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.

Results: In 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.

Keywords: cytomegalovirus; prevention; renal transplantation; valacyclovir; valganciclovir.

Copyright © 2015 by the American Society of Nephrology.

Figures

Figure 1.

Flow of patients through the study. CMV, cytomegalovirus; D, donor; R, recipient.

Figure 2.

Kaplan–Meier curves for the cumulative probability of freedom from (A) cytomegalovirus DNAemia, (B) biopsy-proven acute rejection, and (C) cytomegalovirus disease. Valacyclovir and valganciclovir prophylaxis showed similar efficacy in prevention of cytomegalovirus DNAemia or disease however, the incidence of biopsy-proven acute rejection was significantly higher with valacyclovir. The Cox proportional hazard model adjusting for age, previous transplantation, peak panel reactive antibodies, HLA mismatches, calcineurin inhibitor, induction therapy, donor age, donor type, expanded criteria donor, and delayed graft function was used for comparison. aHR, adjusted hazard ratio; 95% CI, 95% confidence interval.

Figure 3.

Kaplan–Meier curves for the cumulative probability of (A) polyoma BK virus viremia and (B) polyoma BK virus-associated nephropathy. Significantly lower incidence of polyoma BK virus viremia was observed in patients treated with valacyclovir prophylaxis. The Cox proportional hazard model adjusting for age, previous transplantation, peak panel reactive antibodies, HLA mismatches, calcineurin inhibitor, induction therapy, donor age, donor type, expanded criteria donor, and delayed graft function was used for comparison. aHR, adjusted hazard ratio.