UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance

Geretti, AM; White, E; Orkin, C; Tostevin, A; Tilston, P; Chadwick, D; Leen, C; ... UK HIV Drug Resistance Database and UK CHIC Study, .; + view all (2018) Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance. Journal of Antimicrobial Chemotherapy , Article dky468. 10.1093/jac/dky468. (In press). Green open access

[img]
Preview
Text
dky468.pdf - Published version

Download (283kB) | Preview

Abstract

OBJECTIVES: In subjects with transmitted thymidine analogue mutations (TAMs), boosted PIs (PI/b) are often chosen to overcome possible resistance to the NRTI backbone. However, data to guide treatment selection are limited. Our aim was to obtain firmer guidance for clinical practice using real-world cohort data. METHODS: We analysed 1710 subjects who started a PI/b in combination with tenofovir or abacavir plus emtricitabine or lamivudine, and compared their virological outcomes with those of 4889 patients who started an NNRTI (predominantly efavirenz), according to the presence of ≥1 TAM as the sole form of transmitted drug resistance. RESULTS: Participants with ≥1 TAM comprised predominantly MSM (213 of 269, 79.2%), subjects of white ethnicity (206 of 269, 76.6%) and HIV-1 subtype B infections (234 of 269, 87.0%). Most (203 of 269, 75.5%) had singleton TAMs, commonly a revertant of T215Y or T215F (112 of 269, 41.6%). Over a median of 2.5 years of follow-up, 834 of 6599 (12.6%) subjects experienced viraemia (HIV-1 RNA >50 copies/mL). The adjusted HR for viraemia was 2.17 with PI/b versus NNRTI-based therapy (95% CI 1.88–2.51; P < 0.001). Other independent predictors of viraemia included injecting drug use, black ethnicity, higher viral load and lower CD4 cell count at baseline, and receiving abacavir instead of tenofovir. Resistance showed no overall impact (adjusted HR 0.77 with ≥1 TAM versus no resistance; 95% CI 0.54–1.10; P = 0.15). CONCLUSION: In this cohort, patients harbouring ≥1 TAM as the sole form of transmitted drug resistance gained no apparent virological advantage from starting first-line ART with a PI/b.

Type: Article
Title: Virological outcomes of boosted protease inhibitor-based first-line ART in subjects harbouring thymidine analogue-associated mutations as the sole form of transmitted drug resistance
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/jac/dky468
Publisher version: https://doi.org/10.1093/jac/dky468
Language: English
Additional information: © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Keywords: abacavir mutation drug resistance efavirenz cd4 count determination procedure endopeptidases ethnic group follow-up hiv-1 lamivudine thymidine viral load result viremia infection virology tenofovir rna emtricitabine proteolytic enzymes nucleoside reverse transcriptase inhibitors non-nucleoside reverse transcriptase inhibitors men who have sex with men
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/10064735
Downloads since deposit
11Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item