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

12th World AIDS Conference

Abstracts 12273-12277 67

the Cox analyses, the risk of death, unadjusted for treatment, relative to SE was
0.64 (95% Cl: 0.54-0.76, p < 0.0001) in CE and 0.91 (95% CI: 0.78-1.06, p =
0.22) in NE. After adjusting for all treatment, the risk of death in CE relative to SE
became non-significant (relative risk 0.91, 95% CI: 0.75-1.09). The Kaplan-Meier
analysis showed a significantly (p = 0.0031) lower death rate in CE after the CD4
count fell below 200 cells/mm3.
Conclusions: In this analysis, HIV mortality rates in Central Europe seem to be
significantly lower than in both Northern and Southern Europe. This result may be
explained by the earlier access to PI treatment and the greater proportion of HIV
patients in Central Europe who received it. The issue of the correlation between
PI treatment and the steady fall in mortality rates in Europe since 1995 has been
addressed in another paper of the EuroSIDA Study Group, "Reduced mortality
across Europe in patients infected with HIV", presented at this Conference.
112273 Preliminary comparison of outcome in patients starting
either ritonavir (R), Indinavir or saquinavir (S) in 1749
patients from the EuroSIDA study
Ole Kirk. Coord. Cent. Eurosida, Dept. Inf. Dis. 144 Hvidoure Univ. Hospital,
2650 Hvidoure, Denmark
Objectives: To compare the outcome associated with the initiation of different
protease inhibitors (PI).
Design: Since May 1994, the EuroSIDA study (cohort I and II) has prospectively
followed unselected patients with a baseline CD4 count <500 from 50 centres in
17 European countries (total n = 4491). The most recent follow-up was performed
in the summer of 1997.
Methods: Follow-up was measured from the date of first exposure to a PI.
Comparisons of baseline variables were performed, as were comparisons of outcome (mortality or 'progression to a new AIDS defining event or death') depending
on which PI the patient was started on, using Kaplan-Meier plots and Cox models.
Results: In 1749 patients starting PI-therapy (n = 384 for R; n = 826 for I; n =
539 for S), the median CD4 count around the time of starting therapy was 125
cells/mm3, 45% had AIDS, and 95% were previously exposed to one or more
nucleoside analogues. The viral load was available in a subset of patients (median
logo1 = 3.9, n = 586). The median time of starting a PI was September 1996.
During a median of 8 months of follow-up, 28% switched the initial PI, and 214
had disease progression of which 105 died. There were no differences in outcome
(disease progression nor mortality) depending on which PI the patient was started
on. In a multivariate Cox model (adjusted for other available prognostic markers),
compared with R, the relative risk of any disease progression for patients starting
on I was 0.95 (95% Cl: 0.62-1.45) and for S 1.26 (0.81-1.94).
Conclusions: Based on observational data in this large cohort of European
patients, there were no differences in disease progression according to which PI
a patient started; however, follow-up was limited at 8 months. Updated analysis
with more extensive follow-up will be available for presentation.
291*/12274 Treatment of ritonavir (RTV)/saquinavir (SQV)
versus RTV/SQV/stavudine (d4T) (the Prometheus
study): Preliminary results
Elisabeth H. Gisolf1, F. de Wolf', J. Pelgrom2, F. van Wanzeele3, M. Popescu4,
A. Japour5, S.A. Danner1, R. van Leeuwen6. 1Natec, AMC, Meibergdreef 9 1105
AZ Amsterdam; 6National AIDS Therapy Evaluation Center, Amsterdam,
Netherlands; 2lnstitute of Tropical Medicine, Antwerp; 3University Hospital Gent,
Gent, Belgium; 4F Hoffmann-La Roche Ltd. Basel, Switserland; 5Abbott Antiviral
Venture Chicago, USA
Background: Antiretroviral therapy combining RTV and SQV is attractive with
regard to the pharmacokinetic interaction and convenient bid dosing. It is not
known whether immediate addition of a nucleoside analogue reverse transcriptase inhibitor (NRTI) provides additional antiretroviral effect or difference in safety
as compared to dual protease inhibitors (PIs) with intensification for those patients
who did not reach viral load <400 copies/mL after 18 weeks.
Methods: The study is an open label, multi-center, randomized trial in the
Netherlands and Belgium. PI - and d4T-naive HIV-1-infected patients were assigned to RTV (400 mgbid)/SQV (400 mgbid) or RTV/SQV/d4T (40 mgbid). In
patients with a viral load >400 copies/mL at week 18, intensification with NRTIs
was allowed.
Results: 208 patients are enrolled, 111 completed 24 weeks. Mean baseline viral load is 4.3 log copies/mL (SD 0.8 log), mean baseline CD4 260/mm3 (SD175),
50% of patients is pretreated with NRTIs. After 24 weeks of treatment CD4 cells
increase with a mean of 145 cells/mm3 in both treatment arms. Serum HIV-RNA
became <400 copies/mL in 64% of patients on RTV/SQV and in 87% of patients
on RTV/SQV/d4T after 24 weeks. Of 6 patients in the RTV/SQV arm viral load
data after intensification with d4T/3TC are available: all 6 reach undetectable
serum HIV-RNA levels by week 36. Of the first 105 patients evaluated for 18
weeks, seven patients (8%) discontinued study medication permanently because
of clinical (4) or laboratory toxicity (3).
Conclusions: RTV/SQV +/- d4T increases CD4 cell count with 145 cells/mm3

after 24 weeks. It remains uncertain whether there is any difference in virologic
response on the long term with immediate triple versus dual protease inhibitors
with intensification for those patients who need additional drugs. RTV/SQV +/d4T is well tolerated.

12275 Stavudine (d4T), nelfinavir (NFV) and nevirapine (NVP):
Suppression of HIV-1 RNA to fewer than 50 copies/ml
during 5 months of therapy
Gail Skowron', G. Leoung2, B. Yen-Lie Berman3, A. Dusek4, R. Anderson5,
R. Grosso6, S. Beebe4. 1Roger Williams Hosp/Brown University, 825 Chalkstone
Avenue, Providence Rhode Island 02908; 2HIV Care, San Francisco, CA;
3Cleveland Clinic Foundation, Cleveland, OH; 4Boehringer-lngelheim
Phrmaceuticals, Inc., Ridgefield, CT; 5Agouron Pharmaceuticals, Inc., La Jolla,
CA; 6Bristol-Myers Squibb Company, Wallingford, CT USA
Objectives: To assess the ability of the combination of d4T, NFV and NVP (dNN)
to suppress HIV-1 viral load to fewer than 50 copies/ml during 5 months of therapy.
Design: Open label extension study after a 5 week pharmacokinetic (PK)
interaction and safety study.
Methods: Entry criteria for the initial PK study included: no prior NNRTI or
protease inhibitor therapy; <6 months prior d4T therapy; HIV-1 RNA by PCR a
5,000 copies/ml; CD4 cell count >100 cells//1l. d4T (30-40 mg BID) and NFV
(750 mg TID) were initiated on day 0; NVP was added on day 8 at 200 mg
QD, increasing to 200 mg BID after 14 days. Standard Amplicor HIV-1 RNA
PCR assays (cut-off 400 copies/ml) were performed monthly, and Ultrasensitive
Amplicor HIV-1 RNA PCR assays (cut-off 50 copies/ml) were performed at day
36, week 13 and week 21.
Results: 22 of 25 patients (pts) completed the initial 5 week PK portion of
the dNN study; no PK interaction was demonstrated. 20 pts continued into the
extension study. As of 1/98, 17 pts continue in the extension study, with a median
time on study of 17 weeks (range 9-29); three pts withdrew for reasons other
than adverse events. During the extension phase, the proportion of pts with <400
copies/ml were: day 36: 15/20 (75%), wk 13: 15/17 (88%), wk 21: 8/9 (89%). Of
those pts with <400 copies/ml for whom ultrasensitive assay data is available, the
proportion of pts with <50 copies/ml were: day 36: 3/13 (23%), wk 13: 9/12 (75%),
wk 21: 6/6 (100%). No pt achieving viral load suppression to <50 copies/ml has
rebounded to >50 copies/ml.
Conclusions: d4T/nelfinavir/nevirapine triple therapy rapidly suppressed HIV-1
plasma viral load, as measured by a standard RNA PCR assay that is sensitive
to <400 copies/ml. Complete and sustained reductions in viral load, using an
ultrasensitive assay (<50 copies/ml), were observed after prolonged treatment.
No pt achieving viral load suppression to <50 copies/ml has rebounded.
112276 Impact of HAART in a cohort of patients from the Basque
country (Spain)
Jose Antonio Iribarren, Francisco Rodriguez-Arrondo, I. Arrizabalaga, MA. Von
Wichmann, X. Camino. Infections Disease Unit. Hospital Aranzazu San
Sebastian, 20014 (Guipauzcoa), Spain
Objectives: To evaluate the changes due to the implementation of HAART in
overall and short-term mortality from AIDS, new cases of AIDS, hospital admissions, average stay and outpatient care in patients attended to in our hospital.
Methods: From a cohort of 1175 HIV- infected patients in 1996 (440 with
AIDS at 1/1/96), and 1265 (387 with AIDS at 1/1/1997), controlled in our Unit,
we compare between two periods: Period A (from 1-1-96 to 1-11-96) and Period
B (from 1-1-97 to 1-11-97) the following information: Number of patients (Pt)
with antiretroviral therapy, Pt. in HAART, number of new patients with AIDS
(PWA), overall and short-term mortality -in six months after AIDS diagnosis- in
PWA, HIV-related hospital admissions, average of inpatient stay, and number of
outpatient visits. The differences were assessed using Students' t with IC = 95%
or chi square, depending on the nature of the variable.
Results:
Period A Period B
Pts. in ARTV 246 (1-6-96) 564 (1-11-97)
HIV-related admiss. 662 367 (-44.6%)
Pts. in HAART 8(1-6-96) 355 (1-11-97)
New AIDS 88 55 (-37.5%)
No. of deaths 120 43 (-64.2%)
Average stay 10.4 8.7 (-15%)
Short-term deaths 25 2
Outpatient visits 3308 4414 (+33.4%)
p < 0.01; Total admissions in the Unit of Infectoius Diseases: 670 in period A, 476 in period
B Only 16/55 with periodical controls (22, HIV status unknown at presentation).
Conclusions: The progressive implementation of HAART, following international recommendations: 1. Has decreased mortality from AIDS in 64%. 2. Has
diminished new cases of AIDS in 37%. 3. Has decreased admissions for HIVrelated conditions in 45%. 4. Has increased the number of outpatients visits in
33%. This implies a dramatic change in the quality of life of the patients and in
the distribution of the resources needed for their care.

12277 Importance of molecular flexibility for the resistance of
HIV-1 protease inhibitors
Ryohei Kato1, K. Yusa1, S.V. Gulnik1, T. Bhat1, H. Hayashi2, H. Mitsuya1,
J.W. Erickson1. NCI-FCR DC. PB. Box B, Bldg. 322 Frederick, MD 21702,
USA; 2Japan Energy Corporation, Tokyo, Japan
Background: A major obstacle to antiviral therapy for HIV is the emergence of
drug resistance. JE-2147 (KNI-764) is a novel inhibitor of HIV-1 protease that