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

Objective: We analyzed virologic response and safety data from six recent clinical studies conducted in anti retroviral-naive 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 (Cl) 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 (Cl) 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-naive subjects regardless of baseline viral load. The pooled virologic response for ABC/3TC in our analysis is higher than the A5202 estimate.