Grant: Project Grant

HIV/AIDS continues to impact the health of millions of people worldwide. Advances in the treatment of HIV infection have dramatically reduced the death rate from AIDS and improved the quality of life of many HIV-infected patients. Despite this unquestioned success, effective therapy does not eradicate HIV and requires life-long adherence. In addition, the possible long-term toxicity associated with antiretroviral therapy (ART), resistance, stigma and cost all contribute to the necessity of finding a cure. In infected individuals taking ART, HIV persists in a small number of cells that can survive for the lifetime of the infected host. This pool of persistently infected cells, usually referred as the "reservoir for HIV infection", is the main barrier to HIV eradication. The overarching goal of this project is to develop therapeutic strategies aimed at reducing the size of the reservoir, with the ultimate objective of finding a cure for HIV infection. Multiple gaps still exist in our understanding of the basic mechanisms involved in the maintenance of the HIV reservoir. We propose to identify the cells in which HIV persists in the blood and tissues (such as the gut) of HIV-infected individuals taking ART. We will isolate the cells carrying HIV from these anatomical reservoirs. This will allow us to characterize the mechanisms by which HIV is able to persist in these cells. We will then test the ability of several drugs at interfering with HIV persistence in these cells and identify combinations that will lead to the death of the reservoir cells. Our goal is to identify a combination of drugs that can eliminate all latently infected cells in HIV-infected individuals. The results from these studies will constitute the basis for the design of a clinical trial aimed at eradicating HIV.