Immunoguided discontinuation of prophylaxis for cytomegalovirus disease in kidney transplant recipients treated with antithymocyte globulin: A randomized clinical trial

Abstract

Background: Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. The aim of this study was to evaluate whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy. Methods: In this open-label, non-inferiority clinical trial, patients were randomized 1:1 to follow immunoguided strategy, receiving prophylaxis (valganciclovir 900 mg daily) until CMV-CMI recovery or to receive fixed-duration prophylaxis until day +90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed two deleterious events (CMV disease/replication and neutropenia). Results: A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs. 2.7%; P = 0.149) and replication (17.1% vs. 13.5%; log-rank test, P = 0.422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs. 37.8%; OR, 6.0; P < 0.001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome. Conclusions: Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed.