BACKGROUND: Cytomegalovirus (CMV) prophylaxis may prevent CMV indirect effects in renal transplant recipients. This study aimed to compare the efficacy of valganciclovir and valacyclovir prophylaxis for CMV after renal transplantation with the focus on chronic histologic damage within the graft. METHODS: From November 2007 through April 2012, adult renal transplant recipients were randomized, in an open-label, single-center study, at a 1:1 ratio to 3-month prophylaxis with valganciclovir (n = 60) or valacyclovir (n = 59). The primary endpoint was moderate-to-severe interstitial fibrosis and tubular atrophy assessed by protocol biopsy at 3 years evaluated by a single pathologist blinded to the study group. The analysis was conducted in an intention-to-treat population. RESULTS: Among the 101 patients who had a protocol biopsy specimen available, the risk of moderate-to-severe interstitial fibrosis and tubular atrophy was significantly lower in those treated with valganciclovir (22% versus 34%; adjusted odds ratio, 0.31; 95% confidence interval, 0.11-0.90; P = 0.032 by multivariate logistic regression). The incidence of CMV disease (9% versus 2%; P = 0.115) and CMV DNAemia (36% versus 42%; P = 0.361) were not different at 3 years. CONCLUSIONS: Valganciclovir prophylaxis, as compared with valacyclovir, was associated with a reduced risk of moderate-to-severe interstitial fibrosis and tubular atrophy in patients after renal transplantation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12610000016033 ). Registered on September 26, 2007.

• Keywords
• Cytomegalovirus, Fibrosis, Prophylaxis, Renal transplantation, Valganciclovir,
• MeSH
• Intention to Treat Analysis MeSH
• Antibiotic Prophylaxis methods   MeSH
• Antiviral Agents therapeutic use   MeSH
• Cytomegalovirus Infections epidemiology   prevention & control   MeSH
• Cytomegalovirus drug effects   MeSH
• Adult MeSH
• Fibrosis epidemiology   prevention & control   MeSH
• Transplantation, Homologous adverse effects   MeSH
• Incidence MeSH
• Kidney drug effects   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Kidney Diseases epidemiology   prevention & control   MeSH
• Graft Survival drug effects   MeSH
• Kidney Transplantation * adverse effects   statistics & numerical data   MeSH
• Valacyclovir therapeutic use   MeSH
• Valganciclovir therapeutic use   MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH
• Geographicals
• Australia epidemiology   MeSH
• Names of Substances
• Antiviral Agents MeSH
• Valacyclovir MeSH
• Valganciclovir MeSH

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,
• MeSH
• Acyclovir administration & dosage   adverse effects   analogs & derivatives   MeSH
• Acute Disease MeSH
• Intention to Treat Analysis MeSH
• Antiviral Agents administration & dosage   adverse effects   MeSH
• Biomarkers blood   MeSH
• Biopsy MeSH
• Time Factors MeSH
• Cytomegalovirus Infections diagnosis   immunology   prevention & control   virology   MeSH
• Cytomegalovirus drug effects   genetics   MeSH
• DNA, Viral blood   MeSH
• Adult MeSH
• Ganciclovir administration & dosage   adverse effects   analogs & derivatives   MeSH
• Immunosuppressive Agents therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Graft Survival drug effects   MeSH
• Graft Rejection diagnosis   immunology   prevention & control   MeSH
• Drug Administration Schedule MeSH
• Kidney Transplantation adverse effects   MeSH
• Valacyclovir MeSH
• Valganciclovir MeSH
• Valine administration & dosage   adverse effects   analogs & derivatives   MeSH
• Viral Load MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Acyclovir MeSH
• Antiviral Agents MeSH
• Biomarkers MeSH
• DNA, Viral MeSH
• Ganciclovir MeSH
• Immunosuppressive Agents MeSH
• Valacyclovir MeSH
• Valganciclovir MeSH
• Valine MeSH

Prevention of cytomegalovirus (CMV) is essential in organ transplantation. The two main strategies are pre-emptive therapy, in which one screens for and treats asymptomatic CMV viremia, and universal antiviral prophylaxis. We compared these strategies and examined long-term outcomes in a randomized, open-label, single-center trial. We randomly assigned 70 renal transplant recipients (CMV-seropositive recipient or donor) to 3-month prophylaxis with valacyclovir (n=34) or pre-emptive valganciclovir for significant CMV viremia detected at predefined assessments through month 12 (n=36). Among the 55 patients who had a protocol biopsy specimen available at 3 years to allow assessment of the primary outcome, 9 (38%) of 24 patients in the prophylaxis group and 6 (19%) of 31 patients in the pre-emptive therapy group had moderate to severe interstitial fibrosis and tubular atrophy (odds ratio, 2.50; 95% confidence interval, 0.74-8.43; P=0.22). The prophylaxis group had significantly higher intrarenal mRNA expression of genes involved in fibrogenesis. The occurrence of CMV disease was similar in both groups, but pre-emptive therapy improved 4-year graft survival (92% versus 74%; P=0.049) as a result of worse outcomes in patients with late-onset CMV viremia. In conclusion, compared with valacyclovir prophylaxis, pre-emptive valganciclovir therapy may lead to less severe interstitial fibrosis and tubular atrophy and to significantly better graft survival.

• MeSH
• Acyclovir analogs & derivatives   therapeutic use   MeSH
• Antiviral Agents therapeutic use   MeSH
• Atrophy MeSH
• Biopsy MeSH
• Cytomegalovirus Infections mortality   prevention & control   MeSH
• Cytomegalovirus isolation & purification   MeSH
• Adult MeSH
• Fibrosis MeSH
• Ganciclovir analogs & derivatives   therapeutic use   MeSH
• Kaplan-Meier Estimate MeSH
• Kidney pathology   virology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Follow-Up Studies MeSH
• Graft Survival MeSH
• Kidney Transplantation * mortality   MeSH
• Valacyclovir MeSH
• Valganciclovir MeSH
• Valine analogs & derivatives   therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Names of Substances
• Acyclovir MeSH
• Antiviral Agents MeSH
• Ganciclovir MeSH
• Valacyclovir MeSH
• Valganciclovir MeSH
• Valine MeSH