Preclinical Development of Longer Acting Topical Antiretroviral Delivery Systems

Over the last 10 years the Kiser Lab and CONRAD have conducted several effective collaborations together aimed at a series of intravaginal ring products that are now approaching the clinic. This project will leverage these experiences and seeks to develop an intravaginal ring that can deliver elvitegravir (EVG), an integrase inhibitor, and tenofovir up to three months or longer. It will also explore the feasibility of developing intravaginal rings for the delivery of more potent tenofovir prodrugs and/or other integrase inhibitors. The EVG/TFV IVR will be based off of the TFV IVR design and our preliminary data. The indication of this product is to prevent the acquisition of HIV through constant and consistent use of the product. The route of administration is intravaginal and the dosage form is a polyurethane thermoplastic IVR containing at least one segment. The dosing schedule we are targeting is once per 90 days. The average dose over 90 days will be ~ 300 μg/day of elvitegravir and ~10 mg/day of TFV. The device will be composed of one or two or segments of thermoplastic polyurethane. One is highly preferred for manufacturing reasons. The IVR dimensions will be approximately 5 mm in cross section and 55 mm outer diameter. The ring will require approximately 1.5 to 3 N to compress it 10%.