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Basic Characteristics of Mutations
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Mutation Site
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G190A |
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Mutation Site Sentence
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Mutations K103N, Y181C, G190A, M184V and K65R were detected by an oligonucleotide ligation assay (OLA) and confirmed by Sanger and next-generation sequencing (NGS). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
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gag-pol:155348
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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HIV Infections
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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Y |
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Treatment
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nevirapine (NPV);efavirenz (EFV) |
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Location
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Kenyans |
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Literature Information
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PMID
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31956856
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Title
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Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya
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Author
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Beck IA,Levine M,McGrath CJ,Bii S,Milne RS,Kingoo JM,So I,Andersen N,Dross S,Coombs RW,Kiarie J,Chohan B,Sakr SR,Chung MH,Frenkel LM
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Journal
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EClinicalMedicine
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Journal Info
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2020 Jan 14;18:100239
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Abstract
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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.
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Sequence Data
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KF544089-KF544288; KJ395348-KJ395349; MH509760-MH509936; MK512771-MK513407
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