NIH/NIAID R24 AI118397; Charles Flexner (PI); 05/01/15-04/31/20
ABSTRACT: (provided by applicant): Imperfect adherence to daily oral antiretroviral formulations is a major obstacle to the effectiveness of HIV therapy and pre-exposure prophylaxis (PrEP). An important and novel solution to this problem is long-acting/extended-release injectable antiretrovirals (LA/ER ARV's) that can be administered periodically in a clinic setting, eliminating the problems of pill fatigue, forgetfulness, missed doses, and privacy concerns related to pill taking. This strategy is especially important for vulnerable populations, including children, adolescents, pregnant women, intravenous drug users, and when HIV disclosure is associated with risk of stigma and/or violence. Because the development of these products is so complex and challenging, the Long Acting/Extended Release Antiretroviral Resource Program (LEAP) will assist investigators working on these new approaches by identifying solutions to common problems that take advantage of the best available technological and regulatory strategies. This program will provide a centralized resource to: 1) facilitate innovation by providing investigators with access to experts from the scientific, pharmaceutical, regulatory, and HIV-affected communities, 2) develop a web-based portal that will serve as a communications and data hub for researchers by creating a repository for important laboratory and clinical information and results, and 3) provide a state-of-the-art computer based modeling and simulation service that will guide selection of formulation, dose, and route of administration for new products. Because development of LA/ER ARV's currently entails significant scientific and financial risks, the field is moving slowly and resources such a these are necessary to facilitate development of new and existing compounds. Expected outcomes of this Program include more efficient translation of laboratory-based research into clinical trials and eventual drug approval, new products and formulations in preclinical and clinical stages of development, regulatory dialog and guidance for investigators, and print and web-based publications including systematic reviews of shared data that can serve as the basis for future product development.