HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK. (28th September 2016)

• Record Type: Journal Article
• Authors: El Bouzidi, Kate; White, Ellen; Mbisa, Jean L.; Sabin, Caroline A.; Phillips, Andrew N.; Mackie, Nicola; Pozniak, Anton L.; Tostevin, Anna; Pillay, Deenan; Dunn, David T.
• Other Names: Aitken Celia author non-byline.; Asboe David author non-byline.; Pozniak Anton author non-byline.; Cane Patricia author non-byline.; Chadwick David author non-byline.; Churchill Duncan author non-byline.; Clark Duncan author non-byline.; Collins Simon author non-byline.; Delpech Valerie author non-byline.; Douthwaite Samuel author non-byline.; Dunn David author non-byline.; Fearnhill Esther author non-byline.; Porter Kholoud author non-byline.; Tostevin Anna author non-byline.; White Ellen author non-byline.; Fraser Christophe author non-byline.; Geretti Anna Maria author non-byline.; Hale Antony author non-byline.; Hué Stéphane author non-byline.; Kaye Steve author non-byline.; Kellam Paul author non-byline.; Lazarus Linda author non-byline.; Leigh-Brown Andrew author non-byline.; Mbisa Tamyo author non-byline.; Mackie Nicola author non-byline.; Moses Samuel author non-byline.; Orkin Chloe author non-byline.; Nastouli Eleni author non-byline.; Pillay Deenan author non-byline.; Phillips Andrew author non-byline.; Sabin Caroline author non-byline.; Smit Erasmus author non-byline.; Templeton Kate author non-byline.; Tilston Peter author non-byline.; Williams Ian author non-byline.; Zhang Hongyi author non-byline.; Dunn David author non-byline.; Fairbrother Keith author non-byline.; Fearnhill Esther author non-byline.; Porter Kholoud author non-byline.; Tostevin Anna author non-byline.; White Ellen author non-byline.; Greatorex Jane author non-byline.; O'Shea Siobhan author non-byline.; Mullen Jane author non-byline.; Smit Erasmus author non-byline.; Mbisa Tamyo author non-byline.; Cox Alison author non-byline.; Tandy Richard author non-byline.; Fawcett Tracy author non-byline.; Hopkins Mark author non-byline.; Ashton Lynne author non-byline.; Tilston Peter author non-byline.; Booth Clare author non-byline.; Garcia-Diaz Ana author non-byline.; Shepherd Jill author non-byline.; Schmid Matthias L. author non-byline.; Payne Brendan author non-byline.; Chadwick David author non-byline.; Clark Duncan author non-byline.; Hubb Jonathan author non-byline.; Kaye Steve author non-byline.; Kirk Stuart author non-byline.; Gunson Rory author non-byline.; Bradley-Stewart Amanda author non-byline.; Aitken Celia author non-byline.; Ainsworth Jonathan author non-byline.; Allan Sris author non-byline.; Anderson Jane author non-byline.; Babiker Abdel author non-byline.; Chadwick David author non-byline.; Delpech Valerie author non-byline.; Dunn David author non-byline.; Fisher Martin author non-byline.; Gazzard Brian author non-byline.; Gilson Richard author non-byline.; Gompels Mark author non-byline.; Hay Phillip author non-byline.; Hill Teresa author non-byline.; Johnson Margaret author non-byline.; Jose Sophie author non-byline.; Kegg Stephen author non-byline.; Leen Clifford author non-byline.; Mackie Nicola author non-byline.; Martin Fabiola author non-byline.; Nelson Mark author non-byline.; Orkin Chloe author non-byline.; Palfreeman Adrian author non-byline.; Phillips Andrew author non-byline.; Pillay Deenan author non-byline.; Post Frank author non-byline.; Pritchard Jillian author non-byline.; Sabin Caroline author non-byline.; Sachikonye Memory author non-byline.; Schwenk Achim author non-byline.; Tariq Anjum author non-byline.; Walsh John author non-byline.; Hill Teresa author non-byline.; Jose Sophie author non-byline.; Phillips Andrew author non-byline.; Sabin Caroline author non-byline.; Thornton Alicia author non-byline.; Dunn David author non-byline.; Glabay Adam author non-byline.; Orkin Chloe author non-byline.; Lynch Janet author non-byline.; Hand James author non-byline.; de Souza Carl author non-byline.; Fisher Martin author non-byline.; Perry Nicky author non-byline.; Tilbury Stuart author non-byline.; Youssef Elaney author non-byline.; Churchill Duncan author non-byline.; Gazzard Brian author non-byline.; Nelson Mark author non-byline.; Everett Rhiannon author non-byline.; Asboe David author non-byline.; Mandalia Sundhiya author non-byline.; Delpech Valerie author non-byline.; Anderson Jane author non-byline.; Munshi Sajid author non-byline.; Post Frank author non-byline.; Adefisan Ade author non-byline.; Taylor Chris author non-byline.; Gleisner Zachary author non-byline.; Ibrahim Fowzia author non-byline.; Campbell Lucy author non-byline.; Babiker Abdel author non-byline.; Dunn David author non-byline.; Glabay Adam author non-byline.; Chadwick David author non-byline.; Baillie Kirsty author non-byline.; Gilson Richard author non-byline.; Brima Nataliya author non-byline.; Williams Ian author non-byline.; Ainsworth Jonathan author non-byline.; Schwenk Achim author non-byline.; Miller Sheila author non-byline.; Wood Chris author non-byline.; Johnson Margaret author non-byline.; Youle Mike author non-byline.; Lampe Fiona author non-byline.; Smith Colette author non-byline.; Tsintas Rob author non-byline.; Chaloner Clinton author non-byline.; Hutchinson Samantha author non-byline.; Sabin Caroline author non-byline.; Phillips Andrew author non-byline.; Hill Teresa author non-byline.; Jose Sophie author non-byline.; Thornton Alicia author non-byline.; Huntington Susie author non-byline.; Walsh John author non-byline.; Mackie Nicky author non-byline.; Winston Alan author non-byline.; Weber Jonathan author non-byline.; Ramzan Farhan author non-byline.; Carder Mark author non-byline.; Leen Clifford author non-byline.; Wilson Alan author non-byline.; Morris Sheila author non-byline.; Gompels Mark author non-byline.; Allan Sue author non-byline.; Palfreeman Adrian author non-byline.; Memon Khurram author non-byline.; Lewszuk Adam author non-byline.; Kegg Stephen author non-byline.; Faleye Akin author non-byline.; Mitchell Sue author non-byline.; Hunter Meg author non-byline.; Sachikonye Memory author non-byline.; Hay Phillip author non-byline.; Dhillon Mandip author non-byline.; Kemble Christian author non-byline.; Martin Fabiola author non-byline.; Russell-Sharpe Sarah author non-byline.; Gravely Janet author non-byline.; Allan Sris author non-byline.; Harte Andrew author non-byline.; Clay Stephen author non-byline.; Tariq Anjum author non-byline.; Spencer Hazel author non-byline.; Jones Ron author non-byline.; Pritchard Jillian author non-byline.; Cumming Shirley author non-byline.; Atkinson Claire author non-byline.;
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 71:Number 12(2016:Dec.)
• Page Start: 3487
• Page End: 3494
• Publication Date: 2016-09-28
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkw343
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract : 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 PI-naive 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.