title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: 1Denver Public Health, Denver, CO, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Gardner
authors.forename: Andre G
authors.initials: AG
authors.lastname: Melendez
authors.forename: Maria
authors.initials: M
authors.lastname: Astiz
authors.forename: Kimberly
authors.initials: K
authors.lastname: Bray
mesh_terms: D000328:Adult; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D019428:HIV Integrase Inhibitors / Q000627:therapeutic use*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009154:Mutation; D011760:Pyrrolidinones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D012189:Retrospective Studies
chemical_list: D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D011760:Pyrrolidinones; D012367:RNA, Viral; D000068898:Raltegravir Potassium