title: Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study.
abstract: OBJECTIVE
  To determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir.
  
  
  METHODS
  Resistance tests on patients failing atazanavir, conducted as part of routine clinical care in a multicentre observational study, were randomly matched by subtype to resistance tests from PI-naive controls to account for natural polymorphisms. Mutations from the consensus B sequence across the protease region were analysed for association and defined using the IAS-USA 2011 classification list.
  
  
  RESULTS
  Four hundred and five of 2528 (16%) patients failed therapy containing atazanavir as a first PI over a median (IQR) follow-up of 1.76 (0.84-3.15) years and 322 resistance tests were available for analysis. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P < 0.001), including I50L and N88S. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P < 0.05). Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience.
  
  
  CONCLUSIONS
  Viral failure on atazanavir-containing regimens was not common and major resistance mutations were rare, suggesting that adherence may be a major contributor to viral failure. Novel mutations were described that have not been previously documented.
authors.affiliation: Medical Research Council Clinical Trials Unit, London, UK.
authors.forename: David I
authors.initials: DI
authors.lastname: Dolling
authors.forename: David T
authors.initials: DT
authors.lastname: Dunn
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Sutherland
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.forename: Jean L
authors.initials: JL
authors.lastname: Mbisa
authors.forename: Chris M
authors.initials: CM
authors.lastname: Parry
authors.forename: Frank A
authors.initials: FA
authors.lastname: Post
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Sabin
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cane
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D059645:Mutation Rate; D020125:Mutation, Missense; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure; D014481:United States
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D016333:HIV Protease
keywords: HIV; drug resistance mutations; naive patients; protease inhibitors; virological failure