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

34 Abstracts 12114-12118

12th World AIDS Conference

Western blot (WB). HTLV-2 antibodies were detected by ELISA, then confirmed
and typed by WB (HTLV-1 rpg 21e enhanced, Cambridge Biotech, and HTLV 2.4
Genelabs Diagnostic). Subjects identified as being co-infected and in whom the
date of seroconversion for at least one of their viruses was known were followed
prospectively. Clinical evaluations, CD4+ lymphocyte counts and HIV viral load
(when it became available) were performed every 3-4 months.
Results: A total of 27 subjects (15 females, 12 males) were followed for at
least 5 years. Risk factors for infection were: intravenous drug use (18), homosexual/bisexual activity (5) and heterosexual contact (4). In 15 subjects HTLV-2
seroconversion preceded HIV-1 infection (Group 1), and in 12 subjects, HTLV-2
seroconversion followed HIV-1 infection (Group 2). In 13/15 Group 1 subjects
CD4+ counts have remained above normal levels after 5 years ranging from
685-1268/cu mm. Among Group 2 subjects none had CD4+ counts greater than
600 after 5 years, ranging from 2-347/cu mm. Four Group 1 and three Group
2 patients are currently receiving antiretroviral therapy. Eight (7 AIDS) Group 2
and two (1 AIDS) Group 1 patients have died. The geometric mean serum RNA
level was 1830 copies/ml for Group 1 subjects and 158,489 copies/ml for Group
2 subjects.
Conclusion: These data suggest that HIV infection in the presence of HTLV-2
infection may be associated with a milder disease course. The role of higher
CD4+ counts is unclear but may provide some immunologic benefit. HIV disease
progression and CD4+ count decline appear to be accelerated in the subset of
HIV-infected subjects who became co-infected with HTLV-2. These results do not
provide a biologic basis for a hypothesis that HTLV-2 accelerates the course of
HIV infection. Further study is needed to determine a biological effect.
S12114 | Safety and efficacy of reduced doses of ritonavir (RTV)
plus saquinavir (SQV) in the treatment of AIDS patients,
in Brazil
Carlos Brites', A.P. Alcdntara2, A. Gimbo2, N. Silva2, C. Pedroso2,
D. Pedral-Sampalo2. 1Hosp Univ Prof Edgard Santos, Rua Joao Das Botas S/N,
Cane/a; 2Federal University of Bahia, Salvador, BA, Brazil
Objectives: To evaluate the safety and efficacy of the association of RTV plus
SQV, combined with reverse transcriptase inhibitors (RTI), in the treatment of
AIDS patients.
Methods: A combination of SQV (1.2 g/day) and RTV (600 mg/day) was added
to the treatment of 31 consecutive AIDS patients, who were under double therapy
(RTI), and needed to use protease inhibitors. Viral load (NASBA) and CD4 (flow
cytometry) count were measured at baseline, 30, 90 and 180 days. Adverse
reactions were recorded, as caused by the drugs.
Results: After 3 months, adverse reactions were observed in 25/31 patients,
leading to interruption of the treatment in 7 (25%) subjects. Three additional patients stopped the therapy: two due to clinical failure and 1 was intolerant to AZT
and DDI. Lower limbs paresthesia (44%), diarrhea (40%), nausea (32%) vomiting
(24%), and fatigue (16%), were the most frequent side-effects observed. The mean
CD4 count was 110 ~ 84 cells/ml, at baseline, increasing to 185 ~ 89 cell/ml and
221 ~ 112 cells/ml, at day 30 and day 90, respectively, while the mean viral load
decreased from 4.8 ~ 0.6 log to 3.2 ~ 0.9, and 3.6 ~ 0.9 at the same time intervals. Four patients who completed 6 months of treatment had viral load <400 RNA
copies/ml, at that time.
Conclusion: The combination of SQV/RTV and 2 RTI was effective in increasing the CD4 count and reducing viral load after 3 months of treatment. However,
the high frequency of adverse reactions may limit the use of such treatment.
|12115 Haptoglobin polymorphism as determinant of the HIV-1
viral load
Johan R. Boelaert1, J. Delanghe2, M. Langlois, C. Verhofstede, F. van
Wanzeele, J. Plum. 1AZSint-Jan Ruddershove 10 8000 Bruges; 2Clin. Chem.,
Microbiol. & Immunol., U.Z. Gent 9000 Gent, Belgium
Objectives: We previously reported that the polymorphism in the haptoglobin
(Hp) locus, resulting in 3 different phenotypes (Hp 1-1, 2-1 & 2-2) influences the
prognosis after HIV-1 infection, with a higher mortality in Hp 2-2 individuals (P =
0.0001). Here we study whether the Hp polymorphism influences the HIV-1 viral
load in patients prior to the AIDS stage.
Design: Retrospective comparison.
Methods: Caucasian adult patients, followed at 1 reference centre, with confirmed HIV infection, without any AIDS-defining illness, with a CD4+ cell count
>200/j/L and who were naive for antiretroviral therapy were included. A total
of 61 patients fulfilled these criteria. Plasma HIV-1 RNA levels were quantified
with the Amplicor RT-PCR assay. Hp phenotypes were determined using starch
gel electrophoresis of hemoglobin-supplemented serum, followed by peroxidase
staining. The first known plasma HIV-1 RNA level of each patient was related to
the corresponding phenotype.
Results:
Hp 1-1 (n = 12) Hp 2-1 (n = 34) Hp 2-2 (n = 25)

logio RNA copies/mi (mean ~ SD) 3.77 ~ 0.91 4.54 ~ 0.77 4.98 ~ 0.91
P < 0.03 between the 3 Hp-phenotype groups (Kruskal-Wallis test).
Conclusions: We previously found that Hp 2-2 individuals show a worse prognosis after HIV-1 infection and accumulate more iron and oxidize more vitamin
C than Hp 1-1 & 2-1 persons. We proposed that their less efficient protection
against hemoglobin/iron driven oxidative stress might stimulate HIV-1 replication.

The latter is evidenced here by the higher viral loads in non-AIDS patients carrying
Hp 2-2 as compared to those carrying Hp 2-1 and even more Hp 1-1.
12116 1Positive influence of heterozygous chemokine receptor 5
mutation on response to antiretroviral therapy in
HIV-1-infected patients
Thomas Harrer, Andreas Goldwich, S. Kasten, A. Rascu, J.R. Kalden. Dept. of
Medicine III, Univ. of Erlangen, Erlangen, Germany
Background: As the chemokine rezeptor 5 (CCR5) is an important coreceptor
for M-tropic HIV-1 strains, pharmacologic blocking of CCR5 has been proposed
for therapy of HIV-infection. A 32 base pair deletion within CKR-5 is associated
with a more favourable course of HIV-1-infection, but little is known about the
influence of this mutation on the response to antiretroviral therapy.
Methods: PBMC of randomly selected HIV-infected patients were analyzed by
PCR for the presence of the reported 32 base pair deletion within CKR-5. HIV
viremia was analyzed by the b-DNA assay.
Results: 23 of 109 HIV-infected patients were heterozygous for the 32base
deletion in the CCR5 gene (21%). The prevalence of this mutation did not differ
between various risk groups (homosexuals, iv drug abusers, heterosexuals and
hemophiliacs). Among the patients on antiretroviral combination therapies 21 of
23 patients (91.3%) with the CCR5 mutation, but only 48 of 83 patients (57.8%)
with wild type CCR5 showed a suppression of HIV-viremia below the limit of
detection of <500 copies/ml.
Conclusions: Our data indicate that the presence of a heterozygous CCR5
32-base pair deletion is associated with a better response to antiretroviral combination therapy and a lower rate of emergence of drug resistant HIV-strains. This
finding is suggesting that therapeutic strategies targeting CCR5 could be of value
for an enhanced suppression of HIV by antiretroviral combination therapies.
12117 Changing patterns of AIDS due to antiretroviral therapy
within the last thirteen years
Keikawus Arasteh1, T. Zwingers2, V. Simon1, W. Heise1, M. L'Age1.
August-Viktoria-Krankenhause, II. Innere Abteilung Rubenstrasse 125, 12157
Berlin; Institute of Statistic - Estimate, Augsburg, Germany
Objective: To analyse the changing spectrum of AIDS-defining diseases of
hospitalised patients undergoing antiretroviral treatment.
Design: Prospective, longitudinal investigation in a mixed cohort of HIV-1
positive patients.
Methods: During 1985-1997 2.904 in-door patients had been treated in the Auguste-Viktoria-Hospital in Berlin/Germany, and 7.571 distinct treatment episodes
have been evaluated including detailed documentation of physical conditions,
disease history/outcome and treatment. We defined a semi -Markov-process according to Bjorling and Hodges (Stat Med 1997; 16) with five different stages of
increasing disease severity (no AIDS-defining condition- AIDS severity I- AIDS
severity II- AIDS severity Ill-death). The transition probabilities between the different stages as well as the mean duration of the hospitalisation at each stage
were calculated. Covariables like CD4-cell count, CDC classification (1993), age,
gender, prophylaxis and antiretroviral treatment were analysed.
Results: During the 13 year observation period AIDS-defining events of
severity III (i.e. CMV) became the major reason for hospitalisation, whereas
events of severity II (i.e. PcP) decreased significantly (p < 0.05) since
antiretroviral therapy with two or more compounds became more usual. Time
to disease progression has constantly increased, duration and number of
episodes/year of hospitalisation within the first two years after the primary contact
declined significantly (p < 0.05). Patients with antiretroviral combination therapy
had longer intervals without any hospitalisation compared to individuals with no
or later onset of intensified treatment.
Conclusion: Longitudinal observation is a valuable tool to describe changing
patterns of AIDS-associated diseases. Antiretroviral combination therapy revealed
a significant influence on clinical outcome and survival. Our results suggest selective initiation of prophylaxis against opportunistic manifestations and clinical
monitoring depending upon the changed risks to ensure maximum benefit and
life quality.
1 12118 | Plasma zinc, copper, and mortality in HIV-1 infected
homosexual men
Hong Lai, Shenghan Lai, G. Shor-Posner, M.K. Baum. University of Miami,
Room 1022, 1400 NW 10th Ave, Miami, FL, USA
Objective: To investigate the association between plasma zinc, copper, and
mortality among HIV-infected homosexual men.
Design: Observational cohort study.
Methods: HIV-1 infected homosexual men (n = 121) were followed between
May 1987 and April 1991 in Miami, Florida, USA. Measurements including blood
samples for nutritional and immnological evaluation were taken at baseline and

then at semiannual visits. Zinc and copper deficiency were defined as plasma zinc
<75 /lg/dl and plasma copper <85 p g/dl, respectively. HIV-1 related deaths were
confirmed by review of death certificates. Cox's proportional hazards regression
models with time-dependent covariates were used to estimate the relative risks
of plasma zinc and copper on HIV-1 mortality.
Results: Over the average course of the 3.3-year follow-up, 19 participants
(16%) died of HIV-1-related causes. After adjustment for potential confounders