This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is clearly an association between HIV infection and alcohol use. However, determining whether alcohol intake results in physiologic or immunologic conditions that increase the risk or susceptibility to infection rather than simply resulting in persons engaging in riskier behavior simply cannot be easily deciphered in humans. We are continuing to examine the interaction SIV and alcohol use in the well-controlled macaque model, which can distinguish these factors. In previous years we showed that animals receiving alcohol had higher viral loads, more central memory cells in the intestine. We are now focusing on comparative studies of immune responses and systemic inflammation in animals on alcohol, with and without SIV. We are comparing polyfunctional CTL responses by intracellular cytokine staining, and comparing local and systemic inflammation in animals on alcohol and those that are not by histology, immunohistochemistry, and microarray technology for tight junction proteins. Recently, we have shown that alcohol significantly increases LPS levels in plasma, consistent with the hypothesis that bacterial translocation and systemic immune activation may be the reason patients who consume alcohol have a worse prognosis. We are continuing to examine the mechanisms of this phenomenon and are now focusing on turnover of viral target cells in tissues of animals receiving alcohol to confirm this hypothesis.