BACKGROUND: The HIV/AIDS epidemic in the U.S. South is undergoing a marked shift toward a greater proportion of new HIV/AIDS cases in women, African-Americans, and through heterosexual transmission. METHODS: Using consecutive sampling, 611 participants were interviewed from eight Infectious Diseases clinics in five southeastern states in 2001 to 2002. RESULTS: Sixty four percent of participants were African-American, 31% were female, and 43% acquired HIV through heterosexual sex; 25% had private health insurance. Eighty-one percent were on antiretroviral therapy, and 46% had HIV RNA viral loads (VL) <400. Women and racial/ethnic minorities were less likely to be on antiretrovirals and to have VL <400. Probable psychiatric disorders (54%) and history of childhood sexual (30%) and physical abuse (21%) were common. CONCLUSIONS: Prevention and care systems need to address the HIV epidemic's shift into poor, minority, and female populations. High levels of trauma and probable psychiatric disorders indicate a need to assess for and address these conditions in HIV clinical care. © 2007 Southern Medical Association.