title: Effect of long-term prophylaxis in the development of cytomegalovirus-specific T-cell immunity in D+/R- solid organ transplant recipients.
abstract: BACKGROUND
  This study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long-term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease.
  
  
  METHODS
  A prospective multicenter study was conducted in Spain from September 2009 to September 2012. Whole blood specimens were prospectively collected at 30, 90, 120, 200, and 365 days after SOT, and CMI was determined by enumeration of CMV pp65 and IE-1-specific CD69(+) /interferon-γ-producing CD8(+) and CD4(+) T cells by flow cytometry for intracellular cytokine staining. As part of a simultaneous clinical trial, patients received either early prophylaxis (in the first 3 days after transplantation) in the first period of the study or delayed prophylaxis (initiated at day 14) during the second period of the study. The impact of the dynamics of acquisition of CMV-specific CMI on the incidence of CMV disease was evaluated by Kaplan-Meier survival analysis.
  
  
  RESULTS
  A total of 95 SOT recipients were recruited. CMV infection and disease occurred in 38 (40%) and 26 (27.4%) patients, respectively. The proportion of patients achieving any detectable CMV-specific CMI response at each of the different monitoring points was higher in liver transplant recipients, as compared to kidney or heart transplant recipients. The presence of any detectable response at day 120 or 200 was protective against the development of CMV disease (positive predictive values 92% and 93%, respectively).
  
  
  CONCLUSIONS
  The rate of acquisition of CMV-specific CMI in SOT recipients undergoing antiviral prophylaxis differed significantly between different SOT populations. Patients developing any detectable CMI response were protected against the occurrence of CMV disease.
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Universidad Complutense, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: San-Juan
authors.affiliation: Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Universidad de Valencia, Valencia, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Navarro
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Universidad Complutense, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: García-Reyne
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario de Cruces, Bilbao, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Montejo
authors.affiliation: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Muñoz
authors.affiliation: Department of Infectious Diseases, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Carratala
authors.affiliation: Department of Infectious Diseases, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Len
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Fortun
authors.affiliation: Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Universidad de Valencia, Valencia, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Muñoz-Cobo
authors.affiliation: Department of Microbiology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Universidad de Valencia, Valencia, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Gimenez
authors.affiliation: Department of Clinical Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Eworo
authors.affiliation: Department of Infectious Diseases, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Sabe
authors.affiliation: Department of Infectious Diseases, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Meije
authors.affiliation: Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Martín-Davila
authors.affiliation: Department of Nephrology, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Universidad Complutense, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Andres
authors.affiliation: Unit of Heart Transplantation, Department of Cardiology, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Universidad Complutense, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Delgado
authors.affiliation: Department of Abdominal Organ Transplantation and General and Digestive Surgery, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Universidad Complutense, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Jimenez
authors.affiliation: Department of Hematology and Medical Oncology, Hospital Clínico Universitario, Instituto de Investigación Sanitaria INCLIVA, Universidad de Valencia, Valencia, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Amat
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Universidad Complutense, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Ruiz
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Universidad Complutense, Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: López-Medrano
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Universidad Complutense, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Lumbreras
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Instituto de Investigación Hospital 12 de Octubre (i+12), Universidad Complutense, Madrid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Aguado
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007111:Immunity, Cellular; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D011182:Postoperative Care / Q000379:methods; D011183:Postoperative Complications / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D011446:Prospective Studies; D016896:Treatment Outcome; D000077562:Valganciclovir
chemical_list: D000998:Antiviral Agents; D000077562:Valganciclovir; D015774:Ganciclovir
keywords: CMV-specific cell-mediated immunity; D+/R−; long-term prophylaxis; solid organ transplantation