There is an urgent need to establish the etiology and improve diagnostics of HIV-associated meningitis in countries like Zambia given the high rates of mortality. A lack of post-mortem studies in low and middle-income countries prevents in-depth studies on tissue from confirmed meningitis patients. Central nervous system (CNS) co-infection frequently occurs in HIV-associated meningitis, but no study has investigated its impact on mortality. Tuberculous meningitis (TBM), one of the most common causes of HIV-associated meningitis, lacks a sensitive cerebrospinal fluid (CSF) lateral flow assay to serve as a simple point of care diagnostic. The best candidate lipid biomarker for a point of care assay has not been established. Best practices and expertise for CSF and brain tissue handling, processing, and analyses are also lacking in many sub- Saharan African countries. Our long-term goal is to establish causes of mortality, optimal diagnostic biomarkers, and laboratory expertise to improve outcomes of HIV-associated meningitis. We will test the following set of specific aims: Aim 1) Establish comprehensive etiologies of HIV-associated meningitis Aim 2) To improve CSF diagnostics for patients with HIV-associated meningitis in resource-limited settings, we will explore more optimal candidate CSF lipid biomarkers to diagnose TBM. Aim 3) Strengthen laboratory services to improve the diagnosis of meningitis The approach is innovative, because it systematically uses post-mortem tissue from an endemic setting to evaluate HIV-associated meningitis. The proposed research is significant because it allows us to establish etiologies and diagnostic biomarkers in HIV-associated meningitis while improving the laboratory capability in Zambia to diagnose CNS infections. These findings will have an important impact on the clinical management of meningitis and provide specific evidence to guide empiric treatment of patients in the future.