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dc.contributor.authorEl Bouzidi, Kate
dc.contributor.authorDatir, Rawlings P
dc.contributor.authorKwaghe, Vivian
dc.contributor.authorRoy, Sunando
dc.contributor.authorFrampton, Dan
dc.contributor.authorBreuer, Judith
dc.contributor.authorOgbanufe, Obinna
dc.contributor.authorMurtala-Ibrahim, Fati
dc.contributor.authorCharurat, Man
dc.contributor.authorDakum, Patrick
dc.contributor.authorSabin, Caroline A
dc.contributor.authorNdembi, Nicaise
dc.contributor.authorGupta, Ravindra K
dc.date.accessioned2022-02-04T14:22:01Z
dc.date.available2022-02-04T14:22:01Z
dc.identifier.urihttp://hdl.handle.net/10713/17877
dc.description.abstractBackground: Deep sequencing could improve understanding of HIV treatment failure and viral population dynamics. However, this tool is often inaccessible in low- and middle-income countries. Objectives: To determine the genetic patterns of resistance emerging in West African HIV-1 subtypes during first-line virological failure, and the implications for future antiretroviral options. Patients and methods: Participants were selected from a Nigerian cohort of people living with HIV who had failed first-line ART and subsequently switched to second-line therapy. Whole HIV-1 genome sequences were generated from first-line virological failure samples with Illumina MiSeq. Mutations detected at ≥2% frequency were analysed and compared by subtype. Results: HIV-1 sequences were obtained from 101 participants (65% female, median age 30 years, median 32.9 months of nevirapine- or efavirenz-based ART). Thymidine analogue mutations (TAMs) were detected in 61%, other core NRTI mutations in 92% and NNRTI mutations in 99%. Minority variants (<20% frequency) comprised 18% of all mutations. K65R was more prevalent in CRF02_AG than G subtypes (33% versus 7%; P = 0.002), and ≥3 TAMs were more common in G than CRF02_AG (52% versus 24%; P = 0.004). Subtype G viruses also contained more RT cleavage site mutations. Cross-resistance to at least one of the newer NNRTIs, doravirine, etravirine or rilpivirine, was predicted in 81% of participants. Conclusions: Extensive drug resistance had accumulated in people with West African HIV-1 subtypes, prior to second-line ART. Deep sequencing significantly increased the detection of resistance-associated mutations. Caution should be used if considering newer-generation NNRTI agents in this setting.en_US
dc.description.urihttps://doi.org/10.1093/jac/dkab385en_US
dc.description.urihttp://www.ncbi.nlm.nih.gov/pmc/articles/pmc8809188/en_US
dc.language.isoenen_US
dc.publisherOxford University Pressen_US
dc.relation.ispartofJournal of Antimicrobial Chemotherapyen_US
dc.rights© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.en_US
dc.titleDeep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria.en_US
dc.typeArticleen_US
dc.identifier.doi10.1093/jac/dkab385
dc.identifier.pmid35107160
dc.source.journaltitleThe Journal of antimicrobial chemotherapy
dc.source.volume77
dc.source.issue2
dc.source.beginpage474
dc.source.endpage482
dc.source.countryUnited States
dc.source.countryEngland


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