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

Autor:	Beck IA; Center for Infectious Diseases Research, Seattle Children's Research Institute, Seattle, WA, United States., Levine M; Center for Infectious Diseases Research, Seattle Children's Research Institute, Seattle, WA, United States., McGrath CJ; Department of Global Health, University of Washington, Seattle, WA, United States., Bii S; Center for Infectious Diseases Research, Seattle Children's Research Institute, Seattle, WA, United States., Milne RS; Center for Infectious Diseases Research, Seattle Children's Research Institute, Seattle, WA, United States., Kingoo JM; Department of Global Health, University of Washington, Seattle, WA, United States.; Coptic Hope Center for Infectious Diseases, Coptic Hospital, Nairobi, Kenya., So I; Center for Infectious Diseases Research, Seattle Children's Research Institute, Seattle, WA, United States., Andersen N; Center for Infectious Diseases Research, Seattle Children's Research Institute, Seattle, WA, United States., Dross S; Center for Infectious Diseases Research, Seattle Children's Research Institute, Seattle, WA, United States.; Department of Global Health, University of Washington, Seattle, WA, United States., Coombs RW; Department of Medicine, University of Washington, Seattle, WA, United States.; Department of Laboratory Medicine, University of Washington, Seattle, WA, United States., Kiarie J; Department of Obstetrics and Gynecology, University of Nairobi, Nairobi, Kenya., Chohan B; Department of Global Health, University of Washington, Seattle, WA, United States.; Kenya Medical Research Institute, Nairobi, Kenya., Sakr SR; Coptic Hope Center for Infectious Diseases, Coptic Hospital, Nairobi, Kenya., Chung MH; Department of Global Health, University of Washington, Seattle, WA, United States.; Department of Medicine, Aga Khan University, Nairobi, Kenya., Frenkel LM; Center for Infectious Diseases Research, Seattle Children's Research Institute, Seattle, WA, United States.; Department of Global Health, University of Washington, Seattle, WA, United States.; Department of Medicine, University of Washington, Seattle, WA, United States.; Department of Laboratory Medicine, University of Washington, Seattle, WA, United States.; Department of Pediatrics, University of Washington, Seattle, WA, United States.
Jazyk:	angličtina
Zdroj:	EClinicalMedicine [EClinicalMedicine] 2020 Jan 14; Vol. 18, pp. 100239. Date of Electronic Publication: 2020 Jan 14 (Print Publication: 2020).
DOI:	10.1016/j.eclinm.2019.100239
Abstrakt:	Background: 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. Methods: 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. Findings: 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 <  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]. Interpretation: The 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. Funding: NIH, PEPFAR. Competing Interests: The authors have no conflicts of interest to declare. (© 2019 Published by Elsevier Ltd.)
Databáze:	MEDLINE
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