Prolonged Low-Dose Prophylaxis With Valganciclovir in Cytomegalovirus-Negative Recipients of Kidney Transplants From Cytomegalovirus-Positive Donors Allows Seroconversion and Prevents Cytomegalovirus Disease

Abstract

BackgroundCytomegalovirus-negative recipients of kidneys from cytomegalovirus (CMV)-positive donors (D+/R−) are at high risk to develop severe clinical manifestations of CMV disease. Long-term data about incidence and timing of CMV seroconversion, CMV disease, and the influence of prolonged valganciclovir prophylaxis on the clinical course of CMV infection are missing. MethodsWe conducted a retrospective long-term study of 89 consecutive CMV D+/R− kidney transplant recipients transplanted between 2003 and 2012. All recipients received valganciclovir prophylaxis after transplantation (median 187 [126-261] days) with a median dose of 213 (181-338) mg/d. Long-term outcome was assessed over a maximum of 10 years post-transplant. ResultsDuring follow-up (median 62 months) 60 of 89 (67%) patients had CMV seroconversion, and 29 of 89 (33%) developed symptomatic CMV disease. In addition, in 38 of the 60 (63%), seroconversion occurred during prophylaxis (median 154 days post-transplant), and in 22 patients, after the end of prophylaxis (median 320 days after transplantation). Baseline characteristics of the 2 groups did not differ significantly. Seroconversion during prophylaxis vs seroconversion after the end of prophylaxis was associated with significantly lower incidence of CMV disease (34% vs 73%, P = .007), less severe CMV disease (16% vs 64%, P < .001), and fewer organ manifestations (26% vs 64%, P = .006). The risk of CMV disease was limited to the first 475 days after transplantation. Valganciclovir resistance occurred in just 1 case (1%). ConclusionsProlonged prophylaxis with low-dose valganciclovir allowed CMV seroconversion during prophylaxis in a high proportion of D+/R− patients. Seroconversion occurred after a median of 154 days and was associated with significantly lower incidence of CMV disease, less severe CMV disease, and fewer CMV complications.