1. Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study
- Author
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Dolling, David I, Dunn, David T, Sutherland, Katherine A, Pillay, Deenan, Mbisa, Jean L, Parry, Chris M, Post, Frank A, Sabin, Caroline A, Cane, Patricia A, UK HIV Drug Resistance Database (UKHDRD), and UK Collaborative HIV Cohort Study (UK CHIC)
- Subjects
Adult ,Male ,Pyridines ,Anti-HIV Agents ,Atazanavir Sulfate ,Drug Resistance ,protease inhibitors ,HIV Infections ,Microbiology ,Medication Adherence ,Cohort Studies ,HIV Protease ,Mutation Rate ,Humans ,Treatment Failure ,Viral ,drug resistance mutations ,virological failure ,virus diseases ,HIV ,Pharmacology and Pharmaceutical Sciences ,Middle Aged ,United States ,naive patients ,Medical Microbiology ,Mutation ,HIV-1 ,Female ,Missense ,UK Collaborative HIV Cohort Study ,Oligopeptides ,UK HIV Drug Resistance Database - Abstract
ObjectivesTo determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir.MethodsResistance 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.ResultsFour 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.ConclusionsViral 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.
- Published
- 2013