title: Racial differences in virologic failure associated with adherence and quality of life on efavirenz-containing regimens for initial HIV therapy: results of ACTG A5095.
abstract: BACKGROUND
  Blacks had higher rates of virologic failure than whites on efavirenz-containing regimens in the AIDS Clinical Trials Group (ACTG) A5095 study; preliminary analyses also suggested an association with adherence. We rigorously examined associations over time among race, virologic failure, 4 self-reported adherence metrics, and quality of life (QOL).
  
  
  METHODS
  ACTG A5095 was a double-blind placebo-controlled study of treatment-naive HIV-positive patients randomized to zidovudine/lamivudine/abacavir versus zidovudine/lamivudine plus efavirenz versus zidovudine/lamivudine/abacavir plus efavirenz. Virologic failure was defined as confirmed HIV-1 RNA >or=200 copies/mL at >or=16 weeks on study. The zidovudine/lamivudine/abacavir arm was discontinued early because of virologic inferiority. We examined virologic failure differences for efavirenz-containing arms according to missing 0 (adherent) versus at least 1 dose (nonadherent) during the past 4 days, alternative self-reported adherence metrics, and QOL. Analyses used the Fisher exact, log rank tests, and Cox proportional hazards models.
  
  
  RESULTS
  The study population included white (n = 299), black (n = 260), and Hispanic (n = 156) patients with >or=1 adherence evaluation. Virologic failure was associated with week 12 nonadherence during the past 4 days for blacks (53% nonadherent failed vs. 25% adherent; P < 0.001) but not for whites (20% nonadherent failed vs. 20% adherent; P = 0.91). After adjustment for baseline covariates and treatment, there was a significant interaction between race and week 12 adherence (P = 0.02). In time-dependent Cox models using self-reports over time to reflect recent adherence, there was a significantly higher failure risk for nonadherent subjects (hazard ratio [HR] = 2.07; P < 0.001). Significant race-adherence interactions were seen in additional models of adherence: missing at least 1 medication dose ever (P = 0.04), past month (P < 0.01), or past weekend (P = 0.05). Lower QOL was significantly associated with virologic failure (P < 0.001); there was no evidence of an interaction between QOL and race (P = 0.39) or adherence (P = 0.51) in predicting virologic failure.
  
  
  CONCLUSIONS
  There was a greater effect of nonadherence on virologic failure in blacks given efavirenz-containing regimens than in whites. Self-reported adherence and QOL are independent predictors of virologic failure.
authors.affiliation: Department of Public Health, Weill Medical College, New York, NY 10021, USA. brs2006@med.cornell.edu
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Schackman
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.forename: Amy
authors.initials: A
authors.lastname: Krambrink
authors.forename: Valery
authors.initials: V
authors.lastname: Hughes
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.forename: Roy M
authors.initials: RM
authors.lastname: Gulick
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000627:therapeutic use*; D044383:Black People; D003521:Cyclopropanes; D004311:Double-Blind Method; D015658:HIV Infections / Q000188:drug therapy*; D006630:Hispanic or Latino; D006801:Humans; D011788:Quality of Life; D044469:Racial Groups; D012307:Risk Factors; D017211:Treatment Failure; D016312:Treatment Refusal / Q000523:psychology / Q000706:statistics & numerical data*; D014481:United States / Q000453:epidemiology; D044465:White People; D001741:Black or African American
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz