Antiretroviral activity and safety of abacavir in combination with selected HIV-1 protease inhibitors in therapy-naive HIV-1-infected adults

Abstract

Objective: To assess antiretroviral efficacy and safety of abacavir in combination with selected HIV-1 protease inhibitors. Design: A 48-week, open-label study. Materials and methods: Eighty-two antiretroviral naive HIV-1-infected adults (CD4 cell count ≥100 cells/mm3, plasma HIV-1 RNA ≥5000 copies/ml) were randomly assigned to receive abacavir (300 mg twice daily) in combination with standard doses of one of five protease inhibitors: indinavir, saquinavir soft-gel, ritonavir, nelfinavir or amprenavir. Adults who met protocol-defined switch criteria at or after week 8 could modify their randomized therapy. Antiretroviral activity was assessed by the proportion of subjects with plasma HIV-1 RNA ≤400 and ≤50 copies/ml, and by changes in plasma HIV-1 RNA levels and CD4 cell counts. Safety was assessed by monitoring clinical adverse events and laboratory abnormalities. Results: At week 48, the proportion of subjects in the indinavir, saquinavir, ritonavir, nelfinavir and amprenavir groups with plasma HIV-1 RNA ≤400 copies/ml was 53, 50, 50, 41 and 56%, respectively, and the proportion with HIV-1 RNA ≤50 copies/ml was 47, 56, 50, 47, and 44%, respectively (by intent-to-treat analysis). Median reductions from baseline in plasma HIV-1 RNA for each group ranged from 1.7 to 2.4 log10 copies/ml. The median CD4 cell count increase from baseline was 195, 131, 116, 136 and 259 cells/mm3 in the indinavir, saquinavir, ritonavir, nelfinavir, and amprenavir groups, respectively. Overall, the most common adverse events attributed to study drugs were diarrhoea, nausea, malaise/fatigue, headache and perioral paresthesia. The frequency of treatment-limiting adverse events did not differ between groups. Conclusions: Abacavir is safe and effective when used in combination with a protease inhibitor.