This proposal requests support for a Keystone Symposia meeting entitled HIV Evolution, Genomics, and Pathogenesis, organized by Michael Emerman, Melissa Robbiani and Amalio Telenti, which will be held in Whistler, British Columbia, Canada from March 20 - 25, 2011. Elucidating the molecular mechanisms of HIV pathogenesis relies on understanding the complex interplay between the virus and its host. Increasingly, the field is relying on the power of comparative studies of similar viruses in other species and on whole genome analyses to elucidate which pathways are critical to this interplay. The use of evolutionary analyses of both host and virus is also providing novel insights into viral transmission and innate immune responses. This meeting will take advantage of research from diverse disciplines to promote further insights into the dynamic interplay between the virus and the host in areas of pathogenesis, mucosal biology, the roles of viral and host genes, and viral latency. Understanding these issues is critical for the design and development of an effective vaccine and the next generation of antiviral agents. Opportunities for interdisciplinary interactions will be significantly enhanced by the concurrent meeting on Protection from HIV: Targeted Intervention Strategies, which will share a keynote address and two plenary sessions with this meeting. Project Narrative: HIV continues to be a major world health problem with tens of millions of individuals infected worldwide. There has been great progress in the development of drugs to treat infection with HIV;however, the virus can develop resistance to these therapies and, consequently, there is still a great need to develop additional therapies to treat infected individuals. The Keystone Symposia meeting on HIV Evolution, Genomics, and Pathogenesis will gather researchers from diverse disciplines to highlight basic research in the study of HIV virology and immunology, and will promote further insights critical for the design and development of an effective vaccine and the next generation of antiviral agents against HIV.