Background: Although the primary treatment of symptomatic cytomegalovirus (CMV) disease in organ transplant recipients is successful in >90% of individuals, relapsing disease, particularly in those with primary infection, remains an important problem. Previously, we had observed that the rate of symptomatic recurrence was >60% in those with primary disease (seronegative for CMV prior to transplant), and approximately 20% in those who were seropositive prior to transplant. The present study was undertaken to determine whether a maintenance regimen of oral ganciclovir for 2-3 months added to the routine 14-21 days of intravenous ganciclovir would further prevent symptomatic CMV recurrence.
Methods: From May 1995 until June 1998, all kidney and liver transplant recipients with confirmed tissue-invasive CMV disease or CMV syndrome were treated with 14-21 days of intravenous ganciclovir (5 mg/kg b.i.d. with dose adjusted for renal dysfunction) followed by 2-3 months of oral ganciclovir (2 g daily). The incidence of recurrence of CMV disease and/or viremia during and after oral therapy was then determined over a mean follow-up of 530.6 days.
Results: Thirty-seven patients, 19 kidney and 18 liver transplant recipients, were studied; 5 had biopsy-proven tissue-invasive disease (13.5) and 32 suffered a CMV syndrome (86.5). Twenty-one of these patients (58.6) were seronegative for CMV prior to transplant and received an allograft from a seropositive donor (D+/R-). Overall, 10 patients (27.0) developed CMV recurrence. Eight of 21 patients who were D+/R- for CMV (38.1) developed recurrence as opposed to 2 of 16 patients with other serologic status (12.5) (P=0.14). Patients with recurrent CMV disease and/or viremia had a peak antigenemia assay titer during their initial CMV event of 319.2 positive cells/2 slides compared with 109.8 positive cells/2 slides for patients without recurrent CMV infection (P=0.14); the trend of having a higher peak antigenemia assay titer among patients who recurred occurred both in patients who were at risk of primary CMV infection (D+/R- for CMV) and in those who were not. Two patients developed recurrent infection with strains of CMV that were resistant to ganciclovir.
Conclusions: This new therapeutic regimen of oral ganciclovir following intravenous ganciclovir slightly reduced the overall rate of recurrent CMV disease and/or viremia, but it still did not adequately prevent CMV recurrence in patients who are at risk of primary infection prior to transplant. Of particular concern, 2 patients with primary infection treated with this regimen developed ganciclovir-resistant recurrent disease.