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HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK

Lookup NU author(s): Dr Samuel Moses, Dr Brendan Payne, Zac Gleisner

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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.


Publication metadata

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

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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