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    Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria.

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    Author
    El Bouzidi, Kate
    Datir, Rawlings P
    Kwaghe, Vivian
    Roy, Sunando
    Frampton, Dan
    Breuer, Judith
    Ogbanufe, Obinna
    Murtala-Ibrahim, Fati
    Charurat, Man
    Dakum, Patrick
    Sabin, Caroline A
    Ndembi, Nicaise
    Gupta, Ravindra K
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    Journal
    Journal of Antimicrobial Chemotherapy
    Publisher
    Oxford University Press
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.1093/jac/dkab385
    http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8809188/
    Abstract
    Background: 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.
    Rights/Terms
    © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/17877
    ae974a485f413a2113503eed53cd6c53
    10.1093/jac/dkab385
    Scopus Count
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