Neuroimmune Correlates of HIV and Marijuana Use: Peripheral Biomarkers and Cognitive Function.

People with HIV (PWH) exhibit persistent immune activation despite suppressive antiretroviral therapy, contributing to neurocognitive vulnerability. Marijuana use is common among PWH and may influence inflammatory pathways, but its in vivo immunologic effects in treated HIV remain unclear. In this cross-sectional study (Durham, NC; 2021-2023), 238 adults with and without HIV were grouped by chronic marijuana use. Soluble immune biomarkers were measured in plasma/serum, and log-transformed outcomes were analyzed using hierarchical multivariable regression. Seven biomarkers showed significant model fit: sCD163, IFN-γ, TNF-α, TNF-RII, CXCL10, CCL4, and VCAM-1. Among HIV-negative participants, marijuana use was linked to reduced CXCL10, suggesting disruption of IFN-γ-dependent chemotactic signaling. In contrast, HIV infection in the absence of marijuana use was associated with a broad, multi-pathway inflammatory profile, including TNF signaling, interferon activation, monocyte/macrophage activation, and endothelial recruitment. Among PWH, marijuana use did not modulate these effects, although CCL4 and VCAM-1 were not significantly elevated in this group compared to controls. However, these markers did not differ between marijuana-using and non-using PWH, suggesting a potential divergence from the broader inflammatory profile rather than a clear marijuana-associated attenuation. Cognitive analyses demonstrated a modest inverse association between memory performance and TNF-related markers, indicating that HIV-associated inflammatory signaling may relate to memory function, whereas marijuana-related cognitive effects require further study.