Torque Teno Virus Does Not Predict Cytomegalovirus Infection Post-Lung Transplantation

Abstract

Purpose Torque teno virus (TTV) is a highly prevalent, non-pathogenic DNA virus that has been shown to correlate with immunosuppression post-transplantation. Cytomegalovirus (CMV) is the most common opportunistic infection to occur post-lung transplantation and is associated with morbidity and mortality. We evaluated the association between plasma TTV load and subsequent occurrence of CMV infection in lung transplant recipients at moderate risk for a CMV infection. Methods All adult, first-time lung and heart-lung transplant patients with moderate risk serotype for CMV infection [donor positive (D+) / recipient positive (R+)] transplanted between September 2005 and December 2013 in our program were included in the study. During this period, our program's CMV prophylaxis strategy was to use valganciclovir for 3 months post-transplant. Existing stored blood samples were retrieved and TTV DNA was quantified using real-time polymerase chain reaction (PCR), measured at 3, 4 and 5 months after lung transplantation, as well as at the time of detection in those who developed a CMV infection. Paired t-tests were used for serial data comparisons and Cox regression was performed to determine an association between log TTV PCR levels and CMV infection within 6 months of discontinuing antiviral prophylaxis. Results During the study period 297 patients were transplanted. Of these patients, 89 patients had D+/R+ serostatus, of which blood samples for TTV PCR testing were available for 76 patients. Only 1 patient did not have any detectable TTV PCR post-transplant. Within this cohort, 34/75 patients (45%) developed a CMV infection within 6 months of discontinuing antiviral prophylaxis. Baseline mean log TTV PCR levels one week after discontinuation of CMV prophylaxis was no different between those that went on to develop a CMV infection and those that did not (6.80 ± 1.08 vs 7.08 ± 0.75, p=0.20). For those developing CMV infection, mean log TTV PCR levels were slightly lower at the time of CMV infection compared to baseline levels (6.45 ± 1.36 vs 6.98 ± 0.72, p=0.04). TTV viral load was not associated with time to CMV infection, HR 0.76 (95% CI 0.55 - 1.05, p=0.09). Conclusion TTV PCR levels at the time of discontinuation of CMV prophylaxis in CMV D+/R+ lung transplant recipients were not associated with subsequent CMV infection. TTV's role in predicting future infection requires further study.