Meta-Analysis: The Efficacy of Strategies To Prevent Organ Disease by Cytomegalovirus in Solid Organ Transplant Recipients

20 December 2005 | Volume 143 Issue 12 | Pages 870-880

Background: Cytomegalovirus (CMV), the most common opportunistic viral infection in solid organ transplant recipients, is associated with substantial morbidity and mortality.

Purpose: To assess the efficacy of universal prophylaxis and preemptive approaches in preventing CMV organ disease and other complications in solid organ transplant recipients.

Data Sources: Using no language restrictions, the authors searched the following databases from their inception through May 2005: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Evidence-Based Medicine. The authors also reviewed abstracts from scientific meetings and contacted experts and pharmaceutical companies.

Study Selection: Randomized, controlled trials that evaluated antiviral strategies for preventing CMV and associated complications in solid organ transplant recipients were selected.

Data Extraction: Two reviewers independently extracted and assessed the data.

Data Synthesis: The authors found 17 trials involving 1980 patients. Compared with placebo or no therapy, both universal prophylaxis (odds ratio [OR], 0.20 [95% CI, 0.13 to 0.31]) and preemptive strategies (OR, 0.28 [CI, 0.11 to 0.69]) reduced CMV organ disease. However, only universal prophylaxis seemingly reduced CMV organ disease in subgroups of patients at highest risk (donors with positive CMV serostatus and recipients with negative CMV serostatus and induction with antibodies). Both strategies reduced the rate of allograft rejection. Only universal prophylaxis statistically significantly reduced bacterial and fungal infections (OR, 0.49 [CI, 0.36 to 0.67]) and death (OR, 0.62 [CI, 0.40 to 0.96]). Both acyclovir and ganciclovir statistically significantly prevented CMV organ disease in the universal prophylaxis trials.

Limitations: Studies were of modest size, and few studies assessed all outcomes. Studies did not always provide data that discriminated between CMV organ disease and CMV syndrome or data about the timing of CMV organ disease.

Conclusions: Universal prophylaxis and preemptive strategies are beneficial in preventing CMV organ disease in solid organ transplant recipients. Both strategies are associated with a reduction in allograft rejection, but current data suggest that only universal prophylaxis reduces bacterial and fungal infections and death. Acyclovir and ganciclovir are both effective for universal prophylaxis.

Editors' Notes Context Cytomegalovirus is a common opportunistic infection among recipients of organ transplants. Contribution This meta-analysis summarizes 17 randomized trials of antiviral therapy for recipients of liver and kidney allografts. Universal prophylaxis for all high-risk patients and preemptive treatment for patients who had the virus detected during periodic monitoring reduced cytomegalovirus organ disease and allograft rejection more than did no treatment or placebo. Only universal prophylaxis reduced bacterial and fungal infections and death. Cautions Most trials were small and were not blinded. Implications Although the authors prefer universal prophylaxis over preemptive treatment, they recommend a large confirmatory trial to directly compare the 2 strategies. —The Editors

 

Author and Article Information

From University of Nebraska Medical Center, Omaha, Nebraska.

Acknowledgments: The authors thank Elaine Litton for providing outstanding administrative support and Patricia A. Kalil for critical review of the manuscript.

Grant Support: None.

Potential Financial Conflicts of Interest: Consultancies: A.G. Freifeld (Enzon); Honoraria: A.G. Freifeld (Pfizer Inc., Enzon, Merck & Co. Inc.); Grants received: A.G. Freifeld (Ortho-McNeil); Grants pending: A.G. Freifeld (Astellas).

Requests for Single Reprints: Andre C. Kalil, MD, University of Nebraska Medical Center, 985400 Nebraska Medical Center, Omaha, NE 68198-5400; e-mail, akalil{at}unmc.edu.

Current Author Addresses: Drs. Kalil and Freifeld: University of Nebraska Medical Center, 985400 Nebraska Medical Center, Omaha, NE 68198-5400.

Dr. Levitsky: Northwestern Memorial Hospital, 303 East Chicago Avenue, Chicago, IL 60611.

Ms. Lyden and Dr. Stoner: University of Nebraska Medical Center, 985350 Nebraska Medical Center, Omaha, NE 68198-4350.

Author Contributions: Conception and design: A.C. Kalil. Analysis and interpretation of the data: A.C. Kalil, J. Levitsky, E. Lyden, J. Stoner, A.G. Freifeld. Drafting of the article: A.C. Kalil, E. Lyden, J. Stoner, A.G. Freifeld. Critical revision of the article for important intellectual content: A.C. Kalil, J. Levitsky, E. Lyden, J. Stoner, A.G. Freifeld.Final approval of the article: A.C. Kalil, J. Levitsky, E. Lyden, J. Stoner, A.G. Freifeld. Statistical expertise: E. Lyden, J. Stoner. Collection and assembly of data: A.C. Kalil, J. Levitsky.

Read all Rapid Responses

Meta-analysis: The efficasy of strategies to prevent CMV organ disease in SOT

Nina Singh, et al.

Annals Online, 18 Jan 2006 [Full text]

Meta-Analysis: The Efficacy of Strategies to Prevent CMV Organ Disease in SOT

Andre C Kalil, et al.

Annals Online, 26 Jan 2006 [Full text]