Immune Monitoring-Guided Versus Fixed Duration of Antiviral Prophylaxis Against Cytomegalovirus in Solid-Organ Transplant Recipients: A Multicenter, Randomized Clinical Trial
Authors: Manuel Oriol , Laager Mirjam , Hirzel Cédric , Neofytos Dionysios , Walti Laura N , Hoenger Gideon , Binet Isabelle , Schnyder Aurelia , Stampf Susanne , Koller Michael , Mombelli Matteo , Kim Min Jeong , Hoffmann Matthias , Koenig Katrin , Hess Christoph , Burgener Anne-Valérie , Cippà Pietro E , Hübel Kerstin , Mueller Thomas F , Sidler Daniel , Dahdal Suzan , Suter-Riniker Franziska , Villard Jean , Zbinden Andrea , Pantaleo Giuseppe , Semmo Nasser , Hadaya Karine , Enríquez Natalia , Meylan Pascal R , Froissart Marc , Golshayan Dela , Fehr Thomas , Huynh-Do Uyen , Pascual Manuel , van Delden Christian , Hirsch Hans H , Jüni Peter , Mueller Nicolas J ,   Swiss Transplant Cohort Study (STCS), Amico Patrizia , Aubert John-David , Banz Vanessa , Beckmann Sonja , Beldi Guido , Berger Christoph , Berishvili Ekaterine , Berzigotti Annalisa , Binet Isabelle , Bochud Pierre-Yves , Branca Sanda , Bucher Heiner , Catana Emmanuelle , Cairoli Anne , Chalandon Yves , De Geest Sabina , De Rougemont Olivier , De Seigneux Sophie , Dickenmann Michael , Lynn Dreifuss Joëlle , Duchosal Michel , Fehr Thomas , Ferrari-Lacraz Sylvie , Garzoni Christian , Golshayan Déla , Goossens Nicolas , Haidar Fadi , Halter Jörg , Heim Dominik , Hess Christoph , Hillinger Sven , Hirsch Hans H , Hirt Patricia , Hoessly Linard , Hofbauer Günther , Huynh-Do Uyen , Immer Franz , Koller Michael , Laesser Bettina , Lamoth Frédéric , Lehmann Roger , Leichtle Alexander , Manuel Oriol , Marti Hans-Peter , Martinelli Michele , McLin Valérie , Mellac Katell , Merçay Aurélia , Mettler Karin , Mueller Nicolas J , Müller-Arndt Ulrike , Müllhaupt Beat , Nägeli Mirjam , Oldani Graziano , Pascual Manuel , Passweg Jakob , Pazeller Rosemarie , Posfay-Barbe Klara , Rick Juliane , Rosselet Anne , Rossi Simona , Rothlin Silvia , Ruschitzka Frank , Schachtner Thomas , Schaub Stefan , Scherrer Alexandra , Schnyder Aurelia , Schuurmans Macé , Schwab Simon , Sengstag Thierry , Simonetta Federico , Stampf Susanne , Steiger Jürg , Stirnimann Guido , Stürzinger Ueli , Van Delden Christian , Venetz Jean-Pierre , Villard Jean , Vionnet Julien , Wick Madeleine , Wilhelm Markus , Yerly Patrick 
Published: September 2023

Abstract

Background
The use of assays detecting cytomegalovirus (CMV)–specific T cell–mediated immunity may individualize the duration of antiviral prophylaxis after transplantation.

Methods
In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus.

Results
Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, −0.1; 95% confidence interval [CI], −13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, −26.0 days; 95%, CI, −41.1 to −10.8 days; P &lt; .001).

Conclusions
Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection.

Clinical Trials Registration
NCT02538172.