Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation

Background Cytomegalovirus (CMV) disease is a major complication of organ t ransplantation. We hypothesized that prophylactic treatment with valacyclov ir would reduce the risk of CMV disease. Methods A total of 208 CMV-negative recipients of a kidney from a seroposit ive 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 on set of CMV disease in both the seronegative patients (P<0.001) and the sero positive patients (P=0.03). Among the seronegative patients, the incidence of CMV disease 90 days after transplantation was 45 percent among placebo r ecipients and 3 percent among valacyclovir recipients. Among the seropositi ve patients, the respective values were 6 percent and 0 percent. At six mon ths, the incidence of CMV disease was 45 percent among seronegative recipie nts of placebo and 16 percent among seronegative recipients of valacyclovir ; it was 6 percent among seropositive placebo recipients and 1 percent amon g seropositive valacyclovir recipients. At six months, the rate of biopsy-c onfirmed acute graft rejection in the seronegative group was 52 percent amo ng 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 res ources. Hallucinations and confusion were more common with valacyclovir tre atment, but these events were not severe or treatment limiting. The rates o f other adverse events were similar among the groups. Conclusions Prophylactic treatment with valacyclovir is a safe and effectiv e way to prevent CMV disease after renal transplantation. (N Engl J Med 199 9; 340:1462-70.) (C) 1999, Massachusetts Medical Society.