TY - JOUR
T1 - Randomised comparison of ganciclovir and high-dose acyclovir for long-term cytomegalovirus prophylaxis in liver-transplant recipients
AU - Winston, D. J.
AU - Wirin, D.
AU - Shaked, A.
AU - Busuttil, R. W.
N1 - Funding Information:
60% of patients develop CMV disease without any prior viral excretion. Indeed, in our study, 10 of 13 patients had CMV disease without prior viral shedding despite weekly viral cultures. More sensitive laboratory tests for CMV antigen or DNA may lead to a higher detection of viral infection but may also be less predictive of CMV disease.27-29 The relative merits of prophylaxis of all transplant patients compared with early treatment of only those patients with symptomless viral excretion or who are receiving more intensive immunosuppressive therapy,30 need to be evaluated in a randomised controlled trial. Depending on the relative risk for serious CMV disease, it is possible that one prophylactic strategy may be preferable to the other. Of note, none of the 23 patients in our study who received longterm ganciclovir prophylaxis with muromonab-CD3 developed either CMV infection or disease. The results of this study show that CMV can be almost completely eliminated as a significant pathogen in liver transplant patients by the long-term administration of ganciclovir. Ganciclovir had minimal toxicity by comparison with the experience with this drug in patients with bone-marrow transplants or AIDS. We thank Dr Marjorie J Miller, Dr David A Bruckner, and the staff of the UCLA clinical microbiology laboratories for technical assistance; Karen Inouye, Ed Arriola, Ken Babamoto, and the staff of UCLA pharmacy services for administrative assistance; Margaret Frane for statistical analysis; Katharine Fry for preparation of the manuscript; and the nursing staffs who assisted in the care of patients. We also thank Dr William C Buhles and Syntex Research, Palo Alto, California, USA, for providing the ganciclovir used in this study. This work was supported in part by the Joanne Barr Foundation and the Dumont Foundation.
PY - 1995/7/8
Y1 - 1995/7/8
N2 - Summary. Despite current approaches to prophylaxis, cytomegalovirus (CMV) continues to be a common cause of infection and disease in solid-organ-transplant patients. Thus, we conducted a controlled trial comparing long-term administration of ganciclovir with high-dose acyclovir for prevention of CMV infection and disease in liver transplant recipients. At the time of transplant, patients were randomised to receive either ganciclovir (6 mg/kg body weight per day intravenously from postoperative day 1 to day 30, then 6 mg/kg per day Monday through Friday until day 100) or acyclovir (10 mg/kg intravenously every 8 h from postoperative day 1 to day of discharge, then 800 mg orally four times a day until day 100). Patients were followed for development of CMV infection, CMV disease, and drug-related toxicity by frequent cultures, serological tests, laboratory measurements, and tissue biopsies. During the first 120 days after transplant, CMV infection occurred in 48 of 126 (38%) acyclovir patients but in only 6 of 124 (5%) ganciclovir patients (p<0·0001). Similarly, symptomatic CMV disease developed in 12 of 126 (10%) acyclovir patients but in only 1 of 124 (0·8%) ganciclovir patients (p=0·002). Ganciclovir reduced the incidence of CMV infection in both CMV antibody positive (37 vs 4%, p=0·001) and negative patients (42 vs 11%, p=0·06). In a multivariate analysis of donor-recipient CMV antibody status and other risk factors, prophylactic ganciclovir was the most significant factor protecting against CMV infection (p<0·0001) and disease (p=0·001). Ganciclovir and acyclovir were generally well-tolerated. Incidences of leukopenia, thrombocytopenia, renal failure, and other adverse events were similar in the two groups. CMV can be eliminated almost completely as a significant pathogen in liver transplant recipients by the long-term administration of prophylactic ganciclovir. In addition, the treatment is safe.
AB - Summary. Despite current approaches to prophylaxis, cytomegalovirus (CMV) continues to be a common cause of infection and disease in solid-organ-transplant patients. Thus, we conducted a controlled trial comparing long-term administration of ganciclovir with high-dose acyclovir for prevention of CMV infection and disease in liver transplant recipients. At the time of transplant, patients were randomised to receive either ganciclovir (6 mg/kg body weight per day intravenously from postoperative day 1 to day 30, then 6 mg/kg per day Monday through Friday until day 100) or acyclovir (10 mg/kg intravenously every 8 h from postoperative day 1 to day of discharge, then 800 mg orally four times a day until day 100). Patients were followed for development of CMV infection, CMV disease, and drug-related toxicity by frequent cultures, serological tests, laboratory measurements, and tissue biopsies. During the first 120 days after transplant, CMV infection occurred in 48 of 126 (38%) acyclovir patients but in only 6 of 124 (5%) ganciclovir patients (p<0·0001). Similarly, symptomatic CMV disease developed in 12 of 126 (10%) acyclovir patients but in only 1 of 124 (0·8%) ganciclovir patients (p=0·002). Ganciclovir reduced the incidence of CMV infection in both CMV antibody positive (37 vs 4%, p=0·001) and negative patients (42 vs 11%, p=0·06). In a multivariate analysis of donor-recipient CMV antibody status and other risk factors, prophylactic ganciclovir was the most significant factor protecting against CMV infection (p<0·0001) and disease (p=0·001). Ganciclovir and acyclovir were generally well-tolerated. Incidences of leukopenia, thrombocytopenia, renal failure, and other adverse events were similar in the two groups. CMV can be eliminated almost completely as a significant pathogen in liver transplant recipients by the long-term administration of prophylactic ganciclovir. In addition, the treatment is safe.
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U2 - 10.1016/S0140-6736(95)92110-9
DO - 10.1016/S0140-6736(95)92110-9
M3 - Article
C2 - 7603215
AN - SCOPUS:0029065431
SN - 0140-6736
VL - 346
SP - 69
EP - 74
JO - The Lancet
JF - The Lancet
IS - 8967
ER -