Ten percent of individuals infected with HIV-1 infection are carriers of hepatitis B virus (HBV). Patients with HIV-1 infection have a higher risk of HBV-related cirrhosis than HIV-1-negative-HBV-infected individuals, and co-infection with both viruses has been shown to decrease survival in affected individuals. With the advent of effective anti-HIV therapy, liver disease and particularly HBV infection, has become a major cause of morbidity and mortality in HIV-1-HBV co-infected individuals. The immune response to HBV remains poorly characterized and with increasing recognition of the genetic variation of HBV, may indeed differ between HBV genotypes. This project includes the application of an overlapping peptide library designed to quantify HBV-specific T cell responses to all HBV proteins, in all HLA types and with infection of the major HBV genotypes (A-D). HBV-specific responses will be characterized in the peripheral and intra-hepatic compartments of HIV-HBV co-infected individuals prior to HBV-active HAART and over the following 12 months in a prospective study. These studies will identify new immunogenic epitopes associated with HBV clearance and/or worsening liver disease. The specific epitope and HLA association will be identified. Viral dynamic studies will be performed with combination anti-HBV therapy in HBV-infected and HIV-1-HBV co-infected individuals. The half lives of free virions and infected hepatocytes will be calculated in combination with the longitudinal measurement of HBV-specific T cell responses. These studies will allow the rational development of combination anti-HBV therapy or targeted immunomodulatory interventions, such as therapeutic vaccination, that may be necessary for successful treatment of HBV infection in the setting of HIV-1.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI055379-01A1
Application #
6845004
Study Section
Special Emphasis Panel (ZRG1-AARR-C (03))
Program Officer
Brobst, Susan W
Project Start
2004-09-30
Project End
2006-08-31
Budget Start
2004-09-30
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$162,000
Indirect Cost
Name
Macfarlane Burnet Institute for Research/Pub Health
Department
Type
DUNS #
753880624
City
Melbourne
State
Country
Australia
Zip Code
3001
Stohl, Elizabeth A; Lenz, Jonathan D; Dillard, Joseph P et al. (2015) The Gonococcal NlpD Protein Facilitates Cell Separation by Activating Peptidoglycan Cleavage by AmiC. J Bacteriol 198:615-22
Crane, Megan; Sirivichayakul, Sunee; Chang, J Judy et al. (2010) No increase in hepatitis B virus (HBV)-specific CD8+ T cells in patients with HIV-1-HBV coinfections following HBV-active highly active antiretroviral therapy. J Virol 84:2657-65
Chang, J Judy; Sirivichayakul, Sunee; Avihingsanon, Anchalee et al. (2009) Impaired quality of the hepatitis B virus (HBV)-specific T-cell response in human immunodeficiency virus type 1-HBV coinfection. J Virol 83:7649-58
Crane, Megan; Oliver, Ben; Matthews, Gail et al. (2009) Immunopathogenesis of hepatic flare in HIV/hepatitis B virus (HBV)-coinfected individuals after the initiation of HBV-active antiretroviral therapy. J Infect Dis 199:974-81
Lewin, Sharon R; Ribeiro, Ruy M; Avihingsanon, Anchalee et al. (2009) Viral dynamics of hepatitis B virus DNA in human immunodeficiency virus-1-hepatitis B virus coinfected individuals: similar effectiveness of lamivudine, tenofovir, or combination therapy. Hepatology 49:1113-21
Iser, David M; Lewin, Sharon R (2009) Future directions in the treatment of HIV-HBV coinfection. HIV Ther 3:405-415
Desmond, Christopher P; Bartholomeusz, Angeline; Gaudieri, Silvana et al. (2008) A systematic review of T-cell epitopes in hepatitis B virus: identification, genotypic variation and relevance to antiviral therapeutics. Antivir Ther 13:161-75
Chang, J Judy; Thompson, Alexander J V; Visvanathan, Kumar et al. (2007) The phenotype of hepatitis B virus-specific T cells differ in the liver and blood in chronic hepatitis B virus infection. Hepatology 46:1332-40