title: Antiretroviral medication adherence and class- specific resistance in a large prospective clinical trial.
abstract: OBJECTIVE
  To assess the association between adherence to antiretroviral therapy and the presence of class-specific antiretroviral medication resistance.
  
  
  METHODS
  Secondary analysis of prospective clinical trial data.
  
  
  METHODS
  Participants randomized to the protease inhibitor or nonnucleoside reverse transcriptase inhibitor (NNRTI) strategies of the Community Programs for Clinical Research on AIDS (CPCRA) Flexible Initial Retrovirus Suppressive Therapies (FIRST) Study were included. Adherence was measured by 7-day self-report. Virological failure was defined as an HIV-RNA more than 1000 at or after 4 months. The association between cumulative adherence and the development of class-specific genotypic resistance was assessed by Cox regression analysis.
  
  
  RESULTS
  Included were 457 and 446 antiretroviral-naive participants on the protease inhibitor and NNRTI strategies, respectively. The median time to initial virological failure in the protease inhibitor strategy was 1.2 years; 135 (30%) individuals failed with resistance. The median time to initial virological failure in the NNRTI strategy was 3.0 years; 127 (28%) failed with resistance. No association was found between cumulative adherence and protease inhibitor resistance [hazard ratio 1.1, 95% confidence interval (CI) 0.9-1.4 per 10% lower adherence]. However, lower cumulative adherence was associated with an increased risk of NNRTI resistance at initial virological failure (hazard ratio 1.2, 95% CI 1.1-1.3 per 10% lower adherence). In both strategies, lower cumulative adherence was associated with an increased risk of nucleoside reverse transcriptase inhibitor (NRTI) resistance at initial virological failure.
  
  
  CONCLUSIONS
  Adherence-resistance relationships are class-specific. For NRTIs and NNRTIs, initial virological failure with resistance is more likely at lower levels of cumulative adherence.
authors.affiliation: Denver Public Health, 605 Bannock Street, Denver, CO 80204, USA. edward.m.gardner@dhha.org
authors.forename: Edward M
authors.initials: EM
authors.lastname: Gardner
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Hullsiek
authors.forename: Edward E
authors.initials: EE
authors.lastname: Telzak
authors.forename: Shweta
authors.initials: S
authors.lastname: Sharma
authors.forename: Grace
authors.initials: G
authors.lastname: Peng
authors.forename: William J
authors.initials: WJ
authors.lastname: Burman
authors.forename: Rodger D
authors.initials: RD
authors.lastname: MacArthur
authors.forename: Margaret
authors.initials: M
authors.lastname: Chesney
authors.forename: Gerald
authors.initials: G
authors.lastname: Friedland
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Mannheimer
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D017320:HIV Protease Inhibitors / Q000145:classification / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D008297:Male; D011446:Prospective Studies; D019562:Viral Load; D016903:Drug Monitoring
chemical_list: D017320:HIV Protease Inhibitors