Randomized Trial of Valganciclovir Versus Valacyclovir Prophylaxis for Prevention of Cytomegalovirus in Renal Transplantation

Abstract

Background and objectives Both valganciclovir and high-dose valacyclovir are recommended for cytomegalovirus prophylaxis after renal transplantation. A head-to-head comparison of both regimens is lacking. The objective of the study was to compare valacyclovir prophylaxis with valganciclovir, which constituted the control group.Design, settings, participants, & measurements In a randomized, open-label, single-center trial, recipients of renal transplants (recipient or donor cytomegalovirus-seropositive) were randomly allocated (1:1) to 3-month prophylaxis with valacyclovir (2 g four times daily) or valganciclovir (900 mg daily). Enrollment occurred from November of 2007 to April of 2012. The primary end points were cytomegalovirus DNAemia and biopsy-proven acute rejection at 12 months. Analysis was by intention to treat. ResultsIn total, 119 patients were assigned to valacyclovir (n=59) or valganciclovir prophylaxis (n=60). Cytomegalovirus DNAemia developed in 24 (43%) of 59 patients in the valacyclovir group and 18 (31%) of 60 patients in the valganciclovir group (adjusted hazard ratio, 1.35; 95% confidence interval, 0.71 to 2.54; P=0.36). The incidence of cytomegalovirus disease was 2% with valacyclovir and 5% with valganciclovir prophylaxis (adjusted hazard ratio, 0.21; 95% confidence interval, 0.01 to 5.90; P=0.36). Significantly more patients with valacyclovir prophylaxis developed biopsy-proven acute rejection (18 of 59 [31%] versus 10 of 60 [17%]; adjusted hazard ratio, 2.49; 95% confidence interval, 1.09 to 5.65; P=0.03). The incidence of polyomavirus viremia was higher in the valganciclovir group (18% versus 36%; adjusted hazard ratio, 0.43; 95% confidence interval, 0.19 to 0.96; P=0.04).Conclusions Valganciclovir shows no superior efficacy in cytomegalovirus DNAemia prevention compared with valacyclovir prophylaxis. However, the risk of biopsy-proven acute rejection is higher with valacyclovir.

Treatment and prevention of cytomegalovirus infection in heart and lung transplantation: an update

“…Most of the evidence in this field derives from kidney transplantation. 32,36,37 In a series of studies, Reischig demonstrated that acyclovir prophylaxis is as effective as pre-emptive 36 or prophylaxis 37 with valganciclovir in preventing CMV infection and disease, but with a better safety profile. In addition, acyclovir strategy had a significantly better pharmacoeconomic impact in patient management 37,38 .…”

“…32,36,37 In a series of studies, Reischig demonstrated that acyclovir prophylaxis is as effective as pre-emptive 36 or prophylaxis 37 with valganciclovir in preventing CMV infection and disease, but with a better safety profile. In addition, acyclovir strategy had a significantly better pharmacoeconomic impact in patient management 37,38 . The drawbacks of acyclovir strategy were an increased rate of biopsy proven rejection when compared to valganciclovir prophylaxis, and a lower long-term graft survival when compared with pre-emptive valganciclovir.…”

Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: Outcome and risk factors for late CMV disease

“…In a study analyzing the safety and efficacy of induction treatment with low doses of ATG compared with basiliximab, CMV disease was more frequent in the ATG group despite three months of prophylaxis . In another study, even with valganciclovir (VGCV) prophylaxis, CMV viremia occurred in 8% of patients in another study . Antiviral prophylaxis has been associated with late‐disease (after 3‐6 months) more frequently when compared with preemptive therapy …”

Valganciclovir versus valacyclovir prophylaxis for prevention of cytomegalovirus: an economic perspective

“…While the AR‐related costs are not negligible in some European studies, our model may falsely raise the figure in a number of countries with lower hospitalization‐related costs, particularly in the vACV group . Moreover, the difference in the incidence of AR episodes was a result of the increase in less costly mild forms of T cell‐mediated rejection responding well to steroid therapy .…”

“…Except for the effect of AR, our economic analysis did not consider the potential long‐term indirect impact of CMV, particularly its effect on graft and patient survival, potentially highlighting the economic benefit of CMV prevention . Still, no differences were found at 1 year between vGCV and vACV prophylaxis in the incidence of CMV disease and DNAemia, renal function, or graft survival . A remarkable finding in this context is that of inferior long‐term graft survival of patients receiving vACV prophylaxis compared with preemptive vGCV therapy .…”