Hepatitis C virus (HCV) infection has emerged as a major cause of morbidity and mortality in persons living with human immunodeficiency virus (HIV-1). Growing data from studies early in the course of HCV suggests that the cellular immune response is a crucial determinant of the eventual outcome; however, the role of the HCV-specific immune response in HIV-1 infected individuals is not clear. The recent development of sensitive techniques allows comprehensive and detailed assessment of this immune response, and the candidate has begun systematic application of these methods in co-infected patients. This proposal aims to characterize the HCV-specific cellular immune response in co-infected individuals. After determining the breadth, magnitude, and epitope specificity of these responses within this cohort, they will be compared to control subjects who are not infected with HIV. Moreover, these responses will be followed longitudinally to determine their dynamics before and after antiviral therapies, and in particular to find correlates of immune reconstitution. Finally, the lymphocytes specific against HCV will be characterized using tetramer-based methods. These studies will lend important insight into the pathogenesis of HCV, especially in regards to this clinically important group of patients. They will additionally contribute to our understanding of vaccine designs and potential immune-based therapies. ? ? The candidate is currently enrolled in his third year of clinical and research fellowship training in Infectious Diseases at the Massachusetts General Hospital, and seeks further training in both bench and clinical research skills that will allow him to develop into an independent clinical investigator. These skills will be essential to allow translation of this research into novel immunotherapies. This plan will be implemented under the supervision of Dr. Bruce Walker, and will involve bench research, data analysis, and didactic learning. ? ?
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