(taken from application) This award will train Dr. Talal, a gastroenterologist and epidemiologist, in molecular biological techniques as they relate to the virologic and immunologic consequences of HIV infection and its treatment in the gut associated lymphoid tissue (GALT). The two mentors, Dr. David Ho, a very prominent virologist and the director of the Aaron Diamond AIDS Research Center (ADARC), and Dr. Douglas Dieterich, an HIV-experienced gastroenterologist, will provide a multi-disciplinary focus. The clinical environment at the Rockefeller University Hospital combined with state-of the laboratory expertise in HIV at the ADARC will ensure that Dr. Talal receives excellent training in the molecular virology, immunology, and treatment of HIV. Dr. Talal's previous training in study design and data analysis will be an asset to the implementation of the clinical portion of the project. At the end of the training, Dr. Talal will ben an independent scientist who will simultaneously conduct clinical studies and direct his own molecular biological laboratory. There are compelling theoretical reasons to study the viral and immune response in the GALT in treated HIV-infected patients. The GALT contains 45% of the lymphoid tissue in the entire body, it serves as the site of initial HIV inoculation in many patients, and the lymphocytes of the GALT are chronically activated which enhances HIV-infection of these cells. We have recently demonstrated that HIV mRNA persists in the GALT longer than it does in peripheral blood in my patients treated with combination anti- retroviral medications for at least one year. In untreated, chronically HIV-infected individuals, there is a preferential depletion of CD4+ (helper/inducer) lymphocytes in the GALT when compared to the peripheral blood. This project will evaluate decay of HIV in the GALT in chronically HIV-infected patients on combination anti-retroviral medication which will determine the time needed to eliminate HIV from this body compartment. It will also evaluate the repopulation of CD4+ lymphocytes in the GALT which may occur before repopulation in the peripheral blood. This project amy provide important insights into the amount of time needed to treat HIV- infected individuals and may provide novel approaches by which to monitor therapeutic responses in these individuals.
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