A Randomized, Placebo-Controlled Trial of Oral Acyclovir for the Prevention of Cytomegalovirus Disease in Recipients of Renal Allografts

Abstract

Cytomegalovirus is a major viral pathogen in patients who undergo renal transplantation, and cytomegalovirus disease is difficult to treat. We therefore conducted a randomized, placebo-controlled, double-blind trial of acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts from cadavers. Acyclovir was given orally in doses of 800 to 3200 mg per day, according to the patients' estimated level of renal function. Patients took the first dose of either acyclovir or placebo six hours before transplantation and continued to take the assigned medication for 12 weeks. Of 118 patients enrolled in the study, 104 completed at least 30 days on the study medication and were included in our analysis of the results. During the first year after transplantation, 4 of 53 patients (7.5 percent) in the acyclovir group had symptomatic cytomegalovirus disease, as compared with 15 of 51 (29 percent) in the placebo group (P = 0.002). There was a single case of cytomegalovirus pneumonia in the acyclovir group, as compared with nine in the placebo group. The greatest prophylactic benefit of acyclovir was observed among seronegative patients who had received a kidney from a seropositive donor; only one of six such patients in the acyclovir group had cytomegalovirus disease, as compared with all seven in the placebo group. Acyclovir decreased the incidence of documented cytomegalovirus infection (with or without symptomatic disease) to 36 percent from 61 percent among the patients who received the placebo (P = 0.011). Among the patients who received acyclovir, the rates of recovery of virus from the blood and urine were significantly reduced, but the rate of viral shedding from the pharynx was not significantly different from that in the placebo group. There were no differences between the groups in the frequency of adverse events or in the rate of survival of either grafts or patients. We conclude that the oral administration of acyclovir, beginning before the transplantation of a renal allograft from a cadaver, reduces the rate of cytomegalovirus infection and disease without affecting the survival rate of either grafts or patients.

Infectious complications after OKT3 induction in liver transplantation

“…21 We have recently decreased the length of time antibiotics are continued from 5 days to 48 hours in the face of a lack of data supporting any benefit from the longer time period. Certainly the role of viral prophylaxis has been well documented, 13,15,16 and we believe that aggressive fungal prophylaxis is warranted in these high-risk patients as well.…”

“…The optimal prophylaxis against CMV infection after solid organ transplantation has been controversial, and several different combinations of ganciclovir, both intravenous and oral; oral acyclovir; and human anti-CMV immunoglobulin have been described with varying effectiveness. [12][13][14][15][16] We used a short course of intravenous ganciclovir followed by high-dose oral acyclovir for 3 months without regard to serological status. Our incidence of invasive CMV disease was only 14%.…”

Parameters for the Successful Management of Cytomegalovirus

“…Interesting pharmacokinetic studies were conducted to show that the peak level of aciclovir was about 25 J..lM and the trough 18 J..lM; renal transplant patients thus had higher levels than found in normals, presumably because their renal insufficiency was delaying excretion of the drug. Despite these high levels, the values did not approach the mean ID 5 0 for the CMV strains isolated from the same patients, which was around 63 J..lM (Balfour et a/., 1989). The fact that the drug was shown to improve CMV disease compared to placebo suggests that the viruses in the patients did respond to the drug and leads to the inevitable conclusion that the Reed etal., 1990GCV Goodrich et al, 1991IFN Cheeseman et al, 1979Hirsch et al, 1983Lui et al, 1992ACV Prentice et al, 1994Balfour et al, 1989Ig Metselaar et al, 1989GCV Winston etal., 1993Merigan, 1992Goodrich, et al, 1993 Treatment Pre-emptive Suppression Prophylaxis Table 4.…”

The Evaluation of the Renal Transplant Candidates: Clinical Practice Guidelines

“…The incidence and severity of CMV disease are also influenced by the amount of immunosuppression used (188)(189)(190)(191). Chemoprophylaxis for CMV (with acyclovir, ganciclovir, valacyclovir and/or intravenous immunoglobulin) has been shown to be effective in large, randomized controlled trials (192)(193)(194)(195)(196)(197)(198). A meta-analysis of controlled trials also concluded that antiviral agents (acyclovir or ganciclovir) were effective in preventing CMV infection in solid-organ transplant recipients (199).…”