Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya

Pre-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 m...

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Veröffentlicht in:EClinicalMedicine 2020-01, Vol.18, p.100239-100239, Article 100239
Hauptverfasser: Beck, Ingrid A., Levine, Molly, McGrath, Christine J., Bii, Steve, Milne, Ross S., Kingoo, James M., So, Isaac, Andersen, Nina, Dross, Sandra, Coombs, Robert W., Kiarie, James, Chohan, Bhavna, Sakr, Samah R., Chung, Michael H., Frenkel, Lisa M.
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Sprache:eng
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Zusammenfassung:Pre-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. We 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. PDR 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 
ISSN:2589-5370
2589-5370
DOI:10.1016/j.eclinm.2019.100239