Grant: Project Grant

The current antiretroviral therapy (ART) used to fight HIV infection has dramatically improved the lives of people living with HIV (PLWH). Nevertheless, PLWH are at greater risks of age-related disorders which are linked to inflammation and immune dysfunction. Cytomegalovirus is a herpesvirus chronically infecting half of the Canadian population and 85% of PLWH. CMV plays a role in accelerating aging of the immune system as well as increasing the risk of cardiovascular diseases. Although dormant, this virus persists lifelong and hides mostly in deep tissues such as the gut where it continually damages the immune system. Using letermovir, a new oral well-tolerated anti-CMV drug, we will explore the factors responsible for CMV replication in the gut and how this virus increases inflammation in ART-treated PLWH. To this aim: 1) We will compare the degree of inflammation and characterize the immune system in the blood and gut of PLWH having or not CMV. 2) In a clinical trial, we will assess the effect of a 3-month anti-CMV treatment with letermovir on inflammation in the blood and gut of ART-treated PLWH . 3) As CMV can dampen the response to vaccines, we will assess whether letermovir treatment increases the response to the zoster (shingles) vaccine. We expect anti-CMV therapeutic strategies to reduce gut inflammation, contribute to HIV cure research and enhance vaccine response in PLWH and the general population. Our team of gastroenterologists, surgeons, physicians, and immunologists is dedicated to research aiming at improving the lives of PLWH by decreasing the frequency of age-related comorbidities.