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 DT, Sutherland K.A, Pillay D, Mbisa JL, Parry C.M, Post FA, Sabin CA, Cane P A
JournalJ Antimicrob Chemother
Volume68
Pagination2339-43
Date Published2013-10
ISBN Number0305-7453
Accession Number23711895
Keywords*Drug Resistance, Viral, Adult, Anti-HIV Agents/pharmacology/*therapeutic use, Atazanavir Sulfate, Cohort Studies, drug resistance mutations, Female, Hiv, HIV Infections/*drug therapy/virology, HIV Protease/genetics, HIV-1/*drug effects/*genetics/isolation & purification, Humans, Male, Medication Adherence, Middle Aged, Mutation Rate, Mutation, Missense, naive patients, Oligopeptides/pharmacology/*therapeutic use, protease inhibitors, Pyridines/pharmacology/*therapeutic use, Treatment Failure, United States, Virological failure
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.

Short TitleThe Journal of antimicrobial chemotherapy
Alternate JournalThe Journal of antimicrobial chemotherapy