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. ? ?
Showing the most recent 10 out of 28 publications
