Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study.

TitleLow frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study.
Publication TypeJournal Article
Year of Publication2013
AuthorsDolling D, Dunn D, Sutherland K, Pillay D, Mbisa J, Parry C, Post F, Sabin C and Cane P
Corporate AuthorsUK HIV Drug Resistance Database(UKHDRD) and UK Collaborative HIV Cohort Study(UK CHIC)
JournalJ Antimicrob Chemother
Volume68
Issue10
Pagination2339-43
Date Published2013 Oct
ISSN1460-2091
KeywordsAdult, Anti-HIV Agents, Atazanavir Sulfate, Cohort Studies, Drug Resistance, Viral, Female, HIV Infections, HIV Protease, HIV-1, Humans, Male, Medication Adherence, Middle Aged, Mutation Rate, Mutation, Missense, Oligopeptides, Pyridines, Treatment Failure, United States
Abstract

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.

DOI10.1093/jac/dkt199
Alternate JournalJ. Antimicrob. Chemother.
PubMed ID23711895
PubMed Central IDPMC3772741
Grant ListG0600337 / / Medical Research Council / United Kingdom
G0000199 / / Medical Research Council / United Kingdom
G0900274 / / Medical Research Council / United Kingdom
MC_UU_12023/15 / / Medical Research Council / United Kingdom
MR/K006584/1 / / Medical Research Council / United Kingdom