QuantiFERON-CMV as a Predictor of CMV Events During Preemptive Therapy in CMV-seropositive Kidney Transplant Recipients

Abstract

Background. Prevention of cytomegalovirus (CMV) infection after kidney transplantation is costly and burdensome. Methods. Given its promising utility in risk stratification, we evaluated the use of QuantiFERON-CMV (QFCMV) and additional clinical variables in this prospective cohort study to predict the first clinically significant CMV infection (CS-CMV, ranging from asymptomatic viremia requiring treatment to CMV disease) in the first posttransplant year. A cost-effectiveness analysis for guided prevention was done. Results. One hundred adult kidney transplant recipients, CMV IgG+, were given basiliximab induction and maintained on steroid/mycophenolate/tacrolimus with weekly CMV monitoring. Thirty-nine patients developed CS-CMV infection (viral syndrome, n = 1; end-organ disease, n = 9; and asymptomatic viremia, n = 29). A nonreactive or indeterminate QFCMV result using the standard threshold around day 30 (but not before transplant) was associated with CS-CMV rates of 50% and 75%, respectively. A higher QFCMV threshold for reactivity (>1.0 IU interferon-γ/mL) outperformed the manufacturer’s standard (>0.2 IU interferon-γ/mL) in predicting protection but still allowed a 16% incidence of CS-CMV. The combination of recipient age and type of donor, along with posttransplant QFCMV resulted in a prediction model that increased the negative predictive value from 84% (QFCMV alone) to 93%. QFCMV-guided preemptive therapy was of lower cost than preemptive therapy alone (P < 0.001, probabilistic sensitivity analysis) and was cost-effective (incremental net monetary benefit of 210 USD) assuming willingness-to-pay of 2000 USD to avoid 1 CMV disease. Conclusions. Guided CMV prevention by the prediction model with QFCMV is cost-effective and would spare from CMV surveillance in 42% of patients with low risk for CS-CMV.