Prevention of HIV Transmission in Breast Feeding Populations

DESCRIPTION (provided by applicant): The broad long term goal of this project is to prevent mother to child transmission of HIV through breast feeding in resource poor countries. In the developing world, perinatal transmission is greatly reduced through relatively simple expedients such as dosing mother and child around the time of delivery with nevirapine. However breast feeding still accounts for approximately 315,000 cases annually of pediatric AIDS in sub- Saharan Africa. A Phase III trial is underway to study daily oral nevirapine to be given to infants in order to reduce this transmission. We have developed a platform technology for the sustained release of a broad range of drugs by subcutaneous / intramuscular injection that can potentially provide 6 weeks of protection from each injection. A program that incorporates these injections could piggyback onto existing accelerated immunization protocols. The specific aims of this Phase I proposal are to: 1, formulate sustained release suspensions for nevirapine; 2, test the in vitro release characteristics of these formulations into buffer; and 3, test the in vivo pharmacokinetics and the safety of the formulations in rats. The team of investigators is expert in polymer chemistry, pharmacokinetics and drug development. The Vitrasert(r) implant for the treatment of AIDS-related CMV retinitis was developed in the lab of the Principal Investigator of this proposal. The successful completion of this project will lead rapidly to the development of an injectable dosage form that could ideally deliver continuous antiviral blood levels. Completion of these aims will constitute a readily identifiable milestone that will continue in Phase 2, in which we will clarify the pharmacokinetics and safety of the formulation in animal models in order to submit an Investigational New Drug exemption to the FDA.