Clinical Relevance of Transient Nevirapine Resistance
Principal Investigator: Louise Kuhn
Abstract: [unreadable] DESCRIPTION (provided by applicant): Nevirapine (NVP) is a simple, effective and relatively safe antiretroviral drug now widely used in low resource settings around the world to prevent mother-to-child transmission of HIV. NVP is also a useful drug to use as part of treatment regimens. Concern has been raised that exposure to this drug for prevention may compromise its use in treatment. The concern has arisen because viral mutations which confer resistance to NVP appear to be common among HIV-infected women and children after exposure to even single dose NVP. A study is proposed to test whether or not exposure to NVP for prevention of mother-to-child HIV transmission, and the resulting NVP resistance mutations associated with its use, will adversely influence response to a subsequent treatment regimen which includes NVP. The study will recruit HIV-infected women and their children, NVP-exposed and unexposed, in Johannesburg, South Africa, who meet criteria for starting antiretroviral treatment and will start them on a treatment regimen which includes NVP. HIVinfected women and children exposed to NVP prophylaxis will be compared to similar unexposed women and children. Further, among those exposed to NVP prophylaxis, those with NVP resistance mutations at 6 weeks post-NVP exposure will be compared to those exposed to NVP but who do not have detectable mutations. The primary study outcome is treatment failure defined on the basis of virologic outcomes at 6 months after starting treatment. Secondary objectives of the study are to characterize the nature of viral resistance mutations associated with NVP prophylaxis (including the specific mutations present, their occurrence in plasma and/or PBMCs, their frequency if the threshold of detection is lowered to detect mutations present at low frequencies in the viral population) and to investigate whether these characteristics of viral resistance explain treatment failure. The study will generate empirical data essential for formulation of evidence-based treatment policies for the hundreds of thousands of HIV-infected women and children living in low resource settings who are likely to have had prior exposure to NVP. [unreadable] [unreadable]
Funding Period: 2004-09-01 - 2010-06-30
more information: NIH RePORT
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AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa
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IrsiCaixa AIDS Research Institute, Badalona, Catalonia, Spain
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Gertrude H Sergievsky Center, College of Physicians and Surgeons, Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
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Gertrude H Sergievsky Center, College of Physicians and Surgeons, Columbia University Medical Center, 630 W 168th Street, New York, NY 10032, USA
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Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa
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ICAP Columbia University, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
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Gertrude H Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Columbia University, New York, NY 10032, USA
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AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa
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Nordic School of Public Health NHV, Gothenburg, Sweden
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Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
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Gertrude H Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, United States of America
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Division of Infectious Diseases, Department of Medicine, University of Texas Health Sciences Center at San Antonio, USA
AIDS Res Hum Retroviruses 27:945-56. 2011..Only children who received RTV-based ART developed major PI-related resistance mutations, and use of this regimen should be avoided...
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Gertrude H Sergievsky Center and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York City, New York 10032, USA
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Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, Johannesburg, South Africa
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Columbia University College of Physicians and Surgeons, New York, New York, USA
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Empilweni Clinic, Coronation Women and Children Hospital, Johannesburg, South Africa
Clin Infect Dis 48:462-72. 2009....
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Gertrude H, Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY USA
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