A prospective randomized study of acyclovir versus ganciclovir plus human immune globulin prophylaxis of cytomegalovirus infection after solid organ transplantation

D. L. Dunn, K. J. Gillingham, M. A. Kramer, W. J. Schmidt, A. Erice, H. H. Balfour, P. F. Gores, Rainer W G Gruessner, A. J. Matas, W. D. Payne, D. E R Sutherland, J. S. Najarian

Research output: Contribution to journalArticle

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Abstract

Cytomegalovirus disease occurs frequently after solid organ transplantation and has been associated with decreased patient and allograft survival. We hypothesized that CMV transmission or reactivation begins immediately or soon after transplantation, and that a short-duration ganciclovir (GCV*)-based regimen would obviate the need for long-term antiviral agent administration, perhaps serving to interdict CMV infection and disease as well as, or perhaps even more effectively than, a more prolonged, oral acyclovir (ACV)-based form of prophylaxis. A total of 311 patients were stratified according to allograft type, age, and presence or absence or diabetes mellitus, and were then randomized to receive either long-duration ACV prophylaxis (800 mg orally or 400 mg i.v. q.i.d. for 12 weeks after transplantation or 6 weeks after any antirejection therapy) versus short-duration GCV (5 mg/kg/12 hr i.v. for 7 days after transplant or after any antirejection therapy) plus human immune globulin (HIg; Sandoglobulin or Minnesota CMV immune globulin) 100 mg/kg i.v. administered on days 1, 4, and 7 after transplant or after any antirejection therapy. A total of 266 patients (ACV, n=133; GCV+HIg, n=133) completed the protocol and were available for follow-up. CMV disease occurred in fewer patients (n=28, 21.0%) in the ACV group, while significantly more patients (n=42, 31.6%) in the GCV+HIg group developed this process (P=0.029). Patients in the ACV prophylaxis group developed CMV disease slightly later (2.83±0.70 months) than those who received GCV+HIg (2.15±0.21 months, P>0.1). Multivariate analysis demonstrated that receiving antirejection therapy, a liver transplant, or a donor organ from a CMV-seropositive individual if the recipient was CMV seronegative were major risk factors for the development of CMV disease (P<0.001), while the difference between ACV versus GCV+HIg prophylaxis was also significant (P=0.054). No differences in actuarial patient or allograft survival, however, were noted between the 2 prophylaxis groups. Overall, ACV prophylaxis appeared to be more effective in reducing the incidence of posttransplant CMV disease, although this effect was diminished in high-risk groups of patients. Our findings indicate that CMV transmission or reactivation may best be prevented by long-term antiviral agent administration, and that the primary morbidity of CMV disease is the need for rehospitalization when either prolonged ACV or short-duration GCV+HIg prophylaxis is used in this patient population.

Original languageEnglish (US)
Pages (from-to)876-884
Number of pages9
JournalTransplantation
Volume57
Issue number6
StatePublished - 1994
Externally publishedYes

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Ganciclovir
Acyclovir
Cytomegalovirus Infections
Organ Transplantation
Immunoglobulins
Prospective Studies
Immunosuppression
Allografts
Transplants
Antiviral Agents
Transplantation
Group Processes
Intravenous Immunoglobulins
Cytomegalovirus
Diabetes Mellitus
Multivariate Analysis
Tissue Donors
Morbidity
Liver
Incidence

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Dunn, D. L., Gillingham, K. J., Kramer, M. A., Schmidt, W. J., Erice, A., Balfour, H. H., ... Najarian, J. S. (1994). A prospective randomized study of acyclovir versus ganciclovir plus human immune globulin prophylaxis of cytomegalovirus infection after solid organ transplantation. Transplantation, 57(6), 876-884.

A prospective randomized study of acyclovir versus ganciclovir plus human immune globulin prophylaxis of cytomegalovirus infection after solid organ transplantation. / Dunn, D. L.; Gillingham, K. J.; Kramer, M. A.; Schmidt, W. J.; Erice, A.; Balfour, H. H.; Gores, P. F.; Gruessner, Rainer W G; Matas, A. J.; Payne, W. D.; Sutherland, D. E R; Najarian, J. S.

In: Transplantation, Vol. 57, No. 6, 1994, p. 876-884.

Research output: Contribution to journalArticle

Dunn, DL, Gillingham, KJ, Kramer, MA, Schmidt, WJ, Erice, A, Balfour, HH, Gores, PF, Gruessner, RWG, Matas, AJ, Payne, WD, Sutherland, DER & Najarian, JS 1994, 'A prospective randomized study of acyclovir versus ganciclovir plus human immune globulin prophylaxis of cytomegalovirus infection after solid organ transplantation', Transplantation, vol. 57, no. 6, pp. 876-884.
Dunn, D. L. ; Gillingham, K. J. ; Kramer, M. A. ; Schmidt, W. J. ; Erice, A. ; Balfour, H. H. ; Gores, P. F. ; Gruessner, Rainer W G ; Matas, A. J. ; Payne, W. D. ; Sutherland, D. E R ; Najarian, J. S. / A prospective randomized study of acyclovir versus ganciclovir plus human immune globulin prophylaxis of cytomegalovirus infection after solid organ transplantation. In: Transplantation. 1994 ; Vol. 57, No. 6. pp. 876-884.
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abstract = "Cytomegalovirus disease occurs frequently after solid organ transplantation and has been associated with decreased patient and allograft survival. We hypothesized that CMV transmission or reactivation begins immediately or soon after transplantation, and that a short-duration ganciclovir (GCV*)-based regimen would obviate the need for long-term antiviral agent administration, perhaps serving to interdict CMV infection and disease as well as, or perhaps even more effectively than, a more prolonged, oral acyclovir (ACV)-based form of prophylaxis. A total of 311 patients were stratified according to allograft type, age, and presence or absence or diabetes mellitus, and were then randomized to receive either long-duration ACV prophylaxis (800 mg orally or 400 mg i.v. q.i.d. for 12 weeks after transplantation or 6 weeks after any antirejection therapy) versus short-duration GCV (5 mg/kg/12 hr i.v. for 7 days after transplant or after any antirejection therapy) plus human immune globulin (HIg; Sandoglobulin or Minnesota CMV immune globulin) 100 mg/kg i.v. administered on days 1, 4, and 7 after transplant or after any antirejection therapy. A total of 266 patients (ACV, n=133; GCV+HIg, n=133) completed the protocol and were available for follow-up. CMV disease occurred in fewer patients (n=28, 21.0{\%}) in the ACV group, while significantly more patients (n=42, 31.6{\%}) in the GCV+HIg group developed this process (P=0.029). Patients in the ACV prophylaxis group developed CMV disease slightly later (2.83±0.70 months) than those who received GCV+HIg (2.15±0.21 months, P>0.1). Multivariate analysis demonstrated that receiving antirejection therapy, a liver transplant, or a donor organ from a CMV-seropositive individual if the recipient was CMV seronegative were major risk factors for the development of CMV disease (P<0.001), while the difference between ACV versus GCV+HIg prophylaxis was also significant (P=0.054). No differences in actuarial patient or allograft survival, however, were noted between the 2 prophylaxis groups. Overall, ACV prophylaxis appeared to be more effective in reducing the incidence of posttransplant CMV disease, although this effect was diminished in high-risk groups of patients. Our findings indicate that CMV transmission or reactivation may best be prevented by long-term antiviral agent administration, and that the primary morbidity of CMV disease is the need for rehospitalization when either prolonged ACV or short-duration GCV+HIg prophylaxis is used in this patient population.",
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T1 - A prospective randomized study of acyclovir versus ganciclovir plus human immune globulin prophylaxis of cytomegalovirus infection after solid organ transplantation

AU - Dunn, D. L.

AU - Gillingham, K. J.

AU - Kramer, M. A.

AU - Schmidt, W. J.

AU - Erice, A.

AU - Balfour, H. H.

AU - Gores, P. F.

AU - Gruessner, Rainer W G

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AU - Sutherland, D. E R

AU - Najarian, J. S.

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N2 - Cytomegalovirus disease occurs frequently after solid organ transplantation and has been associated with decreased patient and allograft survival. We hypothesized that CMV transmission or reactivation begins immediately or soon after transplantation, and that a short-duration ganciclovir (GCV*)-based regimen would obviate the need for long-term antiviral agent administration, perhaps serving to interdict CMV infection and disease as well as, or perhaps even more effectively than, a more prolonged, oral acyclovir (ACV)-based form of prophylaxis. A total of 311 patients were stratified according to allograft type, age, and presence or absence or diabetes mellitus, and were then randomized to receive either long-duration ACV prophylaxis (800 mg orally or 400 mg i.v. q.i.d. for 12 weeks after transplantation or 6 weeks after any antirejection therapy) versus short-duration GCV (5 mg/kg/12 hr i.v. for 7 days after transplant or after any antirejection therapy) plus human immune globulin (HIg; Sandoglobulin or Minnesota CMV immune globulin) 100 mg/kg i.v. administered on days 1, 4, and 7 after transplant or after any antirejection therapy. A total of 266 patients (ACV, n=133; GCV+HIg, n=133) completed the protocol and were available for follow-up. CMV disease occurred in fewer patients (n=28, 21.0%) in the ACV group, while significantly more patients (n=42, 31.6%) in the GCV+HIg group developed this process (P=0.029). Patients in the ACV prophylaxis group developed CMV disease slightly later (2.83±0.70 months) than those who received GCV+HIg (2.15±0.21 months, P>0.1). Multivariate analysis demonstrated that receiving antirejection therapy, a liver transplant, or a donor organ from a CMV-seropositive individual if the recipient was CMV seronegative were major risk factors for the development of CMV disease (P<0.001), while the difference between ACV versus GCV+HIg prophylaxis was also significant (P=0.054). No differences in actuarial patient or allograft survival, however, were noted between the 2 prophylaxis groups. Overall, ACV prophylaxis appeared to be more effective in reducing the incidence of posttransplant CMV disease, although this effect was diminished in high-risk groups of patients. Our findings indicate that CMV transmission or reactivation may best be prevented by long-term antiviral agent administration, and that the primary morbidity of CMV disease is the need for rehospitalization when either prolonged ACV or short-duration GCV+HIg prophylaxis is used in this patient population.

AB - Cytomegalovirus disease occurs frequently after solid organ transplantation and has been associated with decreased patient and allograft survival. We hypothesized that CMV transmission or reactivation begins immediately or soon after transplantation, and that a short-duration ganciclovir (GCV*)-based regimen would obviate the need for long-term antiviral agent administration, perhaps serving to interdict CMV infection and disease as well as, or perhaps even more effectively than, a more prolonged, oral acyclovir (ACV)-based form of prophylaxis. A total of 311 patients were stratified according to allograft type, age, and presence or absence or diabetes mellitus, and were then randomized to receive either long-duration ACV prophylaxis (800 mg orally or 400 mg i.v. q.i.d. for 12 weeks after transplantation or 6 weeks after any antirejection therapy) versus short-duration GCV (5 mg/kg/12 hr i.v. for 7 days after transplant or after any antirejection therapy) plus human immune globulin (HIg; Sandoglobulin or Minnesota CMV immune globulin) 100 mg/kg i.v. administered on days 1, 4, and 7 after transplant or after any antirejection therapy. A total of 266 patients (ACV, n=133; GCV+HIg, n=133) completed the protocol and were available for follow-up. CMV disease occurred in fewer patients (n=28, 21.0%) in the ACV group, while significantly more patients (n=42, 31.6%) in the GCV+HIg group developed this process (P=0.029). Patients in the ACV prophylaxis group developed CMV disease slightly later (2.83±0.70 months) than those who received GCV+HIg (2.15±0.21 months, P>0.1). Multivariate analysis demonstrated that receiving antirejection therapy, a liver transplant, or a donor organ from a CMV-seropositive individual if the recipient was CMV seronegative were major risk factors for the development of CMV disease (P<0.001), while the difference between ACV versus GCV+HIg prophylaxis was also significant (P=0.054). No differences in actuarial patient or allograft survival, however, were noted between the 2 prophylaxis groups. Overall, ACV prophylaxis appeared to be more effective in reducing the incidence of posttransplant CMV disease, although this effect was diminished in high-risk groups of patients. Our findings indicate that CMV transmission or reactivation may best be prevented by long-term antiviral agent administration, and that the primary morbidity of CMV disease is the need for rehospitalization when either prolonged ACV or short-duration GCV+HIg prophylaxis is used in this patient population.

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