Despite the tremendous progress in the treatment and prevention of HIV infection in the United States there remain significant deficiencies in care and prevention. Antiretroviral therapy failure occurs, unexpected toxicities have emerged, long-term secondary complications have arisen, mother-to-child transmission still befalls mothers and infants in resource poor settings, and the rate of infection continues unabated. The Southeastern United States has the fastest rising number of new HIV infections in the U.S., particularly among African American women. This places Alabama and the University of Alabama Birmingham (UAB) in the heart of this growing epidemic that disproportionately afflicts the most vulnerable populations. This is confounded by the fact that an estimated 50% of infected individuals in this region are unaware they are carrying the virus. The UAB Center for AIDS Research (CFAR) has been at the forefront of HIV prevention and therapeutic investigation for over 18 years. The UAB CFAR is committed to providing the most modern, up to date, therapeutic and prevention interventions to patients and at-risk populations in our State. In response to the NIAID's call for site applications to perform clinical studies that address the emerging issues in HIV treatment and prevention, the UAB CFAR has formed the Alabama-Clinical Trials Unit (A-CTU): A partnership of UAB investigators dedicated to the conduct of high-impact HIV-related studies in a resource poor region of the United States. The A-CTU is comprised of an efficient Central Administration and four Clinical Research Sites (CRS): Alabama Therapeutics-CRS (AT-CRS), The Alabama Vaccine-CRS (AV-CRS), The Alabama Pediatric, Adolescent & Maternal-CRS (APAM-CRS), and The Alabama Microbicide-CRS (AM-CRS). The A-CTU draws on tremendous experience and success in NIAID-sponsored research trials groups, including over 13 years of involvement in the Adult and Pediatric AIDS Clinical Trials Group (AACTG; PACTG), 12 years experience in the HIV Prevention Trials Network (HPTN), and 11 years of continuous involvement as a federally funded HIV vaccine trials site under the AIDS Vaccine Evaluation Group and the HIV Vaccine Trials Network. Owing to this wealth of experience, we are submitting this single coordinated CTU application in response to 5 of the 6 High-Profile Targeted Areas of Investigation: Vaccine research, translational and drug development research, optimization of clinical management research (including comorbidities), microbicide research, and prevention of mother-to-child transmission research. Addressing these Priority Areas will be accomplished through utilization of the A-CTU's genuine partnership with the patient/participant community, its experience in NIAID and industry-funded clinical trials, and through collaborative research among clinical and basic science investigators within the UAB CFAR.