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HIV-1 drug resistance mutations: potential applications for point-of-care genotypic resistance testing | Journal Article / Research | MSF Science Portal
Journal Article
|Research

HIV-1 drug resistance mutations: potential applications for point-of-care genotypic resistance testing

Rhee SY, Jordan MR, Raizes E, chua AC, Parkin N, Kantor R, Van Zyl GU, Mukui I, Hosseinipour MC, Frenkel LM, Ndembi N, Hamers RL, Rinke de Wit TF, Wallis CL, Gupta RS, Fokam J, Zeh C, Schapiro JM, Carmona S, Katzenstein D, Tang M, Aghokeng AF, De Oliveira T, Wensing AM, Gallant JE, Wainberg MA, Richman DD, Fitzgibbon JE, Schito M, Bertagnolio S, Yang C, Shafer RW
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Abstract
The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.

Countries

none

Subject Area

antibiotic resistancediagnostics

Languages

English
DOI
10.1371/journal.pone.0145772
Published Date
30 Dec 2015
PubMed ID
26717411
Journal
PLOS One
Volume | Issue | Pages
Volume 10, Issue 12, Pages e0145772
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