{"doi":"10.1093/jac/dkab385","title":"Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria","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.","journal":"Journal of Antimicrobial Chemotherapy","year":2021,"id":188718,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.96,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":333852,"name":"Rawlings Datir","orcid":"0000-0003-0521-2144","position":1,"is_corresponding":false},{"id":395917,"name":"Vivian Kwaghe","orcid":"0000-0003-1962-4641","position":2,"is_corresponding":false},{"id":395918,"name":"Sunando Roy","orcid":"0000-0001-5968-9111","position":3,"is_corresponding":false},{"id":396680,"name":"Dan Frampton","orcid":null,"position":4,"is_corresponding":false},{"id":289016,"name":"Judith Breuer","orcid":"0000-0001-8246-0534","position":5,"is_corresponding":false},{"id":396681,"name":"Obinna Ogbanufe","orcid":null,"position":6,"is_corresponding":false},{"id":395915,"name":"Fati Murtala-Ibrahim","orcid":"0000-0001-9943-8958","position":7,"is_corresponding":false},{"id":370648,"name":"Man Charurat","orcid":null,"position":8,"is_corresponding":false},{"id":380214,"name":"Patrick Dakum","orcid":"0000-0003-4278-5224","position":9,"is_corresponding":false},{"id":369298,"name":"Caroline Sabin","orcid":"0000-0001-5173-2760","position":10,"is_corresponding":false},{"id":36868,"name":"Nicaise Ndembi","orcid":"0000-0001-5131-3136","position":11,"is_corresponding":false},{"id":69659,"name":"Ravindra K. Gupta","orcid":"0000-0001-9751-1808","position":12,"is_corresponding":false},{"id":395914,"name":"Kate El Bouzidi","orcid":"0000-0002-3614-4570","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-18T23:49:10.350554Z","pmid":"34741609","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}