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Indinavir (IDV), Nevirapine (NVP), Stavudine (d4T) and Lamivudine (3TC) for Amprenavir (APV)-Experienced Subjects—ACTG 373 R. M. GULICK*1, L. SMEATON2, R. T. D'AQUILA3, J. J. ERON4, J. S. CURRIER5, V. DEGRUTTOLA2, J. G. GERBER6, J. P. SOMMADOSSI7, R. TUNG8, D. R. KURITZKES6, R. L. MURPHY9, and The ACTG 373 Team.
1Cornell Univ., NY; 2Harvard Sch. of Publ. Hlth., Boston, MA; 3Massachusetts Gen. Hosp., Boston; 4Univ. of North Carolina at Chapel Hill; 5Univ. of California at Los Angeles; 6Univ. of Colorado, Denver; 7Univ. of Alabama, Birmingham; 8Vertex Pharmaceuticals, Cambridge, MA; and 9Northwestern Univ., Chicago, IL Background: The optimal sequencing of protease inhibitor-containing regimens is not clear.
Objectives: To describe the safety, toxicity and virologic activity of a four drug antiretroviral regimen in protease inhibitor-experienced subjects.
Design: Prospective, open-label study of HIV+, APV-experienced subjects who changed treatment to a four drug regimen of IDV 1000 mg q8h + NVP 200 mg bid + d4T 40 mg bid + 3TC 150 mg bid. Primary endpoints were safety, toxicity, HIV RNA levels and CD4 cell counts at 16 and 48 weeks of study.
Results: 56 subjects were studied on the four drug regimen, including 52 (93%) men and 4 (7%) women who were 48% white, 27% black, and 25% Hispanic and had a median age of 38 years. Prior to the current study, 36 (64%) were taking APV monotherapy; 18 (32%) were taking APV, 3TC and zidovudine; and 2 (4%) were taking other APV-containing regimens on other studies. At baseline, median HIV RNA was 15,488 (4.19 log10) copies/ml (5 subjects had HIV RNA <500 copies/ml) and median CD4 cell count was 346/mm3. 8 (14%) subjects discontinued the study prematurely (4 withdrew consent, 4 lost to follow-up) and a total of 22 (39%) discontinued at least one of the study medications early (including 6 subjects for virologic failure, 5 for toxicity, and 4 for noncompliance). 11 (20%) subjects experienced severe or greater intensity (>grade III) signs/symptoms. The proportions of subjects with HIV RNA <500 copies/ml were 73% and 59% (intent to treat, missing=failure) and 86% and 78% (as treated) at weeks 16 and 48, respectively. Subjects who took APV monotherapy prior to study entry had a higher rate of virologic suppression (p<0.01) than other subjects. CD4 cell counts increased +74 cells/mm3 (week 16) and +94 cells/mm3 (week 48) over baseline levels.
Conclusions: The majority of APV-experienced subjects who changed to a 4 drug regimen of IDV + NVP + d4T + 3TC suppressed plasma viremia for up to 48 weeks.
Key Words: amprenavir, clinical trial, salvage therapy
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