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PLoS One. 2015 Dec 30;10(12):e0145772. doi: 10.1371/journal.pone.0145772. eCollection 2015.

HIV-1 Drug Resistance Mutations: Potential Applications for Point-of-Care Genotypic Resistance Testing.

Author information

1
Department of Medicine, Stanford University, Stanford, CA, United States of America.
2
Tufts University School of Medicine, Boston, MA, United States of America.
3
Division of Global HIV/AIDS, Centers for Disease Control and Prevention, Atlanta, GA, United States of America.
4
Medecins Sans Frontieres, Access Campaign, Geneva, Switzerland.
5
Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore.
6
Data First Consulting, Belmont, CA, United States of America.
7
Alpert Medical School, Brown University, Providence, RI, United States of America.
8
National Health Laboratory Service, Tygerberg, Coastal Branch, South Africa.
9
Division of Medical Virology, Stellenbosch University, Parow, South Africa.
10
National AIDS and Sexually Transmitted Infection (STI) Control Programme, Ministry of Health, Nairobi, Kenya.
11
UNC Project, Lilongwe, Malawi.
12
University of Washington and Seattle Children's Research Institute, Seattle, WA, United States of America.
13
Institute of Human Virology, Abuja, Nigeria.
14
Amsterdam Institute for Global Health and Development (AIGHD), Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, Netherlands.
15
Lancet Laboratories and BARC-SA, Johannesburg, South Africa.
16
Department of Infection, University College London, London, United Kingdom.
17
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé, Cameroon.
18
Faculty of Medicine and Biomedical Sciences (FMBS) of the University of Yaounde 1, Yaounde, Cameroon.
19
Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
20
National Hemophilia Center, Tel Hashomer, Israel.
21
Department of Haematology and Molecular Medicine, University of Witwatersrand, Johannesburg, South Africa.
22
National Health Laboratory Services, Johannesburg, South Africa.
23
Virology Laboratory CREMER-IMPM, Yaoundé, Cameroon.
24
Africa Centre for Health and Population Studies, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
25
Virology, Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
26
Southwest CARE Center, Santa Fe, NM, United States of America.
27
McGill University AIDS Centre, Jewish General Hospital, Montreal, Quebec, Canada.
28
Department of Pathology, University of California San Diego, La Jolla, CA, United States of America.
29
Veterans Affairs San Diego Healthcare System, San Diego, CA, United States of America.
30
Drug Development and Clinical Sciences Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America.
31
HJF-DAIDS, A Division of The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, United States of America.
32
HIV Department WHO, Geneva, Switzerland.

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.

PMID:
26717411
PMCID:
PMC4696791
DOI:
10.1371/journal.pone.0145772
[Indexed for MEDLINE]
Free PMC Article

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