Clinical validation of atazanavir/ritonavir genotypic resistance score in protease inhibitor-experienced patients.
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.
Vora
Samir
S
Laboratory of Virology, Geneva University Hospital, Switzerland.
Marcelin
Anne-Geneviève
AG
Günthard
Huldrych F
HF
Flandre
Philippe
P
Hirsch
Hans H
HH
Masquelier
Bernard
B
Zinkernagel
Annelies
A
Peytavin
Gilles
G
Calvez
Vincent
V
Perrin
Luc
L
Yerly
Sabine
S
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
D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000069446:Atazanavir Sulfate; D019438:Ritonavir