Background:  The reasons for the accelerated course of hepatitis C virus (HCV) disease in HIV co-infection are not understood. It can be hypothesized that HCV-specific T-cell responses are absent or functionally deficient in HIV/HCV co-infection. In addition, a comprehensive approach in the assessment of HCV-specific T-cell responses that analyzes all antigens and both the CD4⁺ and CD8⁺ T-cell response is required in order to understand the mechanisms of HCV persistence in the majority of individuals.

Methods:  HCV-specific CD4⁺ and CD8⁺ T-cell responses were investigated using a panel of 728 overlapping peptides spanning the whole HCV genome in 47 HCV mono-infected and 28 HIV/HCV-co-infected individuals. IFN-γ production was measured using ELISpot and flow cytometry intracellular staining assays. All patients were naïve to anti-HCV treatment. The majority of HIV/HCV-co-infected individuals were under ART for HIV-1 and were at early stage of HIV-1 disease.

Results:  The frequency of HCV-specific T-cell responses was similar (~ 40%) in HCV-mono-infected (19 of 47) and HIV/HCV-co-infected (12 of 28) individuals. Within 9 of 10 HCV proteins, 27 new CD4⁺ or CD8⁺ T-cell-specific epitopes were identified. Interestingly, the number of HCV-derived epitopes recognized was lower in HIV/HCV-co-infected than for HCV-mono-infected individuals (p = 0.048, 2-tailed t-test). More importantly, a dominant HCV-specific CD4⁺ T-cell response (60% of the epitopes recognized) was associated with HCV-mono-infection while a dominant CD8 T-cell response (75% of the epitopes recognized) was associated with HIV/HCV-co-infection (p = 0.01, 2-tailed t-test). The presence of HCV-specific T cells was influenced by CD4⁺ T-cell counts in co-infected patients. We could observe that a significant fraction of IFN-γ-secreting CD4⁺ and CD8⁺ T cells were also able to produce interleukin (IL)-2, both in HCV-mono-infected and in HIV/HCV-co-infected patients. Additional functional characteristics of HCV-specific CD4⁺ and CD8⁺ T-cell responses were investigated in HCV mono-infected and HIV/HCV co-infected individuals.

Conclusions:  HCV-specific T-cell responses were detected in a similar proportion in HCV-mono-infected and HIV/HCV-co-infected patients. However, the HCV-specific T-cell response was narrowed in HIV/HCV-co-infected individuals and mostly composed of CD8⁺ T-cell epitopes. These results may provide new insights in the pathogenesis of the progressive course of HCV disease in HIV/HCV-co-infected individuals.

Keywords: T cell responses; HCV; CD4, CD8 T cells