{"doi":"10.1016/j.eclinm.2019.100239","title":"Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya","abstract":"BackgroundPre-treatment HIV-drug-resistance (PDR) to WHO-recommended 1st-line non-nucleoside reverse transcriptase inhibitors (NNRTI)-based antiretroviral treatment (ART) is increasing in low-resource communities. We evaluated the risk of PDR on treatment failure if detected at single or multiple codons, at minority (2–9%) or higher (≥10%) frequencies during efavirenz- vs. nevirapine-ART.MethodsWe conducted a pooled analysis across three cohorts of Kenyans initiating 1st-line NNRTI-ART between 2006 and 2014. Mutations K103N, Y181C, G190A, M184V and K65R were detected by an oligonucleotide ligation assay (OLA) and confirmed by Sanger and next-generation sequencing (NGS). PDR was defined as detection of any mutation by OLA when confirmed by NGS. Treatment failure, defined as plasma HIV RNA ≥400 copies/mL at month-12 of ART, was compared by PDR genotypes.FindingsPDR was detected in 59/1231 (4·8%) participants. Compared to wild-type genotypes, PDR in participants prescribed nevirapine-ART was associated with increased treatment failure [PDR 69·2% (27/39) vs. wild-type 10·4% (70/674); p = 0·0001], whether detected as minority [66·7% (4/6)] or higher [69·7% (23/33)] frequencies in an individual's HIV quasispecies (p = 0·002 and p < 0·0001, respectively), or mutations at single [50·0% (12/24)] or multiple [100·0% (15/15)] codons (p < 0·0001). During efavirenz-ART, PDR was also associated with increased virologic failure [PDR 25·0% (5/20) vs. wild-type 5·0% (25/498); p = 0·005], but only if detected at multiple drug-resistant codons [50·0% (3/6); p = 0·003] or high frequencies PDR [33·3% (5/15); p = 0·001].InterpretationThe risk that PDR confers for treatment failure varies by number of mutant codons and their frequency in the quasispecies, with a lower risk for efavirenz- compared to nevirapine-based regimens. PDR detection and management could extend the effective use of efavirenz-ART in low-resource settings.FundingNIH, PEPFAR.","journal":"EClinicalMedicine","year":2020,"id":95695,"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":35,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9621,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":476188,"name":"Molly Levine","orcid":null,"position":1,"is_corresponding":false},{"id":412207,"name":"Christine J. McGrath","orcid":"0000-0003-3396-0350","position":2,"is_corresponding":false},{"id":476189,"name":"Steve Bii","orcid":null,"position":3,"is_corresponding":false},{"id":475211,"name":"Ross Milne","orcid":"0000-0002-5216-642X","position":4,"is_corresponding":false},{"id":475212,"name":"James Munyao Kingoo","orcid":"0000-0003-3860-3205","position":5,"is_corresponding":false},{"id":476190,"name":"Isaac So","orcid":null,"position":6,"is_corresponding":false},{"id":475213,"name":"Nina Andersen","orcid":"0009-0004-1284-2069","position":7,"is_corresponding":false},{"id":475214,"name":"Sandra Dross","orcid":"0000-0003-1013-6828","position":8,"is_corresponding":false},{"id":65748,"name":"Robert W. Coombs","orcid":"0000-0003-2709-0512","position":9,"is_corresponding":false},{"id":366536,"name":"James Kiarie","orcid":"0000-0003-4180-7858","position":10,"is_corresponding":false},{"id":331197,"name":"Bhavna Chohan","orcid":"0000-0002-2125-6799","position":11,"is_corresponding":false},{"id":476191,"name":"Samah R. Sakr","orcid":null,"position":12,"is_corresponding":false},{"id":377159,"name":"Michael H. Chung","orcid":"0000-0002-7315-5092","position":13,"is_corresponding":false},{"id":69658,"name":"Lisa M. Frenkel","orcid":"0000-0001-9566-8959","position":14,"is_corresponding":false},{"id":377158,"name":"Ingrid A. Beck","orcid":"0000-0001-7438-3209","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T22:33:57.534608Z","pmid":"31956856","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":[]}