Virologic Response and Safety of the Abacavir/Lamivudine Fixed-Dose Formulation as Part of Highly Active Antiretroviral Therapy: Analyses of Six Clinical Studies

Abstract

Objective: We analyzed virologic response and safety data from six recent clinical studies conducted in antiretroviral-naïve subjects treated with ABC/3TC or its components to assess the impact of baseline viral load on efficacy and safety endpoints used in the ACTG5202 protocol. Methods: Primary endpoints were time to virologic failure (confirmed HIV-1 RNA ⩾1,000 copies/mL at 16–24 weeks or ⩾200 copies/mL at ⩾24 weeks) and time to first grade 3 or 4 adverse event or laboratory abnormality that was at least one grade higher than at baseline. The survival distributions of both endpoints were estimated using the Kaplan-Meier method overall and by baseline viral load (<100,000 vs. ⩾100,000 copies/mL). A weighted mean of the virologic response and 95% confidence intervals (CI) were calculated by inverse-variance weighting for baseline viral load ⩾100,000 copies/mL across studies. Results: For subjects with baseline HIV-1 RNA ⩾100,000 copies/mL, the rate of virologic survival ranged from 87% to 95% by 48 weeks. Few subjects treated with ABC/3TC developed grade 3 or 4 adverse events, laboratory toxicities, or changes in lipid levels. The weighted mean (CI) for the pooled virologic response was 91% (87%–96%). Conclusion: Based on the A5202 endpoints, ABC/3TC-containing regimens in this analysis had a high rate of virologic survival and were generally well tolerated in antiretroviral-naïve subjects regardless of baseline viral load. The pooled virologic response for ABC/3TC in our analysis is higher than the A5202 estimate.

Keywords:

• abacavir/lamivudine
• efficacy
• safety
• virologic survival