Assessing the Effects of HIV Cure Strategies in the Gut-associated Lymphoid Tissue

Icahn School Of Medicine At Mount Sinai, New York NY

Investigators

Abstract

PROJECT SUMMARY This is a resubmission of an application for a K23 Mentored Patient-Oriented Research Award by Dr. Francesca Cossarini, an Assistant Professor of Infectious Diseases at the Icahn School of Medicine at Mount Sinai and a current KL2 Scholar at the same Institution. This application aims to investigate the effects of proposed HIV cure strategies in the gut-associated lymphoid tissue. Despite the remarkable progress in the survival and quality of life of people living with HIV, forty years from its first discovery, HIV infection remains uncurable due to the persistence of a small pool of cells harboring the virus that can replicate if antiretroviral treatment is stopped. These cells constitute the HIV viral reservoir and efforts to identify and eliminate these cells have been ongoing for the past decades. Most of these studies so far have evaluated the effects of cure strategies in the peripheral circulation. With this proposal, I aim to evaluate the gut-specific effects of proposed cure strategies. The overall objective of this proposal is highly significant since a large proportion of the HIV viral reservoir is located in the gut-associated lymphoid tissue, and there is evidence of cross-infection with the peripheral circulation. Additionally, although memory CD4+ T represent the vast majority (if not the entirety) of the viral reservoir in the circulation, other cells likely function as reservoirs in intestinal tissue, however, their response to HIV cure strategies has not been evaluated. Dr. Cossarini is establishing herself as a physician-scientist in the field of HIV pathogenesis, remission, and cure. She has a specific interest in the role of gut-associated lymphoid tissue in the establishment and maintenance of the HIV reservoir, an area that has received less attention in the field compared to systemic circulation but is nonetheless critical for any strategy looking at potential cure strategies. The results of this study will contribute to addressing a gap in knowledge in the field of HIV cure strategies and will allow the PI to acquire robust data that will be tested in future research applications. With the completion of this proposal, the PI will also be able to further her knowledge in the field and master the analytical and laboratory skills to successfully transition to independence.