Coinfection of hepatitis C virus (HCV) with human immunodeficiency virus (HIV) occurs in 20-30% of HIV infected patients. Patients with HCV/HIV coinfection tend to have higher HCV viral loads than controls. Furthermore, there is now evidence that initiation of effective antiretroviral therapy (ART) may be associated with paradoxical increases in HCV viral load. HCV viral flare may be associated with increases in serum tranaminases which affect clinical decision making, vis a vis discontinuation of ART. Previous studies have failed to prospectively evaluate these issues in a systematic, progressive manner. The mechanisms responsible for viral load increase during effective immune reconstitution have also not undergone detailed evaluation. We propose the following Specific Aims to address these issues: 1. To develop and perform a clinical intervention trial in HCV/HIV coinfected subjects treated with ART in order to characterize early/late HCV viral kinetics as well as the prevalence, significance, and pathogenesis of HCV viral load increase. 2. To prospectively evaluate the significance and role of HCV quasispecies emergence following ART initiation between treatment responders and nonresponders. 3. To define immunologic correlates during immune reconstitution that are associated with development of increased HCV viral load and/or liver injury. We will test specific, hypothesis-driven questions to help achieve the broader goals described within our Specific Aims. In an effort to develop a conceptual framework for the relationship between hepatitis C infection and HIV, we will use the tools of mathematical modeling, molecular epidemiology and immunology to study viral selection, mutation and replication. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI065256-03
Application #
7390359
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Brobst, Susan W
Project Start
2006-04-15
Project End
2011-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
3
Fiscal Year
2008
Total Cost
$686,648
Indirect Cost
Name
University of Cincinnati
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
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