Abstract Body

Background:

Cannabis is widely used by people living with HIV (PLWH) both recreationally and to mitigate HIV- or antiretroviral therapy (ART)-associated nausea, pain, anorexia, or other symptoms. Here, we evaluated immune function and intestinal health among a cohort of ART-treated, cannabis-using, and non-using PLWH. We hypothesized that cannabis using PLWH would have reduced inflammation and immune activation linked with a more immunomodulatory gastrointestinal (GI) microbiome.

Methods:

Colon single-cell suspensions from cannabis-using and non-using ART-treated PLWH were analyzed for cellular immune function by multiparameter flow cytometry. Plasma levels of short-chain fatty acids (SCFA) as indicators of colonic function were assessed by GC-MS. GI microbial communities were profiled through colonic mucosa 16s rRNA sequencing. Cannabis use or non-use was verified in all participants by LC-MS.

Results:

Although overall frequencies of CD4+ and CD8+ T-cells were unchanged (p=0.692 and p=0.204, respectively), the frequencies of activated HLA-DR+CD38+ CD4+ and CD8+ T-cells were significantly decreased in the colon of ART-treated cannabis-using as compared to non-using PLWH (p<0.0001 for both subsets). Frequencies of colon IgA+ and IgG+ B cells were significantly increased in cannabis users vs. non-users (p=0.0006 and p=0.0259, respectively). Cannabis users had significantly lower frequencies of colon TNF-α+CD20+B cells as compared to non-users (p=0.0001). Plasma concentrations of the SCFAs acetate (p<0.0001), propionate (p=0.0034), butyrate (p=0.0001), and isobutyric acid (p=0.0043) but not valeric acid and isovaleric acid were increased in cannabis users vs. non-users. Lastly, ART-treated cannabis using PLWH possessed colonic mucosa microbiomes dominated by Prevotella, followed by Bifidobacterium, Faecalibacterium, Succiniclasticum, and Collinsella. No differences in alpha diversity were observed between ART-treated cannabis-using and non-using PLWH.

Conclusions:

ART-treated cannabis using PLWH had significantly lower frequencies of activated CD4+ and CD8+ T-cells and TNF-α+CD20+B cells, suggesting lower inflammation and immune activation as compared to non-cannabis users. Cannabis use has the potential to alleviate HIV-associated inflammation through alterations in microbial community structure and function. Overall, this study provides important insights into the impact of cannabis use on immunity and the microbiome of PLWH.