(P14-003-24) Sex Differences in Gut Integrity in a Sample of Cannabis Users and Non-Users From the Miami Adult Studies on HIV (MASH) Cohort

Objectives: HIV infection disrupts gut integrity even with adherence to antiretrovirals (ART) and is associated with systemic inflammation via microbial translocation. Since cannabis has been shown to have anti-inflammatory properties, we investigated whether the use of cannabis by people with HIV (PWH) is associated with RNA expression of zonulin, a modulator of intestinal barrier function.

Methods: A minoritized sample of PWH was selected from the ongoing MASH Cohort. Informed consent, and sociodemographic data was collected by trained personnel. ART adherence and CD4 counts were recorded from medical records. Cannabis use was assessed via PhenX substance use questionnaire and confirmed with urinalysis. RNA expression of zonulin was determined by relative normalized gene expression from peripheral blood mononuclear cells, reference gene UBE2D2. Mann-Whitney U test compared demographic data between sexes. Wilcoxon signed-rank test compared differences within sex across visits. Generalized linear mixed models examined the temporal association between cannabis, sex, and time interaction with zonulin RNA expression.

Results: The sample (n=137) median age was 54 (49.5-60) years, mostly non-Hispanic Black (59.9%), with 99.3% ART adherence and undetectable HIV viral load. The prevalence of cannabis use was 32% and 33.9% among males and females, respectively. Baseline zonulin expression did not differ between sexes (P=.099). Yet, male cannabis users had a 20.3% lower expression than female cannabis users (P=.034), but male and female non-users did not have significant differences in expression (P=.635). After a 6-month follow-up, zonulin expression did not differ by sex or cannabis use status. Across study visits, zonulin RNA decreased by 4.3% within the entire sample (P < .001). Mixed effect models did not find cannabis use or sex to be associated with the changes in the expression of zonulin (P=.374).

Conclusions: Cannabis use by PWH was associated with better gut integrity, via lowered expression of zonulin, in men. Over six months, cannabis use was not associated with differences in zonulin RNA by sex as the entire sample had lower expression. These findings suggest that cannabis use may influence gut integrity via the regulation of the zonulin gene, but in PWH viral DNA mutations may dysregulate normal expression patterns.

Funding Sources: NIH/NIDA