title: Determination, validation and standardization of a CMV DNA cut-off value in plasma for preemptive treatment of CMV infection in solid organ transplant recipients at lower risk for CMV infection.
abstract: BACKGROUND
  Valganciclovir preemptive therapy guided by the viral load is the current strategy recommended for preventing CMV disease in CMV-seropositive Solid Organ Transplant Recipients (SOTR) at lower risk for developing CMV infection. However, universal viral load cut-off has not been established for initiating therapy.
  
  
  OBJECTIVE
  Our goal was to define and validate a standardized cut-off determined in plasma by real-time PCR assay for initiating preemptive therapy in this population.
  
  
  METHODS
  A prospective cohort study of consecutive cases of CMV-seropositive SOTR was carried out. The cut-off value was determined in a derivation cohort and was validated in the validation cohort. Viral loads were determined using the Quant CMV LightCycler 2.0 real-time PCR System (Roche Applied Science) and results were standardized using the WHO International Standard for human CMV.
  
  
  RESULTS
  A viral load of 3983 IU/ml (2600 copies/ml) was established as the optimal cut-off for initiating preemptive therapy in a cohort of 141 patients with 982 tests and validated in a cohort of 252 recipients with a total of 2022 test. This cut-off had a 99.6% NPV indicating that the great majority of patients at lower risk will not develop CMV disease without specific antiviral therapy. The high sensitivity and specificity (89.9% and 88.9%, respectively) and the relatively small numbers of patients with CMV disease confirm that real-time PCR was optimal.
  
  
  CONCLUSIONS
  We have established a cut-off viral load for starting preemptive therapy for CMV-seropositive SOT recipients. Our results emphasized the importance of a mandatory follow-up protocol for CMV-seropositive patients receiving preemptive treatment.
authors.affiliation: Unit of Infectious Disease, Microbiology and Preventive Medicine, Instituto de Biomedicina de Sevilla, University Hospital Virgen del Rocío/CSIC/University of Sevilla, Spain. cecilia3778@hotmail.com
authors.forename: C
authors.initials: C
authors.lastname: Martín-Gandul
authors.forename: P
authors.initials: P
authors.lastname: Pérez-Romero
authors.forename: M
authors.initials: M
authors.lastname: Sánchez
authors.forename: G
authors.initials: G
authors.lastname: Bernal
authors.forename: G
authors.initials: G
authors.lastname: Suárez
authors.forename: M
authors.initials: M
authors.lastname: Sobrino
authors.forename: L
authors.initials: L
authors.lastname: Merino
authors.forename: J M
authors.initials: JM
authors.lastname: Cisneros
authors.forename: E
authors.initials: E
authors.lastname: Cordero
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D019411:Clinical Laboratory Techniques / Q000379:methods / Q000592:standards*; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000175:diagnosis*; D004279:DNA, Viral / Q000302:isolation & purification*; D005260:Female; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods / Q000592:standards*; D016377:Organ Transplantation / Q000009:adverse effects; D010949:Plasma / Q000821:virology*; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D000077562:Valganciclovir; D019562:Viral Load / Q000379:methods / Q000592:standards*; D014766:Viremia / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D000077562:Valganciclovir; D015774:Ganciclovir