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

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.