Epstein-Barr virus infection monitoring in kidney transplant recipients (EVITA study)-investigating the clinical significance of EBV-DNAemia and the risk of early-onset PTLD.

Epstein-Barr virus (EBV) transmission from donor to naïve recipients (D+/R-) is a major risk for post-transplant lymphoproliferative disorder (PTLD). Blood EBV-DNA monitoring (EBV-DNAemia) is recommended, but the optimal blood matrix remains unclear. This 2-year prospective study of de novo kidney transplant recipients investigated the incidence and clinical significance of EBV-DNAemia in plasma and whole blood. The study estimated the positive and negative predictive values (PPV, NPV) of EBV-DNAemia kinetics for EBV-associated PTLD. Persistent EBV-DNAemia was examined as a predictor of excessive immunosuppression, defined by a composite endpoint of ≥2 infections requiring hospitalization, infection-related death, or EBV-associated PTLD. Of 509 enrolled recipients, 11 developed PTLD; 8 were EBV associated (20% of EBV D+/R- recipients, incidence rate = 8.0 (95% CI, 4.0-16.1) per 1000 patient-years). Plasma or whole-blood EBV-DNAemia were detected in 107 (21.0%) and 311 (61.1%) recipients, respectively, yielding an NPV >99% for EBV-associated PTLD in both matrices. PPVs were highest for a ≥3-fold increase in plasma EBV-DNA (PPV = 88.9%) and whole-blood EBV-DNA levels ≥50 000 IU/mL (PPV = 50.0%) among EBV D+/R- recipients. Persistent plasma EBV-DNAemia was associated with the composite endpoint (HR = 3.2; 95% CI, 1.8-5.7), predominantly driven by PTLD. Recognition of specific EBV-DNA kinetics in plasma and whole blood should promote clinical evaluation for PTLD.