Ganciclovir or acyclovir reduces the rates of mortality infections


BOSTON—Cytomegalovirus infection (CMV) remains an important problem for solid-organ transplant recipients. Available data support either universal prophylaxis against the virus or pre-emptive therapy, according to a transplant infectious disease specialist.

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Both anti-CMV approaches can prevent the direct effects of CMV disease, but only universal prophylaxis protects against indirect effects of the virus, such as opportunistic infections, post-transplantation lymphoproliferative disorder (PTLD), rejection, and mortality, according to Jay A. Fishman, MD, Director of Transplant Infectious Disease at Massachusetts General Hospital and Harvard Medical School in Boston.


CMV infection can cause poor renal-graft function at six months and chronic dysfunction at three years, studies show. Renal transplant recipients who receive prophylaxis with anti-CMV medications such as ganciclovir have a lower risk of CMV infection and disease as well as a lower risk of acute graft rejection, Dr. Fishman said.


Speaking at the World Transplant Congress here, he also noted that universal CMV prophylaxis appears to lower the risk of other opportunistic infections and reduce mortality. Dr. Fishman cautioned, however, that the optimal duration of prophylaxis has not been defined. Once prophylaxis has been discontinued, at least half of transplant recipients will experience symptomatic or asymptomatic CMV viremia, he added.


“We don’t quite know how much and how long to treat,” Dr. Fishman told colleagues. “What we know is that we need to reduce the intensity of immune suppression so that by the time we stop CMV prophylaxis we have now minimized immune suppression to the [maximum] degree possible.”


He cited meta-analyses demonstrating that universal anti-CMV prophylaxis reduces mortality in solid-organ transplant recipients. In one meta-analysis, Andre C. Kalil, MD, of the University of Nebraska Medical Center in Omaha, and his colleagues found that universal prophylaxis with either ganciclovir or acyclovir significantly reduced the risk of death by 38% and the risk of bacterial and fungal infections by 51%, compared with placebo or no treatment (Ann Intern Med. 2005;143:870-880).


Dr. Fishman reviewed the opportunistic infections that CMV can promote in transplant recipients. These include Pneumocystis carinii, Candida, Listeria monocytogenes, Aspergillus, and Epstein-Barr and hepatitis C viruses. Research shows that CMV prevention lowers the incidence of human herpesvirus (HHV) 6 and 7, and, in endemic areas, HHV-8.


If CMV can activate Epstein-Barr virus and papillomavirus, then preventing CMV infection might even reduce the incidence of cancer in transplant recipients, Dr. Fishman said. In a study of renal transplant recipients (Am J Transplant. 2005;5:2894-2900), the risk of renal PTLD—which results from uncontrolled proliferation of B cell lymphocytes following Epstein-Barr virus infection—during the first year post-transplant was reduced by 38% for each 30 days of ganciclovir treatment.