Background: Although substantial progress has been made to identify new biomedical HIV prevention strategies, including topical and oral antiretroviral drug pre-exposure prophylaxis (PrEP) regimens and vaccines, they are not yet approved for general use. However, these preventions (or related derivatives) are likely to be implemented widely in upcoming years. The identification of HIV preventions such as these, despite being only partially efficacious, offer an opportunity for small companies with flexible portfolios to consider the possibility of combining novel or existing biomedical preventions to generate a high probability for complete protection. Because future clinical trials of HIV vaccines will likely incorporate control arms that include PrEP, there is also a need to model whether such combinations may result in additive, synergistic, neutral or even subtractive effects. Non-human primate modeling, to determine the efficacy and interactions of combinations of two partially effective, clinically relevant HIV biomedical prevention approaches, can directly inform clinical trial design and impact the implementation of biomedical preventions against HIV. Project Goal: The long-term goal of this project is to determine, in non-human primates, whether two biomedical HIV preventions, such as vaccines and PrEP, may be combined to achieve additive or synergistic protective efficacy. Proposals are sought where small businesses will combine biomedical preventions, such as vaccines and drugs that are known to have efficacy (complete or partial), to prevent HIV infection in humans or animal models of HIV. In the event that one or both prevention modalities do not have extensive prior assessment in non-human primates or human clinical trials, demonstration of safety and scalability is of primary importance. Safety testing can include use of in vitro or small animal model testing. Proposals should include plans for the design, construction and characterization of prevention modalities suitable for efficacy assessments of the combination of partially effective interventions in a relevant non-human primate model. Proposals should also document a detailed description of the prevention modalities and pre-clinical assessment protocols. Impact: Globally, more than 2.6 million new HIV infections occur each year (>50,000 in the US). As such, the need for efficacious biomedical preventions is urgently needed to complement existing behavioral interventions. This mechanism specifically enables small businesses to rapidly conduct relevant pre-clinical evaluation of combined HIV prevention products in a nonhuman primate model that presages the changing landscape of domestic HIV prevention trials to incorporate PrEP as a standard of care. Combined HIV prevention products in a nonhuman primate model could facilitate the identification of the most promising HIV prevention solutions early in the developmental pipeline, which would accelerate the pace at which they are translated into effective products to prevent HIV infections.