Role Of Everolimus In Providing Protection From Cmv Infection After Transplant By Improving T-Cell Specific Immunity

Introduction Prevention of Citomegalovirus (CMV) infection in heart transplant is currently based on humoral immune status, and mismatch recipients (R-/D+) are the higher risk group. Everolimus is associated with a reduced incidence of CMV infection and regulation of memory T-cell differentiation. Case Report A 63 years old patient with end-stage cardiomyopathy underwent heart transplantation in October 2018 due to advanced heart failure. He was treated with basiliximab, corticosteroids, tacrolimus, and mycophenolic acid (MPA) without complications, with good biventricular function, normal coronariography and no rejection. Beacause of mild pancytopenia during admission, the MPA dose was reduced and because of CMV donor-recipient mismatch, a six months valganciclovir treatment was indicated. To note, we performed an Elispot IFN-γ assay before transplantation, which showed no cellular immunity against CMV.In March 2019 MPA was changed to everolimus due to progressive leukopenia and recurrent urinary tract infections, and valganciclovir was stopped per-protocol. At that moment, we performed an Elispot IFN-γ assay, which showed new-onset cellular immunity against CMV.Four months later everolimus was stopped and low dose MPA reintroduced because of the persistent infections.Twenty days after changing everolimus to MPA, the patient was admitted with late-onset CMV disease, which was diagnosed by fever, gastrointestinal symptoms and high viral load (PCR: 6501UI/ml). The Elispot assay showed loss of cellular immunity against CMV and treatment with valganciclovir was initiated until viral copies were negative. Everolimus treatment was resumed and in December 2019, the Elispot assay showed cellular immunity against CMV once again. Summary It is the first time that everolimus has been shown to provide in vivo protection from CMV infection after transplant by improving T-cell specific immunity as shown by the Elispot assay.