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.

Clinical trials registration: NCT00431353.

Keywords: CMV DNA test; CMV antiviral therapy; World Health Organization international standard; cytomegalovirus; valganciclovir.