Viral load guided Immunosuppression after Lung Transplantation (VIGILung)

• Applicant: Professor Dr. Jens Gottlieb
• Subject Area: Pneumology, Thoracic Surgery
• Term: since 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 329015138

Following lung transplantation, high-dose immunosuppression including calcineurin-inhibitors (CNI) are the accepted cornerstone. Therapeutic drug monitoring represents the current gold standard. Despite rigorous controls, acute rejection in the first year after lung transplantation occurs in 30%-50% of the patients. Immunosuppressive regimens are responsible for considerable toxicity. Approximately 24% of the recipients will develop kidney failure (2% end stage kidney disease) within one year of transplantation. Infections are the leading cause of death during the first postoperative year indicating over-immunosuppression in a subset of patients.Clinical experience suggests that individual tailoring of immunosuppression could potentially optimize patient outcome. Reliable, reproducible, cost effective and non-invasive biomarkers to assess the risk of graft injury and toxicity are needed to adjust immunosuppressant dosage.DNA-viruses in whole blood (Torque-Teno-Virus/TTV, HHV-6, EBV) and urine (BK Virus) are detectable in up to 93% of transplant recipients (Görzer et al 2010). The load of these latent viruses were used as a surrogate biomarker of cell-mediated immunity (load increasing with the strength of immunosuppression) but were never prospectively studied. Guiding immunosuppression by an immune response assay resulted in reductions in CNI doses of 13%-25% within the first year after liver transplantation, with documented reductions in bacterial and fungal infections (Ravaioli et al 2015). In lung transplant recipients, an even greater benefit may be expected by tailoring immunosuppression by DNA virus monitoring. This hypothesis can only be studied in a prospective manner in comparison to conventional therapeutic drug monitoring.The results of this trial might have a large impact on therapeutic strategies for patients after lung transplantation. Furthermore, this study will contribute to improve evidence-based therapy in these patients. Study results are transferable to all other solid organ transplantations.

• DFG Programme: Clinical Trials