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

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.

Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: Outcome and risk factors for late CMV disease.

BACKGROUND: Anti-thymocyte globulin (ATG) therapy is a risk factor for cytomegalovirus (CMV) disease in renal transplant (RTx) recipients and therefore antiviral prophylaxis is commonly used. We evaluated the outcome of our current policy of 90 days of CMV prophylaxis in seropositive recipients given ATG and the risk factors for the occurrence of CMV disease after prophylaxis. METHODS: We studied a retrospective cohort of 423 RTx (2010-2014) CMV-seropositive adults given ATG induction therapy. RESULTS: 54 (13%) patients developed CMV disease at a median of 163 days after transplant, of which 29 (54%) had viral syndrome and 25 (46%) had invasive disease. Median prophylaxis time (94 days) and immunosuppressive drugs were similar between groups (CMV vs no-CMV). Those with CMV disease had more deceased donors and higher donor age, lower lymphocyte count, and lower median eGFR at day 90. Multivariable logistic regression analysis at day 90 and 180 found that eGFR ≤40 ml/min/1.73 m2 (but not acute rejection) was associated with late CMV disease. In a separate validation cohort of 124 patients with 8% late CMV disease, eGFR ≤45 and lymphocyte count ≤800 cells/mm3 at the end of prophylaxis remained predictive of late CMV disease occurrence. CONCLUSIONS: These data indicate that antiviral prophylaxis adequately prevented CMV in seropositive recipients given ATG, but late disease still occurred. Low eGFR and low lymphocyte count at the end of prophylaxis may help identify patients at higher risk of CMV disease.