Introduction: Identifying a biomarker capable of assessing the level of immunosuppression is crucial for solid organ transplant recipients. One such biomarker gaining traction is the torque teno virus viral load (TTV VL). Despite attempts to establish risk thresholds for TTV VL to stratify the risk of inadequate or excessive immunosuppression, findings vary among studies. Therefore, it's vital to identify the factors influencing TTV VL to effectively interpret its fluctuations.
Methods: A cohort of 639 solid organ transplant recipients (including 437 kidney transplant, 110 lung transplant, and 18 combined transplant) was included. TTV VL was assessed via plasma PCR and examined alongside patient characteristics, particularly focusing on their immunosuppressive regimen.
Results: In total, 89% exhibited a positive TTV VL, with an average of 4.6 log10 (SD 1.91). TTV VL showed a decrease with post-transplant duration (ρ=-0.34, p<0.001). Univariate analysis revealed that diabetic and female recipient patients had higher TTV VL (4.8 log10 vs 4.4 log10, p=0.01 and 4.8 log10 vs 4.4 log10, p<0.001, respectively).
TTV VL was higher in lung transplant recipients (5.1 log10 vs 4.4 log10, p=0.01), patients receiving triple immunosuppressive therapy (4.8 log10 vs 3.9 log10, p<0.001), and those on tacrolimus or belatacept compared to those on ciclosporin (4.8 log10 and 4.9 log10 vs 3.8 log10 respectively, p<0.001). Furthermore, TTV VL correlated with the dose of ciclosporin (ρ=0.21, p<0.001) and tacrolimus (ρ=0.29, p<0.001). Interestingly, a tacrolimus concentration/dose ratio below 1 was associated with higher TTV VL (5.2 vs 4.6, p<0.006). Moreover, neutrophil (ρ=-0.13, p<0.001) and lymphocyte (ρ=-0.14, p<0.01) counts inversely correlated with TTV VL. 
Multivariate analysis demonstrated that TTV VL inversely correlated with post-transplant duration (p<0.001), lymphocyte count (p=0.02), neutrophil count (p=0.01), and correlated with female gender (p=0.009), tacrolimus use (p<0.001).
Conclusion: In this extensive cohort, TTV VL was influenced by post-transplant duration, specific comorbidities, the type of immunosuppressive regimen, notably tacrolimus, as well as the duration of exposure to these medications.