title: High levels of adherence do not prevent accumulation of HIV drug resistance mutations.
abstract: OBJECTIVE
  To assess the relationship between development of antiretroviral drug resistance and adherence by measured treatment duration, virologic suppression, and the rate of accumulating new drug resistance mutations at different levels of adherence.
  
  
  METHODS
  Adherence was measured with unannounced pill counts performed at the participant's usual place of residence in a prospective cohort of HIV-positive urban poor individuals. Two genotypic resistance tests separated by 6 months (G1 and G2) were obtained in individuals on a stable regimen and with detectable viremia (> 50 copies/ml). The primary resistance outcome was the number of new HIV antiretroviral drug resistance mutations occurring over the 6 months between G1 and G2.
  
  
  RESULTS
  High levels of adherence were closely associated with greater time on treatment (P < 0.0001) and viral suppression (P < 0.0001) in 148 individuals. In a subset of 57 patients with a plasma viral load > 50 copies/ml on stable therapy, the accumulation of new drug resistance mutations was positively associated with the duration of prior treatment (P = 0.03) and pill count adherence (P = 0.002). Assuming fully suppressed individuals (< 50 copies/ml) do not develop resistance, it was estimated that 23% of all drug resistance occurs in the top quintile of adherence (92-100%), and over 50% of all drug resistance mutations occur in the top two quintiles of adherence (79-100%).
  
  
  CONCLUSIONS
  Increasing rates of viral suppression at high levels of adherence is balanced by increasing rates of drug resistance among viremic patients. Exceptionally high levels of adherence will not prevent population levels of drug resistance.
authors.affiliation: Epidemiology and Prevention Interventions Center, Division of Infectious Diseases, San Francisco General Hospital, California, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Bangsberg
authors.forename: Edwin D
authors.initials: ED
authors.lastname: Charlebois
authors.forename: Robert M
authors.initials: RM
authors.lastname: Grant
authors.forename: Mark
authors.initials: M
authors.lastname: Holodniy
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Sharon
authors.initials: S
authors.lastname: Perry
authors.forename: Kathleen Nugent
authors.initials: KN
authors.lastname: Conroy
authors.forename: Richard
authors.initials: R
authors.lastname: Clark
authors.forename: David
authors.initials: D
authors.lastname: Guzman
authors.forename: Andrew
authors.initials: A
authors.lastname: Zolopa
authors.forename: Andrew
authors.initials: A
authors.lastname: Moss
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006703:Ill-Housed Persons; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010349:Patient Compliance; D011446:Prospective Studies; D014504:Urban Health; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents