title: HCV monoinfection and HIV/HCV coinfection enhance T-cell immune senescence in injecting drug users early during infection.
abstract: 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.
authors.affiliation: Department of Research, Cluster Infectious Diseases, Public Health Service, Amsterdam, The Netherlands ; Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Bart P X
authors.initials: BP
authors.lastname: Grady
authors.affiliation: Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Nening M
authors.initials: NM
authors.lastname: Nanlohy
authors.affiliation: Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands ; Department of Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands ; Present address: Department of Immune Mechanisms, Center for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
keywords: Frailty; Immunosenescence; Longitudinal; People who inject drugs; Substance abuse