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HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK
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 a...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5181398/ https://www.ncbi.nlm.nih.gov/pubmed/27856703 http://dx.doi.org/10.1093/jac/dkw343 |
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author | 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. |
author_facet | 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. |
author_sort | El Bouzidi, Kate |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5181398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-51813982016-12-27 HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK 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. J Antimicrob Chemother Original Research 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. Oxford University Press 2016-12 2016-09-28 /pmc/articles/PMC5181398/ /pubmed/27856703 http://dx.doi.org/10.1093/jac/dkw343 Text en © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research 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. HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK |
title | HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK |
title_full | HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK |
title_fullStr | HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK |
title_full_unstemmed | HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK |
title_short | HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK |
title_sort | hiv-1 drug resistance mutations emerging on darunavir therapy in pi-naive and -experienced patients in the uk |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5181398/ https://www.ncbi.nlm.nih.gov/pubmed/27856703 http://dx.doi.org/10.1093/jac/dkw343 |
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