ABSTRACT The dual impacts of the HIV/AIDS pandemic and unintended pregnancies constitute a major health burden for women worldwide and justify the development of highly-effective next-generation multipurpose prevention technologies (NGM) that combine safe, effective, and easily reversible long-acting contraception with HIV prevention. Here, we propose to adapt a memory wire copper intrauterine device (IUD) frame as a platform for intrauterine delivery of antiretroviral (AVR) drugs to provide user friendly HIV pre-exposure prophylaxis (PrEP) and contraception. We propose to evaluate ARV drug delivery systems compatible with IUD delivery for duel- protection up to three years. In Aim 1, we will formulate candidate antiviral drug/prodrug solid dispersions in matrix, reservoir and electrospun drug delivery systems and integrate these into an existing copper IUD to optimize drug loading, dissolution rate, chemical and functional stability, and stable integration with and functional attributes of the IUD. We will then evaluate the safety and pharmacokinetic effects of intrauterine delivery of candidate devices in baboons, and measure drug concentrations in the vagina, cervix, and endometrium. Finally, in Aim 3 we will use the macaque model to evaluate the protective efficacy of the drug- eluting delivery system for HIV pre-exposure prophylaxis against a repeated low-dose vaginal SHIV162P3 challenge.