Doravirine-associated resistance mutations in antiretroviral therapy naïve and experienced adults with HIV-1 subtype C infection in Botswana.
Antiretroviral (ART) experienced
Antiretroviral (ART) naive
Botswana
Doravirine
Drug resistance mutations
HIV-1C
Journal
Journal of global antimicrobial resistance
ISSN: 2213-7173
Titre abrégé: J Glob Antimicrob Resist
Pays: Netherlands
ID NLM: 101622459
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
29
04
2022
revised:
25
07
2022
accepted:
09
08
2022
pubmed:
17
8
2022
medline:
21
12
2022
entrez:
16
8
2022
Statut:
ppublish
Résumé
There are limited data on the prevalence of doravirine (DOR)-associated drug resistance mutations in people with HIV (PWH) in Botswana. This cross-sectional, retrospective study aimed to explore the prevalence of DOR-associated resistance mutations among ART-naïve and -experienced PWH in Botswana enrolled in the population-based Botswana Combination Prevention Project (BCPP). A total of 6078 HIV-1C pol sequences were analysed for DOR-associated resistance mutations using the Stanford HIV drug resistance database, and their levels were predicted according to the Stanford DRM penalty scores and resistance interpretation. Virologic failure was defined as HIV-1 RNA load (VL) >400 copies/mL. Among 6078 PWH, 5999 (99%) had known ART status, and 4529/5999 (79%) were on ART at time of sampling. The suppression rate among ART-experienced was 4517/4729 (96%). The overall prevalence of any DOR-associated resistance mutations was 181/1473 (12.3% [95% confidence interval {CI}: 10.7-14.1]); by ART status: 42/212 (19.8% [95% CI: 14.7-25.4]) among ART-failing individuals (VL ≥400 copies/mL) and 139/1261 (11.0% [95% CI: 9.3-12.9]) among ART-naïve individuals (P < 0.01). Intermediate DOR-associated resistance mutations were observed in 106/1261 (7.8% [95% CI: 6.9-10.1]) in ART-naïve individuals and 29/212 (13.7% [95% CI: 9.4-8.5]) among ART-experienced participants (P < 0.01). High-level DOR-associated resistance mutations were observed in 33/1261 (2.6% [95% CI: 1.8-3.7]) among ART-naïve and 13/212 (6.1% [95% CI: 3.6-10.8]) among ART-failing PWH (P < 0.01). PWH failing ART with at least one EFV/NVP-associated resistance mutation had high prevalence 13/67 (19.4%) of high-level DOR-associated resistance mutations. DOR-associated mutations were rare (11.0%) among ART-naive PWH but present in 62.7% of Botswana individuals who failed NNRTI-based ART with at least one EFV/NVP-associated resistance mutation. Testing for HIV drug resistance should underpin the use of DOR in PWH who have taken first-generation NNRTIs.
Identifiants
pubmed: 35973671
pii: S2213-7165(22)00198-9
doi: 10.1016/j.jgar.2022.08.008
pmc: PMC9750894
pii:
doi:
Substances chimiques
Anti-HIV Agents
0
doravirine
913P6LK81M
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
128-134Subventions
Organisme : NHGRI NIH HHS
ID : U41 HG006941
Pays : United States
Organisme : CGH CDC HHS
ID : U2G GH001911
Pays : United States
Organisme : FIC NIH HHS
ID : D43 TW009610
Pays : United States
Organisme : CGH CDC HHS
ID : U01 GH000447
Pays : United States
Organisme : PEPFAR
Pays : United States
Organisme : NIAID NIH HHS
ID : K24 AI131928
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None declared.
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