To determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir. 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. 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 testswere 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. 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.
Bibliographical noteFunding Information:
The UK CHIC Study is funded by the Medical Research Council, UK (grants G0000199, G0600337 and G0900274). This work is funded by the Medical Research Council, UK (grant G0900274) and the European Community’s 7th Framework (FP7/2007–2013) under the project Collaborative HIV and Anti-HIV Drug Resistance Network (CHAIN; 223131).
Copyright 2014 Elsevier B.V., All rights reserved.
- Drug resistance mutations
- Naive patients
- Protease inhibitors
- Virological failure