title: Association of pharmacogenetic markers with premature discontinuation of first-line anti-HIV therapy: an observational cohort study.
abstract: BACKGROUND
  Poor tolerance and adverse drug reactions are main reasons for discontinuation of antiretroviral therapy (ART). Identifying predictors of ART discontinuation is a priority in HIV care.
  
  
  METHODS
  A genetic association study in an observational cohort to evaluate the association of pharmacogenetic markers with time to treatment discontinuation during the first year of ART. Analysis included 577 treatment-naive individuals initiating tenofovir (n = 500) or abacavir (n = 77), with efavirenz (n = 272), lopinavir/ritonavir (n = 184), or atazanavir/ritonavir (n = 121). Genotyping included 23 genetic markers in 15 genes associated with toxicity or pharmacokinetics of the study medication. Rates of ART discontinuation between groups with and without genetic risk markers were assessed by survival analysis using Cox regression models.
  
  
  RESULTS
  During the first year of ART, 190 individuals (33%) stopped 1 or more drugs. For efavirenz and atazanavir, individuals with genetic risk markers experienced higher discontinuation rates than individuals without (71.15% vs 28.10%, and 62.5% vs 14.6%, respectively). The efavirenz discontinuation hazard ratio (HR) was 3.14 (95% confidence interval (CI): 1.35-7.33, P = .008). The atazanavir discontinuation HR was 9.13 (95% CI: 3.38-24.69, P < .0001).
  
  
  CONCLUSIONS
  Several pharmacogenetic markers identify individuals at risk for early treatment discontinuation. These markers should be considered for validation in the clinical setting.
authors.affiliation: Institute of Microbiology, University Hospital of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Rubin
authors.initials: R
authors.lastname: Lubomirov
authors.forename: Sara
authors.initials: S
authors.lastname: Colombo
authors.forename: Julia
authors.initials: J
authors.lastname: di Iulio
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.forename: Raquel
authors.initials: R
authors.lastname: Martinez
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Bernard
authors.initials: B
authors.lastname: Hirschel
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Luigia
authors.initials: L
authors.lastname: Elzi
authors.forename: Pietro
authors.initials: P
authors.lastname: Vernazza
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Furrer
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000493:pharmacokinetics; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D005819:Genetic Markers; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D016903:Drug Monitoring
chemical_list: D019380:Anti-HIV Agents; D005819:Genetic Markers