Immunoguided Discontinuation of Prophylaxis for Cytomegalovirus Disease in Kidney Transplant Recipients Treated With Antithymocyte Globulin: A Randomized Clinical Trial
Authors: Páez-Vega Aurora , Gutiérrez-Gutiérrez Belén , Agüera Maria L , Facundo Carme , Redondo-Pachón Dolores , Suñer Marta , López-Oliva Maria O , Yuste Jose R , Montejo Miguel , Galeano-Álvarez Cristina , Ruiz-San Millan Juan C , Los-Arcos Ibai , Hernández Domingo , Fernández-Ruiz Mario , Muñoz Patricia , Valle-Arroyo Jorge , Cano Angela , Rodríguez-Benot Alberto , Crespo Marta , Rodelo-Haad Cristian , Lobo-Acosta María A , Garrido-Gracia Jose C , Vidal Elisa , Guirado Luis , Cantisán Sara , Torre-Cisneros Julian ,   TIMOVAL Study Group, Salinas Ana , Ruiz Tamara , Parra Patricia , López Francisco , Ruiz María , Aguado José María , Fariñas M Carmen , Arnaiz Francisco , Armiñanzas Carlos , Rodrigo Emilio , Piñera Vicente C , Barreda Paloma , Agüero Jesús , de Alegría Carlos Ruiz , González Claudia , Fernandez Miriam , Serrano Maria , Martin Paloma , Martínez Virginia , Bellón Teresa , Jiménez Carlos , González Elena , Gutiérrez Cristina , López Verónica , José Blanco María , Cabezón Itxasne , Gainza Francisco Javier , Len Oscar , Perelló Manel , Prat Oreto , Oriol Ana , Robert Fiona , Pascual Julio , José Pérez Mª , Arias Carlos , Faura Anna , Álvarez Sara , Angel Perez Miguel , Suarez Alejandro , González Carmen , Molina Alejandro , Sanchez Javier , Rodriguez Maria , Dueñas Amelia , Cordero Elisa , Agnelli Caroline , Valerio Maricela , Rodriguez Maria Luisa , Olmedo Maria , Sánchez Luis Alberto , Rodriguez Sara , Fernández Ana , Elías Sandra , Jiménez Sara , Collado Andrea , Escudero Rosa , Fortun Jesús , Serra Nuria , Canal Cristina , Vila Anna , Gelpi Rosana , Silva Irene , Bardají Beatriz 
Published: June 2021

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. Our aim was to determine 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, noninferiority clinical trial, patients were randomized 1:1 to follow an immunoguided strategy, receiving prophylaxis 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 2 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 = .149) and replication (17.1% vs 13.5%; log-rank test, P = .422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs 37.8%; odds ratio, 6.0; P &lt; .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.

Clinical Trials Registration
NCT03123627.