Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study.
OBJECTIVES
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.
['Dolling|David I|DI|', 'Dunn|David T|DT|', 'Sutherland|Katherine A|KA|', 'Pillay|Deenan|D|', 'Mbisa|Jean L|JL|', 'Parry|Chris M|CM|', 'Post|Frank A|FA|', 'Sabin|Caroline A|CA|', 'Cane|Patricia A|PA|', '|||', '|||']
D000328:Adult D019380:Anti-HIV Agents D000069446:Atazanavir Sulfate D015331:Cohort Studies D024882:Drug Resistance, Viral D005260:Female D015658:HIV Infections D016333:HIV Protease D015497:HIV-1 D006801:Humans D008297:Male D055118:Medication Adherence D008875:Middle Aged D059645:Mutation Rate D020125:Mutation, Missense D009842:Oligopeptides D011725:Pyridines D017211:Treatment Failure D014481:United States
protease inhibitors HIV drug resistance mutations naive patients virological failure