Title

Effects of oral cannabinoids on systemic inflammation and viral reservoirs in people with HIV on antiretroviral therapy: results of the CTNPT 028 clinical trial

Presenter

Cecilia Costiniuk

Authors

R.-S. Mboumba Bouassa^1,2, E. Comeau¹, A. Pagliuzza³, Y. Alexandrova^1,2, S. Samarani², J. Needham⁴, J. Singer⁴, T. Lee⁴, F. Bobeuf², C. Vertzagias², G. Sebastiani^2,4, S. Margolese⁴, E. Mandarino⁴, M. Klein^2,4, B. Lebouché^2,4, J.-P. Routy^2,4, N. Chomont³, M.-A. Jenabian^1,4, C. Costiniuk^2,4

Institutions

¹Université du Québec à Montréal (UQAM), Department of Biological Sciences, Montreal, Canada, ²Research Institute of the McGill University Health Centre, Montreal, Canada, ³Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Montreal, Canada, ⁴CIHR Canadian HIV Trials Network, Vancouver, Canada

BACKGROUND: Chronic HIV infection in characterized by persistent chronic inflammation despite antiretroviral therapy (ART). Cannabinoids are reported with anti-inflammatory properties and may represent a potential strategy to reduce systemic inflammation in people with HIV (PWH).
METHODS: Ten PWH (median age: 57.5 years, 8 males) on ART were randomized (n=5/group) to increasing doses of oral ?9-tetrahydrocannabinol (THC): cannabidiol (CBD) combination (THC/CBD: 2.5/2.5 to 15/15mg daily) capsules or CBD-only (200 to 800mg daily) capsules, for 12 weeks. Blood specimens were prospectively analyzed before cannabinoid initiation and after the completion of cannabinoids treatment. Hematology and biochemistry profiles were used to assess the safety of cannabinoids. Plasma levels of inflammatory markers IFN-g, TNF-a, IL-1b, IL-6, IL-8, and IP-10, and anti-inflammatory IL-10 were determined using a Luminex assay, and LPS, sCD14, sCD27, gut damage markers REG-3a and I-FABP were quantified by ELISA. Multi-color flow cytometry was used to immunophenotype T-cells. HIV DNA and cell-associated RNA (LTR-gag) were measured in blood CD4 T-cells and in cell pellets from semen by ultra-sensitive qPCR, and cell-free viral RNA was measured in semen supernatant.
RESULTS: Eight individuals completed the study. Cannabinoids did not alter participants’ hematology/biochemistry profiles. CD4 count and CD4/CD8 ratio were stable and viral load remained suppressed throughout the study. Cannabinoids significantly reduced plasma levels of the following inflammatory markers from initiation versus the end of the intervention: IFN-g (p=0.03), TNF-a (p=0.02), IL-1b (p=0.02), and REG-3a (p=0.04). In addition, cannabinoids also significantly reduced the frequency of PD1+ memory CD4 T-cells (p=0.02), CD28-CD57+ senescent CD4 and CD8 T-cells (p=0.05 and p=0.04, respectively) and CD39+ regulatory T-cells (p=0.01). There was no significant change in HIV DNA and RNA levels in blood or semen nor in other plasma inflammatory markers.
CONCLUSIONS: Cannabinoids reduced markers of systemic and gut inflammation, as well as senescence and exhaustion markers in T-cells in PWH, providing rationale for a larger clinical trial.

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