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Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations Associated with First-Line Stavudine-Containing Antiretroviral Therapy: Programmatic Implications for Countries Phasing Out Stavudine

Tang, Michele W. ; Rhee, Soo-Yon ; Bertagnolio, Silvia ; Ford, Nathan ; Holmes, Susan ; Sigaloff, Kim C. ; Hamers, Raph L. ; de Wit, Tobias F. Rinke ; Fleury, Herve J. ; Kanki, Phyllis J. ; Ruxrungtham, Kiat ; Hawkins, Claudia A. ; Wallis, Carole L. ; Stevens, Wendy ; van Zyl, Gert U. ; Manosuthi, Weerawat ; Hosseinipour, Mina C. ; Ngo-Giang-Huong, Nicole ; Belec, Laurent ; Peeters, Martine ; Aghokeng, Avelin ; Bunupuradah, Torsak ; Burda, Sherri ; Cane, Patricia ; Cappelli, Giulia ; Charpentier, Charlotte ; Dagnra, Anoumou Y. ; Deshpande, Alaka K. ; El-Katib, Ziad ; Eshleman, Susan H. ; Fokam, Joseph ; Gody, Jean-Chrysostome ; Katzenstein, David ; Koyalta, Donato D. ; Kumwenda, Johnstone J. ; Lallemant, Marc ; Lynen, Lutgarde ; Marconi, Vincent C. ; Margot, Nicolas A. ; Moussa, Sandrine ; Ndung'u, Thumbi ; Nyambi, Phillipe N. ; Orrell, Catherine ; Schapiro, Jonathan M. ; Schuurman, Rob ; Sirivichayakul, Sunee ; Smith, Davey ; Zolfo, Maria ; Jordan, Michael R. ; Shafer, Robert W.

In: The Journal of Infectious Diseases, 2013, vol. 207, p. S70-S77

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    Title
    • Nucleoside Reverse Transcriptase Inhibitor Resistance Mutations Associated with First-Line Stavudine-Containing Antiretroviral Therapy: Programmatic Implications for Countries Phasing Out Stavudine
    Author
    • Tang, Michele W.. Division Infectious Diseases, Department of Medicine, Stanford University, California
    • Rhee, Soo-Yon. Division Infectious Diseases, Department of Medicine, Stanford University, California
    • Bertagnolio, Silvia. WHO/HTM/TCO, Geneva, Switzerland
    • Ford, Nathan. WHO/HTM/TCO, Geneva, Switzerland
    • Holmes, Susan. Department of Statistics, Stanford University, California
    • Sigaloff, Kim C.. PharmAccess Foundation, Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam Institute for Global Health and Development, The Netherlands
    • Hamers, Raph L.. PharmAccess Foundation, Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam Institute for Global Health and Development, The Netherlands
    • de Wit, Tobias F. Rinke. PharmAccess Foundation, Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam Institute for Global Health and Development, The Netherlands
    • Fleury, Herve J.. Laboratoire de Virologie (WHO accredited), CHU de Bordeaux, Bordeaux, France
    • Kanki, Phyllis J.. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
    • Ruxrungtham, Kiat. Department of Medicine, Chulalongkorn University, and Thai Red Cross AIDS Research Center, Bangkok, Thailand
    • Hawkins, Claudia A.. Northwestern University, Chicago, Illinois
    • Wallis, Carole L.. Lancet Laboratories, Johannesburg, South Africa
    • Stevens, Wendy. Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa, and National Laboratory Health Services, South Africa
    • van Zyl, Gert U.. Division of Medical Virology, Stellenbosch University, Tygerberg, Cape Town, South Africa
    • Manosuthi, Weerawat. Department of Medicine, Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand
    • Hosseinipour, Mina C.. University of North Carolina Project, Kamuzu Central Hospital, Lilongwe, Malawi
    • Ngo-Giang-Huong, Nicole. Institut de Recherche pour le Developpement IRD U174, Program for HIV Prevention and Treatment, Chiang Mai, Thailand
    • Belec, Laurent. Laboratoire de Virologie, Hôpital Européen Georges Pompidou, 75908 Paris Cedex 15, France, and Université Paris Descartes, Sorbonne Paris Cité, Paris, France
    • Peeters, Martine. UMI233, TransVIHMI, Institut de Recherche pour le Développement (IRD) and Université Montpellier 1, Montpellier, France
    • Aghokeng, Avelin. UMI233, TransVIHMI, Institut de Recherche pour le Développement (IRD) and Université Montpellier 1, Montpellier, France
    • Bunupuradah, Torsak. The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), The Thai Red Cross AIDS Research Centre
    • Burda, Sherri. Department of Pathology, New York University School of Medicine, New York, New York
    • Cane, Patricia. Health Protection Agency, London, United Kingdom
    • Cappelli, Giulia. Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé, Cameroon
    • Charpentier, Charlotte. Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Université Paris Diderot, Paris 7, PRES Sorbonne Paris Cité, EA4409, Paris, France
    • Dagnra, Anoumou Y.. Centre National de Référence des tests VIH-IST/PNLS and Laboratoire BIOLIM, FMMP/UL, Lomé, Togo
    • Deshpande, Alaka K.. ART Center, Sir JJ Hospital, Byculla, Mumbai, India
    • El-Katib, Ziad. Division of Cancer Epidemiology; McGill University, Montreal, Canada
    • Eshleman, Susan H.. Dept. of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
    • Fokam, Joseph. Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé, Cameroon
    • Gody, Jean-Chrysostome. Faculté des Sciences de la Santé Bangui, République Centrafricaine
    • Katzenstein, David. Division Infectious Diseases, Department of Medicine, Stanford University, California
    • Koyalta, Donato D.. Hôpital Général de Référence Nationale, N'Djamena, Chad
    • Kumwenda, Johnstone J.. Dept. of Medicine, College of Medicine, University of Malawi, Blantyre, Malawi
    • Lallemant, Marc. Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts
    • Lynen, Lutgarde. Institute of Tropical Medicine (ITM), Antwerp, Belgium
    • Marconi, Vincent C.. Emory University School of Medicine, Atlanta, Georgia
    • Margot, Nicolas A.. Gilead Sciences Inc., Foster City, California
    • Moussa, Sandrine. Unité des Rétrovirus et des Virus Oncogènes, Institut Pasteur de Bangui, Bangui, Central African Republic
    • Ndung'u, Thumbi. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa
    • Nyambi, Phillipe N.. Department of Pathology, New York University School of Medicine, New York, New York
    • Orrell, Catherine. Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa
    • Schapiro, Jonathan M.. National Hemophilia Center, Tel Hashomer, Israel
    • Schuurman, Rob. Department of Virology, University Medical Center Utrecht, The Netherlands
    • Sirivichayakul, Sunee. Department of Medicine, Chulalongkorn University, and Thai Red Cross AIDS Research Center, Bangkok, Thailand
    • Smith, Davey. Division of Infectious Diseases, University of California San Diego, San Diego, California
    • Zolfo, Maria. Institute of Tropical Medicine (ITM), Antwerp, Belgium
    • Jordan, Michael R.. Tufts University School of Medicine, Boston, Massachusetts
    • Shafer, Robert W.. Division Infectious Diseases, Department of Medicine, Stanford University, California
    Document Type
    • Postprint
    Language
    • English
    Published in
    • The Journal of Infectious Diseases, 2013, vol. 207, p. S70-S77. Oxford University Press
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:298986
    Summary
    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. Methods We 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. Results Mutations 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. Conclusions Regardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therapy