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.
Below: Absolute and Cumulative Prevalence of Major
Lopinavir-Associated Mutations in 203 Viruses with Intermediate or High-Level
Lopinavir (LPV) Resistance from 1,214 Previously PI-Naïve Individuals with
Virological Failure on a Ritonavir-Boosted LPV (LPV/r)-Containing Regimen.
Full article at: http://goo.gl/moEYwZ
By:
Soo-Yon Rhee, David Katzenstein, Michele Tang, Robert W.
Shafer
Department of Medicine, Stanford
University, Stanford, CA, United States of America
Michael R. Jordan
Tufts University School of
Medicine, Boston, MA, United States of America
Elliot Raizes, Chunfu Yang
Division of Global HIV/AIDS,
Centers for Disease Control and Prevention, Atlanta, GA, United States of
America
Arlene Chua
Medecins Sans Frontieres, Access
Campaign, Geneva, Switzerland
Arlene Chua
Institute of Infectious Diseases
and Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore
Neil Parkin
Data First Consulting, Belmont,
CA, United States of America
Rami Kantor
Alpert Medical School, Brown
University, Providence, RI, United States of America
Gert U. Van Zyl
National Health Laboratory
Service, Tygerberg, Coastal Branch, South Africa
Gert U. Van Zyl
Division of Medical Virology,
Stellenbosch University, Parow, South Africa
Irene Mukui
National AIDS and Sexually
Transmitted Infection (STI) Control Programme, Ministry of Health, Nairobi,
Kenya
Mina C. Hosseinipour
UNC Project, Lilongwe, Malawi
Lisa M. Frenkel
University of Washington and
Seattle Children’s Research Institute, Seattle, WA, United States of America
Nicaise Ndembi
Institute of Human Virology,
Abuja, Nigeria
Raph L. Hamers, Tobias F. Rinke de Wit
Amsterdam Institute for Global
Health and Development (AIGHD), Department of Global Health, Academic Medical
Center of the University of Amsterdam, Amsterdam, Netherlands
Carole L. Wallis
Lancet Laboratories and BARC-SA,
Johannesburg, South Africa
Ravindra K. Gupta
Department of Infection,
University College London, London, United Kingdom
Joseph Fokam
Chantal BIYA International
Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé,
Cameroon
Joseph Fokam
Faculty of Medicine and
Biomedical Sciences (FMBS) of the University of Yaounde 1, Yaounde, Cameroon
Clement Zeh
Division of HIV/AIDS Prevention,
Centers for Disease Control and Prevention, Atlanta, Georgia, United States of
America
Jonathan M. Schapiro
National Hemophilia Center, Tel
Hashomer, Israel
Sergio Carmona
Department of Haematology and
Molecular Medicine, University of Witwatersrand, Johannesburg, South Africa
Sergio Carmona
National Health Laboratory
Services, Johannesburg, South Africa
Avelin F. Aghokeng
Virology Laboratory CREMER-IMPM,
Yaoundé, Cameroon
Tulio De Oliveira
Africa Centre for Health and
Population Studies, School of Laboratory Medicine and Medical Sciences,
University of KwaZulu-Natal, Durban, South Africa
Annemarie M. J. Wensing
Virology, Department of Medical
Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands
Joel E. Gallant
Southwest CARE Center, Santa Fe,
NM, United States of America
Mark A. Wainberg
McGill University AIDS Centre,
Jewish General Hospital, Montreal, Quebec, Canada
Douglas D. Richman
Department of Pathology,
University of California San Diego, La Jolla, CA, United States of America
Douglas D. Richman
Veterans Affairs San Diego
Healthcare System, San Diego, CA, United States of America
Joseph E. Fitzgibbon
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
Marco Schito
HJF-DAIDS, A Division of The
Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.,
Bethesda, MD, United States of America
Silvia Bertagnolio
HIV Department WHO, Geneva,
Switzerland
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