Current ideas about HIV prevention include a mixture of primarily biomedical interventions, socio-mechanical interventions such as sterile syringe and condom distribution, and behavioral interventions. This article presents a framework for socially-integrated transdisciplinary HIV prevention that may improve current prevention efforts. It first describes one socially-integrated transdisciplinary intervention project, the Transmission Reduction Intervention Project. We focus on how social aspects of the intervention integrate its component parts across disciplines and processes at different levels of analysis. We then present socially-integrated perspectives about how to improve combination antiretroviral treatment (cART) processes at the population level in order to solve the problems of the treatment cascade and make treatment as prevention more effective. Finally, we discuss some remaining problems and issues in such a social transdisciplinary intervention in the hope that other researchers and public health agents will develop additional socially-integrated interventions for HIV and other diseases.