Longitudinal analysis of CD8 T-cell responses to HIV and hepatitis C virus in a cohort of co-infected haemophiliacs.
Harcourt GC., Donfield S., Gomperts E., Daar ES., Goulder P., Phillips RE., Klenerman P., Hemophilia Growth and Development Study (HGDS) None.
OBJECTIVE: To investigate CD8 T-cell responses to HIV and hepatitis C virus (HCV) over time in a group of co-infected children with haemophilia to assess the influence of the virus infections on each other and on clinical outcome. DESIGN: The HIV and HCV CD8 T-cell response of HLA-A2 co-infected individuals in the cohort were analysed at two time points, looking at the frequency and phenotype of HIV-specific T cells and assessing overall responses to the two viruses. METHODS: Peripheral blood mononuclear cells (PBMC) from 72 HLA-A2 co-infected individuals were analysed using an HIV HLA-A2 tetramer and by IFN-gamma ELISpot using a panel of HIV and HCV antigens. PBMC from a group of 26 HLA-A2 HIV mono-infected adults were also analysed as a comparison. RESULTS: We identified two distinct patterns of response: some patients had a limited response to either virus whilst others made responses to a range of HIV epitopes. HCV responses were detected only in those who made multiple responses to HIV epitopes (P<0.0001). HCV infection had an influence on the phenotype of HIV-specific CD8 T cells, with a reduction in relative perforin and CD57 expression. Lack of functional or tetramer-positive HIV-specific T cells was associated with a decline in absolute CD4 T-cell counts between the time points (up to 7 years; P = 0.005). CONCLUSION: HCV infection has an impact on the phenotype of HIV-specific CD8 T cells. In this well-defined cohort, failure to maintain effective CD8 T-cell responses against HIV may contribute to disease progression.