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

12th World AIDS Conference

Abstracts 12282-12286 69

1 12282 Factors associated with progression to a new AIDS
defining event or death in patients receiving a protease
inhibitor
Sophie Grabar, D. Costagliola. INSERM SCG Faculte De Medicine S'Antoine 27
Rue Chaligny 75571 Paris Cedex 112; Clinical Epidemiology Group From Cisim,
France
Objectives: To determine factors associated with progression to a new AIDS
defining event (ADE) or death in patients with triple therapy including a Protease
Inhibitor (PI).
Methods: From the French Clinical Epidemiology Database on HIV-seropositive subjects followed in hospitals, data of patients that used for the first time a
triple therapy including a protease inhibitor (PI) were analysed. The study was
restricted to adults who had at least one follow-up after PI, who had never taken
any Non Nucleoside Reverse Transcriptase Inhibitor (NNRTI) prior to triple therapy (N = 260) and whose first PI was not nelfinavir (N = 11). Multivariate analyses
using Cox model were performed for time to the first ADE or to death whichever
occurred first. The main variable of interest was the first PI prescribed. Models
were adjusted on log2 (CD4), AIDS status, sex, associated NRTI, transmission
group, age at initiation of PI and stratified on hospital centres and on starting periods. Separated analyses were performed for AntiRetroviral Therapy (ART)-naive
patients and for pretreated patients.
Results: The analyses involved 1529 (16.7%) ART-naive patients and 7537
(83.3%) pretreated. The median duration of follow-up was 6.6 months for ARTnaive and 9.3 months for pretreated. First prescribed PI was for ART-naive
patients: Indinavir (66.7%), Saquinavir (23.7%) and Ritonavir (19.9%) and for
pretreated respectively 56.4%, 23.7%, 19.9%. After controlling on confounding
factors, AIDS status and CD4 count were highly significant in the 2 groups. In
pretreated patients, homosexuals were found at higher risk of developing new
clinical events than injecting drug users (relative risk RR = 0.7 IC95% = 0.6-0.8)
or heterosexuals patients (RR = 0.8 IC95% = 0.7-0.9). Saquinavir was associated
with lower risk than Indinavir (RR = 0.7 IC95% = 0.6-0.9) in pretreated patients.
In ART-naive patients, no difference between PI were evidenced although results
showed a tendency to lower risk with Saquinavir versus Indinavir (RR = 0.6 IC95%
= 0.3-1.0). The NRTI associated with PI were not significant in both groups.
Conclusion: Although in clinical trials Indinavir had shown better effect than
Saquinavir on biological markers such as viral load, in this observational study
with a limited follow-up, this tendency was not evidenced for clinical events.
S12283 Effect of dose escalation on the safety, tolerability and
efficacy of ritonavir
Geertrui van Hove1, Jose Ramon Arribas2, A. Lazzarin3, T. Martin4, M. Moroni3,
G. Vanhove1, C. MacLeod'. The collaborative group on Ritonavir Dose
Escalation (CGRDE). Multinational; 1ABBOTT Laboratories, 200 ABBOTT Park
RD ABBOTT Park IL 60064, USA; 2Hospital La Paz, Madrid; 4Clinica Puerta De
Hierro, Madrid, Spain; 3University of Milan, Milan, Italy
Introduction: Transient adverse events (AEs) frequently occur at the start of
ritonavir (RTV) therapy, possibly related to high RTV plasma levels when initiated at 600 mg BID. Because RTV induces its own metabolism, plasma levels
decrease, reaching steady state after 14 days. Dose escalation may help avoid
high initial RTV plasma levels, reducing transient AEs.
Objective: To investigate the safety, tolerability and efficacy of two schemes of
RTV dose escalation.
Design: Phase IV, randomized, open-label, multicenter, multinational study.
Methods: One hundred HIV-infected, protease-inhibitor naive adults were assigned to 2 arms. In Arm A, RTV was initiated at 300 mg BID for 2 days, increased
by 100 mg BID every 2 days until reaching 600 mg BID at Day 7; in Arm B, RTV
was initiated at 300 mg BID for 2 days, increased to 400 mg BID for 4 days, 500
mg BID for 8 days, and 600 mg BID at Day 14. RTV is given in combination with
2 nucleoside analogues. Duration of treatment is 24 weeks.
Results: The following are safety results obtained for 79 patients enrolled at
the time of analysis:
Arm A (n = 39) Arm B (n = 40)
Nausea 19 (49%) 12 (30%)
Vomiting 7 (18%) 5 (12.5%)
Circumoral Paresthesia 26 (67%) 13(33%)
Diarrhea 17 (44%) 24 (60%)
Patient discontinuation for Aes 15 (38%) 9 (23%)
Using a Wilcoxon two-sample test, both arms showed no differences in median
CD4+ cell counts (cells/Il) at baseline (226 and 251 for Arms A and B, respectively) and Week 4 (288 and 357), and no differences in median HIV RNA levels
(log1o copies/ml) at baseline (4.6 and 4.8 for Arms A and B, respectively), Week
4 (2.7 and 3.1) and Week 24 (3.1 and 3.0).
Conclusion: RTV 600 mg BID seems to be better tolerated after an initial
dose-escalation of 14 days rather than 7 days, with similar efficacy. Updated

results will be presented.

12284 1 HIV RNA load in blood and seminal plasma of patients
receiving antiretroviral therapy with protease inhibitors
Emmanuel Dulioust', Anne Tachet des Combes2, L. Finkielsztejn3, M. de
Almeida3, D. Salmon-Ceron3, P. Jouannet3, C. Rouzioux2, D. Sicard3. 1Biologie
de la Reproduction, Hopital Cochin, Paris; 2Hospital Necker. Paris; 3Hospital
Cochin, Paris, France
Objective: To assess the effect of treatments including protease inhibitors (PI) on
HIV-RNA load in seminal plasma, and to compare it with the evolution of plasma
HIV-RNA load.
Subjects: patients beginning their first therapy by PI, irrespective to their
previous treatments and to the other anti-retroviral drugs associated.
Methods: HIV-RNA was quantified (kit Roche, silica extraction, detection
threshold: 20-500 copies/ml) on paired seminal (SP) and blood (BP) plasma
samples collected before the onset of PI (JO) and after one (M1), three (M3) and
six (M6) months of treatment.
Results: 25 men (median CD4+ cell count: 272/mm3, range: 1-781) were
enrolled in the study. 15 (60%) of them had never received antiretroviral drugs
before. 12 (48%) presented with AIDS symptoms.
The main results are summarized in the following table:
HIV-RNA (log cop/mi) JO M1 M3 M6
No. of samples n = 25 n = 22 n =19 n =13
BP Median (range) 4.9 (3.3-6.3) 2.65 (<2.1-3.7) 2.4 (<2-4.6) 2.6 (<2.1-4.6)
Undetectable (%) 0/25 (0) 5/22 (23) 9/19 (47) 5/13 (38)
No. of samples n = 25 n = 20 n =16 n =12
SP Median (range) 3.7 (<2.1-6.5) 2.35 (<2.1-4.6) 2.3 (<1.7-4) 2.4 (<2.2-3.1)
Undetectable (%) 1/25 (4) 13/20 (65) 13/16 (81) 10/12 (83)
From JO to M1, HIV-RNA load decreased in almost all subjects both in BP (med:
2.1 log, range: 0-3.1) and in SP (med: 1.1 log, range: >0.1->2.2). Between M1
and M6, 7/12 men showed a general tendancy to undetectable level of HIV-RNA
in both blood plasma and seminal plasma.
Conclusion: These results indicate that treatments with PI can reduce HIVRNA load in seminal plasma as efficiently (rapid and dramatic decrease) as in
blood plasma. HIV-DNA quantification in PBMC and semen non spermatozoal
cells is under study.
i12285 Salvage therapy with a combination including nelfinavir
in patients failing treatment including a protease inhibitor
(PI)
Sharon Walmsley, C. Walach, A. Moses, I. Salit, A. Humar, D. Fletcher.
University of Toronto, The Toront Hospital, ENG-222, 200 Elizabeth St. Toronto,
ON M5G2C4, Canada
Background: Despite the emergence of non-overlapping genotypic mutational
sites with antiretroviral therapy, data is emerging that treatment with one PI blunts
the response to a second PI containing combination.
Objective: To characterize the antiviral effect and predictors of antiviral response to nelfinavir based combinations among advanced HIV-infected patients
failing combination therapy which includes a PI.
Methods: All HIV positive subjects attending The Toronto Hospital Immunodeficiency Clinic from 04/97 to 12/97 who had detectable viral loads (VL), defined as
> 500 copies/ml (Chiron, bDNA), on a PI containing regime who were switched
to a new combination containing nelfinavir (750 mg po tid) were studied. Only
patients who had at least 4 weeks of follow-up were included in the analysis.
Results: The 56 patients (pts) were 95% male, 80% Caucasian, with a mean
age of 41 yr. At entry the mean plasma VL was 4.59 log copies/mi (range
3.20-5.75) and the mean CD4 was 115/mm3 (range < 10-389/mm3). The pts
were followed for a median of 12 weeks (range 4-36 weeks). During the study
period, 20 pts (36%) had a decrease in VL to levels <500 copies/ml, and an
additional 10 pts (18%) had partial VL suppression with a greater than 1 log
decrease. Twenty-six pts (46%) were non-responders with less than a 1 log
decrease in VL. On univariate analysis, no relationship could be found (p >.05)
between baseline VL, baseline CD4, previous PI, number of agents changed
in addition to nelfinavir, and complete viral suppression. Similarly none of these
parameters could distinguish those who had partial or complete suppression from
non-responders.
Conclusion: Of pts failing PI containing combinations, only 36% had viral
suppression <500 copies/ml and an additional 10% had at least a 1 log decrease
when started on a new combination containing nelfinavir. No pt factors could be
identified that would predict who would respond.
| 12286 Correlation between plasmatic levels of indinavir and
inmunologic and virologic parameters in HIV-patients
Anna Ochoa de Echaguen, David Dalmau Juanola, M. Xercauins, J. Vidal,
X. Martinez, C. Sanchez, X. Garau. Dr. Robert IV.5 Hospital Mutua de Terrassa,

Terrassa-Barcelona 08221, Spain
Objective: To evaluate the correlation between plasmatic levels for the HIV protease inhibitor indinavir and their intersubject variability with immunologic (CD4+
cell counts) and virologic (plasma HIV-1 RNA) parameters.
Methods: We prospectively evaluated 31 compliant HIV-1 infected patients
who were using indinavir (800 mg every 8 hours) as part of their antiretroviral
regimen during at least 24 weeks prior to the study. Plasma concentrations of