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Journal of Virology, March 2005, p. 3038-3051, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3038-3051.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Reduced Hepatitis B Virus (HBV)-Specific CD4+ T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy

J. Judy Chang,1 Fiona Wightman,2 Angeline Bartholomeusz,3 Anna Ayres,3 Stephen J. Kent,1,4 Joseph Sasadeusz,4,5 and Sharon R. Lewin1,2,4,5*

Department of Microbiology and Immunology, University of Melbourne,1 Department of Medicine, Monash University,2 Victorian Infectious Diseases Reference Laboratory,3 Infectious Diseases Unit, Alfred Hospital,4 National Health and Medical Research Council Centre for Clinical Research Excellence in Infectious Diseases, Royal Melbourne Hospital, Melbourne, Australia5

Received 30 June 2004/ Accepted 14 October 2004

Functional hepatitis B virus (HBV)-specific T cells are significantly diminished in individuals chronically infected with HBV compared to individuals with self-limiting HBV infection or those on anti-HBV therapy. In individuals infected with human immunodeficiency virus type 1 (HIV-1), coinfection with HBV is associated with an increased risk of worsening liver function following antiviral therapy and of more rapid HBV disease progression. Total HBV-specific T-cell responses in subjects with diverse genetic backgrounds were characterized by using a library of 15-mer peptides overlapping by 11 amino acids and spanning all HBV proteins. The magnitude and breadth of CD4+ and CD8+ T-cell responses to HBV in peripheral blood were examined by flow cytometry to detect gamma interferon production following stimulation with HBV peptide pools. Chronic HBV carriers (n = 34) were studied, including individuals never treated for HBV infection (n = 7), HBV-infected individuals receiving anti-HBV therapy (n = 13), and HIV-1-HBV-coinfected individuals receiving anti-HBV therapy (n = 14). CD4+ and CD8+ HBV-specific T-cell responses were more frequently detected and the CD8+ T-cell responses were of greater magnitude and breadth in subjects on anti-HBV treatment than in untreated chronic HBV carriers. There was a significant inverse correlation between detection of a HBV-specific T-cell response and HBV viral load. HBV-specific CD4+ and CD8+ T-cell responses were significantly (fivefold) reduced compared with HIV-specific responses. Although, the frequency and breadth of HBV-specific CD8+ T-cell responses were comparable in the monoinfected and HIV-1-HBV-coinfected groups, HBV-specific CD4+ T-cell responses were significantly reduced in HIV-1-HBV-coinfected individuals. Therefore, HIV-1 infection has a significant and specific effect on HBV-specific T-cell immunity.

* Corresponding author. Mailing address: Infectious Diseases Unit, Alfred Hospital, Commercial Rd., Melbourne, Victoria 3004, Australia. Phone: (613) 9276 3009. Fax: (613) 9276 2431. E-mail: S.Lewin{at}alfred.org.au.

Journal of Virology, March 2005, p. 3038-3051, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3038-3051.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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