Prevention of recurrent cytomegalovirus disease in renal and liver transplant recipients: effect of oral ganciclovir.
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.
Turgeon
N
N
Transplantation Unit, Massachusetts General Hospital, Boston, Massachusetts 02114-2696, USA.
Fishman
J A
JA
Doran
M
M
Basgoz
N
N
Tolkoff-Rubin
N E
NE
Cosimi
A B
AB
Rubin
R H
RH
D000212:Acyclovir / Q000627:therapeutic use; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003586:Cytomegalovirus Infections / Q000517:prevention & control*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007275:Injections, Intravenous; D016030:Kidney Transplantation; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000382:microbiology*; D013997:Time Factors
D000998:Antiviral Agents; D016756:Immunoglobulins, Intravenous; D015774:Ganciclovir; D000212:Acyclovir