Please use this identifier to cite or link to this item:
Title: Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: Programmatic implications for countries phasing out stavudine
Authors: Michele W. Tang
Soo Yon Rhee
Silvia Bertagnolio
Nathan Ford
Susan Holmes
Kim C. Sigaloff
Raph L. Hamers
Tobias F.Rinke De Wit
Herve J. Fleury
Phyllis J. Kanki
Kiat Ruxrungtham
Claudia A. Hawkins
Carole L. Wallis
Wendy Stevens
Gert U. Van Zyl
Weerawat Manosuthi
Mina C. Hosseinipour
Nicole Ngo-Giang-Huong
Laurent Belec
Martine Peeters
Avelin Aghokeng
Torsak Bunupuradah
Sherri Burda
Patricia Cane
Giulia Cappelli
Charlotte Charpentier
Anoumou Y. Dagnra
Alaka K. Deshpande
Ziad El-Katib
Susan H. Eshleman
Joseph Fokam
Jean Chrysostome Gody
David Katzenstein
Donato D. Koyalta
Johnstone J. Kumwenda
Marc Lallemant
Lutgarde Lynen
Vincent C. Marconi
Nicolas A. Margot
Sandrine Moussa
Thumbi Ndung'U
Phillipe N. Nyambi
Catherine Orrell
Jonathan M. Schapiro
Rob Schuurman
Sunee Sirivichayakul
Davey Smith
Maria Zolfo
Michael R. Jordan
Robert W. Shafer
Keywords: Medicine
Issue Date: 15-Jun-2013
Abstract: Background The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure.MethodsWe analyzed HIV-1 resistance mutations following first-line stavudine failure from 35 publications comprising 1,825 individuals. We also assessed the influence of concomitant nevirapine vs. efavirenz, therapy duration, and HIV-1 subtype on the proportions of mutations associated with zidovudine vs. tenofovir cross-resistance.ResultsMutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. Nevirapine increased the risk of TAMs, K65R, and Q151M. Longer therapy increased the risk of TAMs and Q151M but not K65R. Subtype C and CRF01-AE increased the risk of K65R, but only CRF01-AE increased the risk of K65R without Q151M.ConclusionsRegardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therapy. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
ISSN: 00221899
Appears in Collections:CMUL: Journal Articles

Files in This Item:
There are no files associated with this item.

Items in CMUIR are protected by copyright, with all rights reserved, unless otherwise indicated.