Pre-Transplant Plasma Torque Teno Virus Load and Increase Dynamics after Lung Transplantation

Background The human Torque Teno virus (TTV) causes persistent viremia in most immunocompetent individuals. Elevated TTV levels are observed after solid organ transplantation and are related to the extent of immunosuppression especially during the phase of maintenance immunosuppression. However, the extent to which the TTV increase in the early phase post-transplantation is associated with the patient's immunosuppressive state is unclear. Objectives In this study, we assessed the TTV increase dynamics in detail during the first three months after lung transplantation under a defined immunosuppressive regimen and in relation to the pre-transplant TTV level. Study Design Forty-six lung transplant recipients (LTRs) were included in this prospective longitudinal study. All received alemtuzumab induction combined with tacrolimus and corticosteroids immunosuppressive therapy. Plasma TTV DNA was monitored before transplantation and regularly within the first three months post-transplantation (n = 320 samples; mean sampling interval: 12.2 days). Results In 43/46 LTRs (93%), TTV DNA was detectable before transplantation (median 4.4 log(10) copies/mL; range: 2.0-6.4). All 46 LTRs showed a TTV increase post-transplantation, which followed a sigmoidal-shaped curve before the median peak level of 9.4 log(10) copies/ mL (range: 7.6-10.7) was reached at a median of day 67 (range: 41-92). The individual TTV DNA doubling times (range: 1.4-20.1 days) significantly correlated with the pre-transplant TTV levels calculated over 30 or 60 days post-transplantation (r = 0.61, 0.54, respectively; both P < 0.001), but did not correlate with the mean tacrolimus blood levels. Pre-transplant TTV levels were not associated with time and level of the patients' post-transplant TTV peak load. Conclusion The TTV level may be used to mirror the state of immunosuppression only after the patients' initial peak TTV level is reached.