Early virologic response to abacavir/lamivudine and tenofovir/emtricitabine during ACTG A5202

HIV Clin Trials. 2013 Nov-Dec;14(6):284-91. doi: 10.1310/hct1406-284.

Abstract

Background: ACTG A5202 randomized treatment-naïve individuals to tenofovir-emtricitabine (TDF/FTC) or abacavir-lamivudine (ABC/3TC) combined with efavirenz (EFV) or atazanavir/ritonavir (ATV/r). Individuals in the high screening viral load (VL) stratum (≥100,000 copies/mL) had increased rates of virologic failure with ABC/3TC.

Objective: To compare regimen-specific early virologic response.

Methods: Using Wilcoxon rank-sum tests, we compared regimen-specific VL changes from entry to week 4 in A5202 subjects (N = 1,813) and from entry to week 1, 2, and 4 in substudy subjects (n = 179). We evaluated associations between week 4 VL change and time to virologic failure with Cox proportional hazards models.

Results: TDF/FTC and ABC/3TC produced similar week 4 VL declines in the entire study population and in the high VL stratum. EFV produced greater VL declines from baseline at week 4 than ATV/r (median -2.1 vs -1.9 log10 copies/mL; P < .001). In the substudy of subjects with week 1, 2, and 4 VL data, there was no difference in VL decline in individuals randomized to TDF/FTC versus ABC/3TC, but EFV resulted in greater VL decline from entry at each of these timepoints than ATV/r. Smaller week 4 VL decline was associated with increased risk of virologic failure.

Conclusions: Within all treatment arms, a less robust week 4 virologic response was associated with higher risk for subsequent virologic failure. However, between-regimen differences in week 4 VL declines did not parallel the previously reported differences in longer term virologic efficacy in A5202, suggesting that between-regimen differences in responses were not due to intrinsic differences in antiviral activity.

Keywords: HIV infections; anti-HIV agents; drug therapy; treatment outcome; virology.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use
  • Dideoxynucleosides / therapeutic use*
  • Drug Combinations
  • Drug Therapy, Combination
  • Emtricitabine
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Lamivudine / therapeutic use*
  • Male
  • Middle Aged
  • Organophosphonates / administration & dosage
  • Organophosphonates / therapeutic use*
  • Tenofovir
  • Viral Load

Substances

  • Anti-HIV Agents
  • Dideoxynucleosides
  • Drug Combinations
  • Organophosphonates
  • abacavir, lamivudine drug combination
  • Deoxycytidine
  • Lamivudine
  • Tenofovir
  • Emtricitabine
  • Adenine