title: Virologic suppression measured by a cytomegalovirus (CMV) DNA test calibrated to the World Health Organization international standard is predictive of CMV disease resolution in transplant recipients.
abstract: BACKGROUND
  Cytomegalovirus (CMV) load measurement is used to assess the efficacy of treatment of CMV disease, but lacks standardization. Using the World Health Organization (WHO) international standard for reporting, we correlated viral load with CMV disease resolution.
  
  
  METHODS
  CMV load was quantified in plasma using a test calibrated to the WHO standard. Three predictive rules were predefined to determine association between CMV DNAemia and outcome: (1) pretreatment CMV DNA of <18,200 (4.3 log(10)) IU/mL; (2) viral load declines of 1.0, 1.5, 2.0, and 2.5 log(10) IU/mL from baseline to days 7, 14, and 21 of treatment, respectively; and (3) viral suppression <137 (2.1 log(10)) IU/mL at days 7, 14, and 21. Analysis was performed using Cox proportional hazard models.
  
  
  RESULTS
  Of 267 patients, 251 had CMV disease resolution by day 49 of treatment. Patients with pretreatment CMV DNA of <18,200 (4.3 log(10)) IU/mL had faster time to disease resolution (adjusted hazard ratio [AHR], 1.56; P = .001). Patients with CMV load suppression (<137 IU/mL [<2.1 log(10)]) at days 7, 14, and 21 had faster times to clinical disease resolution (AHRs, 1.61, 1.73, and 1.64, and P = .005, <.001, and <.001, respectively). Relative CMV load reductions from baseline were not significantly associated with faster resolution of CMV disease.
  
  
  CONCLUSIONS
  Patients with pretreatment CMV DNA of <18,200 (4.3 log(10)) IU/mL are 1.5 times more likely to have CMV disease resolution. CMV suppression (<137 [2.1 log(10)] IU/mL), as measured by a test calibrated to the WHO Standard, is predictive of clinical response to antiviral treatment.
  
  
  BACKGROUND
  NCT00431353.
authors: Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905-0002, USA. razonable.raymund@mayo.edu
authors: Raymund R
authors: RR
authors: Razonable
authors: Anders
authors: A
authors: Åsberg
authors: Halvor
authors: H
authors: Rollag
authors: John
authors: J
authors: Duncan
authors: Denis
authors: D
authors: Boisvert
authors: Joseph D
authors: JD
authors: Yao
authors: Angela M
authors: AM
authors: Caliendo
authors: Atul
authors: A
authors: Humar
authors: Tri D
authors: TD
authors: Do
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D004279:DNA, Viral / Q000097:blood; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012016:Reference Values; D012189:Retrospective Studies; D016896:Treatment Outcome; D000077562:Valganciclovir; D019562:Viral Load / Q000187:drug effects; D014944:World Health Organization
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D000077562:Valganciclovir; D015774:Ganciclovir
keywords: CMV DNA test; CMV antiviral therapy; World Health Organization international standard; cytomegalovirus; valganciclovir