The effect of anti-thymocyte globulin and everolimus on the kinetics of cytomegalovirus viral load in seropositive kidney transplant recipients without prophylaxis

Abstract

Background: The use of mTOR inhibitors is associated with lower incidence of CMV infections but its effect on viral load has not been investigated.

Aims, materials and methods: This post-hoc analysis included data from 273 CMV seropositive kidney transplant recipients randomized to receive anti-thymocyte globulin and everolimus (rAGT/TAC/EVR, n = 81), basiliximab and everolimus (BAS/TAC/EVR, n = 97) or basiliximab and mycophenolate (BAS/TAC/MPS, n = 95). All patients received tacrolimus (TAC) and corticosteroids. Preemptive CMV therapy based on weekly pp65 antigenemia test was used during the first 6 months. Blinded weekly CMV DNAemia was compared among the groups.

Results: The proportion of patients with undetectable CMV DNAemia (23.4% vs 56.7% vs 22.1%, P < .001) was higher in the BAS/TAC/EVR. The median number of study visits with positive CMV DNAemia (2.0 vs 0.0 vs 4.6, rATG/EVR vs BAS/MPS, P = .354; BAS/EVR vs BAS/MPS, P < .0001; rATG/EVR vs BAS/EVR, P < .001) were lower in the BAS/TAC/EVR. The proportion of patients with positive CMV DNAemia who were not treat for CMV infection/disease based on pp65 antigenemia was higher in rATG/TAC/EVR group (74.1% vs 36.1% vs 44.2%, P < .001) but mean CMV DNAemia was comparable to BAS/TAC/EVR and lower than BAS/TAC/MPS (8536 ± 15 899 vs 7975 ± 17 935 vs 16 965 ± 37 694 copies/mL, P < .05), respectively. The proportion of patients with CMV DNAemia below 5000 copies/mL was higher in patients receiving EVR (74.1% vs 83.5% vs 50.0%, P = .000), respectively.

Discussion and conclusion: These data suggest that mTOR inhibitors reduce the incidence of CMV infection by limiting CMV viral replication.

Keywords: Anti-thymocyte globulin; cytomegalovirus; everolimus; kidney; kinetics; postranplant infectious; transplant.