Validation of plasma Torque Teno viral load applying a CE-certified PCR for risk stratification of rejection and infection post kidney transplantation

Background: Torque Teno virus (TTV) is non-pathogenic, highly prevalent and reflects the immune status of its host. TTV plasma load was suggested for risk stratification of graft rejection and infection post kidneytransplantation, for which most studies applied an in-house PCR. Recently, a commercial PCR was CEcertified for clinical use. The present study was designed to assess the performance of TTV load as quantified by the commercial PCR in the prediction of graft rejection and infection. Methods: Patients and events were selected from the prospective TTV-POET trial, including 683 consecutive adult recipients of a kidney-graft transplanted at the Medical University Vienna, 2016-2020. TTV was quantified in plasma drawn in Months 4-12 post-transplant by in-house and commercial PCR and associated with consecutive infections and graft rejections until Month 12 post-transplantation.Results: A total of 342 samples from 314 patients with 85 biopsies (rejection, n = 18) and 79 infectious events were assessed. The two PCRs were highly associated (estimate 0.91, 95%CI 0.89-0.93), with a mean difference of 1.38 log10 copies/mL (95%CI 1.46-1.30). The risk of rejection decreased by 25% with every log10 increase in TTV load as quantified by commercial PCR (RR 0.75, 95%CI 0.67-0.85), and the risk of infection increased by 6% (RR 1.06, 95%CI 1.00-1.12). Conclusion: These data support the value of TTV quantification by commercial PCR for the risk stratification of graft rejection and infection in the first year post kidney-transplantation. The test performance determined within this study may serve to design clinical trials and subsequently, support application in clinical routine.