779)
Pearson, A, TP.250 (704); WP.94 (726)
Peckham, C, MP. 47 (78)
Pedersen, C, MP.224 (47); T.3.5 (53); TR81 (76)
Pedersen, N, TP.54 (77); F.7.5 (272)
Pederson, C, TP.123 (83)
Pedro, M, THR88 (778)
Peixinho, Z, THP.85 (777)
Pekovic, D, MR102 (27)
Pelissier, J, T.5.6 (55)
Pellet, P, MR26 (14)
Penhallow, R, MP.12 (72)
Penley, K, TP.70 (74); TP.71 (74); THP.58 (775)
Penny, R, MP.63 (20); TP.101 (79); WP.86 (124)
Pepkowitz, S, MP.169 (38)
Pepose, J, MP.10 (77)
Perdices, M, WP.149 (755)
Perez, E, THP.171 (792)
Perez, G, THP.171 (792)
Perez Garcia, R, MP.167 (38)
Perkins, H, M.3.2 (7); M.3.5 (2); W.4.3 (708);
WP.237 (749); THP.53 (772)
Perkins, J, THP.194 (795); THP.200 (796)
Perno, C, THR10 (765)
Perol, Y, MP.149 (35); TP.142 (86)
Perronne, C, WP.138 (755)
Perry, J, TP.206 (96)
Perry, S, MP.195 (42)
Pert, C, M.5.1 (3)
Perucci, C, WP.248 (757)
Perumal, V, WP.69 (727); HR147 (788); THP.157
(189)
Pesce, A, T.10.3 (60)
Petat, E, WP.27 (774)
Peterlin, B, M.9.1 (6)
Peterman, T, M.3.4 (2); WP.42 (777); TH.10.1
(760)
Peters, S, MP.18 (75)
Petersen, C, TH.8.4 (759)
Petersen, E, MP.225 (47)
Petersen, H, MP.62 (20); TP.41 (69)
Petersen, L, THP.44 (770)
Petersen, V, MP.223 (47)
Peterson, K, THP.58 (775)
Petillo, J, MP.240 (50)
Petit, A, WP.125 (757); THR126 (784)
Petrella, R, TP.131 (84); WP.114 (729); THP.117
(183)
Petrov, R, MP.97 (26)
Petrus, D, THP.66 (774)
Petteway, S, M.10.3 (8); MP.36 (76); T.3.1 (53);
TP.35 (68); TR85 (76); WP.226 (748); TH.9.1
(759); THP.26 (767); THP.27 (768)
Peutherer, J, MP.245 (57); TP.124 (83); TP.238
(702); WP.102 (727)
Pezeshkpour, G, MP.144 (34); TR151 (87)
Pfenninger, L, TR22 (66)
Phair, J, MP.142 (33); MR92 (25); T.10.6 (60);
T.3.1 (53); T.3.2 (53); T.3.6 (53); THP.64
(774); TP.72 (74); TP.73 (74); WP.67 (727);
WP.117 (729); WP.129 (757)
Phelan, J, TH.3.5 (755)
Phillips, A, TH.4.3 (755)
Philpott, K, M.4.3 (5)
Pialoux, G, MP.189 (47); TP.126 (83)
Piazza, R WP.106 (727)
Picard, C, WP.164 (757); THP.123 (784)
230
INDEX
Piccardo, P, THP.108 (181)
Picchio, G, MP.134 (32)
Pickering, J, TP.91 (77)
Pickles, H, TP.194 (94)
Pieper, A, TP.14 (64)
Pies, C, MP.75 (22); T.6.5 (56),
Pignon, J, WP.138 (133)
Piland, T, T.49 (70)
Pinching, A, TP.lll (81); TH.4.4 (156); TH.8.3
(159)
Pindborg, J, MP.207 (44); TP.161 (89)
Pindyck, J, MP.247 (51); TP.240 (102); TP.247
(103); WP.236 (149)
Pinsky, P, T.5.2 (55)
Pinter, A, TP.110 (80)
Piot, D, MP.217 (46)
Piot, P, M.2.3 (7); M.8.4 (6); MP.82 (25J; MP.91
(25); TP.63 f7j;,- TP.139 (&5J; TP.145 (86);
W.2.4 (706); WP.43 (117); WP.51 (778);
THP.139 (786); THP.227 (201)
Pitchenik, A, TP.168 (90); THP.143 (187)
Pitha, P, WP.38 (116)
Pitlik, S, MP. 51 (18)
Pizzuti, D, TH.4.6 (756)
Plata, F, WP.127 (131); THP.32 (168)
Plescia, O, MP.226 C47)
Plummer, F, M.8.4/^- MR91 (25); TH.5.5
(157); TH.7.5 (758); THP.68 (774)
Podapati, N, THR147 (188)
Pohle, H, TP.157 (88)
Poiesz, B, WP.23 (114); WP.226 (748); F.2.3
(207)
Polesky, H, MP.237 (49); WP.235 (749)
Poli, F, MP.249 (51)
Poli, G, TP.106 (80); THP.118 (183)
Polis, M, T.3.2 (53)
Polk, B, MP.66 (27); MP.92 (25); T.3.2 (55);
TP.73 (74); WP.66 (727); WP.116 (729); WP.129
(757); F.8.4 (213)
Polk, F, WP.241 (750); THP.119 (183)
Pollak, M, M.5.4 (4); M.6.6 (5)
Pollard, R, TP.159 (89); WP.140 (133)
Pollet, S, THP.215 (799)
Pollowy-Domek, M, WP.44 (777)
Polmar, S, WP.108 (728)
Poncin, M, THP.61 (773)
Pontani, D, MP.226 (47)
Poole, L, WP.57 (779)
Popescu, M, THP.166 (797)
Popovic, M, MP.104 (27); MP.131 (32); T.120
(82); F.4.3 (209); F.9.1 (274)
Popovsky, M, THP.246 (204)
Porwit, A, WP.128 (757)
Poser, S, TP.157 (88)
Potasman, I, TH.8.6 (759)
Pottage, J, TP.225 (700)
Pottathil, R, MP.238 (49)
Pottenger, L, TP.212 (97)
Potz, J, M.4.6 (3); THP.6 (764)
Poulsen, A, MP.57 (79); MP.224 (47)
Poust, B,TH.11.5 (762)
Powell, D, T.9.3 (59)
Powell, K, THP.22 (767)
Preble, O, MP.70 (27)
Price, R, T.5.1 (55); WP.148 (755); THP.153 (189)
Prieto, V, MP.173 (39)
Primm, B, MP.203 (44); TP.54 (77); THP.95
(779)
Pristera, R, THP.89 (178)
Prodouz, K, TP.245 (705)
Proudfoot, A, T.6.1 (56)
Prusoff, W, THP.8 (764)
Przedborski, S, MP.154 (35)
Puissant, F, WP.80 (725)
Pulsatelli, L, TP.113 (81)
Purifoy, D, THP.22 (767)
Purvis, S, TP.97 (78)
Putnam, D, WP.61 (720)
Putney, S, M.10.3 (8); MP.17 (75); T.16.4 (62);
TP.132 (84); WP.33 (775); THP.35 (769)
Pyle, S, TP.10 (64); TP.13 (64); F.7.6 (272)
-Q-
Quackenbush, M, THP.187 (794)
Quader, A, THP.216 (799)
Quadland, M, WP.183 (740)
Quattara, A, TP.153 (88)
Quinn, T, M.3.6 (2); M.8.5 (6); MP.10 (77);
WP.84 (724); TH.3.6 (755); TH.7.5 (758);
THP.18 (766); THP.19 (766); THP.63 (174);
THP.68 (774); THP.139 (186); THP.159 (790);
F.9.6 (274)
Quinnan, G, MP.125 (57); T.9.2 (59); THP.120
(183); THP.122 (183)
Qureshi, N, THP.112 (182)
-R-
Rabin, D, MP.188 (47)
Rabin, H, TH.9.1 (759)
Rabin, L, TP.114 (81)
Rabkin, B, T.10.5 (60)
Rabkin, C, TP.247 (705)
Rabson, A, MP.19 (75); MP.22 (75)
Rademaker, M, MP. 67 (27)
Raevsky, C, TP.239 (702); TP.58 (72); WP.176
(759); THP.174 (792)
Raghunath, J, THP.216 (799)
Ragni, M, TP.236 (707)
Ragone, V, THP.124 (184); WP.227 (148)
Rahman, R, TP.21 (66)
Rai, A, TP.94 (78)
Rainer, C, MP.130 (57); THP.154 (189)
Raise, E, TP.112 (81); TP.113 (81)
Raj, N, WP.38 (776)
Ram Ayyar, D, MP. 139 (33)
Ramey, W, THP.62 (775)
Ramsey, K, MP.128 (57)
Ranee, N, TP.140 (85)
Ranki, A, M.10.4 (8); MP.17 (75); MP.119 (30);
W.3.6 (707); TH.9.1 (759)
Rao, N, TP.160 (89)
Rao, T MP.157 (36)
Raphael, B, WP.230 (148)
Raphael, M, MP.123 (30)
Rappersberger, K, TP.107 (80)
Rappocciolo, G, WP.106 (128)
Rarick, M, THP.49 (777); THP.144 (187)
Rasheed, S, T.4.6 (54); WP.146 (754); THP.49
(/77)
Raska, K, THP.82 (777)
Ratner, L, M.9.5 (7); WP.108 (128)
Raum, M, THP.17 (766)
Rautmann, G, THP.32 (168)
Rawlinson, V, MP.233 (49)
Rawson, D, WP.214 (746)
Rayner, M, TP.35 (68)
Razin, A, WP.209 (745)
Read, S, MP. 49 (18); MP.50 (18); TP.224 (99);
WP.121 (750); TH.4.3 (755); TH.8.1 (758)
Reagan, K, TP.14 (64); WP.4 (777)
Reaman, G, WP.239 (750); THP.242 (203)
Reddy, M, MP. 90 (25)
Redfield, R, M.ll.l (8); T.7.1 (57); W.3.5 (707);
WP.17 (775); WP.66 (727); WP.110 (728);
THP.99 (780); THP.105 (787); TP.166 (90); El!
(206)
Reed, C, WP.29 (775)
Reed, D, MP.36 (76); TP.85 (76); THP.26 (767)
Reesink, H, WP.73 (722)
Reeves, J, TP.45 (70)
Reff, V, TP.77 (75)
Regnier, B, THP.141 (787)
Regueiro, J, THP.116 (782)
Rehm, S, TP.162 (89); WP.222 (747)
Reibnegger, G, MP.99 (26)
Reid, B, MP. 42 (77)
Reife, R, WP.109 (728); THP.228 (207)
Reimer, C, MP.127 (57)
Reinarz, J, MP.128 (57)
Reitz, M, MP.25 (74); MP.33 (75); T.4! (54)
Rekart, M, TP.192 (94); WP.191 (742); THP.189
(795)
Rekosh, D, MP. 30 (75)
Remington, J, TH.8.6 (759)
Renner, M, WP.132 (752)
Renz, M, WP.35 (776)
Renzullo, P, TP.237 (702)
Repetti, C, MP.114 (29)
Resnick, L, MP.109 (28); MP.146 (34); TP.136
(85); TP.141 (86); WP! (770); TH.8.6 (759);
THP.155 (789)
Reuben, J, TP.134 (84); TP.218 (98); WP.131
(752); THP.135 (786); THP.236 (202)
Reupke, H, TP.24 (66)
Reuter, P, TP.59 (72)
Revuz, J, WP.164 (757)
Rey, F, F.2! (207)
Rey, J, F.6.2 (277)
Rey, M, MP.189 (47); T.5.4 (55); TP.27 (67);
TP.37 (68); TP.153 (88); WP.87 (724); THP.33
(769); THP.24 (767); THP.169 (797); F.6! (277)
Reyes, G, TP.114 (87); TP.115 (87)
Rhame, F, TP.231 (707); MP.250 (57)
Rhoads, J, TP.166 (90); WP.110 (728), THP.105
(181)
Rhodes, R, THP.30 (768)
Ricard, D, THP.7 (764); F.6.6 (277)
Ricci, L, MP.155 (36); THP.201 (797)
Rich, R, THP!14(782)
Richardson. H, MP.211 (45)
Richardson, S. MP.197 (43)
Richman, D, MP.145 (34); MP.200 (43); T.8.3
(58); T.8.4 (58); TP.9 (64); TP.61 (72)
Richwald. G. WP.189 (141)
Rickard, K, M.11.5 (9)
Riedel, N. WP.15 (772); TH.2.2 (153); THP.5
(764)
Riedener, H, MP.179 (40); MP.180 (40)
Rieder, H, THP.86 (777)
Riefel, S, F.5.3 (270)
Riethmueller, G, T.46 (70)
Rietmeijer, C, TP.70 (74); WP.181 (740)
Riggin. C. THP.19 (766)
231
INDEX
Rinaldo, C, M.6.2 (4); MP.121 (30); T.3.1 (53);
T.3.2 (53); TP.72 (74); TP.73 (74); WP.106
(128); WP.117 (729); WP.129 (131); F.8.3 ^iJ;
Rindum, J, MP.207 (44); TP.161 (89^
Rios, A, TP.134 (84); TP.218 f9£j; THP.135
(186); THP.236 (202)
Ripper, M, TH.11.1 (161)
Rivera, J, THP.214 (199)
Rivera, Y, WP.187 (141)
Riviere, Y, M.10.1 (7)
Rizza, C, M.11.5 (9); TP.250 (104)
Rizzardini, G, THP.84 (177)
Robbins, F, THP.109 (181)
Robert-Guroff, M, T.3.3 (53); W.3.2 (106);
WP.33 (115); THP.35 (169); F.1.2 (206)
Roberts, A, TH.8.3 (759)
Roberts, J, TP.195 (95)
Roberts, P, WP.76 (123); THP.73 (175)
Roberts, R, MP.195 (42); T.8.5 (58)
Roberts, W, M.11.6 (9)
Robertson, J, MP.59 (20); TP.195 (95); WR40
(117)
Robertson, P, THP.115 (182)
Robertson, V, MP.156 (36); THP.140 (186)
Robey, E, WP.2 (110)
Robey, F, F.4.2 (209)
Robey, W, M.10.2 (8); M.10.4 (8); MP.17 (75);
MP.31 (15); TP.10 (64J; WP.3 (770); W.3.6
(107); F.7.6 (272)
Robinowitz, M, M.11.6 (9)
Robinson, H, THRU (165)
Robinson, W, MP.5 (11); MP.6 (11); WP.97
(126); THP.l (163); TP.98 (78j
Roboz, J, W.5.6 (109); WP.115 (729)
Rodrigues, L, THP.138 (186)
Rodriguez, G, MP.210 (45); TP.206 (96); TH.11.4
(162)
Rodriguez, K, WP.167 (138)
Rodriguez, M, TR147 (87); WP.120 (130);
THP.92 (178)
Rodriguez, S, THP.98 (179); THP.234 (202)
Rogers, M, TP.67 (73); TP.88 (77); TH.7.1 (157);
TH.7.2 (757); THP.140 (186); THP.197 ^796;
Rohrschneider, L, T.4.3 (54)
Rokos, H, TP.25 (66)
Rokovich, J, WP.246 (151)
Rolan, N, MP.107 (28)
Roland, A, THP.57 (173)
Roland, J, MP.158 (36)
Rolsma, G, THP.191 (195)
Rolston, K, TP.147 (87)
Romano, M, THP.118 (183)
Romet-Lemonne, J, THP.7 (164)
Rompalo, A, F.1.6 (206)
Ronspeck, W, TP.25 (66)
Roodman, S, THP.127 (184)
Rook, A, MP.103 (27); TP.96 (78)
Roos, M, THP.136 (186)
Rosci, M, WP.122 (130)
Rosello, P, THP.138 (186)
Rosen, C, M.4.6 (3); M.9.2 (7); T.16.2 (62);
WP.16 (775)
Rosenberg, A, WP.100 (127)
Rosenberg, B, THP.249 (205)
Rosenberg, M, T.6.3 (56)
Rosenfeld, L, THP.85 (177)
Rosengren, O, THP.96 (779;
Rosenheim, M, WP.79 (123); THP.24 (167)
Rosenthal, K, TP.114 (81)
Rossi, G, WP.124 (131); THP.248 (204)
Rosso, J, WP.164 (137)
Rotenbourg, J, WP.87 (124)
Roth, D, TP.82 (76); WP.59 (120)
Rotkiewicz, L, TP.206 (96); TH.5.2 (156)
Roux, J, TP.95 (78)
Rouzioux, C, MR79 (23); TH.7.4 (158); F.6.3
(211)
Rouzuette, B, WP.216 (146)
Rowe, M, MR190 (41)
Rowland, J, THP.18 (166)
Roy, A, MP.54 (19)
Roy, M, THP.152 (188)
Royce, R, M.3.2 (1)
Rozakis, M, THP.96 (179)
Rozenbaum, W, M.5.4 (4); MP.112 (28); WP.126
(131); THP.76 (176); TP.229 (100); F.2.1 (207)
Rubin, D, F.3.6 (208)
Rubinow, D, THP.146 (187)
Rubinstein, A, TP.146 (86); W5.3 (109); WP.153
(135); THP.156 (189)
Rubinstein, R T.7.4 (57); THP.156 (189); THP.9
(165); THP.98 (179)
Riibsamen-Waigmann, H, WR24 (114)
Rucker, R, THP.193 (195)
Rudd, R, TR227 (700)
Ruddle, N, WP.108 (128)
Ruff, M, M.5.1 (3)
Ruger, R, TP.35 (68)
Rugunda, R, T.1.2 (52)
Ruitenberg, E, MP. 74 (22)
Ruprecht, R, TP.62 (72)
Rusche, J, T.16.4 (62); WP.33 (775); THP.35
(169)
Russo, R, WP.126 (757)
Rutherford, G, M.3.1 (1); T.49 (70); T.6.5 C56;;
TP.51 (77 ); TR91 (77); W46 (778); THP.207
(198); F.1.4 (206;
Rutledge, J, WP.174 (759)
Ryan, C, MP.190 (41)
Ryder, L, TP.123 (83)
Ryder, R, M.3.6 (2); MP.61 (20); MR73 (22);
T.7.6 (57); WP.43 (777); TH.7.6 (7587; THP.159
(190); F.9.6 (274;
Ryser, H, MP.179 (40)
-s-
Saag, M, W.3.3 (107)
Saah, A, MP.92 (25); T.3.1 (55); T.3.2 (53);
WR64 (727); WP.117 (729); WP.129 (131)
Sabella, W, TP.181 (92)
Sadaie, M, M.9.6 (7)
Safary, A, THR131 (785;
Saidi, R THR82 (177)
Saimot, A, MP.161 (37); TP.27 (67); TP.165 (90);
WP.32 (775;; WP.160 (757); THP.141 (787);
THP.161 (790); THP.169 (797); F.2.4 (207)
Saimot, G, THP.106 (787)
St. John, R, MP. 44 (17)
St. Lawrence, J, MR174 (39)
Salahuddin, Z, MP.32 (75); MP.34 (75); MP.146
(34); TP.20 (65); WP.5 (777); THP.3 (164)
Salaun, D, WR77 (723)
Salaun, J, T.16.5 (62)
Salit, I, TH.8.1 (758)
Salmon, C, THR132 (785)
Salmon, D, T.5.4 (55)
Salmon, R M.10.1 (7); TP.105 (80)
Saltzman, B, TP.67 (73); W.2.5 (706)
Saltzman, S, TP.64 (73); TP.174 (97)
Samarasinghe, R WP.173 (759)
Samet, R, MP.197 (43)
Sampalis, J, THP.133 (785)
Samson, S, W.4.3 (708); WP.237 (749); THR53
(772)
Samuel, M, THP.46 (777); THR47 (777)
Sanchez, M, WP.72 (722)
Sandstrom, E, MP.93 (25); WP.83 (724);
THP.130 (785)
Sangare, A, F.2.5 (207); F.6.2 (277)
Sano, K, MP.8 (77)
Santa Maria, I, TP.102 (79)
Santil, J, TP.43 (69)
Saracco, A, WP.89 (725); THP.84 (777)
Sardet, A, MP.117 (29)
Sargent, R THR187 (794)
Sarin, R MR1 (70); MP.24 (74); MP.226 (47);
TR22 (66); TP.220 (99); WP.18 (775); THR107
(181)
Sarngadharan, M, TP.19 (65); TP.21 (66);
THR97 (779)
Sattentau, Q, TP.4 (63); TH.9.4 (760); TH.9.6
(160)
Sattler, F, MP.175 (39); TH.11.1 (767)
Sauk, J, WP.84 (724)
Saulsbury, F, MP. 43 (77)
Saxinger, C, F.4.1 (209)
Saxinger, W, F.6.4 (277); F.6.5 (277)
Saykin, A, T.5.2 (55)
Scalia, V, TP.45 (70)
Scesney, S, WP.171 (758); THP.2 (765)
Schaab, C, THP.186 (794)
Schaaf, K, WP.39 (776)
Schable, C, MP.72 (22); MP.241 (50); TH.3.5
(755); THP.52 (772)
Schaeffler, B, WP.145 (754)
Schafer, A, THR94 (779)
Schaffner, C, MP.226 (47)
Schatz, B, THP.210 (798); F.5.5 (270)
Schechter, M, M.3.3 (2); M.6.3 (5); MP.lll (28);
TR99 (79)
Schechter, R TH.4.2 (755)
Scheffel, C, MP.135 (32)
Scheffel, J, MP.135 (32)
Scheibel, E, TR161 (89)
Scheiermann, N, THP.131 (785)
Schellekens, R THP.126 (784); THP.136 (786)
Schenk, R TP.107 (80)
Schenmetzler, C, THP.170 (797)
Scheppler, J, WR99 (726)
Schiattone, M, TP.113 (87)
Schieb, R, TP.220 (99)
Schietinger, H, TH.3.4 (755)
Schiltz, M, M.6.6 (5)
Schimpf, K, TH.10.4 (767)
Schiodt, M, MR207 (44)
Schi0dt, M, TP.161 (89)
Schirm, J, TH.8.2 (758)
Schito, G, WP.151 (755)
Schletty, S, T.7.5 (57); WR235 (749)
Schmidt, R, TR200 (95)
Schmitz, H, MP.28 (74)
232
INDEX
Schneider, C, WP.48 (118)
Schneider, J, MP.28 (14)
Schocheiman, G, THP.28 (168); THP.52 (172)
Schoenbaum, E, M.3.4 (2); MP.156 (36); WP.41
(117); TH.7.2 (157); THP.41 (170); THP.140
(186)
Schonberger, L, T.5.2 (55)
Schooley, R, T.9.1 (59); WP.104 (127)
Schorr, J, THP.77 (176)
Schorr, R, MP.86 (24)
Schoub, B, MP.58 (19)
Schppers, W, WP.51 (118)
Schrager, L, MP.155 (36); TP.143 (86)
Schramm, W, TH.10.4 (161); TH.10.6 (161)
Schreiber, K, TP.143 (86)
Schroder, H, MP.l (10)
Schulman, D, F.5.6 (210)
Schulman, S, M.11.5 (9)
Schulof, R, MP.24 (14); MP.216 (46); T.8.6 (58);
TP.220 (99)
Schultz, S, MP.83 (24); TP.42 (69); WP.155 (136)
Schulze, T, THP.36 (169)
Schumacher, R, WP.244 (151)
Schuman, R, WP.183 (140)
Schupbach, J, THP14 (165)
Schwartlander, B, TP.25 (66)
Schwartz, T, MP.51 (18)
Scott, A, TP.239 (102)
Scott, G, MP.38 (16); MP.116 (29); WP.105 (127);
WP.166 (138); THP.91 (178); THP.167 (797);
F.2.2 (207)
Scott, H, MP.185 (41)
Scrobohaci, M, MP.98 (26)
Seage, HI, G, MP.89 (25); TP.47 (70); WP.210
(145)
Seale, J, THP.205 (197)
Secord, K, MP.232 (48)
Seebacher, C, THP.89 (178)
Segal, A, THP.92 (178)
Sehgal, P, TP.94 (78); F.7.3 (272;
Sei, Y, MP.132 (32); TP.131 (84); WP.114 (129);
THP117 (785)
Seibert, G, THP.221 (200)
Seidl, O, TP.213 (98)
Seidlin, M, THP.214 (199)
Seligmann, M, TP.216 (98); WP.228 (148)
Selik, R, TP.88 (77); WP.56 (779)
Selleri, L, TP.112 (81)
Seines, O, MP.142 (33)
Selwyn, P, M.3.4 (2); MP.156 (36); WP.41 (777);
TH.7.2 (757); THP.41 (170); THP.140 (786)
Sension, M, THP.19 (766); THP.159 (790)
Serrato, C, TP.59 (72)
Sethi, N, F.3.2 (208)
Sette, P, THP.76 (776)
Sever, J, MP.144 (34); TP.151 (87); THP.108 (181)
Shah, K, TP.68 (73); WP.153 (135)
Shah, P, THP.158 (789)
Shahied, S, MP. 226 (47)
Shapshak, P, MP.8 (77); MP.108 (28); MP.109
(28); THP.160 (790)
Sharer, L, THP.21 (767)
Sharma, O, WP.55 (779)
Sharma, V, TP.114 (81)
Sharpe, A, TP.62 (72)
Shattls, W, WP.183 (140)
Shaukat, M, TP.141 (86)
Shaw, G, W.3.3 (707); WP.ll (772); TH.2.3 (153)
Shearer, G, TP.116 (81); WP.IOO (727)
Shelov, S, TH.3.3 (154)
Shepard, C, MP.75 (22)
Shepard, D, THP.138 (186)
Shepherd, F, MP. 49 (18); MP.50 (18); MP.209
(45); TP.224 (99)
Shepp, D, T.9.2 (59); WP.85 (124); THP.120
(183)
Sher, J, WP.170 (138)
Sher, R, M.8.2 (6); MP. 42 (77)
Sherr, L, T.6.2 (56)
Shih, J, WP.249 (757)
Shiigi, S, WP.34 (776)
Shimasaki, C, WP.12 (772)
Shine, K, WP.178 (740)
Shinozuka, K, T.4.4 (54)
Shiota, J, W.4.3 (108)
Shriver, C, MP.84 (24)
Shriver, K, MP.35 (76); TP.32 (67); WP.65 (727);
WP.145 (134)
Shu, S, T.4.6 (54)
Shuh, M, TP.39 (69)
Shulman, J, MP.156 (36)
Shultz, J, MP.193 (42)
Shuster, J, TP.89 (77); WP.163 (757)
Sicard, J, MP.158 (36)
Siccardi, A, WP.124 (757)
Sidhu, G, F.3.6 (208)
Sidorovich, I, MP.97 (26)
Sidtis, J, T.5.1 (55); WP.148 (755); THP.153 (789)
Siegal, F, TP.68 (73); TP148 (87); WP.29 (775);
WP.109 (128); THP.228 (207); THP.233 (202)
Siegel, K, T.10.2 (60); TP.171 (97)
Siegenthaler, W, WP.81 (725)
Siegler, M, TP.212 (97)
Siegman-Igra, Y, MP.51 (18)
Sijin, O, TP.78 (75); WP.75 (722)
Sikes, R, W.2.1 (705)
Silcott, J, THP.158 (189)
Silva, D, MP.72 (22)
Silverman, H, MP.181 (40)
Simberkoff, M, TP.163 (89); F.3.6 (208)
Simek, L, WP.21 (775)
Simmonds, P, MP.245 (57)
Simmons, J, TP.209 (97)
Simoen, E, THP.131 (185)
Simon, G, MP.216 (46); TP.220 (99)
Simonsen, J, M.8.4 (6); MP.91 (25)
Simooya, O, MP. 77 (23)
Simpson, M, MP.193 (42)
Sims, J, THP.45 (777); THP.83 (777)
Sinclair, A, MP.122 (30)
Singer, M, MP.205 (44)
Singer, R, THP.2 (765)
Singh, B, TH.9.2 (759)
Sisson, B, WP.22 (114)
Sito, A, MP.107 (28)
Sivertson, K, TH.3.6 (755)
Siziya, S, MP.77 (23)
Sjoerdsma, A, TH.4.2 (755)
Skidmore, C, MP.59 (20); TP.195 (95); WP.40
(117)
Skinner, K, WP.204 (144)
Sklizovic, D, THP.110 (181)
Skurkovich, S, MP.18 (13)
Slaterus, K, MP.220 (46)
Slim, J, MP.160 (36); THP.171 (792)
Small, C, THP.201 (797)
Smiley, L, MP.78 (23)
Smit Sibinga, C, TP.193 (94); THP.191 (795)
Smith, A, MP.9 (77); MP.58 (79)
Smith, C, M.5.1 (5)
Smith, D, M.4.4 (5); TP.31 (67)
Smith, G, MP.16 (72); W.3.4 (707)
Smith, L, THP.105 (181)
Smith, P, MP.133 (32); TP.133 (84); WP.130
(752); THP.134 (185)
Smith, R, MP.237 (49)
Smith, S, MP.196 (42)
Smith, T, TP.32 (67)
Snape, T, TP.250 (104)
Snider, D, THP.86 (777)
Sninsky, J, WP.23 (114); F.2.3 (207)
Sninski, J, THR28 (168)
Snyder, H, MP.231 (48)
Sobel, A, WP.164 (757); THP.123 (184)
Sobesky, G, MP.96 (26)
Sodroski, J, M.4.6 (3); M.9.2 (7); T.16.2 (62);
T.4.3 (54); WP.16 (775)
Soeken, K, TP.172 (97)
Solinger, A, WP.133 (752)
Solomon, G, M.5.5 (4)
Solomon, S, WP.55 (779)
Somaini, B, MP.56 (79); MP.179 (40); MP.180
(40)
Somasundaran, M, THRU (765)
Sonigo, P, TH.2.1 (755)
Sonnerborg, A, TH.1.3 (755)
Sonnex, C, WP.173 (759)
Sooy, C, TP.130 (84)
Soskolne, C, MP. 49 (18); MP.50 (78)
Sotheran, J, THP.67 (174); THP.178 (795)
Soumenkoff, G, WP.80 (725)
Sparger, E, F.7.5 (272)
Spear. J, TP.225 (700); WP.9 (777)
Spech, T, TP.162 (89)
Spechko, P, WP.234 (149)
Spector, S, MP.145 (34); MP.200 (43); TP.61 (72)
Spencer, N, MP.192 (42); TP.185 (93); WP.176
(759); THP.174 (792)
Sperling, J, MP.175 (39)
Spero, J, TP.236 (707)
Spira, T, MP.127 (57); T.5.2 (55); WP.99 (726);
THP.42 (770); THP.69 (775); THP.100 (180)
Spire, B. MP.37 (76); WP.37 (776)
Spooner. R, TP.250 (704)
Sprecher-Goldberger. S, MP.124 (30); MP.154
(35); WP.80 (725); THP.227 (207)
Sprenger, H, TH.8.2 (158)
Spross, J, THP.219 (200)
Squillace, K, THP.146 (187)
Sridhar, P, T.9.5 (59)
Srinivasan, A, MP.26 (14); TP.36 (68)
Sroka, S. TP.182 (92)
Stall. R, THP.80 (776); F.8.2 (275)
Staloch, L, TP.208 (97)
Stamm. W. F.1.6 (206)
Stanback. M. M.8.6 (6), TP.43 (69)
Stapleton, D, TP.18 (65); WP.6 (777;
Starcher, T. TP.57 (72); TP.84 (76); WP.88 (725)
Starcher, II, E, WP.190 (742)
Starcich, B, WP.20 (775); TH.2.4 (154)
Staub, R. MP.179 (40); MP.180 (40)
233
INDEX
Stavrou, D, MP.104 (27)
Steben, M, WP.179 (140)
Steel, C, MP.137 (33); MP.245 (51); TP.124 (83);
TP.238 (102); WP.102 (127)
Steel, M, MP.59 (20)
Stehr-Green, J, WP.82 (124)
Steigbigel, N, W2.5 (106); TH.3.5 (755)
Steigman, C, TP.169 (90)
Steimer, K, TP.39 (69); TH.9.2 (159); THP.38
(169)
Stein, A, WP.90 (125)
Stein, B, MP12 (12)
Stein, J, TP.191 (94); WP.185 (141); THP.184
(294
Stein-Streilein, J, THP.143 (187)
Steinbeck, A, THP.168 (191)
Steinhauer, E, THP.156 (189)
Steis, R, THP.226 (201)
Stempel, R, WP.199 (143)
Stenberg, M, TP.229 (100)
Stepanova, L, THP.40 (170)
Stephans, J, TP.39 (69); THP.38 (769)
Sterk, C, THP.196 (796)
Stern, M, THP.239 (203)
Stevens, C, T.7.4 (57); TP.12 (64); THP.98 (779)
Stevens, R, THP.45 (777); THP.83 (777)
Stingl, G, TP.107 (80)
Stites, D, M.5.5 (4); MP.120 (30); T.121 (82);
T.4.5 (54); TH.9.2 (759); WP.lll (725); F.9.5
(214)
Stocking, C, TP.212 (97)
Stoddard, A, TP.64 (73); TP.174 (97); WP.172
(139)
Stoler, M, TP.149 (87)
Stoller, E, T.6.5 (56)
Stoller, L, WP.178 (140)
Stone, G, THP.108 (787)
Stoneburner, R, MP.83 (24); TP.42 (69); TP.75
(75); WP.70 (722); WP.71 (722); THP.67 (774)
Stool, E, MP.217 (46)
Strang, J, THP.137 (186)
Strawczynski, H, TP.89 (77); WP.163 (137)
Strayer, D, MP.216 (46)
Strebel, K, M.9.4 (7)
Strehl, L, TP.35 (68); WP.28 (775); THP.27 (168)
Strickland, P, MP.95 (26); WP.85 (124)
Stringari, S, T.5.5 (55)
Strobert, E, MP.27 (14); F.7.2 (272)
Stroud, F, WR178 (140)
Strunin, L, T.6.6 (56)
Strykowski, H, MP.102 (27)
Stuck, B, THP.94 (779)
Stutsman, A, TP.191 (94)
Stutz, T, MP.56 (79)
Su, P, TP.32 (67)
Su, S, WP.146 (134)
Sugita, K, MP.8 (77); THP.160 (790)
Sukrow, S, THP.36 (769)
Sullivan, C, TP.231 (707)
Sullivan, J, M.11.4 (9); MP.86 (24); MP.240 (50);
TP.144 (86); WP.171 (138); THP.2 (163)
Sullivan, M, WP.239 (750)
Sun, D, MP.24 (14); MP.226 (47)
Sun, N, THP.160 (790)
Sunderland, A, THP.209 (198)
Suni, J, TH.9.3 (760)
Sutherland, S, THP.137 (186)
Sutjipto, S, MP.230 (48)
Sutoh, H, W.3.2 (706)
Suurmeyer, T, TP.193 (94); THP.191 (795)
Svejgaard, A, WP.101 (727)
Svenson, M, MP.113 (29)
Swack, N, MP.129 (31)
Sweet, D, WP.201 (143)
Swenson, R, F.7.2 (272)
Swerdloff, M, MP.139 (33)
Swift, R, TH.5.1 (756)
Switzer, W, MP.27 (14); MP.72 (22); F.7.1 (272)
Szapocznik, J, MP.116 (29)
-T-
Taelman, H, MP.82 (23); MP.154 (35); TP.82
(76); W.2.4 (706); THP.227 (207)
Taggart, V, MP.188 (41)
Tagliabue, A, THP.118 (183)
Takatsuki, K, W.3.2 (706)
Takeda, A, WP.30 (775)
Takeuchi, Y, WP.31 (775)
Tam, M, WP.145 (134)
Tambussi, G, WP.89 (725)
Tan, P, WP.247 (757)
Tan, S, WP.215 (146); THP.96 (779)
Tapko, J, T.5.6 (55)
Tasker, M, MP.213 (45); WP.213 (745)
Taswell, H, MP.147 (34)
Tateno, M, WP.7 (777)
Tatuta, C, WP.30 (775)
Tauber, M, WP.81 (725)
Taylor, D, TH.4.4 (756)
Taylor, E, WP.66 (727)
Taylor, H, M.6.4 (5)
Taylor, J, MP.199 (43)
Taylor, M, TH.2.3 (755)
Taylor, P, T.7.4 (57); TP.12 (64); THP.98 (779)
Taylor-Robinson, D, TH.4.4 (756)
Tedder, R, MP. 9 (77)
Tegtmeier, G, WP.244 (757)
Teirlynck, O, THP.227 (207)
Temoshok, L, M.5.5 (4); WP.201 (143)
Tennant, F, TP.54 (77); THP.95 (779)
Tenneriello, L, TH.11.5 (762)
Tenorio, A, TP.102 (79)
Terpstra, F, WP.125 (757); THP.126 (184)
Terragna, A, TP.83 (76); WP.134 (132)
Tersmette, M, TP.33 (68); WP.36 (776); WP.73
(722); WP.125 (757); THP.90 (178)
Terwilliger, E, M.4.6 (3); M.9.2 (7); T.16.2 (62);
WP.16 (113)
Teschke, R, T.8.3 (58); TP.158 (88)
The, G, TP.52 (77)
The, T, TH.8.2 (158)
Theodore, T, M.4.5 (3)
Thies, H, TP148 (87)
Thind, D, TP.103 (79)
Thiry, L, MP.124 (30)
Thomas, D, TP.248 (705); WP.244 (757)
Thomas, F, MP.69 (27)
Thomas, J, MP.250 (57); WP.227 (148)
Thomas, P, TP.76 (75); WP.155 (756); WP.71
(722); TH.7.1 (757); THP.69 (775); THP.199
(796)
Thompson, D, TP.233 (707)
Thong, K, TP.90 (77)
Thouless, M, MP.15 (72)
Tielman, R, M.6.1 (4)
Tijmstra, T, TP.193 (94); THP.191 (795)
Tillett, G, F.5.4 (270)
Tindall, B, MP.63 (20); TP.101 (79); WP.86 (724)
Ting, R, WP.21 (775)
Tipple, J, TP.208 (97)
Tirelli, U, WP.95 (726)
Tong-Sarksen, S, M.9.1 (6)
Tonnessen, G, THP.171 (792)
Toossi, Z, MP.105 (27)
Tor, J, MP.165 (37); TP.167 (90)
Torensma, R, TH.8.2 (758)
Torseth, J, THP.125 (784)
Tosato, G, THP.10 (765)
Tourani, J, THP.239 (203)
Tourtellotte, W, MP.108 (28); MP.109 (28)
Tracey, E, THR12 (765)
Tramont, E, TP.183 (93); WP.195 (742); THP.173
(192)
Tran, C, MP.128 (31)
Traylor, D, MP.135 (32)
Tremblay, M, TP.26 (66)
Trepo, C, THP.216 (799)
Tribe, D, TP.85 (76); THP.26 (767); THP.193
(195)
Tross, S, T.10.5 (60)
Truman, B, TP.177 (92); WP.74 (722); WP.61
(720); THP.70 (775)
Tsai, C, THP.30 (768)
Tsang, P, MP.132 (32)
Tschachler, E, TR107 (80)
Tsoukas, C, TP.89 (77); WP.163 (757); THP.133
(785)
Tuazon, C, TH.4.1 (755)
Tucker, J, WP.102 (727)
Tung, C, MP.14 (72)
Turbitt, P, THP.222 (200)
Turshen, J, TP.208 (97)
Tyms, A, TH.4.4 (756)
Tyms, S, TH.8.3 (759)
Tyson, R, TP.14 (64)
-u-
Ujhelyi, E, MP.21 (75); MP.236 (49)
Ullrich, P, F.2.3 (207)
Ulrich, K, MP.62 (20); TP.81 (76); WP.101 (727);
WP.162 (757)
Ulrich, P, W.4.5 (708)
Ungerer, L, F.5.3 (270)
Usategui, M, MP.238 (49)
Ussery, F, MP.217 (46)
Uttamchandani, R, TP.168 (90); WP.167 (758)
Uyeda, A, TP.6 (63)
-V-
Vacante, D, MP.159 (36)
Vaccher, E, WP.95 (726)
Vaglia, A, MP.153 (35)
Vaheri, A, TH.9.3 (760)
Valdiserri, R, M.6.2 (4); F.8.3 (275); F.8.4 (275)
Valdivia, L, MP.244 (50); TP.235 (707); WP.44
(777)
Valentine, F, THP.9 (765)
Valentine, J, WP.187 (747)
Valette, I, MP.96 (26)
Valinsky, J, WP.236 (749)
Valle, S, MP.119 (30)
Valleron, A, TP.180 (92)
234
INDEX
Valway, S, TP.58 (72); THP.174 (192)
Van Dam, J, MP.60 (20)
Van Den Hoek, J, TP.40 (69); F.8.5 (213)
Van de Perre, P, THP.61 (173)
Van Der Groen, G, MP.82 (23); W.2.4 (106);
WP.51 (118); THP.139 (186)
Van Der Maaten, M, TH.2.5 (154)
Vander Noordaa, J, M.6.1 (4)
Van Der Poel, K, WP.73 (122)
Van Devanter, N, TP247 (103)
Van Druten, H, MP.74 (22)
Van Geel, G, WP.51 (118)
Van Griensven, G, M.6.1 (4); MP.177 (39)
Van Haastrecht, H, TP.40 (69)
Van Home, J, THP.215 (199)
Van Ness, P, W.1.3 (105)
Van Raden, M, TH.5.6 (157); F.8.4 (213)
Varela-Millot, C, MP.112 (28)
Varnier, O, TP83 (76); WP151 (755)
Vaughan, D, TP.191 (94); WP185 (747)
Vazeux, R, MP.2 (10); THP.161 (790)
v. d. Bij, W, TH.8.2 (755)
v. d. Poel, C, THP.90 (178)
Veber, F, TH.7.4 (758)
Vedrenne, C, THP.161 (790)
Vellend, H, MP.209 (45); H, TH.8.1 (758)
Venet, A, THP.239 (203)
Venkatesan, S, THP.17 (766)
Verani, P, THP.248 (204)
Vercauteren, G, TP.63 (73); WP.51 (118); TH.7.5
(758)
Verdier, R, M.8.6 (6); MP.68 (27); MP.69 (27);
MP.136 (32)
Vergeront, J, MP.182 (40); F.5.2 (270)
Vermund, S, TP.66 (73); WP.52 (779)
Vernon, A, T.8.6 (58)
Vernon, D, THP.167 (797)
Veronese, F, TP.20 (65); TP.21 (66)
Veronesi, R, MP. 48 (18)
Verroust, F, MP. 45 (17)
Vestergaard, B, T.3.5 (53)
Via, C, WP.100 (727)
Viallefont, A, M.5.4 (4)
Vianello, L, MP.249 (57)
Vieira, J, TP.221 (99)
Viglianti, G, WP.15 (772); TH.2.2 (755); THP.5
(164)
Vigneau, B, WP.179 (140)
Vilde, J, WP.138 (133); WP.160 (137)
Vinceguerra, V, THP.16 (766)
Virmani, R, M.11.6 (9)
Vishnubhakat, S, WP.159 (756)
Visscher, B, TP.72 (74); WP.63 (720); WP.64
(727); WP.67 (727); THP.60 (173); THP.64
(774); F.8.4 (275)
Visser, O, MP.220 (46)
Vittecoo, D, MP.149 (35); WP.216 (146)
Vittecoq, D, TP.142 (86); F.4.6 (209)
v Krogh, G, THP.130 (785)
Vogel, R, TP.154 (88)
Vogt, M, WP.104 (727)
Vogt, R, THP.192 (795)
Vogt, W, TP.30 (67)
Volberding, P, M.11.2 (9); M.11.3 (9); T.8.1 (58);
WP.47 (778); WP.58 (720); WP.150 (135);
THP.56 (772); THP.57 (173)
Voltolin, L, TP.230 (700)
Von Briesen, H, Wp.24 (114)
Vonk, M, TP.193 (94)
Voordecker, P, MP.154 (35)
Vorkauf, H, MP. 56 (79)
Voskovitch, J, T.7.1 (57)
Vrang, L, THP.13 (765)
Vuillecard, E, MP.164 (37)
Vujcic, L, THP.120 (785)
Vyas, G, W.4.3 (708); W.4.5 (708)
Vyas, R, MP.60 (20)
-w-
Wachter, H, MP.99 (26); THP.166 (797)
Wada, S, THP.107 (787)
Wadsworth, J, THP.202 (797)
Wagner, B, MP.199 (43)
Wagner, K, TP.135 (85)
Wahl, L, MR133 (32); TP.133 (84); WP.130 (752);
THP.134 (785)
Wahl, S, MP.133 (32); THP.134 (785)
Wahren, B, TP.132 (84)
Wain-Hobson, S, T.16.3 (62); WP.32 (775);
WP.127 (757); F.2.4 (207)
Wainberg, M, TP.26 (66); WP.8 (777)
Wakefield, D, THP.115 (782)
Waldenlind, L, THP.130 (785)
Waldman, A, TP.240 (702); WP.236 (149)
Walker, B, T.4.3 (54); T.9.1 (59); THP.6 (764)
Walker, C, MP.163 (37); WP.13 (772); F.9.5 (274)
Walker, J, TP.75 (75); TR91 (77); WP.71 (722);
THP.199 (796)
Walker, R, T.8.2 (58)
Wallace, B, MP.126 (57)
Wallace, J, WP.55 (779); WP.115 (729); THP.55
(772)
Wallemark, C, T.3.6 (53)
Walmsley, S, TH.8.1 (758)
Walsh, M, TP.14 (64)
Walters, D, MP.243 (50)
Walters, W THP.lll (782)
Walton, R, MP.172 (38)
Walzer, P, MP. 219 (46)
Wan, W, TP.160 (89)
Wang, C, MP.243 (50); TP68 (73); THP.lll
(182)
Wang, J, MP.243 (50); THP.lll (782)
Wang, L, MP.95 (26)
Wang, S, WP.18 (775)
Wang, Y, MP.120 (30)
Wara, D, MP.163 (37)
Ward, H, THP.202 (797)
Ward, J, M.3.5 (2); MP.169 (38); MP.241 (50);
W.4.1 (707); WP.190 (742); WP.237 (749);
THP.30 (768); THP.53 (772)
Ware, G, TP.185 (93)
Warfield, D, THP.42 (770)
Warren, R, THP.31 (768)
Waselefsky, D, MP. 36 (76)
Wassef, M, MP.54 (79)
Waters, M, THP.31 (768)
Watkins, S, MP.85 (24)
Watson, A, MP.35 (76)
Watson, E, WP.19 (775); THP.113 (782)
Watson Martin, P THP.128 (784)
Watson-Williams, E, TP.28 (67)
Watters, J, T.10.4 (60)
Waxdal, M. WP.117 (729)
Weatherly, B, WP.100 (727)
Weaver, M, M.3.3 (2); M.6.3 (5); TP.99 (79)
Webb, G, THP.137 (786)
Webber, J, WP.242 (750)
Weber, J, M.10.5 (8); T.3.4 (53); TP.78 (75);
TP.lll (87); WP.2 (770); WP.75 (722); TH.9.4
(760)
Week, K, MP.19 (75); MP.22 (75)
Wei, C, M.4.6 (3)
Weidlein, D, MP.152 (35)
Weigel, I, TH.10.6 (767)
Wein, A, TH.11.2 (767)
Weinhold, K, M.10.3 (8); MP.78 (23); T.9.4 (59);
TP.128 (83); THP.235 (202)
Weintrub, P, MP.163 (37)
Weiser, B, THP.228 (207); THP.233 (202)
Weisman, H, MP.150 (35)
Weiss, H, THP.156 (789)
Weiss, L, WP.72 (722); WP.154 (756)
Weiss, R, M.10.5 (8); MP.20 (75); T.3.4 (53);
TP.4 (63); WP.2 (770); TH.9.4 (760); THP.20
(766)
Weiss, S, F.6.5 (277); TP.87 (77)
Weits, J, TH.8.2 (758)
Welck, U, THP.59 (775)
Wells, M, WP.85 (724)
Werdegar, D, T.49 (70); TP.51 (77); W.46 (778)
Werner, E, MP.99 (26)
Wernz, J, WP.230 (748)
Westphal, H, F.7.4 (272)
Wetterberg, L, M.5.2 (3); TH.1.3 (755)
Whal, S, WP.130 (752)
Whalen, M, WP.13 (772)
Whaun, J, TP.237 (702)
Whitaker, G, TP.57 (72)
White, C, T.7.3 (57); TP.84 (76)
White, G, MP.78 (23); F.1.3 (206)
Whyte, B, MP.64 (20); MP.186 (47)
Widmark, T, F.8.6 (275)
Wiebel, W, THP.80 (776)
Wigdahl. B, TP.22 (66)
Wigzell, H, MP.30 (75); MP.39 (76)
Wiley, A, THP.183 (794)
Wiley, C, TP.158 (88)
Wiley, J, TP.91 (77); THP.48 (777); F.1.4 (206);
F.8.2 (275)
Wilfert, C, THP.235 (202)
Wilhelm, S, TP.248 (705)
Wilkinson, D, WP.152 (755)
Willey, R. M.4.5 (3)
Williams, A, TP.59 (72); WP.239 (750); THP.44
(770^; THP.242 (203); THP.246 (204)
Williams, B. WP.121 (130)
Williams, K, MP.181 (40); THP.246 (204)
Willingmann. P, WP.26 (774)
Willitts. D. MP.86 (24)
Willoughby, A, WP.157 (756); TH.7.3 (758);
THP.158 (789)
Willoughby, B, M.3.3 (2); M.6.3 (5); MP.lll
(28); TP.99 (79)
Wilson. B, WP.34 (776)
Wilson, V, TP.96 (78)
Winborne, R. WP.185 (747)
Winchurch. R, WP.123 (750)
Winkel, I, WP.36 (776)
Winkelstein, A, MP. 121 (50)
Winkelstein. W M.3.2 (7); THP.46 (777);
THP.47 (777); THP48 (777); F.1.4 (206)
235
INDEX
Winkler, J, WP.143 (134); WP.144 (134); THP.142
(187)
Winn, R, T.7.2 (57); WP.156 (136)
Winslow, D, TP.85 (76)
Winter, K, TH.7.1 (757)
Wintfeld, N, MP. 205 (44)
Wisniewolski, R, THP.lll (182)
Witebsky, F, WP.152 (135)
Withum, D, THP.45 (171)
Witte, J, W.2.1 (105); W.2.3 (106); THP.45 (171);
THP.83 (177); THP.86 (177)
Wittek, A, MP.125 (31); THP.71 (175); THP.122
(183)
Wiznia, A, TP.146 (86); WP.153 (735); THP.156
(189)
Wodak, A, MP.186 (41)
Woelfel, M, WP.61 (720); THP.70 (175)
Woerle, R, WP.216 (146)
Wofsy, C, MP.221 (47); TP.219 (99); W5.5 (709);
WP.57 (119); THP.154 (7S9); F.3.1 (20S); F.3.3
(208)
Wolf, F, TP.239 (102); TP.58 (72); WP.176 (739);
THP.174 (192)
Wolf, S, F.5.1 (210)
Wolfe, P, THP.232 (202)
Wolff, A, TP.29 (67)
Wolff, M, T.5.4 (55)
Wolska, J, THP.133 (185)
Wong, G, T.4.5 (54)
Wong-Staal, F, M.9.5 (7); M.9.6 (7); MP.23 (74);
MP.25 (14); MP.33 (75); T.16.1 (67); TP.ll (64);
TP.125 (83); W.3.3 (707); W.3.5 (707); WP.20
(775); TH.2.3 (753); TH.2.4 (754); TH.9.1
(759); THP.15 (766); THP.23 (767)
Wood, C, WP.225 (147)
Wood, R, F.1.6 (206)
Wood, T, THP.34 (769)
Woodard, D, TP.103 (79)
Woodard, L, THP.51 (772)
Woods, W WP.186 (747)
Woolridge, T, THP.200 (796)
Wormser, G, TP.154 (88); TP.211 (97); WP.74
(722)
Worobec, S, TP.235 (707)
Worrell, C, TH.4.5 (756)
Worthington, G, MP.173 (39); TP.204 (96)
Woweries, J, THP.94 (779)
Wright, C, THP.105 (181)
Wright, D, TP.166 (90); WP.110 (128); THP.99
(180)
Wright, H, TP.214 (98)
Wu, W, T.3.6 (53)
Wunderlich, C, MP.234 (49)
Wunderlich, G, THP.183 (794)
Wykoff, R, MP. 43 (77)
-Y-
Yala, F, WP.79 (723)
Yamaguchi, E, WP.167 (138)
Yamamoto, J, F.7.5 (272)
Yamamoto, N, M.4.2 (2); MP.235 (49)
Yanagihara, R, TP.29 (67)
Yap, P, MR137 (33)
Yarchoan, R, WP.223 (747); THP.10 (765)
Yee, J, MP.151 (35); TP.6 (63); TP.28 (67)
Yeh, C, MP.152 (35)
Yemane-Berhan, T, MP.214 (45)
Yeoh, E, TP.90 (77)
Yetter, R, THP.12 (765)
Ying, W TP.240 (702); THP.243 (204)
Yocum, D, MP.225 (47)
Yoffe, B, WP.113 (729); THP.114 (182)
Yokoyama, M, TP.131 (84); WP.114 (729);
THP.117 (183)
Yoshihara, P, THP.128 (184)
Young, L, THP.232 (202)
Young, S, MP.208 (44); TP.206 (96)
Yourno, J, MP.23 (74)
-z-
Zabay, J, WP.96 (726); WP.120 (730)
Zacarias, F, THP.138 (186)
Zacarias, R, MP. 44 (77)
Zacchello, F, MP.153 (35)
Zachar, V, WP.37 (776)
Zadelhoff, A, TP.40 (69)
Zagury, D, MP.23 (74); T.16.5 (62)
Zagury, J, TH.2.4 (754)
Zaizov, R, TH.10.5 (767)
Zajac, R, T.7.2 (57)
Zajdowicz, T, MP.71 (22)
Zajowicz, T, TP.135 (85)
Zanella, A, MP.249 (57)
Zaner, R, THP.194 (795)
Zang, E, T.7.4 (57)
Zapka, J, TP.174 (97); WP.172 (739)
Zarling, J, T.9.5 (59)
Zazula, T, WP.148 (735)
Zegans, L, TP.203 (96); THP.218 (799)
Zeichhardt, H, WP.26 (774)
Zeleniuch-Jacquotte, A, THP.69 (775)
Zeli, P, THP.84 (777)
Zelnick, R, TP.87 (77)
Zerboni, R, TP.164 (89); WP.161 (737)
Zhdanov, V, MP.7 (77); WP.98 (726); THP.40
(770)
Zhou, E, TH.9.5 (760)
Zich, J, M.5.5 (4); WP.201 (743)
Ziegler, J, WP.58 (720); WP.lll (128); THP.57
(773); THP.218 (799)
Ziegler, S, MP.241 (50)
Ziegler- Heitbrock, L, T.46 (70)
Zimmerman, D, TP.248 (703); F.6.5 (277)
Zissis, G, TP.82 (76); WP.59 (720); WP.80 (723)
Zito, J, WP.109 (128)
Zolla-Pazner, S, TP.110 (80); THP.69 (775)
Zon, G, T.4.4 (54)
Zon, L, TP.122 (82)
Zones, J, THP.207 (198)
Zook, B, WP.18 (773)
Zorr, B, TP.34 (68); WP.26 (774); THP.25 (767);
THP.94 (779)
Zoubi, D, MP.161 (37); THP.141 (187)
Zoulek, G, THP.93 (779)
Zuck, T, THP.52 (772)
Zuckerman, A, TP.4 (63)
Zuckerman, C, TP.199 (95)
Zuger, A, THP.206 (797)
236
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