Amprenavir in combination with lamivudine and zidovudine versus lamivudine and zidovudine alone in HIV-1-infected antiretroviral-naive adults. Amprenavir PROAB3001 International Study Team.

Abstract

OBJECTIVES:

To compare the antiviral activity and safety of a new protease inhibitor, amprenavir (141W94) in combination with lamivudine and zidovudine, versus lamivudine and zidovudine alone in HIV-1 infected, antiretroviral-naive subjects.

DESIGN:

Subjects (n=232) with a CD4 T cell count of > or =200 cells/mm3, plasma HIV-1 RNA levels of > or =10000 copies/ml, and < or =4 weeks of prior nucleoside antiretroviral therapy, were stratified according to baseline plasma HIV-1 RNA level (10000-30000; 30000-100000; or >100000 copies/ml). Subjects received double-blind treatment with either 1200 mg amprenavir twice daily in combination with lamivudine (150 mg twice daily) and zidovudine (300 mg twice daily) (amprenavir/lamivudine/zidovudine) or matched placebo, lamivudine and zidovudine for 16 weeks. Thereafter, subjects with confirmed plasma HIV-1 RNA levels of > or =400 copies/ml could add open-label amprenavir or switch to other antiretrovirals and continue treatment for up to a minimum of 48 weeks. The primary endpoint of the study was defined as the proportion of subjects with plasma HIV-1 RNA of <400 copies/ml at 48 weeks.

RESULTS:

At 48 weeks, a significantly greater proportion of amprenavir/lamivudine/zidovudine subjects had plasma HIV-1 RNA levels <400 copies/ml than lamivudine/ zidovudine subjects in the overall population: 41 versus 3% (intent-to-treat missing equals failure analysis) (P<0.001); 93 versus 42% (as-treated analysis) (P<0.001); and within each of the three randomization strata (P<0.001). Subjects on amprenavir/lamivudine/zidovudine experienced longer time to event (permanent discontinuation of randomized therapy or viral rebound) than those on lamivudine/zidovudine (median of 33 versus 13 weeks; P<0.001). A significantly greater incidence of drug-related nausea, vomiting, rash and oral/perioral paresthesia was observed with amprenavir/lamivudine/zidovudine than with lamivudine/zidovudine.

CONCLUSIONS:

Amprenavir, in combination with lamivudine and zidovudine, has potent and durable antiviral activity in antiretroviral-naive subjects over 48 weeks. Amprenavir was safe and generally well tolerated.

• Authors: J C Goodgame, J C Pottage Jr, H Jablonowski, W D Hardy, A Stein, M Fischl, P Morrow, J Feinberg, C H Brothers, I Vafidis, P Nacci, J Yeo, L Pedneault
• Journal: Antiviral therapy (Antivir Ther) Vol. 5 Issue 3 Pg. 215-25 (Sep 2000) ISSN: 1359-6535 [Print] England
• PMID: 11075942 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Carbamates
• Furans
• RNA, Viral
• Reverse Transcriptase Inhibitors
• Sulfonamides
• Lamivudine
• Zidovudine
• amprenavir

Topics

• Adolescent
• Adult
• Anti-HIV Agents (therapeutic use)
• CD4 Lymphocyte Count
• Carbamates
• Drug Therapy, Combination
• Female
• Furans
• HIV Infections (drug therapy, virology)
• HIV-1 (physiology)
• Humans
• Lamivudine (therapeutic use)
• Male
• Middle Aged
• RNA, Viral (blood)
• Reverse Transcriptase Inhibitors (therapeutic use)
• Sulfonamides (therapeutic use)
• Zidovudine (therapeutic use)