Grant: Team Grant: P/T Inflammation for Chronic Conditions-HIV/AIDS Research Initiative

People Living with HIV (PLWH) in the modern antiretroviral therapy era suffer from many comorbidities including cardiovascular disease, HIV-associated neurocognitive disorders (HAND) and non-alcoholic fatty liver disease (NAFLD). Furthermore, Hepatitis C virus co-infection can also impact liver health, even following Hepatitis C cure. Chronic inflammation and disruption of the gut microbes (microbiome) are shared features amongst all these conditions. Interestingly, PLWH with who use cannabis have lower levels of inflammatory markers compared to PLWH who do not use cannabis. Furthermore, PLWH with Hepatitis C co-infection using cannabis had improvements in insulin resistance over time, suggesting that the anti-inflammatory properties of cannabis may improve some chronic conditions characterized by inflammation. The expanded Endocannabinoid (eCB) system is a key player in the maintenance of heart and blood vessel, brain and liver functions under healthy conditions and differs depending on biological sex and age. The eCB is comprised of the endocannabinoids (ECs), which are chemical messengers naturally produced by the body, their building and metabolizing enzymes, and EC receptors. Using banked blood and stool from 4 national CIHR-funded cohorts of PLWH including the Canadian HIV and Aging Cohort Study, Brain Health Now, The Canadian HIV HepC Co-infection Cohort and the Liver Disease in HIV cohort, we will characterize the eCB in PLWH with various chronic inflammatory conditions to determine whether there is dysregulation in the eCB. We will also examine whether disruption in the eCB system correlates with measures of clinical outcomes and composition of the gut microbiome. If disturbances within the eCB system are confirmed in PLWH, interventions aimed at targeting pathways involved in the ECS will be investigated in future clinical trials.