Woridwide, -40 million people live with Human Immunodeficiency Virus (HIV)-I disease and associated Acquired Immune Deficiency Syndrome (AIDS), half are women. HIV/AIDS has affected more women than any other disease over the past two decades. Women of color, particularly, African American and Hispanic American women carry the most significant burden of this disease. Clearly, HIV/AIDS in minorities and women will continue to be a significant burden and a critical area of Health Disparities research. Importantly, almost 50% of HIV/AIDS patients suffer from some neurocognitive impairment. Thus, studies that pertain to identification of novel biomarkers that predict disease progression and neurocognitive impairment are critical. Recent data demonstrate that sCD40L, a novel biomarker is significantly elevated in HIV-infected patients with neurocognitive impairment. However, no information is available regarding patterns of sCD40L changes in context of race and gender. This is important, as expression of disease characteristics in HIV/AIDS can be race- and/or gender-specific. Viral loads, metabolic parameters and body composition, plasma lipid levels etc. differ in the setting of specific race and gender. In this application, we propose to investigate the role of SCD40L as a prognostic marker for disease progression in HIV-1 neurological manifestations in the context of race and gender. Although limited to evaluations of race and gender as statistical risk factors, this work will synergize basic science with issues related to health disparities. Specifically, we will identify and analyze plasma sCD40L levels in a cohort of HIV+/- patients and correlate these to standard disease variables and cognitive function. All parameters will be correlated with each other and against neurocognitive measures to test the hypothesis that sCD40L levels correlate with neurocognitive impairment in the context of race and gender. We will also analyze the immune activation status of diverse patient leukocytes. Levels of sCD40L & other proinflammatory cytokines including TNF-a will be analyzed. Ours will be one ofthe first studies to fully describe the HIV-1-positive population characteristics in relation to specific cognitive outcomes, socioeconomic strata and sCD40L and will likelv vield data that will have direct therapeutic implications.