CORE B Highly Active Antiretroviral Therapy (HAART), where antiretroviral (ARV) drugs are given in combination, has become the standard in treatment of HIV/AIDS. There is growing consensus that combinations of ARV agents are going to be needed for an optimally effective non-vaccine biomedical prevention (nBP) strategy for HIV. Difficulty in formulation and delivery of ARV combinations has limited the ability to determine efficacious and safe nBP products for vaginal topical application. Additionally, difficulty in determining adherence in topical microbicide clinical trials has limited the ability of these trials to measure efficacy of HIV prevention in human populations. The long-term goal of this IPCP-MBP effort is to develop intravaginal ring (IVR) formulations of multiple ARV drugs for prevention of sexual HIV transmission, emphasizing the needs of women in the developing world. The specific objective of Core B is to formulate a library of IVRs for delivering ARV combinations consisting of FDA-approved drugs and to provide these formulations to the component projects of the IPCP: Project 1-pharmacokinetics (PK), Project 2-safety, Project 3-efficacy, Project 4-(pre-Phase I) Exploratory Clinical Trial. Selection of the best performing candidate combination will be accomplished through a novel screening process involving iterative formulation development informed by PK, safety, and efficacy results. This optimized formulation will be transitioned into Project 5 to develop methods and capacity to manufacture clinical cGMP lots of the best performing candidate IVR at GMOs. The formulation efforts throughout this multi-faceted IND-enabling critical path will enable advancement of the lead formulation of the safest and most efficacious combination into post-IPCP Phase I clinical trials. In order to address the difficulty microbicide trials have encountered in assessing adherence to treatment, a novel adherence IVR has been developed that uses temperature measurement to determine and record hourly if an IVR is being worn. The prototype device will be optimized for use in women and evaluated in a pilot clinical study.