دورية أكاديمية
High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment
| العنوان: | High prevalence of integrase mutation L74I in West African HIV-1 subtypes prior to integrase inhibitor treatment |
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| المؤلفون: | El, Bouzidi, K., Kemp, S.A., Charurat, M.E. |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2020 |
| المجموعة: | UMB Digital Archive (University of Maryland, Baltimore) |
| مصطلحات موضوعية: | integrase L74I mutation, HIV Integrase Inhibitors, HIV-1, Africa, Western |
| الوصف: | 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. Copyright The Author(s) 2020. ; https://doi.org/10.1093/jac/dkaa033Test |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | The Journal of antimicrobial chemotherapy; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85084717778&doi=10.1093%2fjac%2fdkaa033&partnerID=40&md5=277fe6b3b47b946788ca899eeb461748Test; http://hdl.handle.net/10713/12825Test |
| DOI: | 10.1093/jac/dkaa033 |
| الإتاحة: | https://doi.org/10.1093/jac/dkaa033Test http://hdl.handle.net/10713/12825Test |
| رقم الانضمام: | edsbas.A8B2381B |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/jac/dkaa033 |
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