HIV AIDS News [International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

Indinavir with stavudine vs. IDV alone vs. stavudine alone in zidovudine experienced, HIVinfected patients (MSD protocol 037) [Abstract #12335]
12th World AIDS Conference
June 28 - July 3, 1998
Geneva, Switzerland
Roy T. Steigbigel, D. Cooper, N. Clumeck, K. Ghosh, B.-Y. Nguyen
Merck Protocol 037 Study Group; Division of Infectious Diseases; HSC Suny SB Stony Brook NY
11794-8153; Merck Research Laboratories, West Point PA, USA St. Vincent Medical Centre,
Darlinghurst, Australia Hopital St Pierre, Brussels, Belgium
Background: This study was designed and implemented when the potential advantage of
combination therapy for HIV was unknown. To determine the utility of combination therapy
with a potent protease inhibitor and reverse transcriptase inhibitor, we compared the effects on
CD4 cells, vRNA, and safety of a) Indinavir (IDV) alone to Stavudine (d4T) alone and of b)
concomitant therapy with IDV and d4T to IDV alone and to d4T alone. Methods: A multiclinic,
international, double-blind, randomized, one year study. HIV-1 seropositive, zidovudine
(ZDV) experienced patients (pts) with CD4 counts between 50-500 cells/mm^{3} were
randomized to either Group 1: IDV 800 mg q8h plus d4T 30 or 40 mg q12h; OR Group 2: IDV
800 mg q8h plus matching placebo to d4T; OR Group 3: d4T 30 or 40 mg q12h plus matching
placebo to IDV. Efficacy, as measured by CD4 counts and serum vRNA; and safety, as assessed
by physical examination and laboratory tests of blood and urine, were evaluated every 2 weeks
(wks) for the first 4 wks and every 4 wks thereafter. Results: Preliminary data on the 613
randomized pts revealed that baseline median CD4 was 221, 202, and 208 cells/mm^A{3} for
group 1, 2, and 3, respectively; and baseline median vRNA was 4.44, 4.44, and 4.49 log10
copies/mL, respectively. At wk 52, the median change in CD4 was 144, 109, and 35
cells/mm^{3}, respectively. At wk 52, the proportion of pts with serum vRNA < 500 copies/mL
was 45.9%, 34.5%, 24.1%, respectively. All 3 treatment regimens were generally well tolerated
with only 3.9% (8/207 pts), 5.0% (10/202 pts), and 4.9% (10/204 pts) discontinuations due to an
adverse event from group 1, 2, and 3, respectively.
Conclusion: In ZDV experienced patients, preliminary data showed that IDV with d4T or IDV
monotherapy were associated with greater increases in CD4 cell counts and viral suppression
than those seen with d4T over 52 wks. The IDV and d4T combination showed the greatest
increase in CD4 and viral suppression. All three treatment regimens were generally well
tolerated. Detailed efficacy and safety data will be presented.