Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

12th World AIDS Conference

Abstracts 60647-60651 1119

HHV-8 antibodies. Dependent on the stage of HIV disease, HHV-8 antibodies
could be detected in 7% of asymptomatic, 37% of symptomatic and 42% of AIDS
patients. 11 patients, among them 10 homosexual men, showed seroconversion
for HHV-8 during the study period. One of them developed Kaposi sarcoma (KS).
HIV viremia and CD4 counts at the time of study did not differ between HHV-8
positive and negative patients. However, in HHV-8 positive patients, there was a
trend of a higher HIV viral load before the start of antiretroviral therapy (p = 0.16),
of a higher maximal HIV RNA level (p = 0.06) and of a lower minimal CD4 count
(p = 0.06) compared to HHV-8 negative patients.
Conclusion: Our data support suggestions that HHV-8 infection is sexually
transmitted and that HHV-8 is associated with an increased risk for KS development. The higher prevalence of HHV-8 antibodies in symptomatic stages of HIV
disease could indicate a negative influence of HHV-8 on the course of HIV-disease.
HHV-8 seroconversions during the study period demonstrate, HHV-8 infection is
still spreading in HIV-infected patients, predominantly within the homosexual risk
group.
S60647 Necropsy-proven Toxoplasma ecephalitis without evident
focal lesions: Diagnosis by CSF PCR
Aina Veny1, J. Romev', C. Mohuz2, R. Llatjos', J. Morillas1, E. Davant1,
G. Sirera1. 1Hospital Germans Trias 1 Pujol, Badalona; 2Hospital Santa Crev I
Sant Pay, Barcelona, Spain
Purpose of the Study: Few instances of toxoplasmic meningoencephalitis (TE)
without focal lesions in computed tomography (CT) or nuclear magnetic resonance (NMR) have been reported mainly from autopsy records of patients with
HIV infection. We report a case of TE and antemortem diagnosis established by
cerebrospinal fluid (CSF) polymerase chain reaction (PCR).
Report of the Case: A 40-year-old man, former intravenous drug user, with
HIV infection and history of pulmonary tuberculosis was admitted because of a
change in his behavior, fever and headache. No focal neurological signs were
found in physical examination. CT and NMR showed brain atrophy without focal
lesions. CSF exam revealed: 43 leucocytes/mm3 (90% neutrophils), and high
adenosine deaminase (19U/I) and protein (1.7g/l) values, smears for acid-fast
bacilli and cultures for bacteria and fungi were negative. CD4 cell count was
16/mm3. Diagnosis of probable tuberculous meningoencephalitis was made and
empirical treatment was started. Because of the lack of clinical improvement a
CSF PCR for the detection of Toxoplasma gondii assay was performed. The
result was positive and anti-toxoplasma therapy was instituted. The patient didn't
improve clinically and died after 2 weeks of therapy. Toxoplasma gondii cysts were
found at both basal ganglia at microscopical exam. Macroscopic exam showed
periventricular small foci of necrosis.
Conclusions: CSF PCR for Toxoplasma gondii may be a useful tool to diagnose Toxoplasma encephalitis when no focal lesions are observed by imaging
techniques. A lack of response to antituberculous drugs may be another indication
to perform the test.
60648 Chronic use of protease inhibitors is associated with
hormonal abnormalities in otherwise healthy adult HIV-1
infected individuals
E. Martinez, R. Casamitjana, A. del Rio, J. Mallolas, J.M. Miro, J.M. Gatell.
Hospital Clinic, Barcelona, Spain
Background: Anecdotical reports of hyperlipemia, hyperglycemia and abnormal
distribution of fat (central obesity with thin extremities) have been reported in
HIV-1 infected patients treated with protease inhibitors (PI). However, their cause
and its relationship with PI are not known.
Objective: To determine if there are hormonal or metabolical differences between 2 groups of otherwise healthy adult HIV-1 infected patients treated with or
without PI.
Methods: We recruited 10 consecutive patients never treated with PI and 10
patients treated with a PI for at least 6 months. Patients should be younger than
40 years, clinically stable, with a plasma viral load -5000 copias/mL, with a CD4
cell count -350/p L, and with a body mass index (BMI) <25. They should not have
antecedents of lipid or glucose abnormalities, nor should have a recent weight
change. Finally, they should have normal liver, pancreas, and kidney function
tests. For each patient, we measured plasma levels of triglycerides, cholesterol,
glucose, insulin, and cortisol on fasting in the morning.
Results: PI in patients treated with them were: indinavir, 5 patients; saquinavir,
3 patients; and ritonavir, 2 patients. No differences were found in age, gender,
BMI, CD4 cell counts and viral load. Triglycerides (196+/ 87 versus 135+/-54
mg/dL, p = 0.07) and cholesterol (217+/ 58 versus 172+/ 26 mg/dL, p = 0.04)
plasma levels were higher and glycemia was lower (85+/-9 versus 96+/-6
mg/dL, p = 0.008) in patients treated with PI than in those not. Insulin (16.8+/-10
versus 8.5+/ 3.2 mU/L, p = 0.03) and cortisol (19.8+/ 5.8 versus 13.6 +/-3.9
vg/dL, p = 0.01) were higher in those patients treated with PI than in those not.
Conclusions: Chronic use of PI is associated with increased plasma levels of
insulin, cortisol and lipids and with decreased levels of glucose. None of these

abnormalities was clinically symptomatic at the time of the study.

60649 Changes in markers of T-cell differentiation and function
during progression of HIV-1 infection and T-cell
homeostasis failure
Joseph Margolick1, C.R. Rinaldo2, S.J. Gange1, P. Gupta2, H. Farzadegan1,
J.I. Mullins2. 615 N Wolfe St Dept MMi E4014 Baltimore Maryland 21205-2103.
Johns Hopkins Univ Baltimore; 2Univ Pittsburgh, Pittsburgh PA, USA
Objective: To define phenotypic changes in T cell maturity and differentiation
over the course of HIV-1 infection. Because failure of T cell homeostasis (i.e.,
onset of a rapid decline in circulating T cells) has been shown to be a precursor
of clinically-defined AIDS in a high proportion of cases, particular emphasis was
placed on determining the timing of the changes observed relative to the onset of
T cell decline (i.e., the T-cell inflection point (IP)).
Methods: Cryopreserved peripheral blood mononuclear cells obtained at
6-month intervals from seroconversion to the IP and/or AIDS were studied from
participants in the Multicenter AIDS Cohort Study (MACS) who were selected for
well-defined IP (n = 7), decline of CD4+ T cells to very low levels with no definite
IP (n = 2), or no change in T-cell levels (n = 4). T cell markers were analyzed by
3-color flow cytometry with gating on light scatter and expression of CD4 or CD8.
Results: In relation to the T cell IP, HIV disease progression was characterized
by consistent increases in the activation markers HLA-DR and/or CD38 (by both
CD4+ and CD8+ T cells) and a decrease in the proportion of cells expressing the
CD45RA marker of naive cells (CD4+ T cells only). These changes accelerated
markedly around the T cell IP. CD28 showed different patterns of expression.
Among CD8+ cells, there was a consistent gradual decline, which did not accelerate around the T cell IP. Among CD4+ cells, in contrast, CD28 expression
remained high ( 80%) until a sharp fall which occurred close to the T cell IP in
about half of the subjects with IPs. None of these changes was seen in the 4
MACS participants who had stable T cell levels over 8 years of follow-up post
seroconversion.
Conclusions: These data are consistent with previous cross-sectional analyses of these markers but extend these studies by showing that 1) changes in
these markers can be either gradual or abrupt with progression of HIV-1 disease;
2) T cell inflection is associated with rapid changes in activated T cells and naive
CD4+ T cells; and 3) the close parallel between the declines in naive CD4+ T cells
and CD8+ T cells expressing CD28, as well as the loss of CD28+ CD4+ T cells,
suggest that declining thymic T-lymphopoiesis may contribute to failure of T cell
homeostasis.
60650 rComparison of two instruments for assessing HIV risk in
drug abusers
Marek Chawarski, J.C. Baird. Applied Behavioral Research, LLC, Yale
University, CMHC/SAC 34 Park Street, New Haven, CTD 06519, USA
Objective: To compare assessments of HIV risk obtained by administering two
different assessment instruments in a sample of 73 treatment seeking drug
abusers.
Design: A within-subject comparison of scores on the AIDS Risk Inventory
(ARI-I) and the Risk for AIDS Behavior (RAB).
Methods: At entry into a drug treatment program 73 subjects (33 Females
and 40 Males) completed the RAB, a self-administered questionnaire, and then
were interviewed using the ARI-I in a structured interview format. The ARI-I
questionnaire consists of 50 questions, in three sections, covering the following
areas: intravenous drug use, sexual behaviors, and general knowledge of AIDS
prevention. The questions probe both frequency and recency of the behaviors
associated with high risk of HIV infection. The RAB consists of 38 questions
focusing on drug use and sexual behaviors. All questions are answered in a
multiple-choice format. Subjects were treatment seeking volunteers who were
diagnosed with combined heroin and cocaine dependency or addiction (DSM-III
criteria).
Results: Descriptive statistics, between-scale correlations, frequency histograms, and plots of cumulative frequencies were obtained. The correlation
between the two measures is r = 0.63 (p. 0.01), indicating a moderately strong
positive relationship between the scores on both scales. However, the range of
scores from the ARI-I is approximately 4 times the range of scores on the RAB,
indicating greater sensitivity for the ARI-I. The cumulative frequency function
grows much slower with increases in the ARI-I scores as compared to the same
function for the RAB scores.
Conclusion: The ARI-I is more sensitive than the RAB to differences in HIV
risk levels among treatment seeking drug abusers.
60651 Thiosemicarbazone-derivatives inhibit cytomegalovirus
replication in human cells
Miriam Margalith1, M. Simkin1, G. Shohat1, Y. Teitz2. 1Department of Virology
Faculty Health Sciences Ben-Gurion University of the Negev Beer-Sheva 84105;
2 Tel-Aviv University Sackler School of Medicine Tel-Aviv, Israel
Objective: To provide new non cytotoxic and efficient anti-CMV drugs.

Design: Newly synthesized two Thiosemicarbazone derivatives (TSCDs) were
chosen for study.
Methods: Human foreskin fibroblasts (HFF) and engineered human osteosarcoma cells (HOS-HXG) which contain a defective HIV-1 provirus genome were
used. CMV (Towne strain) antigens were measured in the infected cells by immunoperoxidase (IPA) and immunofuorescence (IFA) assays and infectious CMV