The Efficacy and Safety of 200 Days Valganciclovir Cytomegalovirus Prophylaxis in High‐Risk Kidney Transplant Recipients

Abstract

Late-onset cytomegalovirus (CMV) disease is a significant problem with a standard 3-month prophylaxis regimen. This multicentre, double-blind, randomized controlled trial compared the efficacy and safety of 200 days' versus 100 days' valganciclovir prophylaxis (900 mg once daily) in 326 high-risk (D+/R-) kidney allograft recipients. Significantly fewer patients in the 200-day group versus the 100-day group developed confirmed CMV disease up to month 12 posttransplant (16.1% vs. 36.8%; p < 0.0001). Confirmed CMV viremia was also significantly lower in the 200-day group (37.4% vs. 50.9%; p = 0.015 at month 12). There was no significant difference in the rate of biopsy-proven acute rejection between the groups (11% vs. 17%, respectively, p = 0.114). Adverse events occurred at similar rates between the groups and the majority were rated mild-to-moderate in intensity and not related to study medication. In conclusion, this study demonstrates that extending valganciclovir prophylaxis (900 mg once daily) to 200 days significantly reduces the incidence of CMV disease and viremia through to 12 months compared with 100 days' prophylaxis, without significant additional safety concerns associated with longer treatment. The number needed to treat to avoid one additional patient with CMV disease up to 12 months posttransplant is approximately 5.

Impact of Antiviral Preventive Strategies on the Incidence and Outcomes of Cytomegalovirus Disease in Solid Organ Transplant Recipients

“…CMV disease incidence was 16.9% in high-risk patients (CMV Dþ/RÀ) and 4.4% in the intermediate-risk patients (CMV Rþ). These numbers are similar to or lower than those observed in the most recent published prospective cohort studies (9,26) or randomized controlled trials (15,16,27), reflecting the improved management on the prevention of CMV disease over the last years. Some patients took sequentially more than one drug, so the addition of numbers may result in >100%.…”

“…First, a significant number of patients (approximately 20-30% of Dþ/RÀ patients) may still develop CMV disease after discontinuation of prophylaxis (15,16). This is termed ''late-onset CMV disease'' and some studies suggest that it remains associated with poor outcomes in SOT recipients (17,18).…”

Easier Control of Late-Onset Cytomegalovirus Disease Following Universal Prophylaxis Through an Early Antiviral Immune Response in Donor-Positive, Recipient-Negative Kidney Transplants

“…CMV incidence remains elevated in these patients, at between 16% and 37%, depending on the duration of preventive therapy (1,2). In one study directly comparing prophylactic and preemptive approaches, it was clearly demonstrated that late DNAemia occurs much more frequently in the prophylactic versus the preemptive setting (3,4).…”

A stringent preemptive protocol reduces cytomegalovirus disease in the first 6 months after kidney transplantation

“…The ease of prophylaxis treatment and the documented benefits in term of mortality is counterbalanced by the potential side effects, such as cytopenia and the occurrence of late-onset CMV disease. A longer period of prophylaxis (6 months) has been shown to further reduce late-onset CMV disease [1], but increased costs are an issue. Important considerations are the indirect effects of CMV on transplant-related endpoints, such as rejection and long-term graft function, which are linked to CMV by circumstantial evidence.…”

“…It has recently been shown that high-risk (D?/R-) kidney allograft recipients who receive prolonged prophylaxis for 6 months have a lower rate of CMV disease, although late-onset CMV disease still manifests in 16 % of the high-risk recipients [1]. In a similar study performed in high-risk kidney transplant recipients in Europe, 37 % of the investigated patients developed a CMV infection, and the majority were symptomatic after 6 months of valganciclovir prophylaxis [2].…”