Mother to child transmission (MTCT) is the second leading mode of Human Immunodeficiency Virus (HIV) transmission worldwide, after heterosexual transmission. Although single dose nevirapine prophylaxis given to the mother during labor and to the baby after birth has prevented many perinatal infections, drug resistance develops in over half of those mothers treated and may limit future treatment options. The small molecule CCR5 (R5) inhibitors are ideal candidates to safely prevent MTCT using a single dose, with less risk of selecting for drug resistance. We propose a collaborative project to test R5 inhibitors in the prevention of MTCT of SIV (simian immunodeficiency virus) and SHIV (simian HIV) in macaques. Our long-term goals are to determine the effectiveness and optimal strategy of R5 inhibitors in the prevention of MTCT in a macaque model, and ultimately in HIV+ pregnant women. The initial steps in pursuit of this goal and the specific aims of this small grant R03 application are to obtain preliminary data on specific drugs and viruses to use in the macaque model. We will: 1) determine in vitro susceptibility of selected SIV and SHIVs to maraviroc, an R5 inhibitor late in development, 2) optimize previously described R5 receptor occupancy assays for use in macaques, and 3) determine the pharmacokinetics and placental transfer of maraviroc in pregnant macaques and their newborns.PROJECT NARRATIVE Nearly 700,000 children per year acquire HIV from their mothers, mostly in developing countries. Developing simple and affordable strategies to prevent mother-to-child transmission of HIV is a high priority.
| Winters, Mark A; Van Rompay, Koen K A; Kashuba, Angela D M et al. (2010) Maternal-fetal pharmacokinetics and dynamics of a single intrapartum dose of maraviroc in rhesus macaques. Antimicrob Agents Chemother 54:4059-63 |
