Adherence and preexisting major protease inhibitor resistance mutations are associated with virologic failure of a dual-class antiretroviral regimen with inhibitors of HIV-1 viral protease and integrase

J Int Assoc Physicians AIDS Care (Chic). 2012 Jan-Feb;11(1):34-9. doi: 10.1177/1545109711422124. Epub 2011 Oct 4.

Abstract

Objectives: Novel treatment strategies are needed for treatment-experienced HIV-infected individuals. We retrospectively evaluated virologic outcomes on a dual-class, protease inhibitor (PI) plus raltegravir, antiretroviral (ARV) regimen.

Methods: Virologic success was defined by a plasma HIV-RNA level ≤200 copies/mL. Adherence was measured using pharmacy refill data. The association between adherence and virologic failure was assessed using bivariate logistic regression.

Results: In 39 individuals, median prior antiretroviral therapy (ART) exposure was 11 years. Of 39 individuals, 36 (92%) achieved an HIV-RNA ≤200 copies/mL. After a median follow-up of 328 days (interquartile range [IQR] 190-737 days), 74% maintained an HIV-RNA <200 copies/mL but only 44% had <50 copies/mL. Median adherence was 96.4% (IQR 83.3%-100%). For every 10% decrease in adherence, the odds of virologic failure increased by 90% (odds ratio [OR] = 1.9, 95% confidence interval [CI] 1.1-3.3). In all, 4 individuals had ≥2 preexisting major PI resistance mutations and all 4 had virologic failure.

Conclusions: Most treatment-experienced individuals achieved virologic suppression on a dual-class regimen of a PI plus raltegravir. Success was limited by poor medication adherence and preexisting major PI resistance mutations.

MeSH terms

  • Adult
  • Drug Resistance, Viral / genetics
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV Integrase Inhibitors / therapeutic use*
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / genetics*
  • Humans
  • Male
  • Medication Adherence*
  • Middle Aged
  • Mutation
  • Pyrrolidinones / therapeutic use*
  • RNA, Viral / blood
  • Raltegravir Potassium
  • Retrospective Studies

Substances

  • HIV Integrase Inhibitors
  • HIV Protease Inhibitors
  • Pyrrolidinones
  • RNA, Viral
  • Raltegravir Potassium