ABSTRACT Despite the access to antiretroviral therapy (ART), and its effectiveness controlling viral load and disease progression, HIV-associated cognitive impairment (HIV-CI) prevail in 20-50% of the people with HIV infection (PWH). The mechanisms involved in HIV neuropathogenesis remain to be elucidated. Health disparities have been identified in the prevalence of HIV-CI being more prevalent in Hispanics, women, and older PWH. A recent study on PWH in the United States (US) revealed that Hispanics (of Puerto Rican [PR] and Mexican self-reported descent) are at higher risk of developing cognitive impairment compared to non-Hispanic white. Moreover, Hispanics of PR descent, in this sample largely from New York City (NYC), demonstrated increased rates of HIV-CI when compared to Mexicans from San Diego, CA. Health literacy, access to health care, and language barrier have been attributed to these disparities. However, these factors alone may not justify the observed disparities among Hispanics. Structural racism and discrimination (SRD) may contribute to these discrepancies and lead to poorer health outcomes for racial/ethnic minorities. SRD refers to the totality of ways in which societies foster racial discrimination (e.g., housing, education, employment, healthcare, and criminal justice). There are limited studies evaluating SRD as determinants of health in biomedical research including HIV-CI. Our overall objective is to determine the biological, behavioral, and environmental factors within the cohorts of PWH in PR (PR-PR), Puerto Ricans in the US (PR-NYC), and Mexicans in San Diego (Mex-SD) to determine similarities and differences that could identify unique factors explaining the disparities in HIV-CI among Hispanics. By bringing together diverse national Hispanic cohorts we will have a unique opportunity to address a common hypothesis. The following aims are proposed: 1. Determine the association between SRD and perceived/felt stigma, stress, and systemic inflammation. 2. Determine the association between SRD and HIV-CI. 3. Test our hypothesis that PWH living in Puerto Rico show greater association between SRD and HIV- CI, compared to the other two groups. The findings from this study will increase our understanding about the relationship between SRD and HIV-CI in a Hispanic HIV infected population and identify factors that may be modified. These are important steps in advancing towards health equity, improve HIV outcomes, and end the HIV epidemic.