Virologic response and safety of the abacavir/lamivudine fixed-dose formulation as part of highly active antiretroviral therapy: analyses of six clinical studies

HIV Clin Trials. 2009 Mar-Apr;10(2):65-75. doi: 10.1310/hct1002-65.

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 > or = 1,000 copies/mL at 16-24 weeks or > or = 200 copies/mL at > or = 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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / standards
  • Antiretroviral Therapy, Highly Active / methods
  • Antiretroviral Therapy, Highly Active / standards*
  • Carbamates / pharmacology
  • Clinical Trials as Topic
  • Dideoxynucleosides
  • Drug Combinations
  • Female
  • Furans
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • Humans
  • Lamivudine / pharmacology*
  • Lamivudine / standards
  • Lopinavir
  • Male
  • Middle Aged
  • Organophosphates / pharmacology
  • Pyrimidinones / pharmacology
  • RNA, Viral / blood
  • Randomized Controlled Trials as Topic
  • Sulfonamides / pharmacology
  • Survival Analysis
  • Viral Load
  • Young Adult

Substances

  • Anti-HIV Agents
  • Carbamates
  • Dideoxynucleosides
  • Drug Combinations
  • Furans
  • Organophosphates
  • Pyrimidinones
  • RNA, Viral
  • Sulfonamides
  • abacavir, lamivudine drug combination
  • Lopinavir
  • Lamivudine
  • fosamprenavir