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

12th World AIDS Conference

Abstracts 12236-12240 59

ment of HIV-infection without notable adverse events. Complete data for each
treatment group will be available for presentation.
|12236 Retrospective analysis of protease inhibitor efficacy
among patients failing a delavirdine regimen
Michael Para, M. Weinstock. Ohio State University ACTU, 456 West Tenth Ave,
Room 4725, Columbus OH 43210, USA
Objective: To determine if patients who failed treatment with delavirdine and at
least one nucleoside reverse transcriptase inhibitor (NRTI) can achieve viral loads
<400 copies/mL (Amplicor) 6 months after switching to an antiretroviral regimen
containing a protease inhibitor and at least one new NRTI.
Design: Retrospective, chart review
Methods: Chart review of all patients involved in clinical trials containing
delavirdine (Upjohn #17, #21, #23 and ACTG #260, #261) at the Ohio State
University AIDS Clinical Trials Unit. Eligible patients had used delavirdine plus
1-2 NRTIs for at least 3 months, had a viral load which was greater than 400
copies/mL, and were then switched to an antiviral regimen containing at least one
new NRTI plus their initial protease inhibitor (PI). Viral load and CD4 count were
measured 6 months after the change.
Results: 103 charts were reviewed and 18 patients met the above criteria. The
median number of NRTI used with delavirdine was 2 (range 1-3). The median
number of months on NRTI and delavirdine was 19 (range 7-30). Prior to starting
the protease inhibitor containing regimen, the median CD4 count = 337 (range
30-662), median viral load was 38,331 (range 1,918-750,000) or 4.6 log 10. The
median number of new NRTIs in the protease containing regimen was 1 (range
1-2). After 6 months on the protease inhibitor containing regimen, median rise
in CD4 counts was 129 (range -106 to +697) and 14/18 (78%) of the patients
achieved a viral load <400 copies/mL. Of the 4 patients who did not achieve viral
load <400 copies/mL, 2 had more than a 2 log fall in their viral load.
Conclusions: A high percentage of patients initially treated with delavirdine
and NRTIs were able to achieve a viral load <400 copies/mL after switching to a
regimen containing a protease inhibitor and at least one new NRTI.
Supported in part by NIAID AI259424
132*/12237 A multicenter randomised study comparing
ritonavir and indinavir in 1251 previously treated
patients with CD4 below 50/mm3 (Italian ISS-IP1
Study Group)
Carlo Tomino, Stefano Vella, F.V. Fragola, R.D. Ricciardulli, S.A.C. Seeber,
G.G. Giannini, P.M.F. Pirillo, F.M. Floridia. Instituto Speriore Di Sanita'- Lab.
Virology, Viale Regina Elena, 299 - Rome, Italy
Objective: To compare ritonavir and indinavir in patients with CD4+ below 50/mm3
and previous antiretroviral experience, examining the tolerability of the two drugs
and clinical, virological and immunological aspects of response to treatment.
Design: Phase III, open, randomised multicenter trial. Concomitant use of
nucleoside analogues was allowed. Daily dosages of ritonavir and indinavir were
600 mg bid and 800 mg tid, respectively. Patients were enrolled in 80 hospital or
university clinical center. Study duration was 48 weeks. Relative risks (RR) were
estimated using the Cox proportional hazards model.
Results: 1339 patients were randomised and 1251 started treatment (ritonavir
630, indinavir 621). More than 60% had clinical AIDS before entry. Mean baseline
CD4 was 18.8/mm3 in the ritonavir and 19.2/mm3 in the indinavir group. The
results of preliminary analysis based on 19 weeks of mean follow up showed a
significantly higher risk of definitive treatment discontinuation with ritonavir (ritonavir/indinavir: 256/143, RR 1.9, CI 95% 1.736-2.137, p = 0.0001), and an overall
higher number of grade 3-4 or serious adverse events reported on treatment with
this drug (ritonavir/indinavir 317/223, RR 1.6, CI 95% 1,343-1,893, p = 0.0001),
but no significant differences in events leading to hospitalisation (ritonavir/indinavir
113/101, RR 1.2, CI 95% 0.887-1.517, p = 0.28), number of AIDS/death events
(ritonavir/indinavir 110/107, RR 1.1, CI 95% 0.870-1.441, p = 0.38) and deaths
(ritonavir/indinavir 30/30, RR of death 0.9, CI 95% 0.564-1.553, p = 0.80).
Conclusions: A higher risk of treatment discontinuation and an overall
higher number of grade 3-4 or serious adverse events was observed with
ritonavir, indicating a lower tolerability of this drug during a period of about
20 weeks of observation. No differences were however observed in events
leading to hospitalisation. During the same follow up, no differences in clinical outcomes were also observed between the two treatments. Final data,
based on 48-weeks results, including CD4 and RNA response, will be presented.
122381 An open randomized study comparing he influence of
different therapeutic strategies (no treatment vs double
therapy (ZDV/D4T+3TC) vs triple therapy (D4T + 3TC +
indinavir) in the progression of chronic HIV-1 infected
patients in very early stages (Spanish Early Antiretroviral

Therapy in HIV: Spanish EARTH-2 Study)
F. Garcia, J. Romeu, I. Grau, M.A. Sambeat, D. Dalmau, H. Knobel, J.M. Gatell,
J.M. Miro. For the Spanish EARTH Study Co-ordinating Committee, Spain
Background: The objective was to test whether maintaining a pre-established
viral load (VL) reduction can delay progression in asymptomatic HIV-1 infected
patients with CD4+T cell count -500 x 106/L and viral load >5000 copies/ml.

End points were evolution to <500 CD4+ plus 2 symptoms of the category B,
<350 CD4+, category C or death.
Methods: Patients were randomly assigned to no treatment (N = 16), ZDV
plus 3TC (N = 29), d4T plus 3TC (N = 30), d4t plus 3TC plus Indinavir (N = 39).
Recruitment of the control group was discontinued when the preliminary analysis
of a similar study (Spanish EARTH-1) showed a worse outcome compared to all
treatment arms. VL was measured at baseline at 1/2, 1,2 and 4 months and every
4 months thereafter. Active treatment could be modified whenever necessary to
maintain the targeted viral load reduction (<1500 copies/ml in double therapy
groups and <200 copies/ml in triple therapy group). VL was also measured after
1/2 month and one month after every change in the therapeutic strategy.
Results: After 16 weeks of follow-up the virological response was:
(n) Peak mean <200 copies/ml
reduction 2 mo n % 4 mo n %

1. Controls
2. ZDV+3TC
3. D4T+3TC
4. D4T+3TC+indinavir
P

(16)
(29)
(30)
(39)

-0.53
-2.1
-1.88
-1.86

(15)
(24)
(20)
0.67

8 53 (12)
12 50 (14)
14 70 (17)
0.002

33
71
94

Within brackets are number of patients at risk
No patients progressed to study end-points. Pre-established viral load reduction
was maintained in all the patients.
Conclusions: At 16 weeks of follow-up the proportion of patients with an undetectable level of viral load (<200 copies/ml) was significantly higher in patients
on triple therapy than in patients with double therapy in individuals with CD4+ T
cell count >500 x 106/L and viral load >5000 copies/ml. Longer follow-up, and
VL measurements with an ultrasensible assay will be presented.
12239| Stavudine-didanosine-nevirapine: A convenient highly
active triple combination for first line antiretroviral
therapy
Francois Raffil, V. Reliquet2, C. Francois2, M. Garrel, C. Hascoet1,
C. Allavena2, C. Arvieux1. 2Cisih hotel-Dieu, Nantes, France
Background: Although triple drug combination therapy with 2 nucleoside analogues and a protease inhibitor (PI) produces reduction in HIV viral load to
undetectable plasma levels in >80% of subjects, drawbacks of this regimen are
numerous including pills number, side effects, compliance issue, emergence of
resistant virus with cross-resistance to other Pis. New highly active antiretroviral
regimens more convenient and leaving open options for second-line therapy are
needed.
Objective: To evaluate the virological and immunological effect of triple therapy
with stavudine (40 mg bid if >60 kg, 30 mg bid if <60 kg)/didanosine (400 mg qd
if >60 kg, 300 mg qd if <60 kg)/nevirapine (200 mg/day from Day 1 to 14 then
200 mg bid).
Design/Methods: VIRGO trial is a prospective, multicenter open-label study
in 60 antiretroviral naive HIV-infected adults with a CD4 cell count >200/1pL
and plasma HIV-RNA > 5,000 copies/ml. Immunologic (CD4/CD8 cell counts,
T-cell subtyping, memory and naive T cells) and virologic (HIV-RNA, genotyping
including 181 mutation) markers are measured at regular intervals, for 52 weeks.
Results: At present, 35 patients have started the trial regimen. Characteristics
of patients at baseline were as follow: 26 male/9 female, CDC stage A: 63%, mean
CD4 cell count: 437/1tL, mean HIV-RNA: 89,155 copies/ml (4.5 logio copies/ml).
Mean decrease of viral load was - 2.0 loglo at week 4 (n = 24), - 2.2 loglo at week
8 (n = 4) with HIV-RNA under detectable level (<500 copies/ml) in 67% of patients
at week 4 and 3/4 at week 8. Mean CD4 cell count increase was + 158 at week
4. Cutaneous intolerance occurred within the first 4 weeks in 8/30 (27%) patients
after a mean of 12 days (range 3-25) and led to nevirapine discontinuation in 2/8.
Updated immunological and virological efficacy and additional safety data will
be presented.
Conclusion: Combination therapy with stavudine/didanosine/nevirapine is a
convenient triple therapy regimen with rapid immunologic and antiviral effect.
Cutaneous intolerance, frequent in the first weeks of therapy, can be usually
managed without stopping nevirapine. Long-term suppression of plasma HIV
RNA with this combination needs to be confirmed but could legitimate nevirapine
as a component of first-line anti-HIV regimen along with 2 nucleosides.
12240 Study HIV-NAT 001: A randomized double-blind,
comparative trial to evaluate the efficacy of combination
antiviral therapy with ZDV 200 mg TID plus ddC 0.75 mg
TID versus ZDV 100 mg TID plus ddC 0.375 mg TID for the
treatment of HIV-1 infection in a Thai study population
Eugene Kroon1, M. Chuenyam1, R. Van Leeuwen2, W. Poolcharoen3, J. Lange2
D. Cooper4, P. Phanuphak5. 1HIV-NAT, TRCS 1871 Rama IV Road,
Chulalongkorn Hospital, Pratumwan Bangkok 10330; 3AIDS Division, Ministry of
Public Health, Bangkok; 5Program on AIDS, TRCS, Bangkok, Thailand;
2NATEC, Amsterdam, Netherlands; 4NCHECR, Sidney, Australia
Objectives: CD4+ cell and clinical outcomes of several phase II studies suggested that daily doses of AZT as low as 300 mg may be effective in suppressing
HIV-1 replication, but viral load data from these studies are not available. Since
AZT and ddC may potentiate one another, this study aimed to establish whether
the combination of these drugs in half the recommended doses may be as effec