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T-cell Response against Hepatitis B Virus Is Impaired in HIV-HBV Coinfected Individuals

CD8 T-cells targeting hepatitis B virus (HBV) are less effective in HIV positive people, producing less cytokines and responding to fewer HBV proteins, according to a study reported in the August 2009 Journal of Virology.

Judy Chang from the University of Melbourne and colleagues examined HBV-specific T-cell responses in treatment-naive HIV-HBV coinfected and HBV monoinfected Asian patients.

HBV-specific T-cells play a key role in both the control of HBV replication and the pathogenesis of liver disease, the study authors noted as background, and HIV coinfection and the presence of hepatitis B "e" antigen (HBeAg) may significantly alter the natural history of chronic hepatitis B.

The investigators looked at blood samples from 48 treatment-naive HIV-HBV coinfected patients -- 24 of them HBeAg positive and 24 HBeAg negative -- and 39 HBV monoinfected individuals. Blood was exposed to peptides representing the entire HBV genome. The researchers measured tumor necrosis factor-alpha and gamma interferon cytokine expression in CD8 T-cells using intracellular cytokine staining and flow cytometry.


There was no difference in the overall magnitude of HBV-specific T-cell responses.
The quality of response, however, was significantly impaired in HIV-HBV coinfected patients compared with HBV monoinfected individuals.
Among coinfected patients, HBV-specific T-cells rarely produced more than 1 cytokine and responded to fewer HBV proteins than those of monoinfected patients.
Overall, the frequency and quality of HBV-specific T-cell responses were significantly increased in association with higher CD4 T-cell counts.
There was no relationship between circulating HBV-specific T-cells and degree of liver damage as measured by histological activity and fibrosis scores.
HBV-specific T-cell responses were not significantly different in patients with HBeAg positive versus HBeAg negative disease.

Based on these findings, the investigators concluded, "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."

University of Melbourne, Melbourne, Australia; HIV-NAT and Chulalongkorn University, Bangkok, Thailand; Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia; St. Vincent's Hospital, Melbourne, Australia; National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia; Infectious Diseases Unit, Alfred Hospital, Melbourne, Australia; Monash University, Melbourne, Australia; Royal Melbourne Hospital, Melbourne, Australia.


JJ Chang, S Sirivichayakul, A Avihingsanon, and others. Impaired quality of the hepatitis B virus (HBV)-specific T-cell response in human immunodeficiency virus type 1-HBV coinfection. Journal of Virology 83(15): 7649-7658. August 2009. (Abstract).




















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