HCV monoinfection and HIV/HCV coinfection enhance T-cell immune senescence in injecting drug users early during infection

Background: Injecting drug users (IDU) are at premature risk of developing multimorbidity and mortality from causes commonly observed in the elderly. Ageing of the immune system (immune-senescence) can lead to premature morbidity and mortality and can be accelerated by chronic viral infections. Here we investigated the impact of HCV monoinfection and HIV/HCV coinfection on immune parameters in (ex-) IDU. We analyzed telomere length and expression of activation, differentiation and exhaustion markers on T cells at baseline (t = 1) and at follow-up (t = 2) (median interval 16.9 years) in IDU who were: HCV mono-infected (n = 21); HIV/HCV coinfected (n = 23) or multiple exposed but uninfected (MEU) (n = 8). Results: The median time interval between t = 1 and t = 2 was 16.9 years. Telomere length within CD4(+) and CD8(+) T cells decreased significantly over time in all IDU groups (p <= 0.012). CD4(+) T-cell telomere length in HCV mono-infected IDU was significantly reduced compared to healthy donors at t = 1 (p < 0.008). HIV/HCV coinfected IDU had reduced CD4(+) and CD8(+) T-cell telomere lengths (p <= 0.002) to healthy donors i at t = 1. This was related to persistent levels of immune activation but not due to increased differentiation of T cells over time. Telomere length decrease was observed within all T-cell subsets, but mainly found in immature T cells (CD27(+)CD57(+)) (p <= 0.015). Conclusions: HCV mono-infection and HIV/HCV coinfection enhance T-cell immune-senescence. Our data suggest that this occurred early during infection, which warrants early treatment for both HCV and HIV to reduce immune senescence in later life.