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Lookup NU author(s): Dr Samuel Moses, Dr Brendan PayneORCiD, Zac Gleisner
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author 2016. Background: Darunavir 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. Objectives: We examined darunavir DRMs emerging in clinical practice in the UK. Patients and methods: Baseline 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 PInaive controls. Results: Of 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. Conclusions: Our 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.
Author(s): El Bouzidi K, White E, Mbisa JL, Sabin CA, Phillips AN, Mackie N, Pozniak AL, Tostevin A, Pillay D, Dunn DT, Aitken C, Asboe D, Pozniak A, Cane P, Chadwick D, Churchill D, Clark D, Collins S, Delpech V, Douthwaite S, Fearnhill E, Porter K, Fraser C, Geretti AM, Hale A, Hue S, Kaye S, Kellam P, Lazarus L, Leigh-Brown A, Mbisa T, Moses S, Orkin C, Nastouli E, Sabin C, Smit E, Templeton K, Tilston P, Williams I, Zhang H, Fairbrother K, Greatorex J, O'Shea S, Mullen J, Cox A, Tandy R, Fawcett T, Hopkins M, Ashton L, Booth C, Garcia-Diaz A, Shepherd J, Schmid ML, Payne B, Hubb J, Kirk S, Gunson R, Bradley-Stewart A, Allan S, Anderson J, Babiker A, Fisher M, Gazzard B, Gilson R, Hill T, Johnson M, Jose S, Kegg S, Leen C, Palfreeman A, Pritchard J, Sachikonye M, Schwenk A, Tariq A, Walsh J, Thornton A, Glabay A, Lynch J, Hand J, de Souza C, Perry N, Tilbury S, Youssef E, Nelson M, Everett R, Mandalia S, Munshi S, Post F, Adefisan A, Taylor C, Gleisner Z, Ibrahim F, Campbell L, Baillie K, Brima N, Ainsworth J, Miller S, Wood C, Youle M, Lampe F, Smith C, Tsintas R, Chaloner C, Hutchinson S, Huntington S, Winston A, Weber J, Ramzan F, Carder M, Wilson A, Morris S, Gompels M, Allan S, Memon K, Lewszuk A, Faleye A, Mitchell S, Hunter M, Hay P, Dhillon M, Kemble C, Russell-Sharpe S, Gravely J, Harte A, Clay S, Spencer H, Jones R, Cumming S, Atkinson C
Publication type: Article
Publication status: Published
Journal: Journal of Antimicrobial Chemotherapy
Year: 2016
Volume: 71
Issue: 12
Pages: 3487-3494
Print publication date: 01/12/2016
Online publication date: 28/09/2016
Acceptance date: 25/07/2016
Date deposited: 30/05/2018
ISSN (print): 0305-7453
ISSN (electronic): 1460-2091
Publisher: Oxford University Press
URL: https://doi.org/10.1093/jac/dkw343
DOI: 10.1093/jac/dkw343
PubMed id: 27856703
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