Clinical validation of atazanavir/ritonavir genotypic resistance score in protease inhibitor-experienced patients

AIDS. 2006 Jan 2;20(1):35-40. doi: 10.1097/01.aids.0000196179.11293.fc.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Antiretroviral Therapy, Highly Active / methods*
  • Atazanavir Sulfate
  • Cohort Studies
  • Drug Resistance, Viral
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • Humans
  • Male
  • Mutation / genetics
  • Oligopeptides / therapeutic use*
  • Pyridines / therapeutic use*
  • RNA, Viral / analysis
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Ritonavir / therapeutic use*
  • Treatment Outcome

Substances

  • HIV Protease Inhibitors
  • Oligopeptides
  • Pyridines
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Atazanavir Sulfate
  • Ritonavir