Prospective follow-up of primary CMV infections after 6 months of valganciclovir prophylaxis in renal transplant recipients

Background. The occurrence and clinical course of late primary CMV infections developing after valganciclovir prophylaxis in high-risk renal transplant recipients are poorly described. Methods. Helsinki University Hospital district kidney allograft recipients between January 2004 and March 2007 (N = 175) were prospectively investigated. Patients with D+/R− CMV serostatus and 1-year follow-up were included (N = 25). After 6 months of oral valganciclovir prophylaxis, the patients were monitored for CMV-DNAemia with real-time quantitative plasma PCR at 2–6 weeks interval and if CMV infection was suspected. Infections were treated with i.v. ganciclovir or high-dose valganciclovir, followed by 1–3 months of secondary valganciclovir prophylaxis. Results. CMV infection developed in 12/25 patients a mean of 107 days (range 26–330 days) after prophylaxis ended. Two were asymptomatic. In 10 patients symptoms included fever (N = 7), gastrointestinal (N = 5), upper respiratory tract (N = 3) and hepatopathy (N = 2). One patient with infection had prophylaxis terminated after 5 months (leukopenia). The mean viral load at diagnosis was 49 517 (range 490–325 300), and peak viral load was 84 654 (range 1250–527 400) copies/ml. Five infections were treated with valganciclovir and six with i.v. ganciclovir resulting with negative PCR results. One mild infection with low viral load was treated successfully with minimization of immunosuppression. Infection relapse developed in three patients a mean of 31 (range 15–61) days after the end of the therapy. Relapses were treated with valganciclovir. Conclusions. CMV primary infections were common after 6 months of valganciclovir prophylaxis and mostly symptomatic. Relapses commonly occurred. Primary infections seem to be delayed, but were not efficiently prevented by 6 months of prophylaxis.