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.
Source Information
Department of Laboratory Medicine, University of Minnesota Health Sciences Center, Minneapolis 55455.
This article has been cited by other articles:
Zeng, L., Nath, C. E., Blair, E. Y. L., Shaw, P. J., Stephen, K., Earl, J. W., Coakley, J. C., McLachlan, A. J.
(2009). Population Pharmacokinetics of Acyclovir in Children and Young People with Malignancy after Administration of Intravenous Acyclovir or Oral Valacyclovir. Antimicrob. Agents Chemother.
53: 2918-2927
[Abstract][Full Text]
Baillie, G. M.
(2006). Prevention of cytomegalovirus disease in solid organ transplant patients: Prophylactic versus preemptive therapy.. Am J Health Syst Pharm
63: S10-S16
[Abstract][Full Text]
Cochrane, A. B.
(2006). Antiviral dosing and efficacy for prophylaxis of cytomegalovirus disease in solid organ transplant recipients.. Am J Health Syst Pharm
63: S17-S21
[Abstract][Full Text]
Tan, B. H.
(2006). CMV prophylaxis--to do or not to do, that is the question. Nephrol Dial Transplant
21: 1757-1761
[Full Text]
Kalil, A. C., Levitsky, J., Lyden, E., Stoner, J., Freifeld, A. G.
(2005). Meta-Analysis: The Efficacy of Strategies To Prevent Organ Disease by Cytomegalovirus in Solid Organ Transplant Recipients. ANN INTERN MED
143: 870-880
[Abstract][Full Text]
Uknis, M. E.
(2005). Prophylaxis of cytomegalovirus disease in transplant patients. Am J Health Syst Pharm
62: S3-S6
[Abstract][Full Text]
Kern, E. R., Bidanset, D. J., Hartline, C. B., Yan, Z., Zemlicka, J., Quenelle, D. C.
(2004). Oral Activity of a Methylenecyclopropane Analog, Cyclopropavir, in Animal Models for Cytomegalovirus Infections. Antimicrob. Agents Chemother.
48: 4745-4753
[Abstract][Full Text]
Kern, E. R., Collins, D. J., Wan, W. B., Beadle, J. R., Hostetler, K. Y., Quenelle, D. C.
(2004). Oral Treatment of Murine Cytomegalovirus Infections with Ether Lipid Esters of Cidofovir. Antimicrob. Agents Chemother.
48: 3516-3522
[Abstract][Full Text]
Ljungman, P., de la Camara, R., Milpied, N., Volin, L., Russell, C. A., Crisp, A., Webster, A., Valacyclovir International Bone Marrow Transplant,
(2002). Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants. Blood
99: 3050-3056
[Abstract][Full Text]
Krosky, P. M., Borysko, K. Z., Nassiri, M. R., Devivar, R. V., Ptak, R. G., Davis, M. G., Biron, K. K., Townsend, L. B., Drach, J. C.
(2002). Phosphorylation of {beta}-D-Ribosylbenzimidazoles Is Not Required for Activity against Human Cytomegalovirus. Antimicrob. Agents Chemother.
46: 478-486
[Abstract][Full Text]
Griffiths, P. D.
(2002). The treatment of cytomegalovirus infection. J Antimicrob Chemother
49: 243-253
[Abstract][Full Text]
Brumble, L. M., Milstone, A. P., Loyd, J. E., Ely, E. W., Pierson, R. N. III, Gautam, S., Dummer, J. S.
(2002). Prevention of Cytomegalovirus Infection and Disease After Lung Transplantation : Results Using a Unique Regimen Employing Delayed Ganciclovir. Chest
121: 407-414
[Abstract][Full Text]
BRENNAN, D. C.
(2001). Cytomegalovirus in Renal Transplantation. J. Am. Soc. Nephrol.
12: 848-855
[Full Text]
(2000). Management of herpes virus infections following transplantation. J Antimicrob Chemother
45: 729-748
[Full Text]
Sia, I. G., Patel, R.
(2000). New Strategies for Prevention and Therapy of Cytomegalovirus Infection and Disease in Solid-Organ Transplant Recipients. Clin. Microbiol. Rev.
13: 83-121
[Abstract][Full Text]
Shapiro, M. E., Abrams, J. M., Lowance, D., Keating, M. R.
(1999). Valacyclovir to Prevent Cytomegalovirus Disease after Renal Transplantation. NEJM
341: 921-921
[Full Text]
Talarico, C. L., Burnette, T. C., Miller, W. H., Smith, S. L., Davis, M. G., Stanat, S. C., Ng, T. I., He, Z., Coen, D. M., Roizman, B., Biron, K. K.
(1999). Acyclovir Is Phosphorylated by the Human Cytomegalovirus UL97 Protein. Antimicrob. Agents Chemother.
43: 1941-1946
[Abstract][Full Text]
Lowance, D., Neumayer, H.-H., Legendre, C. M., Squifflet, J.-P., Kovarik, J., Brennan, P. J., Norman, D., Mendez, R., Keating, M. R., Coggon, G. L., Crisp, A., Lee, I. C., The International Valacyclovir Cytomegalovirus Pro,
(1999). Valacyclovir for the Prevention of Cytomegalovirus Disease after Renal Transplantation. NEJM
340: 1462-1470
[Abstract][Full Text]
Balfour, H. H.
(1999). Antiviral Drugs. NEJM
340: 1255-1268
[Full Text]
Krosky, P. M., Underwood, M. R., Turk, S. R., Feng, K. W.-H., Jain, R. K., Ptak, R. G., Westerman, A. C., Biron, K. K., Townsend, L. B., Drach, J. C.
(1998). Resistance of Human Cytomegalovirus to Benzimidazole Ribonucleosides Maps to Two Open Reading Frames: UL89 and UL56. J. Virol.
72: 4721-4728
[Abstract][Full Text]
Conti, D. J., Freed, B. M., Singh, T. P., Gallichio, M., Gruber, S. A., Lempert, N.
(1995). Preemptive Ganciclovir Therapy in Cytomegalovirus-Seropositive Renal Transplants Recipients. Arch Surg
130: 1217-1222
[Abstract]
Hibberd, P. L., Tolkoff-Rubin, N. E., Conti, D., Stuart, F., Thistlethwaite, J. R., Neylan, J. F., Snydman, D. R., Freeman, R., Lorber, M. I., Rubin, R. H.
(1995). Preemptive Ganciclovir Therapy To Prevent Cytomegalovirus Disease in Cytomegalovirus Antibody-Positive Renal Transplant Recipients: A Randomized Controlled Trial. ANN INTERN MED
123: 18-26
[Abstract][Full Text]
Gallant, J. E., Moore, R. D., Chaisson, R. E.
(1994). Prophylaxis for Opportunistic Infections in Patients with HIV Infection. ANN INTERN MED
120: 932-944
[Abstract][Full Text]
Conti, D. J., Freed, B. M., Gruber, S. A., Lempert, N.
(1994). Prophylaxis of Primary Cytomegalovirus Disease in Renal Transplant Recipients: A Trial of Ganciclovir vs Immunoglobulin. Arch Surg
129: 443-447
[Abstract]
Singh, N., Yu, V. L., Mieles, L., Wagener, M. M., Miner, R. C., Gayowski, T.
(1994). High-Dose Acyclovir Compared with Short-Course Preemptive Ganciclovir Therapy To Prevent Cytomegalovirus Disease in Liver Transplant Recipients: A Randomized Trial. ANN INTERN MED
120: 375-381
[Abstract][Full Text]
Snydman, D. R., Werner, B. G., Dougherty, N. N., Griffith, J., Rubin, R. H., Dienstag, J. L., Rohrer, R. H., Freeman, R., Jenkins, R., Lewis, W. D., Hammer, S., O'Rourke, E., Grady, G. F., Fawaz, K., Kaplan, M. M., Hoffman, M. A., Katz, A. T., Doran, M., The Boston Center for Liver Transplantation CMVIG,
(1993). Cytomegalovirus Immune Globulin Prophylaxis in Liver Transplantation: A Randomized, Double-blind, Placebo-controlled Trial. ANN INTERN MED
119: 984-991
[Abstract][Full Text]
Sawyer, M. D., Mayoral, J. L., Gillingham, K. J., Kramer, M. A., Dunn, D. L.
(1993). Treatment of Recurrent Cytomegalovirus Disease in Patients Receiving Solid Organ Transplants. Arch Surg
128: 165-170
[Abstract]
George, D. L., Arnow, P. M., Fox, A., Thistlethwaite, J. R., Emond, J. C., Broelsch, C. E., Whitington, P. F.
(1992). Patterns of Infection After Pediatric Liver Transplantation. Arch Pediatr Adolesc Med
146: 924-929
[Abstract]
Brayman, K. L., Stephanian, E., Matas, A. J., Schmidt, W., Payne, W. D., Sutherland, D. E. R., Gores, P. F., Najarian, J. S., Dunn, D. L.
(1992). Analysis of Infectious Complications Occurring After Solid-Organ Transplantation. Arch Surg
127: 38-48
[Abstract]
Stratta, R. J., Shaefer, M. S., Cushing, K. A., Markin, R. S., Reed, E. C., Langnas, A. N., Pillen, T. J., Shaw, B. W. Jr
(1992). A Randomized Prospective Trial of Acyclovir and Immune Globulin Prophylaxis in Liver Transplant Recipients Receiving OKT3 Therapy. Arch Surg
127: 55-64
[Abstract]
Wong, T., Toupance, O., Chanard, J.
(1991). Acyclovir To Prevent Cytomegalovirus Infection after Renal Transplantation. ANN INTERN MED
115: 68-68
[Abstract]
Schulman, L. L., Reison, D. S., Austin, J. H. M., Rose, E. A.
(1991). Cytomegalovirus Pneumonitis After Cardiac Transplantation. Arch Intern Med
151: 1118-1124
[Abstract]
Plotkin, S. A., Starr, S. E., Friedman, H. M., Brayman, K., Harris, S., Jackson, S., Tustin, N. B., Grossman, R., Dafoe, D., Barker, C.
(1991). Effect of Towne Live Virus Vaccine on Cytomegalovirus Disease after Renal Transplant: A Controlled Trial. ANN INTERN MED
114: 525-531
[Abstract]
Balfour, H. H. Jr.
(1991). Options for Prevention of Cytomegalovirus Disease. ANN INTERN MED
114: 598-599
[Abstract]
Marchbanks, C. R., Rowley, K. A.
(1991). Update on Infections in the Immunocompromised Host. Journal of Pharmacy Practice
4: 282-294
[Abstract]
King, S. M., Petric, M., Superina, R., Graham, N., Roberts, E. A.
(1990). Cytomegalovirus Infections in Pediatric Liver Transplantation. Arch Pediatr Adolesc Med
144: 1307-1310
[Abstract]
Balfour, H. H. Jr, Englund, J. A.
(1989). Antiviral Drugs in Pediatrics. Arch Pediatr Adolesc Med
143: 1307-1316
[Abstract]
Previous
