title: Predictors of HIV drug-resistance mutations in a large antiretroviral-naive cohort initiating triple antiretroviral therapy.
abstract: OBJECTIVE
  The objective of this study was to systematically characterize the incidence and determinants of antiretroviral resistance in the HOMER (Highly Active Antiretroviral Therapy [HAART] Observational Medical Evaluation and Research) cohort of 1191 human immunodeficiency virus-infected, antiretroviral-naive adults initiating HAART in British Columbia, Canada.
  
  
  METHODS
  All plasma samples with plasma virus loads (pVLs) >1000 copies/mL collected during the first 30 months of follow-up were genotyped for drug resistance. The primary outcome measure was time to the first detection of major drug-resistance mutation(s). Cox proportional hazard regression was used to identify factors significantly associated with the detection of drug-resistance mutations.
  
  
  RESULTS
  Drug-resistance mutations were detected in 298 subjects (25%). Factors significantly associated with detection of drug-resistance mutations included high baseline pVL (multivariate hazard ratio [HR], 1.59; P<.001) and adherence (estimated using prescription-refill data and/or untimed plasma drug-concentration measurements). When compared with subjects with low (0%-<20%) prescription-refill percentages, subjects at an elevated risk of harboring drug-resistance mutations were those with relatively high but imperfect prescription-refill percentages (80%-<90%; multivariate HR, 4.15; P<.001) and those with essentially perfect (>/=95%) refill percentages but with 2 plasma drug concentrations below the steady-state trough concentration minus 1 standard deviation (multivariate HR, 4.57; P<.001). Initial use of nonnucleoside reverse-transcriptase inhibitor-based HAART was significantly associated with multiclass drug resistance (multivariate HR, 1.84; P=.001).
  
  
  CONCLUSIONS
  High baseline pVLs and substantial but imperfect levels of adherence were major predictors of antiretroviral resistance.
authors.affiliation: British Columbia Centre for Excellence in HIV/AIDS, and Department of Medicine, University of British Columbia, Vancouver, Canada. lab@hivnet.ubc.ca
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hogg
authors.forename: Winnie W Y
authors.initials: WW
authors.lastname: Dong
authors.forename: Benita
authors.initials: B
authors.lastname: Yip
authors.forename: Brian
authors.initials: B
authors.lastname: Wynhoven
authors.forename: Justin
authors.initials: J
authors.lastname: Woodward
authors.forename: Chanson J
authors.initials: CJ
authors.lastname: Brumme
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.forename: Theresa
authors.initials: T
authors.lastname: Mo
authors.forename: Chris S
authors.initials: CS
authors.lastname: Alexander
authors.forename: Julio S G
authors.initials: JS
authors.lastname: Montaner
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001955:British Columbia / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D015994:Incidence; D015999:Multivariate Analysis; D009154:Mutation; D010349:Patient Compliance; D019562:Viral Load
chemical_list: D054303:HIV Reverse Transcriptase; D016333:HIV Protease