title: Multicenter comparison of laboratory performance in cytomegalovirus and Epstein-Barr virus viral load testing using international standards.
abstract: BACKGROUND
  Infections with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) remain important in solid organ transplantation. Quantitative viral nucleic acid testing is a major advance to patient management. These assays are limited by a lack of standardization, resulting in viral load measurements that differ among clinical laboratories. The variability in viral load measurements makes interpretation of multicenter clinical trials data difficult. This study compares the current practices in CMV and EBV viral load testing at four large transplant centers participating in multicenter Clinical Trials in Organ Transplantation and the Clinical Trials in Organ Transplantation in Children (CTOT and CTOTC).
  
  
  METHODS
  Viral load testing was performed on well-defined viral preparations according to standard operating procedures at each site.
  
  
  RESULTS
  Among centers, CMV viral load testing was accurate compared to WHO International Standards and within acceptable variation for this testing method. Epstein-Barr virus viral load data were more variable and less accurate despite the use of international standards.
  
  
  CONCLUSIONS
  These data suggest that comparison of CMV, but not EBV, viral load measurements at these sites is possible using current assays and control standards. Standardization of these assays is facilitated using the WHO International Standards and will allow comparison of viral load results among transplant centers. Assay standardization must be performed prior to initiation of multicenter trials.
authors.affiliation: Clinical Microbiology Laboratory, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Rychert
authors.forename: Lara
authors.initials: L
authors.lastname: Danziger-Isakov
authors.forename: Belinda
authors.initials: B
authors.lastname: Yen-Lieberman
authors.forename: Gregory
authors.initials: G
authors.lastname: Storch
authors.forename: Richard
authors.initials: R
authors.lastname: Buller
authors.forename: Stewart C
authors.initials: SC
authors.lastname: Sweet
authors.forename: Aneesh K
authors.initials: AK
authors.lastname: Mehta
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Cheeseman
authors.forename: Peter
authors.initials: P
authors.lastname: Heeger
authors.forename: Eric S
authors.initials: ES
authors.lastname: Rosenberg
authors.forename: Jay A
authors.initials: JA
authors.lastname: Fishman
mesh_terms: D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000821:virology*; D004279:DNA, Viral / Q000097:blood* / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007390:International Agencies; D007753:Laboratories / Q000592:standards*; D016377:Organ Transplantation; D016133:Polymerase Chain Reaction / Q000592:standards*; D011933:Reagent Kits, Diagnostic; D012015:Reference Standards; D019562:Viral Load / Q000379:methods*
chemical_list: D004279:DNA, Viral; D011933:Reagent Kits, Diagnostic
keywords: Epstein-Barr virus; WHO standards; clinical trial; cytomegalovirus; quantitative nucleic acid testing; viral load