Cannabis Use is Associated with Altered Peripheral Biomarker Profiles in People Living with HIV

Suzanne E. Queen, MS
Johns Hopkins University

Co-authors: Suzanne E Queen¹, Hayley Romero¹, Erin N Shirk¹, Raha M Dastgheyb¹, Leah H Rubin¹, Rebecca T Veenhuis^1
1Johns Hopkins University

Background: Despite effective antiretroviral therapy (ART), latent HIV reservoirs persist in brain-resident microglia. These reservoirs promote HIV-associated neuropathology through chronic neuroinflammation and the continued production of neurotoxic viral proteins. Cannabis use is common among people living with HIV (PLWH). The major cannabinoids, ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), regulate microglial activation and inflammatory signaling pathways linked to HIV-associated neurotoxicity. These properties suggest that cannabinoids may modulate pathways involved in HIV-driven neuroinflammation.

Objectives: To determine whether cannabis use and detectable THC exposure are associated with differences in inflammatory, immune, neurovascular, and neuronal injury biomarkers, as well as circulating monocyte and lymphocyte subsets in PLWH.

Methods: A total of 187 virally suppressed PLWH (plasma HIV RNA <150 copies/mL) enrolled in the Johns Hopkins Brain Health Program (BHP) cohort were categorized into four groups based on cannabis use history assessed using the Structured Clinical Interview for DSM-IV (SCID-IV) and urine THC status: current cannabis users who tested THC-positive (n = 44), current users who tested THC-negative (n = 26), former users who tested THC-negative (n = 49), and never-users who tested THC-negative (n = 68). Thirty-six plasma biomarkers covering inflammation, immune activation, neuronal injury, and vascular function, along with phenotypic subsets of circulating monocytes and lymphocytes, were compared across cannabis use groups using linear regression after log transformation and windsorized 3-standard deviation thresholding. Multivariable models were subsequently adjusted for age and sex.

Results: Compared with never-users, current cannabis users had lower plasma concentrations of the proinflammatory cytokines IL-18 (β=-0.170, p=0.033) and MIP-1β (β=-0.17, p=0.030), but higher concentrations of IL-15 (β=0.20, p=0.010). Current cannabis use was also associated with trends toward altered concentrations of biomarkers involved in myeloid regulation including cystatin-C (β=0.149, p=0.076), VEGFR (β=0.15, p=0.070), and M-CSF (β=-0.141, p=0.081). Conversely, markers of neuronal injury and endothelial dysfunction, neurofilament-light (NfL; β=0.18, p=0.010) and vonWillebrand factor (vWF; β=0.27, p=0.001) were higher among current THC-positive users. No significant differences were observed in circulating monocyte and T-cell subsets across cannabis use groups.

Conclusion: Current cannabis use was associated with a distinct peripheral biomarker profile involving inflammatory, neurovascular, and neuronal injury pathways compared to former and never users. These findings support the hypothesis that cannabinoids influence biological mechanisms relevant to brain health in PLWH while highlighting the need for larger sample, and longitudinal studies to determine whether these biomarker changes are associated with cognitive trajectories and long-term clinical outcomes.