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Previous Volume 340:1462-1470 May 13, 1999 Number 19 Next

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ABSTRACT

Background Cytomegalovirus (CMV) disease is a major complication of organ transplantation. We hypothesized that prophylactic treatment with valacyclovir would reduce the risk of CMV disease.

Methods A total of 208 CMV-negative recipients of a kidney from a seropositive donor and 408 CMV-positive recipients were randomly assigned to receive either 2 g of valacyclovir or placebo orally four times daily for 90 days after transplantation, with the dose adjusted according to renal function. The primary end point was laboratory-confirmed CMV disease in the first six months after transplantation.

Results Treatment with valacyclovir reduced the incidence or delayed the onset of CMV disease in both the seronegative patients (P<0.001) and the seropositive patients (P=0.03). Among the seronegative patients, the incidence of CMV disease 90 days after transplantation was 45 percent among placebo recipients and 3 percent among valacyclovir recipients. Among the seropositive patients, the respective values were 6 percent and 0 percent. At six months, the incidence of CMV disease was 45 percent among seronegative recipients of placebo and 16 percent among seronegative recipients of valacyclovir; it was 6 percent among seropositive placebo recipients and 1 percent among seropositive valacyclovir recipients. At six months, the rate of biopsy-confirmed acute graft rejection in the seronegative group was 52 percent among placebo recipients and 26 percent among valacyclovir recipients (P=0.001). Treatment with valacyclovir also decreased the rates of CMV viremia and viruria, herpes simplex virus disease, and the use of inpatient medical resources. Hallucinations and confusion were more common with valacyclovir treatment, but these events were not severe or treatment limiting. The rates of other adverse events were similar among the groups.

Conclusions Prophylactic treatment with valacyclovir is a safe and effective way to prevent CMV disease after renal transplantation.

Source Information

From the Department of Internal Medicine, Piedmont Hospital, Atlanta (D.L.); the Department of Nephrology, Medizinische Klinik, Universität Erlangen–Nürnberg, Erlangen, Germany (H.-H.N.); Service de Réanimation et Transplantation, Hôpital Necker, Paris (C.M.L.); the Department of Transplantation, Université Catholique de Louvain, Cliniques Universitaires, St. Luc, Brussels, Belgium (J.-P.S.); the Department of Nephrology and Dialysis, University Clinic III, Vienna, Austria (J.K.); Infection Control Office, Hospital of the University of Pennsylvania, Philadelphia (P.J.B.); the Department of Immunogenetics, Oregon Health Sciences University, Portland (D.N.); the National Institute of Transplantation, Los Angeles (R.M.); Mayo Clinic, Rochester, Minn. (M.R.K.); and the Departments of Infectious Diseases Clinical Research (G.L.C., I.C.L.) and Clinical Statistics (A.C.), Glaxo Wellcome Research and Development, Greenford, United Kingdom.

Address reprint requests to Dr. Lowance at the Department of Internal Medicine, Suite 610, Piedmont Professional Bldg., Piedmont Hospital, 35 Collier Road, N.W., Atlanta, GA 30367, or at dlowa80715{at}aol.com.

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