Evaluating the Role of Immune Responses in the Emergence of Protease Inhibitor Mutations
Evaluating the Role of Immune Responses in the Emergence of Protease Inhibitor Mutations
The major goal of this project is to identify the role of the immune responses in the
 emergence of protease inhibitor mutants during therapy.
Objective 1: Evaluate the role of the immune responses in determining the emergence of HCV
 NS3 resistance mutation during protease inhibitor therapy

 Hypothesis 1 (HT 1): Low HLA binding to peptides containing protease inhibitor resistance
 mutations is associated with the emergence of protease inhibitor mutants during therapy and
 failure of the treatment.

 Hypothesis 2 (HT 2): A hole in T cell repertoire may allow emergence of protease inhibitor
 mutants during protease inhibitor therapy which leads to loss of the immune responses to
 these mutants and failure of treatment.
Inclusion Criteria: All chronically HCV-infected patients who fail peg-IFN and RBV therapy
 and are eligible for combined treatment with PI therapy will be enrolled. Briefly, this
 includes:

 1. Male or female

 2. Age 18 to 65

 3. Chronic HCV infection evidenced by liver biopsy or persistent HCV viremia for >6
 months

 4. Treatment experienced and classified as non-responder or relapser to prior
 interferon-based therapy.

 Exclusion criteria:

 1. Treatment naïve chronically HCV-infected patients.

 2. Patients with a history of inflammatory bowel diseases (IBD) or suspected IBD,
 autoimmune diseases, including rheumatoid arthritis, and any patients on systemic
 immunomodulators.

 3. Pregnancy

 4. HIV