Grant: Operating Grant - PA: HIV/AIDS Bridge Funding - Biomedical/Clinical Stream

Human immunodeficiency virus type 1 (HIV-1) is able to enter the central nervous system (CNS), and cause important neurocognitive impairment. The exact mechanism by which HIV-1-infected monocytes enter the CNS throughout the course of HIV-1 disease is still unknown. Chemokine receptor CCR7 is a very important player in cellular migration. In our laboratory, we showed the exposition of infected monocytes to the immunonodulatory molecule prostaglandin E2 (PGE2), which is up-regulated during HIV infection, the migration of infected monocyte. The first part of this research project will permit to shed the light on the mechanism leading to the entry of monocytes in the CNS. This understanding will provide information crucial to the development of strategies to selectively target infected monocytes migration. On the other hand, current antiretroviral drugs often fail to effectively reduce the HIV viral load in the brain. The second part of the project is designed to explore a cell-based nanoformulated antiretroviral therapy delivery system to the CNS using CCR7+ monocytes. Drug development must move into a more rational phase aimed at optimizing conditions for efficient delivery to the CNS.