Viral-specific cytotoxic T-cell responses in HLA-sensitized kidney transplant patients maintained on everolimus and low-dose tacrolimus.

Abstract

Maintenance with "everolimus + reduced dose tacrolimus" (Ev + Taclow ) was reported to reduce the risk of viral infections compared to "tacrolimus + mycophenolate mofetil" (Tac + MMF). Here we examined viremia and viral-specific T-cell (viral-Tc) responses in patients treated with Ev + Taclow versus Tac + MMF in highly-human leukocyte antigen (HLA)-sensitized patients. HLA-sensitized (HS) kidney transplant patients were monitored pre- and post-transplant for viremia (cytomegalovirus (CMV), BK, and Epstein-Barr virus (EBV)) by polymerase chain reaction (PCR) in 19 Ev + Taclow and 48 Tac + MMF patients. For CMV PCR analysis, we compared infection rates in 19 Ev + Taclow patients to 48 CMV D+/R- (#28) or CMV D-/R- (#20) Tac + MMF patients. CMV-specific cytotoxic T cell (CMV-Tc) and EBV-specific cytotoxic T cell (EBV-Tc) were evaluated by cytokine flow cytometry, and donor-specific antibody (DSA) levels by Luminex for selected patients in both groups. CMV and EBV viremia rates were similar in Ev + Taclow versus Tac + MMF patients, but BK virus (BKV) rates were significantly higher in Ev + Taclow patients. No patient in either group developed BK virus-associated allograft nephropathy (BKAN) or post-transplant lymphoproliferative disorders (PTLD). CMV-Tc and EBV-Tc decreased significantly after alemtuzumab induction but returned to pre-treatment levels 1-2 months post-transplant in most patients. de novo DSA was similar in both groups as were patient and graft survival and graft rejection. CMV-Tc and EBV-Tc were similar in Ev + Taclow and Tac + MMF patients. EBV and CMV viremia rates were similar over 1 year. BKV rates were significantly higher in Ev + Taclow patients suggesting no benefit for Ev + Taclow in enhancing viral-Tc effector functions or limiting viral infections.