The Effect of Antithymocyte Globulin and Everolimus on the Kinetics of Cytomegalovirus Viral load in Seropositive kidney Transplant Recipients without prophylaxis.
Basso G, Felipe CR, et al.Transplant Infectious Disease 2018; 20(4): e12919.
Aims
To conduct a retrospective analysis and compare the kinetics of Cytomegalovirus (CMV) replication during the first 6 months after kidney transplantation in the absence of pharmacological prophylaxis.
Interventions
All patients received tacrolimus (TAC) and corticosteroids. No pharmacological prophylaxis for CMV infection/disease was used and preemptive strategy monitoring CMV viral replication using pp65 CMV antigenemia test was implemented during the first 6 months. Blinded weekly CMV DNAemia was compared among the groups.
Participants
273 CMV positive kidney transplant recipients from the previous study* randomised to receive one of three treatment regimens, anti-thymocyte globulin and everolimus (rAGT/TAC/EVR), basiliximab and everolimus (BAS/TAC/EVR) or basiliximab and mycophenolate (BAS/TAC/MPS).
Outcomes
Measured outcomes included acute rejection, treated episodes of CMV infection/disease, and CMV viral load kinetics.
Follow-up
6 months
CET Conclusions
In this large trial carried out over two years between 2011 and 2013, some 273 CMV sero positive kidney transplant recipients (both living-related and cadaver transplant recipients) were randomized to receive ATG induction with tacrolimus (TAC) and everolimus (EVR), Basiliximab (BAS) induction/TAC and EVR or BAS and TAC with mycophenolate (MPS). All patients received tacrolimus and steroids. No prophylactic CMV therapy was given, although pre-emptive therapy based on the pp65 antigenemia test was used during the first six months. The pp65 antigenemia was higher in the ATG group but CMV DNAemia was comparable to the BAS/TAC/EVR group and lower than in the BAS/TAC/MPS group. Thus in CMV seropositive kidney transplant recipients receiving tacrolimus and prednisone and no pharmacological prophylaxis for CMV infection, the use of EVR was associated with lower incidence of CMV infection/disease, but there was no differences in the magnitude of viral load, and there was lower number of recurrent episodes compared to MPS. Overall, the use of BAS/EVR but not rATG/EVR was associated with lower proportion of patients with positive CMV viral load compared to BAS/MPS. On the other hand, among patients that were not treated for CMV infection/disease, the use of rATG/EVR or BAS/EVR was associated with significant lower viral load compared to BAS/MPS. The data suggests that use of mTOR inhibitors (everolimus) reduced the incidence of CMV infection by limiting CMV replication. The authors point out the limitations of this study, namely a single centre study, the use of a single dose of ATG, including the higher risk CMV population and excluding the high risk CMV population (D+/R-) and those patients receiving CMV prophylaxis. In patients that were not treated for CMV infection/disease, the use of ATG/EVR or BAS/EVR was associated with a significant lower viral load compared to BAS/MPS.
Data analysis
Modified intention-to-treat analysis
Quality notes
Previously assessed as *Tedesco-Silva H et al. Reduced Incidence of Cytomegalovirus Infection in Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses. Am J Transplant. 2015; 15(10):2655-2664.
Trial registration
Clinicaltrials.gov - NCT01354301