Transplant Infectious Disease · 2018 · 11 citations · 19 references
PharmacyImmunologyPharmacotherapyImmunotherapyKidney TransplantationTransplant ImmunologyImmunosuppressionImmunosuppression In Kidney TransplantationImmunosuppressive TherapyMtor Inhibitor TherapyTransplant ImmunotherapyTransplant RejectionAnti-thymocyte Globulin ConditioningCytomegalovirus TherapyEverolimus-based RegimensMtor InhibitionMtor SignalingPost Hoc AnalysisPost-transplant Cytomegalovirus InfectionViral Replication Kinetics
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.
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mTOR regulates memory CD8 T-cell differentiation
Koichi Araki, Alexandra P. Turner, Virginia Shaffer et al. · Nature · 2009 · 1.6K citations · Full text
Cláudia Rosso Felipe, Alexandra Ferreira, Marina Pontello Cristelli et al. · American Journal of Transplantation · 2015 · 157 citations · Full text