Grant: Fellowship - Priority Announcement - HIV/AIDS and/or STBBI

Today, 37 million people are living with HIV including 85,000 Canadians. Despite the great strides made in treating HIV with antiretroviral therapy (ART), which has dramatically improved the life expectancy of people living with HIV (PLWH), they still have high levels of inflammation and immune over-reactivity which drives accelerated aging and comorbidities such as cardiovascular disease and non-AIDS malignancies. Thus, calming immune activation and inflammation will be highly beneficial and novel strategies targeting chronic inflammation are needed to achieve this goal. Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are cannabinoids derived from the cannabis plant which show therapeutic potential. Indeed, cannabis was historically used for relieving many symptoms experienced by PLWH and continues to be used for various reasons in the ART era. In observational studies, cannabis has demonstrated anti-inflammatory properties in PLWH. Furthermore, through laboratory studies and in animal models, cannabinoids have demonstrated ability to suppress immune activation and inflammation, suggesting their potential to temper excessive inflammation in PLWH. We therefore hypothesize that using medical cannabinoids in ART-treated PLWH will result in reduced immune activation and inflammation. The purpose of this research project is to determine the safety and tolerability of oral CBD/THC capsules in PLWH under long-term effective ART in a clinical trial. In parallel, we will also assess the effect of oral CBD/THC on inflammation and immune activation, gut mucosal and microbiome composition and HIV reservoir size. We will also explore, through laboratory experiments, the effect of CBD and THC on differentiation of pro-inflammatory or anti-inflammatory macrophages. The study outcomes will have implications beyond HIV and will inform the scientific community about the broader implications of cannabinoid use for conditions with chronic inflammation.