Immune monitoring-guided vs fixed duration of antiviral prophylaxis against cytomegalovirus in solid-organ transplant recipients. A Multicenter, Randomized Clinical Trial.

cell-mediated immunity personalized medicine prevention transplant viral infection

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
22 Sep 2023
Historique:
received: 06 07 2023
revised: 06 09 2023
accepted: 20 09 2023
medline: 22 9 2023
pubmed: 22 9 2023
entrez: 22 9 2023
Statut: aheadofprint

Résumé

The use of assays detecting cytomegalovirus (CMV)-specific T-cell-mediated immunity may individualize the duration of antiviral prophylaxis in transplant recipients. In this open-label randomized trial, adult kidney and liver transplant recipients from six centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving anti-thymocyte 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-specific interferon gamma release assay (T-Track® CMV); prophylaxis in the intervention group was stopped if the assay was positive. The 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. Overall, 193 patients were randomized (92 in the immune-monitoring and 101 in the control group) of which 185 had evaluation of the primary endpoint (87 and 98 patients, respectively). Clinically significant CMV infection occurred in 26/87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32/98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference -0.1, 95%CI -13.0%, 12.7%; p = 0.064). The duration of antiviral prophylaxis was shorter in the immune-monitoring group (adjusted difference -26.0 days, 95%-CI -41.1 to -10.8 days, p < 0.001). Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary endpoint of CMV infection.

Sections du résumé

BACKGROUND BACKGROUND
The use of assays detecting cytomegalovirus (CMV)-specific T-cell-mediated immunity may individualize the duration of antiviral prophylaxis in transplant recipients.
METHODS METHODS
In this open-label randomized trial, adult kidney and liver transplant recipients from six centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving anti-thymocyte 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-specific interferon gamma release assay (T-Track® CMV); prophylaxis in the intervention group was stopped if the assay was positive. The 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 RESULTS
Overall, 193 patients were randomized (92 in the immune-monitoring and 101 in the control group) of which 185 had evaluation of the primary endpoint (87 and 98 patients, respectively). Clinically significant CMV infection occurred in 26/87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32/98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference -0.1, 95%CI -13.0%, 12.7%; p = 0.064). The duration of antiviral prophylaxis was shorter in the immune-monitoring group (adjusted difference -26.0 days, 95%-CI -41.1 to -10.8 days, p < 0.001).
CONCLUSIONS 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 endpoint of CMV infection.

Identifiants

DOI: 10.1093/cid/ciad575 PMID: 37738676
pubmed: 37738676
pii: 7280465
doi: 10.1093/cid/ciad575
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Investigateurs

Patrizia Amico (P)
John-David Aubert (JD)
Vanessa Banz (V)
Sonja Beckmann (S)
Guido Beldi (G)
Christoph Berger (C)
Ekaterine Berishvili (E)
Annalisa Berzigotti (A)
Isabelle Binet (I)
Pierre-Yves Bochud (PY)
Sanda Branca (S)
Heiner Bucher (H)
Emmanuelle Catana (E)
Anne Cairoli (A)
Yves Chalandon (Y)
Sabina De Geest (S)
Olivier De Rougemont (O)
Sophie De Seigneux (S)
Michael Dickenmann (M)
Joëlle Lynn Dreifuss (JL)
Michel Duchosal (M)
Thomas Fehr (T)
Sylvie Ferrari-Lacraz (S)
Christian Garzoni (C)
Déla Golshayan (D)
Nicolas Goossens (N)
Fadi Haidar (F)
Jörg Halter (J)
Dominik Heim (D)
Christoph Hess (C)
Sven Hillinger (S)
Hans H Hirsch (HH)
Patricia Hirt (P)
Linard Hoessly (L)
Günther Hofbauer (G)
Uyen Huynh-Do (U)
Franz Immer (F)
Michael Koller (M)
Bettina Laesser (B)
Frédéric Lamoth (F)
Roger Lehmann (R)
Alexander Leichtle (A)
Oriol Manuel (O)
Hans-Peter Marti (HP)
Michele Martinelli (M)
Valérie McLin (V)
Katell Mellac (K)
Aurélia Merçay (A)
Karin Mettler (K)
Nicolas J Mueller (NJ)
Ulrike Müller-Arndt (U)
Beat Müllhaupt (B)
Mirjam Nägeli (M)
Graziano Oldani (G)
Manuel Pascual (M)
Jakob Passweg (J)
Rosemarie Pazeller (R)
Klara Posfay-Barbe (K)
Juliane Rick (J)
Anne Rosselet (A)
Simona Rossi (S)
Silvia Rothlin (S)
Frank Ruschitzka (F)
Thomas Schachtner (T)
Stefan Schaub (S)
Alexandra Scherrer (A)
Aurelia Schnyder (A)
Macé Schuurmans (M)
Simon Schwab (S)
Thierry Sengstag (T)
Federico Simonetta (F)
Susanne Stampf (S)
Jürg Steiger (J)
Guido Stirnimann (G)
Ueli Stürzinger (U)
Christian Van Delden (C)
Jean-Pierre Venetz (JP)
Jean Villard (J)
Julien Vionnet (J)
Madeleine Wick (M)
Markus Wilhelm (M)
Patrick Yerly (P)

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Auteurs

Oriol Manuel (O)

Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Transplantation Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
ORCID: 0000-0001-7607-0943

Mirjam Laager (M)

Department of Clinical Research, University of Basel and University Hospital Basel, Basel, Switzerland.

Cédric Hirzel (C)

Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Dionysios Neofytos (D)

Transplant Infectious Diseases Unit, University Hospitals Geneva and Faculty of Medicine, Geneva, Switzerland.

Laura N Walti (LN)

Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Gideon Hoenger (G)

Department of Biomedicine, Immunobiology, University of Basel and University Hospital of Basel, Basel, Switzerland.

Isabelle Binet (I)

Nephrology and Transplantation Medicine, Kantonsspital St Gallen, Sankt Gallen, Switzerland.

Aurelia Schnyder (A)

Nephrology and Transplantation Medicine, Kantonsspital St Gallen, Sankt Gallen, Switzerland.

Susanne Stampf (S)

Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.

Michael Koller (M)

Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.

Matteo Mombelli (M)

Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Transplantation Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Min Jeong Kim (MJ)

Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
Department of Nephrology, Kantonsspital Aarau, Aarau, Switzerland.

Matthias Hoffmann (M)

Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St.Gallen, St.Gallen, Switzerland.
Department of Internal Medicine, Infectious Diseases and Hospital Epidemiology, Kantonsspital Olten, Olten, Switzerland.

Katrin Koenig (K)

Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
Department of Nephrology, Kantonsspital Liestal, Liestal, Switzerland.

Christoph Hess (C)

Department of Biomedicine, Immunobiology, University of Basel and University Hospital of Basel, Basel, Switzerland.
Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, United Kingdom.

Anne-Valérie Burgener (AV)

Department of Biomedicine, Immunobiology, University of Basel and University Hospital of Basel, Basel, Switzerland.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel, Basel, Switzerland.

Pietro E Cippà (PE)

Clinic of Nephrology, University Hospital Zurich, Zurich, Switzerland.
Division of Nephrology, Ente Ospedaliero Cantonale, Lugano, Switzerland.

Kerstin Hübel (K)

Clinic of Nephrology, University Hospital Zurich, Zurich, Switzerland.

Thomas F Mueller (TF)

Clinic of Nephrology, University Hospital Zurich, Zurich, Switzerland.

Daniel Sidler (D)

Division of Nephrology and Hypertension, University Hospital Bern, Bern, Switzerland.

Suzan Dahdal (S)

Division of Nephrology and Hypertension, University Hospital Bern, Bern, Switzerland.

Franziska Suter-Riniker (F)

Institute for Infectious Diseases, University of Bern, Bern, Switzerland.

Jean Villard (J)

Department of Immunology and Allergy and Department of Laboratory Medicine, Geneva University Hospital, Geneva, Switzerland.

Andrea Zbinden (A)

Institute of Medical Virology, University of Zurich, Zurich, Switzerland.

Giuseppe Pantaleo (G)

Service of Immunology and Allergy, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Nasser Semmo (N)

Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland.

Karine Hadaya (K)

Department of Nephrology and Hypertension, Geneva University Hospitals, Geneva, Switzerland.
Clinique des Grangettes, Hirslanden, Geneva, Switzerland.

Natalia Enríquez (N)

Transplant Infectious Diseases Unit, University Hospitals Geneva and Faculty of Medicine, Geneva, Switzerland.

Pascal R Meylan (PR)

Infectious Diseases Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Marc Froissart (M)

Clinical Trial Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Dela Golshayan (D)

Transplantation Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Thomas Fehr (T)

Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel, Basel, Switzerland.
Department of Medicine, Cantonal Hospital of Chur, Chur, Switzerland.

Uyen Huynh-Do (U)

Division of Nephrology and Hypertension, University Hospital Bern, Bern, Switzerland.

Manuel Pascual (M)

Transplantation Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Christian Van Delden (C)

Transplant Infectious Diseases Unit, University Hospitals Geneva and Faculty of Medicine, Geneva, Switzerland.

Hans H Hirsch (HH)

Infectious Diseases & Hospital Epidemiology, University Hospital of Basel, Basel, Switzerland.
Transplantation & Clinical Virology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.

Peter Jüni (P)

Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, United Kingdom.

Nicolas J Mueller (NJ)

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.

Classifications MeSH