Immune Monitoring-Guided Cytomegalovirus Surveillance in Preemptive Therapy After Kidney Transplantation: A Randomized Clinical Trial

Background: Preemptive therapy for cytomegalovirus (CMV) prevention requires weekly monitoring of CMV DNAemia. The use of CMV-specific cell-mediated immunity (CMV-CMI) may individualize CMV monitoring to guide preemptive therapy. Methods: In open-label, single-center, randomized trial, kidney transplant recipients were enrolled if they were CMV-seronegative with seropositive donor (D+R-) or CMV-seropositive (R+) between May 2018 and October 2024. Patients were randomized in a 1:1 ratio to immune-guided monitoring based on CMV-CMI (QuantiFERON-CMV) assessed at 3 weeks after transplantation or to standard monitoring by weekly CMV PCR for 4 months. In immune-guided group, CMV PCR was performed every 4 weeks between 1 and 4 months if CMV-CMI assay was positive. Preemptive valganciclovir therapy was initiated after detection of CMV DNAemia (≥1000 IU/mL). The primary outcome wasthe incidence of significant CMV DNAemia (≥2000 IU/mL) at 12 months. Results: Overall, 189 patients were randomized (97 in the immune-guided group and 92 in the standard group), of whom 60 immune-guided patients (62%; D+R-, 0%; R+, 74%) had positive CMV-CMI test and were scheduled to less frequent monitoring. The incidence of significant CMV DNAemia was comparable in both groups (49% vs 47%, P=0.838) including sub-analysis in R+ patients (44% vs 41%, P=0.766). Both regimens prevented CMV disease (3% vs 2%, P=0.712), however a numerically higher incidence of high-grade (≥10,000 IU/mL) CMV DNAemia was observed in immune-guided group (28% vs 19%, P=0.147). In immune-guided group, 9 patients received rescue valganciclovir for high-grade CMV DNAemia detected outside the specified monitoring. There were no differences in acute rejection and graft survival. Conclusion: Compared to standard 4-month weekly monitoring, the use of CMV-CMI to guide CMV surveillance in preemptive therapy resulted in similar incidence of significant CMV DNAemia with very low CMV disease rates and enabled less frequent monitoring in majority of R+ patients. Funding: Government Support – Non-U.S.