Grant: Operating Grant - PA: HIV/AIDS Research Initiative - Biomedical/Clinical Stream

Despite major improvements in the treatments of HIV infected individuals, the mechanisms that contribute to AIDS development is not fully understood. It is important to understand how HIV attacks the immune system both in the circulating blood and at the primary site of viral replication, the mucosal rectum. Recently, it has been shown that the cells that fight HIV (immune memory CD4 T cells) express mucosa marker called alpha4beta7 that can be preferentially infected and killed by HIV. These memory alpha4beta7 CD4 T cells have a very important role in mucosa protection. It has been hypothesized that the loss of these cells may facilitate the microbes present in the stools that inflame and activate a large number of the body's immune cells, leading to a rapid progression to AIDS. The following proposal will measure how memory alpha4beta7 CD4 T immune cells change over time in both blood and mucosa tissue. We will do this by obtaining a small piece of the rectum using a non-invasive method. We will assess the effect of HIV on these cells and their potential reconstitutions while patient undergo treatment for their infection. We will also compare the changes of these memory alpha4beta7 CD4 T immune cells in relation with factors associated with fast progression to AIDS such as inflammation, viral load, CD4 cells decay, and neurological testing changes. To address these important questions, we plan to expand the well established Montreal primary HIV cohort throughout many hospitals and private medical clinics across Canada. We will collect clinical, socio-demographic, neurocognitive and behavioural data, which will be analyzed in association with study immunological findings. Collectively, new data generated will allow the expansion of how HIV attacks the immune system and will contribute to the development of new therapeutic HIV vaccines.