PROJECT SUMMARY/ABSTRACT Neurocognitive impairment (NCI) has disproportionately impacted the HIV+ population since the height of the AIDS crisis. Though modern antiretroviral therapy has afforded vast improvements in longevity, the overall prevalence of HIV-associated neurocognitive disorders (HAND) has remained stable for three decades. Sexual minority men (SMM) have comprised the majority of all HIV diagnoses in the U.S. for the duration of the epidemic. However, few studies have explored the notion that SMM may be correspondingly overrepresented in the high proportion of HIV+ individuals impacted by NCI. Moreover, understanding of HAND etiology is currently limited, which has hindered the development of empirically supported prevention and treatment strategies for HAND. Research suggests that the chronic inflammatory action of HIV infection places HIV+ individuals at a higher risk for NCI, but despite common vulnerability to neuroinflammation, approximately half of HIV+ individuals exhibit normative cognitive function across the lifespan, suggesting that individual-level contextual factors underlie cognitive risk and resiliency. Chronic stress has also been associated with neuroinflammation, via increases in pro-inflammatory cytokines. Building upon theories of syndemics and minority stress, this investigation is based on a novel hypothesis that socio-structural syndemic factors (e.g., poverty, trauma) additively interact with minority stress (i.e., chronic psychological stress related to one’s sexual identity) to diminish cognitive reserve (i.e., neuronal resilience against injury). Furthermore, we hypothesize that chronically high levels of inflammatory cytokines represent a potential causative mechanism through which minority stress negatively impacts cognitive health. As such, the project focuses on three aims: (1) to test the hypothesis the NCI risk will increase with the number of psychological (i.e., minority stress) and socio-structural syndemic (e.g., low education, homelessness) factors reported by HIV+SMM; (2) examine the interactive impact of minority stress and socio-structural syndemic vulnerabilities on NCI risk; and (3) assess the mediating role of elevated pro-inflammatory cytokines (e.g., IL-6) in the hypothesized association between minority stress and NCI risk. The proposed project will be embedded into a larger study (R01MH114735, PI: Rendina), referred to herein as the parent project, which is actively enrolling 250 HIV+ SMM to examine the role of minority and HIV-related stress on psychological, behavioral, and immunological health outcomes. The proposed project will add one assessment to the parent project’s existing neurocognitive test battery to allow for a more nuanced understanding of the cognitive health profile of HIV+ SMM. The research and training plans guiding this proposal have been carefully crafted to optimize my ongoing doctoral training experiences and foster my development as a future independent research...