HIV-1 drug resistance mutations: Potential applications for point-of-care Genotypic resistance testing

Soo Yon Rhee, Michael R. Jordan, Elliot Raizes, Arlene Chua, Neil Parkin, Rami Kantor, Gert U. Van Zy, Irene Mukui, Mina C. Hosseinipour, Lisa M. Frenkel, Nicaise Ndembi, Raph L. Hamers, Tobias F Rinke De Wit, Carole L. Wallis, Ravindra K. Gupta, Joseph Fokam, Clement Zeh, Jonathan M. Schapiro, Sergio Carmona, David KatzensteinMichele Tang, Avelin F. Aghokeng, Tulio De Oliveira, Annemarie M J Wensing, Joel E. Gallant, Mark A. Wainberg, Douglas D. Richman, Joseph E. Fitzgibbon, Marco Schito, Silvia Bertagnolio, Chunfu Yang, Robert W. Shafer

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere0145772
JournalPLoS One
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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