Changes in Immune-Related Biomarkers and Endocannabinoids as a Function of Frequency of Cannabis Use in People Living With and Without HIV.

Background: Cannabis use is common among people living with HIV (PLWH). Some observational studies of PLWH have linked cannabis use to lower immune markers; however, this is yet to be confirmed. In addition, whether HIV affects the endogenous cannabinoid system has not been studied. Our objective was to examine changes in immune-related biomarkers and endocannabinoids as a function of cannabis use frequency in people living with and without HIV. Materials and Methods: Data were obtained from a longitudinal study of men who have sex with men living in Los Angeles with, or at risk for, HIV. By design, half were PLWH. Those eligible for the parent study were willing and able to return for follow-up every 6 months. Those eligible for inclusion in this study reported varying levels of current cannabis use at follow-up. Specifically, one visit corresponded to a period of daily use and another to a period of infrequent use (weekly, monthly, or less than monthly). Banked serum from all eligible participants was analyzed for immune-related biomarkers, endocannabinoids, and paracannabinoids. Results: The analysis included 36 men, 19 of whom were PLWH. PLWH reported greater lifetime methamphetamine or amphetamine use (68% vs. 0%) and current cigarette use (55% vs. 20%) than people without HIV. Serum levels of HIV-related immune biomarkers including tumor necrosis factor receptor 2 (TNFR2; p=0.013) and CD27 (p=0.004) were greater in PLWH, alongside lower anandamide (AEA) (F(1,34)=5.337, p=0.027) and oleoylethanolamide (OEA) (F(1,34)=8.222, p=0.007) levels relative to people without HIV. Frequency of cannabis use did not impact the serum analytes in our study. Conclusions: Higher levels of TNFR2 and CD27 and lower levels of AEA and OEA in PLWH underscore the role of the TNF/TNFR superfamily in HIV, while highlighting a new role for the enzymatic activity of fatty acid amide hydrolase (the enzyme that hydrolyzes AEA and OEA) in HIV. Findings that cannabis frequency did not impact the immune phenotype may not generalize to other populations of PLWH. Additional work is required to further clarify the relationship between immune markers and endocannabinoids as a function of cannabis use frequency in PLWH. ClinicalTrials.gov ID: NCT01201083.