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Andre Kalil, M.D. |
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Alison Freifeld, M.D. |
The study was designed to address how to best prevent a disease caused by a virus called cytomegalovirus (CMV) in patients who are recipients of solid organ transplantation. CMV is the most common opportunistic viral infection seen in transplant patients. In mild cases, it presents with fever and malaise. In more severe cases, it can result in bloodstream infections, pneumonia, hepatitis, bowel infections and death.
The study analyzed approximately 2,000 patients from 17 clinical trials on how to prevent CMV in transplant recipients. The goal was to clarify major questions surrounding prevention of CMV and ultimately determine the most effective prevention for patients.
Two major approaches have been used to prevent CMV in transplant patients. One is called the preemptive approach in which the patient is monitored for CMV every two weeks for 3 months. If the virus is detected, the treatment is initiated independent of the presence of symptoms. The idea is to catch the infection early and treat it before the development of disease. The other approach is called universal prophylaxis in which the patient is given an anti-viral drug daily and continuously for three months. The idea here is to prevent CMV from ever occurring.
The study results showed that both approaches are highly effective in preventing CMV, but the universal prophylaxis approach – which is used at UNMC – resulted in several other very important benefits to the patient. These benefits include a 26 percent reduction in graft rejection, a 51 percent reduction in other major infections such as bacterial and fungal infections, and a 38 percent reduction in deaths.
“We were amazed by these results, because we didn’t expect that universal prophylaxis would provide so many other benefits with statistically significant results,” said Andre Kalil, M.D., the principal investigator on the study, associate director of the Immunocompromised Host Infectious Diseases Program, and assistant professor at UNMC. “These findings are biologically plausible, because CMV not only causes infections in transplant patients, but also weakens the immune system in a way that the patients become more susceptible to other major and life-threatening infections.”
Dr. Kalil also said the study supports the effectiveness of acyclovir, a drug that has basically been abandoned for use in universal prophylaxis of CMV. In recent years, however, newer anti-viral agents such as valganciclovir and ganciclovir have gained in popularity, causing acyclovir to be phased out. He said the cost difference between the old and the new drugs is dramatic.
“Acyclovir has been replaced by more potent and very expensive drugs, but the study results indicate that the older drug is also very effective,” Dr. Kalil said. “The new drugs have not been adequately tested against the old drugs in head-to-head clinical trials, and this will be our next step.”
Dr. Kalil said he and Alison Freifeld, M.D., co-author of this study and director of the Immunocompromised Host Infectious Diseases Program, hope that the UNMC infectious diseases and transplantation teams will develop and lead a multi-center national trial to compare these different anti-viral drugs in the near future.