title: Progress in Quantitative Viral Load Testing: Variability and Impact of the WHO Quantitative International Standards.
abstract: It has been hoped that the recent availability of WHO quantitative standards would improve interlaboratory agreement for viral load testing; however, insufficient data are available to evaluate whether this has been the case. Results from 554 laboratories participating in proficiency testing surveys for quantitative PCR assays of cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK virus (BKV), adenovirus (ADV), and human herpesvirus 6 (HHV6) were evaluated to determine overall result variability and then were stratified by assay manufacturer. The impact of calibration to international units/ml (CMV and EBV) on variability was also determined. Viral loads showed a high degree of interlaboratory variability for all tested viruses, with interquartile ranges as high as 1.46 log10copies/ml and the overall range for a given sample up to 5.66 log10copies/ml. Some improvement in result variability was seen when international units were adopted. This was particularly the case for EBV viral load results. Variability in viral load results remains a challenge across all viruses tested here; introduction of international quantitative standards may help reduce variability and does so more or less markedly for certain viruses.
authors.affiliation: Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA Randall.Hayden@stjude.org.
authors.forename: R T
authors.initials: RT
authors.lastname: Hayden
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: L
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: G W
authors.initials: GW
authors.lastname: Procop
authors.affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Hillyard
authors.affiliation: Departments of Pathology and Medicine, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: B A
authors.identifier: 0000-0001-8751-4810
authors.initials: BA
authors.lastname: Pinsky
authors.affiliation: Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.|TriCore Reference Laboratories, Albuquerque, New Mexico, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Young
authors.affiliation: Department of Medicine, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Caliendo
mesh_terms: D000256:Adenoviridae / Q000302:isolation & purification*; D006564:Herpesviridae / Q000302:isolation & purification*; D006801:Humans; D059021:Laboratory Proficiency Testing; D015203:Reproducibility of Results; D019562:Viral Load / Q000379:methods* / Q000592:standards*; D014777:Virus Diseases / Q000821:virology*; D014944:World Health Organization
keywords: PCR; WHO; calibration; quantitative; variability; viral load