Grant: Operating Grant: Innovative Biomedical and Clinical HIV/AIDS Research

Movement of white blood cells to different sites of the body is critical to effective host immune responses. However, in some cases the blocking of inappropriate cells from going to certain places can have therapeutic benefits, such as for inflammatory bowel disease (IBD). In the case of HIV, the virus gains access to new T-cell rich areas by the movement of infected cells. We and others have shown evidence that the gut-homing integrin a4b7 plays an important role in HIV pathogenesis, and blockade of this molecule using a monoclonal antibody (Act1 or Vedolizumab) in monkey models of HIV represent a promising new treatment or prevention method. However many basic questions remain as to how this antibody works in vivo in humans. This proposal takes advantage of the fact that Vedolizumab is licensed in Canada for the treatment of IBD. Here we propose a prospective study of mucosal immune cell distribution in individuals who are starting Vedolizumab in order to address basic science questions of how a4b7+ cells migrate around the human body. As Vedolizumab has already been entered into human clinical trials for HIV, these data could have important implications for HIV cure efforts.