title: Clinical validation of atazanavir/ritonavir genotypic resistance score in protease inhibitor-experienced patients.
abstract: OBJECTIVE
  To develop a clinically relevant genotypic resistance score for boosted atazanavir (ATV) in protease inhibitor-experienced patients.
  
  
  METHODS
  At baseline, 62 patients with HIV-1 RNA > 1000 copies/ml switched to a boosted ATV regimen (300 mg ATV, 100 mg ritonavir once daily); two were excluded from analysis at 3 months as they had undetectable plasma ATV. The impact of baseline protease mutations on virological response (> 1 log10 copies/ml plasma HIV RNA decrease) at 3 months was analysed using Fisher's exact test. Mutations with prevalence > 8% and P < 0.2 were retained. Cochran-Armitage's test was used to select the combination of mutations most strongly associated with reduced virological response. Robustness of the score was investigated using bootstrap resampling.
  
  
  RESULTS
  At 3 months, 82% of patients had a virological response and 56% had RNA < 50 copies/ml. Eight mutations (10F/I/V, 16E, 33I/F/V, 46I/L, 60E, 84V, 85V and 90M) were retained in the genotypic resistance score (P = 8.67 x 10) and virological response was observed in 100%, 100%, 80%, 42%, and 0% of patients with none, one, two, three, and four/five mutations, respectively. There was 100% response in patients with a score < 2 independently of the number of active drugs, whereas in patients with a score > or = 3 there was a gradient of response according to the number of active drugs (0%, 29% and 60% with none, one and two/three active drugs, respectively).
  
  
  CONCLUSIONS
  The occurrence of three of the eight mutations in the ATV/RTV genotypic resistance score predicted a clinically identifiable reduced response in patients.
authors.affiliation: Laboratory of Virology, Geneva University Hospital, Switzerland.
authors.forename: Samir
authors.initials: S
authors.lastname: Vora
authors.forename: Anne-Geneviève
authors.initials: AG
authors.lastname: Marcelin
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Philippe
authors.initials: P
authors.lastname: Flandre
authors.forename: Hans H
authors.initials: HH
authors.lastname: Hirsch
authors.forename: Bernard
authors.initials: B
authors.lastname: Masquelier
authors.forename: Annelies
authors.initials: A
authors.lastname: Zinkernagel
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Luc
authors.initials: L
authors.lastname: Perrin
authors.forename: Sabine
authors.initials: S
authors.lastname: Yerly
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000069446:Atazanavir Sulfate; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D009842:Oligopeptides / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000069446:Atazanavir Sulfate; D019438:Ritonavir