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Cannabinoids and inflammation

implications for people living with HIV

Costiniuk, Cecilia T.a,b,c,d; Jenabian, Mohammad-Alid,e,f

doi: 10.1097/QAD.0000000000002345
EDITORIAL REVIEW
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Thanks to the success of modern antiretroviral therapy (ART), people living with HIV (PLWH) have life expectancies which approach that of persons in the general population. However, despite the ability of ART to suppress viral replication, PLWH have high levels of chronic systemic inflammation which drives the development of comorbidities such as cardiovascular disease, diabetes and non-AIDS associated malignancies. Historically, cannabis has played an important role in alleviating many symptoms experienced by persons with advanced HIV infection in the pre-ART era and continues to be used by many PLWH in the ART era, though for different reasons. Δ9-Tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are the phytocannabinoids, which have received most attention for their medicinal properties. Due to their ability to suppress lymphocyte proliferation and inflammatory cytokine production, there is interest in examining their therapeutic potential as immunomodulators. CB2 receptor activation has been shown in vitro to reduce CD4+ T-cell infection by CXCR4-tropic HIV and to reduce HIV replication. Studies involving SIV-infected macaques have shown that Δ9-THC can reduce morbidity and mortality and has favourable effects on gut mucosal immunity. Furthermore, Δ9-THC administration was associated with reduced lymph node fibrosis and diminished levels of SIV proviral DNA in spleens of rhesus macaques compared with placebo-treated macaques. In humans, cannabis use does not induce a reduction in peripheral CD4+ T-cell count or loss of HIV virological control in cross-sectional studies. Rather, cannabis use in ART-treated PLWH was associated with decreased levels of T-cell activation, inflammatory monocytes and pro-inflammatory cytokine secretion, all of which are related to HIV disease progression and comorbidities. Randomized clinical trials should provide further insights into the ability of cannabis and cannabinoid-based medicines to attenuate HIV-associated inflammation. In turn, these findings may provide a novel means to reduce morbidity and mortality in PLWH as adjunctive agents to ART.

aChronic Viral Illness Service, Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montreal

bInfectious Diseases and Immunity in Global Health Program, Research Institute of McGill University Health Centre

cMcGill Research Centre for Cannabis and the Mark Wainberg Centre for Viral Diseases

dDepartment of Microbiology and Immunology, McGill University

eDepartment of Biological Sciences, University of Quebec at Montreal (UQAM)

fDepartment of Microbiology, Infectiology and Immunology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.

Correspondence to Dr Cecilia T. Costiniuk, Chronic Viral Illnesses Service, Division of Infectious Diseases, McGill University Health Centre, Montreal, Quebec, Canada, Royal Victoria Hospital: Glen Site, 1001 boulevard Decarie, Montreal, QC H4A 3J1, Canada. Tel: +1 48432090; fax: +1 514 843 2092; e-mail: cecilia.costiniuk@mcgill.ca

Received 6 August, 2019

Accepted 8 August, 2019

Copyright © 2019 Wolters Kluwer Health, Inc.