Challenge: End stage renal disease (ESRD) causes high socioeconomic burden for citizens and the healthcare system in Europe. Kidney transplantation represents the treatment standard for ESRD. Graft rejection due to inadequate immunosuppression is the leading cause for chronic graft dysfunction and infectious disease due to reduced immune function is a major cause of death. Optimisation of immunosuppressive drugs is a crucial step to minimize the risk of infection and rejection and thereby prolonging patient and graft survival. Background: The peripheral blood copy number of the highly prevalent and non-pathogenic Torque Teno virus (TTV) is associated with the grade of the immunosuppression of the host. Non-interventional studies suggest superiority of TTV copy number guided immunosuppression compared to standard strategies. Objectives: To demonstrate the safety and preliminary efficacy of TTV-guided dosing of immunosuppressive drugs in kidney transplant recipients. Method: A phase II clinical trial comparing infection and rejection rate between TTV-guided immunosuppression and the clinical routine strategy. Ambition: TTV allows for a comprehensive and personalised assessment of the function of the immune system. For the first time this novel and original approach will be tested in an interventional randomised and controlled setting. Impact: The proposed project has the potential to reduce infection and graft rejection by 20% thereby significantly improving graft and patient survival of kidney transplant patients. The improved survival will reduce healthcare costs by ~€ 50 million in the EU per year. The project will serve as a proof-of-concept for TTV-based assessment of the immune system, with potential applications in solid organ transplantation, autoimmune and infectious disease and oncology.