Kinetics of Cytomegalovirus (CMV) Viral Replication in Tacrolimus (TAC) Treated Kidney Transplant Recipients Receiving Everolimus (EVR) or Mycophenolate (MPA)

Introduction: EVR has been associated with reduced incidence of CMV infection but little information is known regarding the kinetics of viral load and response to treatment. Methods: In this one year prospective randomized study 288 kidney transplant recipients received (G1, n=85) single 3 mg/kg dose of antithymocyte globulin, reduced exposure TAC, EVR; (G2, n=102) basiliximab, reduced exposure TAC; (G3, n=101) basiliximab, TAC, MPA. All patients received prednisone. None of the patients received any CMV prophylaxis. CMV viral replication was monitored weekly using pp65 antigenemia and PCR (blinded). The primary outcome is the incidence of CMV infection (viremia or disease). Treatment was initiated based on 10 pp65 positive cells and ended one week after a negative test. Results: The incidence of first CMV infection was lower in EVR treated patients (4.7 vs. 7.8 vs. 35.6%, p<0.0001). The proportion of CMV viremia/disease was 25% vs. 13% vs. 53%, respectively. Recurrence occurred in 40% of patients none from G1, 4/19(21%) from G2 and 15/19(79%) from G3. Similar proportion of patients had recurrence regarding the previous classification of viremia (9/26) or disease (10/22). In addition, the incidence of recurrence was higher in patients presenting a PCR+ at the last day of treatment (10/19 vs 9/29). PCR viral load was positive in 88% of patients one week before the diagnosis of CMV infection by pp65 antigenemia. Median PCR viral load was lower in EVR patients at the time of CMV infection (20,144 vs. 21,684 vs. 44,376 copies) and one week before (358 vs. 898 vs. 5,289) and at the end of treatment (0 vs. 0 vs. 77.5 copies). Conclusion: Patients receiving EVR showed lower incidence of CMV infection, recurrence of CMV infection and viral load compared to those receiving MPA.