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Journal of Virology, August 2009, p. 7649-7658, Vol. 83, No. 15
0022-538X/09/$08.00+0 doi:10.1128/JVI.00183-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia,1 HIV-NAT and Chulalongkorn University, Bangkok, Thailand,2 Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia,3 Gastroenterology Unit, St. Vincent's Hospital, Melbourne, Australia,4 National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia,5 Infectious Diseases Unit, Alfred Hospital, Melbourne, Australia,6 Department of Immunology, Monash University, Melbourne, Australia,7 Department of Medicine, Royal Melbourne Hospital, Melbourne, Australia,8 Department of Medicine, Monash University, Melbourne, Australia9
Received 26 January 2009/ Accepted 12 May 2009
Hepatits B virus (HBV)-specific T cells play a key role both in the control of HBV replication and in the pathogenesis of liver disease. Human immunodeficiency virus type 1 (HIV-1) coinfection and the presence or absence of HBV e (precore) antigen (HBeAg) significantly alter the natural history of chronic HBV infection. We examined the HBV-specific T-cell responses in treatment-naïve HBeAg-positive and HBeAg-negative HIV-1-HBV-coinfected (n = 24) and HBV-monoinfected (n = 39) Asian patients. Peripheral blood was stimulated with an overlapping peptide library for the whole HBV genome, and tumor necrosis factor alpha and gamma interferon cytokine expression in CD8+ T cells was measured by intracellular cytokine staining and flow cytometry. There was no difference in the overall magnitude of the HBV-specific T-cell responses, but the quality of the response was significantly impaired in HIV-1-HBV-coinfected patients compared with monoinfected patients. In coinfected patients, HBV-specific T cells rarely produced more than one cytokine and responded to fewer HBV proteins than in monoinfected patients. Overall, the frequency and quality of the HBV-specific T-cell responses increased with a higher CD4+ T-cell count (P = 0.018 and 0.032, respectively). There was no relationship between circulating HBV-specific T cells and liver damage as measured by activity and fibrosis scores, and the HBV-specific T-cell responses were not significantly different in patients with either HBeAg-positive or HBeAg-negative disease. The quality of the HBV-specific T-cell response is impaired in the setting of HIV-1-HBV coinfection and is related to the CD4+ T-cell count.
Published ahead of print on 20 May 2009.
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