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Full text of "III International Conference on Acquired Immunodeficiency Syndrome (AIDS) : June 1-5, 1987, Washington Hilton and Towers, Washington, D.C."

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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 CD a . 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 "P lds es B Bl,e ot action lor developing novel entl-vlral agents: 
Studies with AL721. A. S. Lippa 1 , F. T. Crews 2 , M. H. Grieco 3 , E. Buimovicl-Klein 3 . M. 
Lange 3 , D. I. Scheer 4 , and C. A. Klepner 1 ; 1 Praxis Pharmaceuticals Inc., Beverly Hills, 
CA , 2 Universitv ol Florida Medical School, Gainesville, FLA, 3 S1. Luke's/Roosevelt Hospital Center, 
New York, NY, 4 Yale 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 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. K ATZENSTEIN* . 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 STI 1 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 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 












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 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 9 ene 0f HTLV-III/HIV 

AMANDA FISHER 1 , B.Ensoli 1 , 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 Pr559 a 9 and Prl709 a 9-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 LAWRENCE 1 , S SCHULMAN 2 , C R RIZZA 3 , T LAMBERT 4 , E P MAUSER- 
BUNSCHOTEN 3 , K RICKARD 6 , et al., Centers for Disease Control, 
Atlanta, GA, 2 Swedish Hemophilia Fdn, Stockholm, ^ Oxford Hemophilia 
Ctr, UK, 4 Hopital Bicetre, Paris, FR, 5 Van Creveldcllnic, Bilthoven, 
NL, 6 Royal 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 (<150 f 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 immunod efici ency 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 



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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 
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with A 
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W , E -. G . 

(1986) 



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|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 rl n -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 
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human 
cells 
and a 
days 
Elisa 
drama 
first 
inf ec 
HIV a 
as we 



HI 
PAUL 
GITA, H. 
509 & Ne 
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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/ tat IT 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 ^ ver i"fi ca ti on 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. B ELLAN TI*. 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 10 6 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 
Complexes 

BUKI ,A.HORVATH + + ,E.UjHELYI + ,G.KRALL"' 
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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 3 r 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 T 4 + 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 refer red by 
81% of interviewed DA. The relative risk (RR) of this practice was 4.07 ( C.L.9 5%: 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 - 197 1 * 

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 Sero P osit i v i t y i n 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 HIV 1 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. 



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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 immu ne d efici ency 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 (ijv 3 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 Eva lua tion 
(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 longitudi n al 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%) 





3 (43%) 


3 (18%) 


1 (20%) 


1 (14%) 


2 (12%) 


1 (20%) 





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 SIV mac 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 SIV mac 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 (X 2 = 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 infect ion 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 
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( 72X re 
time pe 
nonbeha 
suscept 



HI 
Ev 
£-__SEA 
Y*. G 
Is. Bo 
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va lua t 

we 

serop 
l ti vi t 
s of A 
l t l ve 
at l ves 
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V Iran 
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sexual Male Part 
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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 
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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: 
12 3 



T4 (x10/l) 
T8 (x10 9 /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 'AIDS 1 ) 



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/mm 3 and 10% - 255 cells/mm 3 ). 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 T H 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 Se q uent i a l 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. C0GNIAUX t+ , 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* 

178 b 
231 b 



413 a 
347 a 

454 a 



<5 


<5 U 


<5 


<5 


<5 


<5 


8 


55 C 



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 Mon ocyte 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 ( 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 ( 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 (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 i m P ort ance 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 preval e nce of nsurcpsycrdatric diarn ue r s 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. COUDERC 1 , S. MATHER0N2, F. BRUN-VEZINET 2 , P. HERVE 3 , C. MICHON 2 , 
J. P. CLAUVEL 1 . 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 


Pa0 2 

mm Hg 


PMN 


PMN/L 


Pa0 2 <50 
n pts/N 


PMN>5/mm 3 
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 










2(2) 


1(1) 


'83 


2 




1(1) 


2 9(7) 





'84 


1 




8(4) 


4 9(7) 


4(4) 


'85 


1 




1(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****, 
A N.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 ( y t 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 HEHLMANN J, 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 



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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/mm 3 and 31 
(48%) had below 300 cells/mm 3 (mean 468 cells/mm 3 ). Thirty-one 
(89%) of Group 2 had less than 500 T4 cells/mm 3 and 16 (46%) had 
less than 300 cells/mm 3 (mean 324 cells/mm 3 ). Group 3 had the 
lowest T4 counts (mean 84 cells/mm 3 ). 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 fl IDS 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 , * 

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of Bait 
dangers 
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imen tal 
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number 
an anti 
line, 
and eff 
ting th 
The exp 
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that th 
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street 



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i te In tr 
S. MCAUL 



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IFFE* 



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of 
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of e 
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ntion ( 

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Will 
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ddict Outreach workers to Edu- 
ers about AIDS Prevention. 
G** , P . BREER* , H. SILVERMAN*** , 
*Harvard Medical School, Cam- 
Maryland Drug Abuse Administra- 



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MP184 Knowledge and Attitudes About AIDS Among College Freshmen in 

Louisiana 
WILLIAM L. ATKINSON 1 ' 2 , V. KTSANES 1 , S. HASSIG 1 * 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 (X 2 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 
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did 
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al di 
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sampl 
amina 



ally 
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ample 
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uidan 
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n fet 
ocyte 
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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 



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Immunodeficiency Virus 
BROWN, JR.**, B.J. PRIMM*. *Addiction 
Corporation, Brooklyn, NY, **Harlem 

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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 Th e 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 P 24 , P 34 , gp 41 , P", P 64 , gp 120 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 Rlsin 8 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 10 9 /lung to 0-1+ (neg-light) and 
10 5 -10 6 /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. 



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Randomized Prospective Trial of Ganciclovir Maintenance 
Therapy for Cy tomega 1 ovri us (CMV) Retinitis 
Jacobson*, HR Brodie*. J J ' Donnel 1 * , CC Wofsy*, J Mills' 
of Medicine and S.F. General Hospital, San Francisco, 



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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 10 3 U/kg/d, 
2.6 x 10 3 U/kg/d, 5.2 x 10 3 U/kg/d and 1.0 x 10 4 U/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 10 3 U/kg/d) , 2675 to 8650/ul (at 2.6 x 10 3 U/kg/d) , 1900 to 
8743/ul (at 5.2 x 10 3 U/kg/d) , and 2600 to 17,300/ul (at 1.0 x 10 4 U/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 mm 3 ) 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/M 2 (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 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 10 3 Pit/mm 3 
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/10 6 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/10 6 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=10 3 ) was placed on 1/2-in 2 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 

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GEORGE FUST 



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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 t emperature-Dried 

to 577 



Day 

1 
3 
5 
6 



4°C-Liquid 
_ L0^' 
10 4.8 
10 7.0 
103.9 
1C-4-1 



1CP 



10-3.5 1 3.9 

1 1.9 102.4 

1C-2-1 i 3.9 

101.4 10 2.1 

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 10 J -°/10 J -^ 10 J -*/10 J . u lC-O/Not Done 

Serum 10*- 8 /10 3 - 4 10 3 - 8 /<10l-° 10 3 - /<10 1 - 

Blood 10 4 - 3 /<10 2 - 10 5 -°/<10 1 - 10 3 - 8 /<10 2 - 

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 Antibod Y and Virus Detection in a Cohort of Haemophiliacs. 

P. SIMMONDS , ROBERT J.G. CUTHBER T**, 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 Relat i° nsh ip 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, FL f ** 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,p2 i t,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-p2 l, .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. RHAME 1 ' 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/mn 3 1 164 
(s.d.). Mean CD4 counts in the 10 men with HIVAg who did not develop AIDS (Gp 2) was 481 
cells/mil 3 * 202 (p=0.03 vs Gp 1), and in seropositive men without HIVAg (Gp 3) 710 
cells/nm 3 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-2 f ,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 
2 1 ,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/mm 3 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/mm 3 ) 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 

MICHAE L J. ROSENBERG 1 ' 2 . R. K0HMESCHER 3 , M. B0NH0MME 2 , R. LAZAROUICZ 1 , 
^American Social Health Association, Palo Alto, CA, 2 Family 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 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 

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 (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 ga g (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 ga g - 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-III B 
strain of HIV. The same target cells infected with recombinant vaccinia 
lacking this insert served as controls. Targets were labelled with 51 Cr 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 
SCOT T K0ENI 6, 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 [ 35 S] -methionine-labeled HIV-infected cells, it was 
shown that antibody to the HIV envelope protein, gp 120 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 P 1 ™^ 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 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 Th e 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. LAURENT 1 , A. LE GUERN 2 , 0. JEANNEQUIN 2 , L. M0NTAGNIER 1 
and A. G. HOVANESSIAN 1 . 'Unite d'Oncologie Virale, 2 Hybridolab, 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 32 P-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.STAPLETON 1 , S.CUMMINGS D.MCPHEE 2 , B. KEMP 1 , R.DOHERTY 2 . 
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-III B . 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-III B , 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 VERONESE 1 , R. RAHMAN 1 , T. COPELAND 2 , S. OROSZLAN 2 , 
R.C. GALLO 3 , M.G. SARNGADHARAN 1 , 1 Bionetics Research, Inc., Rockville , MD; 
2 Lab. of Molecular virology and carcinogenesis, NCI-FCRF, Frederick, MD, 3 Lab. 
of Tumor Cell Biology, NCI, Bethesda, MD. 

The first open reading frame of HTLV-III B 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-III B were then labeled with [ 35 S]-cysteine 
and [ 3 H]-leucine, immunoprecipitated with M35/2F8 and analyzed by SDS-PAGE. 
No immunoprecipitation of p6 has been observed when cells or virus were 
labeled with ( 35 S)-cysteine. However p6 was distinctly immunoprecipitated 
when [ 3 H]-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, [ 3 H] -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 Leu 448 . 



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 [ 125 l ]-F(ab' )2 fragments of antlmouse IgG or 
[ 125 l ]-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 [ 3 H]- Rlcln communis 
or gal oxidase technique with LI 3 hb 4 , 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 
M r 15,000 polypeptide. We discuss possible mechanisms whereby the 
interaction of pl Stat 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-III B 
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 
immunob 1 
sence of 
blood f i 
found re 
province 
minan tly 
years (r 
dividual 

Only 1 
ELISA an 
conf iden 
adul t s 
22% of v 
ch ildren 
PGL. 

Ne i the 
lence of 
with res 



Pre va 

H.D.P 

*** , A 

*The F 

mark, 

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blood 

o 1 1 ing 

HIV a 

1 1 er-p 

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in We 

rural 

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lences 
ETERSE 
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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 
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non- ac 
cases 
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regist 
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consi d 
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wh ich 
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def i m 
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( 14%) , 
was 90 



Val 
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M.__DAY A 
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on of AIDS Surveillance Through a One-Year 
rtificate Review. 
KUNCHES**, GR SEAGE 
Hospitals. AA Massac 



MA BARRY*. 
:husetts Dept. 



Boston 
of Public 



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TP5D Tne Descri P tive 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 
(56 Q ")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 — Vi vo Analysis, of AntiretroviraJ. Treatment Strategies in Mice. 
1 ,f . RUTH M. RUPRECHT *. ARLENE SHARPE*'', RUDOLF , JAENISCH and DAVID 
CH0U XXK , '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 

log 2 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 l e ast 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 
3 1 * 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 
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and *♦ 
s sugge 
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agnos i s 
em. The 
nderest 
d post- 
qgress i 
s of HI 



he 
ead 
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tal i ty. 
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pro- 

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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 ID 50 = 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 

Teste d 
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 





Sisexual"' 
Heterosexuals 2* 1 

with prostitute contact 

Transfusion 2+ 



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 on i v ) 

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 . 
W ILLY 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<iin 8 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 10 5 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 10 J 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 g enetlc 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 HI 17 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%) 



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 






ARC(13) 


AIDS(8) 


tot. (64) 


7(54%) 


5(63%) 


22(34%) 


4(31%) 


1(13%) 


18(28%) 


5(38%) 


3(38%) 


17(27%) 












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 t CD4 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, Uahren 1 , E.M. FENYO 2 , F. CHIODI 2 , R. KURTH 3 , J. GHP.AYEB 4 , S. PUTNEY 5 , 
R. GALLON & D. BOLOGNESI 7 , National Bacteriological Laboratory and 2 Karolinska 
Institute, Stockholm, Sweden, 3 Paul Ehrlich Institut, Frankfurt, FRG, ^Cento- 
cor, Malvern, PA, 5 Repligen, 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 ga g 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/mm 3 ) 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. Elec ti i i liagr ps tical l y, 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" ^u w h 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 c y tome ftalovirus (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 
R IED LUER* , W. BUTTNER* S. POSER*, D. EICHENLAUB** , 

K. Felgenhauer* , * Georg-August Universitat Gottin- 
f T Virchow 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 * 10S r as e s ° a 

feet of R 
PETER KERN* , W. ME 
Nocht-Institut, Ha 
Georg, Hamburg, Ge 
Twenty-eight pat 
treated with inter 
of 18x 10 6 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. q non-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 carini i. 

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 Pajol n «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 invaaive t esophagitis.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 (Wilks 1 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 Antibod y 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 AlternaC i v e 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 (X 2 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 KntMled 9 e 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 (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 



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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, 



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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 
L AUREN 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- 



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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 ^^ I s °l a t e d 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 well 1 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 Res P° 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 Educa t'°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. ' 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. 



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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.MATHERON 2 , M. JANIERl, P.M. GIRARD 2 , M. SELIGMANNl, 
J. P. CLAUVEL l. 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/m 2 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 # P 1 Concentration in BAL (ng/ml) Day 3 Plasma (ng/ml) 4 

1 ND 2 - 3.1 

2 55.3+17.1 1 14.7 

3 28.6+10 4 16.9 

4 66.8+16 3 

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 Hi 8 n 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