Torque teno virus viral load and hospitalisation for infections in long-term kidney transplant recipients: a single-centre prospective cohort study

BACKGROUND: Torque teno virus (TTV) viral loads may reflect patients' net state of immunosuppression and identify patients at risk of infections and rejection early after solid organ transplantation. However, its role in long-term kidney recipients (KTRs) is less clear. METHODS: This single-centre prospective cohort study evaluated the association between TTV viral load at recruitment and severe infections requiring hospitalisation within 12 months as the primary outcome in kidney recipients > 1-year post-transplant and on stable immunosuppression for > 3 months. Participants were followed up for 12 months, until change of immunosuppression, graft loss, or death. Pre-specified, exploratory secondary outcomes, including opportunistic infections, malignancy, composite outcomes were also analysed. RESULTS: Median time after transplant amongst the 171 included participants was 10.3 years (interquartile range (IQR) 4.9-16.0). Thirty-one developed severe infections 105 days (IQR 65-204) after baseline TTV measurement. Higher baseline log10-transformed TTV viral load (logTTV) was associated with severe infections within 12 months (odds ratio (OR) 1.37, 95% confidence interval (CI) 1.01-1.86, p = 0.045) with a modest area under receiver operating characteristics curve of 0.60 (95% CI 0.50-0.71). Compared to logTTV < 4.6 copies/mL, logTTV > 6.6 copies/mL (hazard ratio (HR) 3.45, 95% CI 1.10-10.9, p = 0.04) was associated with time to hospitalisations for infections but not logTTV 4.6-6.6 copies/mL (HR 2.30, 95% CI 0.97-5.47, p = 0.06). The ORs for the association between logTTV and malignancy, opportunistic infection and biopsy-proven rejection were 1.86 (95% CI 1.09-3.16), 1.21 (95% CI 0.69-2.13) and 1.09 (95% CI 0.70-1.69) respectively. CONCLUSION: Elevated TTV viral loads were associated with severe infections amongst our cohort of long-term KTRs and may be a useful biomarker in this population.