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BackgroundDarunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings.ObjectivesWe examined darunavir DRMs emerging in clinical practice in the UK.Patients and methodsBaseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PI-naive controls.ResultsOf 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group.ConclusionsOur findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility.

Original publication

DOI

10.1093/jac/dkw343

Type

Journal article

Journal

The Journal of antimicrobial chemotherapy

Publication Date

12/2016

Volume

71

Pages

3487 - 3494

Addresses

Research Department of Infection and Population Health, University College London, London, UK k.elbouzidi@ucl.ac.uk.

Keywords

UK HIV Drug Resistance Database, (UKHDRD) and the UK Collaborative HIV Cohort (UK CHIC) Study Steering Committees, UK HIV Drug Resistance Database (UKHDRD) and the UK Collaborative HIV Cohort (UK CHIC) Study Steering Committees, Humans, HIV-1, HIV Infections, HIV Protease Inhibitors, Cohort Studies, Drug Resistance, Viral, Mutation, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Darunavir, United Kingdom