Lead


Lay summary
Background: Chronic hepatitis C is a leading cause of death in HIV-infected individuals. In the Swiss HIV Cohort Study, around one third of HIV-infected individuals are also infected with the Hepatitis C Virus (HCV). The liver damage through HCV is particularly severe in HIV infected individuals. The current treatment strategies have important side effects and the virus cannot be eradicated in the majority of cases. The reasons for the detrimental effects of HIV on Hepatitis C are poorly understood. It is also poorly understood, whether the immune recovery through treating HIV influences the evolution of HCV and of HCV specific immune responses.Aims: We aim to investigate the influence of HIV and of HIV-therapy on HCV. Specifically, we want to analyse, whether the loss of immune control in untreated HIV-infection leads to changes in the viral sequence and to a less effective control through cellular immunity and whether these changes explain some of the harmful effects of HIV on HCV. We also aim to analyse, whether improving the cellular immunity by treating HIV also improves the HCV specific immunity and whether HCV adapts to improving immune responses.Methods: We will study longitudinally the evolution of HCV and of HCV specific immune responses in around 150 participants of the Swiss HIV Cohort Study. The longitudinal design allows to study the influence of HIV and of HIV-therapy on HCV in single individuals over time.Significance: This study will contribute to our current knowledge of HCV evolution and of the dynamics of Hepatitis C specific immunity during untreated and treated HIV infection. Understanding the host-viral interactions is the basis for the prediction of the course of HCV infection and for an optimized timing of antiviral therapies. In a broader context, this study allows to study the impact of a changing immunological environment on host-viral interactions.