Journal article
High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment
- Abstract:
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OBJECTIVES: HIV-1 integrase inhibitors are recommended as first-line therapy by WHO, though efficacy and resistance data for non-B subtypes are limited. Two recent trials have identified the integrase L74I mutation to be associated with integrase inhibitor treatment failure in HIV-1 non-B subtypes. We sought to define the prevalence of integrase resistance mutations, including L74I, in West Africa.
METHODS: We studied a Nigerian cohort of recipients prior to and during receipt of second-line PI-based therapy, who were integrase inhibitor-naive. Illumina next-generation sequencing with target enrichment was used on stored plasma samples. Drug resistance was interpreted using the Stanford Resistance Database and the IAS-USA 2019 mutation lists.
RESULTS: Of 115 individuals, 59.1% harboured CRF02_AG HIV-1 and 40.9% harboured subtype G HIV-1. Four participants had major IAS-USA integrase resistance-associated mutations detected at low levels (2%-5% frequency). Two had Q148K minority variants and two had R263K (one of whom also had L74I). L74I was detected in plasma samples at over 2% frequency in 40% (46/115). Twelve (26.1%) had low-level minority variants of between 2% and 20% of the viral population sampled. The remaining 34 (73.9%) had L74I present at >20% frequency. L74I was more common among those with subtype G infection (55.3%, 26/47) than those with CRF02_AG infection (29.4%, 20/68) (P = 0.005).
CONCLUSIONS: HIV-1 subtypes circulating in West Africa appear to have very low prevalence of major integrase mutations, but significant prevalence of L74I. A combination of in vitro and clinical studies is warranted to understand the potential implications.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 259.2KB, Terms of use)
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- Publisher copy:
- 10.1093/jac/dkaa033
Authors
- Publisher:
- Oxford University Press
- Journal:
- Journal of Antimicrobial Chemotherapy More from this journal
- Volume:
- 75
- Issue:
- 6
- Pages:
- 1575-1579
- Publication date:
- 2020-02-27
- Acceptance date:
- 2020-01-16
- DOI:
- EISSN:
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1460-2091
- ISSN:
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0305-7453
- Pmid:
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32105319
- Language:
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English
- Keywords:
- Pubs id:
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1094655
- Local pid:
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pubs:1094655
- Deposit date:
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2021-01-09
Terms of use
- Copyright holder:
- El Bouzidi et al.
- Copyright date:
- 2020
- Rights statement:
- © The Author(s) 2020. 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 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.
- Licence:
- CC Attribution (CC BY)
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