title: Effect of delaying prophylaxis against CMV in D+/R- solid organ transplant recipients in the development of CMV-specific cellular immunity and occurrence of late CMV disease.
abstract: OBJECTIVE
  Evaluate the protective effect against late CMV disease of delaying antiviral prophylaxis initiation in D+/R- patients receiving solid organ transplant (SOT).
  
  
  METHODS
  Prospective multicenter study in D+/R- SOT recipients in Spain (Sept/09-Sept/12). Whole blood specimens were prospectively collected after Tx for CMV-specific cell-mediated immunity (CMI) determination. Two prophylaxis strategies were compared: early prophylaxis (EP; starting within the first 3 days after Tx) and delayed prophylaxis (DP; starting 14 days after Tx). Risk factors for the occurrence of CMV disease were determined by survival analysis and proportional risk Cox regression models.
  
  
  RESULTS
  We included 95 patients (50 EP V 45 DP). Twenty six patients (27.4%) developed CMV disease: 32.7% EP vs. 20% DP; (p = 0.2). No cases of CMV disease were reported previously to beginning delayed prophylaxis. The percentage of individuals with detectable CMI response was higher in patients with DP although differences did not reach statistic significance (42% vs 29.6% at day 200 after Tx; p = 0.4). There was a clear trend towards less end-organ CMV disease in patients receiving DP (18.2% EP vs 5% DP; p = 0.09) and DP was the only protective factor in the multivariate analysis (HR: 0.26; CI: 0.05-1.2; p = 0.09).
  
  
  CONCLUSIONS
  A 14-day delay in CMV prophylaxis in D+/R- SOT recipients is safe and may reduce the incidence of late CMV end-organ disease although correlation of this effect with CMI responses was not complete.
authors.affiliation: Unit of Infectious Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), University Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain. Electronic address: rafasjg@yahoo.es.
authors.forename: R
authors.initials: R
authors.lastname: San-Juan
authors.affiliation: Microbiology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Navarro
authors.affiliation: Unit of Infectious Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), University Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: García-Reyne
authors.affiliation: Unit of Infectious Diseases, University Hospital de Cruces, Bilbao, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Montejo
authors.affiliation: Department of Clinical Microbiology and Infectious Diseases, University Hospital Gregorio Marañon, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Muñoz
authors.affiliation: Department of Infectious Diseases, Department of Infectious Diseases, University Hospital Bellvitge-IDIBELL, Universidad de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Carratala
authors.affiliation: Department of Infectious Diseases, University Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Len
authors.affiliation: Infectious Diseases Unit, University Hospital Ramon y Cajal, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Fortun
authors.affiliation: Microbiology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Muñoz-Cobo
authors.affiliation: Microbiology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Gimenez
authors.affiliation: Department of Clinical Microbiology and Infectious Diseases, University Hospital Gregorio Marañon, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Eworo
authors.affiliation: Department of Infectious Diseases, Department of Infectious Diseases, University Hospital Bellvitge-IDIBELL, Universidad de Barcelona, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Sabe
authors.affiliation: Department of Infectious Diseases, University Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Meije
authors.affiliation: Infectious Diseases Unit, University Hospital Ramon y Cajal, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Martin-Davila
authors.affiliation: Nephrology Service, Kidney Transplant Unit, Instituto de Investigación Hospital 12 de Octubre (i+12), University Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Andres
authors.affiliation: Cardiology Service, Heart Transplant Unit, Instituto de Investigación Hospital 12 de Octubre (i+12), University Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Delgado
authors.affiliation: General Abdominal Surgery Service, Intra-abdominal Transplant Unit, Instituto de Investigación Hospital 12 de Octubre (i+12), University Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Jimenez
authors.affiliation: Haematology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Amat
authors.affiliation: Unit of Infectious Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), University Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Fernández-Ruiz
authors.affiliation: Unit of Infectious Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), University Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: López-Medrano
authors.affiliation: Unit of Infectious Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), University Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Lumbreras
authors.affiliation: Unit of Infectious Diseases, Instituto de Investigación Hospital 12 de Octubre (i+12), University Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Aguado
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000187:drug effects / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use*; D006801:Humans; D007111:Immunity, Cellular; D015994:Incidence; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D016019:Survival Analysis; D066027:Transplant Recipients
chemical_list: D000998:Antiviral Agents; D015774:Ganciclovir
keywords: CMV disease; CMV-specific cellular immunity; D+/R−; Delayed CMV prophylaxis