A phase II safety and efficacy study of amprenavir in combination with zidovudine and lamivudine in HIV-infected patients with limited antiretroviralexperience

Objective: To determine the safety and efficacy of amprenavir (APV) in comb ination with lamivudine (3TC) and zidovudine (ZDV). Design: Multicenter, randomized, partially blinded trial. Setting: Nine study sites in the United States and Europe. Patients: A group of 84 HIV-infected subjects with no prior 3TC or protease inhibitor therapy experience, CD4 cell count greater than or equal to 150 x 10(6) cells/l, and plasma HIV RNA > 10 000 copies/ml. Interventions: 3TC/ZDV with one of three doses of APV (900, 1050, or 1200 m g) versus 3TC/ZDV with 1050 mg placebo. All medications were dosed twice da ily. The 1050 mg placebo and the APV 1050 mg dose were administered blinded . After 12 weeks, APV 1050 mg was substituted for 1050 mg placebo in the co ntrol group and the blind was maintained. Main outcome measures: Reduction in plasma HIV RNA from baseline; proportio n of subjects with plasma HIV RNA < 400 copies/ml; and an increase in CD4 c ell count from baseline. Results: During the initial 12-week study period, APV/3TC/ZDV-treated subje cts had greater viral suppression than the group receiving two nucleosides. By 48 weeks, 89% of subjects in the group taking the highest APV dose (120 0 mg) had plasma HIV RNA < 400 copies/ml while 42% of the 900 mg group and 60% of the 3TC/ZDV group (1050 mg APV added at week 12) had plasma HIV RNA < 400 copies/ml using an as-treated analysis. By 60 weeks, 86% of subjects in the APV 1200 mg group had plasma HIV RNA < 400 copies/ml in the as-treat ed analysis, while 25% (900 mg), 43% (1050 mg), and 20% (1200 mg) of subjec ts had viral load <400 copies/ml in a strict intent-to-treat analysis owing to treatment discontinuations. Median CD4 cell count increases at week 60 were highest for the three treatment groups who received APV throughout the study, by intent-to-treat and as-treated analyses. The most common adverse events considered to be possibly drug related were nausea, rash, oral pare sthesia, diarrhea, and fatigue. Conclusions: Treatment with APV, dosed at 1200 mg twice daily in combinatio n with 3TC/ZDV, resulted in sustained viral suppression. This combination r epresents a potent alternative initial antiretroviral regimen for protease inhibitor-naive individuals. (C) 1999 Lippincott Williams & Wilkins.