This study has been designed with the recognition that the concurrence of alcohol use and HIV infection are escalating worldwide, and of critical concern is the significantly impairing immune responses and cognitive performance among those HIV infected individuals in their more productive years. Recognizing the involvement of the immune system in the neurobiological mechanisms that underlie cognitive impairment, we will also investigate its action, through the evaluation of platelets and platelet associated factors (i.e. serotonin, PAF, BDNF) on both immune and cognitive dysfunction. Support for this potential mechanism is based upon our preliminary findings and evidence that 1) both HIV and alcohol use affect and are affected by platelets and platelet associated factors, 2) platelets are a source of neurotransmitters and immunomodulators;3) platelet drops have been associated with HIV disease progression and 4) platelets have been proof a good peripheral model to study CNS compromise. Over the past six years, we have evaluated the deleterious effects of combined alcohol abuse and HIV infection over the neuroimmune system, in an ethnically diverse clinical sample. The proposed application will build upon our previous studies. Using an observational clinic based longitudinal study we will evaluate platelets, platelet associated factors, immune and cognitive function in four groups: hazardous and non-hazardous alcohol consuming HIV-infected subjects and hazardous and non-hazardous alcohol consuming HIV sero-negative subjects (n=540). Using standard questionnaires, a detailed sociodemographic, medical, nutritional, alcohol use and HIV medication history will be obtained. Biological measures (i.e. alcohol levels, platelet counts, serotonin, brain derived neurotrophic factors, platelet activator factor, CD4, CD8, markers or apoptosis, TNF viral load, nutrition status, biochemical profile) followed longitudinally will complement the evaluation. Cognitive function will be evaluated at baseline, 6, 12 and 18 months using a cognitive test battery that incorporates recommendations from the NIMH Workgroup on Neuropsychological Assessment Approaches in HIV. We will then establish cross-sectional and longitudinal within-subject relationships among platelets system measures, cognitive performance, and clinical status by study groups. Our long-term objectives are to extend biomedical knowledge related to mechanism mediating alcohol/HIV damage. magebocytopenia and platelet associated factors on the observations. PUBLIC HEALTH RELEVANCE: Collectively, this information will broaden the scope of therapeutic interventions that might be used to enhance or restore host defense mechanisms and neuroimmune modulation that have been altered as a result of HIV infection and drinking. By increasing understanding of the new mechanistic insights related to the role of thrombocytopenia in the pathogenesis of HIV, scientist can manipulate them to therapeutic advantage.