The impact of HIV infection on the hepatitis B (HBV)-specific CD8 response in HIV/HBV coinfected patients
     RM Lascar ¹ , RJC Gilson ¹ , R Johnstone ¹ , R Bertoletti ² , MK Maini ¹, Department of Sexually Transmitted Diseases and the ² Institute of Hepatology, Royal Free and University College Medical School, London, UK

Objective:
To investigate the effect of HIV-related immunodepletion on the specific immune response against a common co-infection. The HBV-specific CD8 response has a critical role in controlling HBV infection, but there are no data on how this is affected by the presence of HIV infection.

Methods:
We are using four human leucocyte antigen (HLA)-A2- peptide tetramers to quantify HBV-specific CD8 responses in HIV/HBV co-infected patients. The functional capacity of HBV-specific cells is being analysed with intracellular staining for interferon (IFN)• following specific stimulation with 10 HLA-A2-restricted peptides. This allows direct ex-vivo evaluation of the HBV-specific CD8 response.

Results:
We studied 16 patients with natural immunity following HBV infection (nine HIV-negative and seven HIV co-infected). The HIV-infected subjects have a median CD4 count of 400 cells/µl and are antiretroviral therapy-naive. Persistent multispecific HBV-specific CD8 responses are detectable both by tetramer and intracellular cytokine staining in the HBV-immune HIV-negative group but they have not been detected in the HIV-infected group. Similarly, HBV-specific CD8 responses were not detected in a group of HIV-positive HBV co-infected carriers of low infectivity (e-antigen negative).

Conclusion:
These data suggest impairment of the size, multispecificity and function of the HBV-specific CD8 response in HIV-infected patients. This impairment of the CD8 response to HBV could be due toimpaired CD4 help. The impact of highly active antiretroviral therapy on HBV-specific immune responses will be analysed prospectively. (Commentary from Jules Levin: I suspect that the presence of HIV acts similarly regarding the HCV-specific CD4 and/or CD8 response to HCV as well).