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Cytomegalovirus in transplantation – challenging the status quo


Corresponding author: Marc E. Uknis, MD, FACS, Associate Professor of Surgery, Molecular Genetics and Microbiology, University of Massachusetts Medical School, Associate Director of Kidney and Pancreas Transplantation, St. Barnabas Health Care System, 94 Old Short Hills Road, Livingston, NJ 07039, USA.
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Abstract:  Background:  Cytomegalovirus (CMV) infection of solid organ transplant (SOT) recipients causes both ‘‘direct’’ and ‘‘indirect’’ effects including allograft rejection, decreased graft and patient survival, and predisposition to opportunistic infections and malignancies. Options for CMV prevention include pre-emptive therapy, whereby anti-CMV agents are administered based on sensitive viral assays, or universal prophylaxis of all at-risk patients. Each approach has advantages and disadvantages in terms of efficacy, costs, and side effects. Standards of care for prophylaxis have not been established.

Methods:  A committee of international experts was convened to review the available data regarding CMV prophylaxis and to compare preventative strategies for CMV after transplantation from seropositive donors or in seropositive recipients.

Results:  Pre-emptive therapy requires frequent monitoring with subsequent treatment of disease and associated costs, while universal prophylaxis results in greater exposure to potential toxicities and costs of drugs. The advantages of prophylaxis include suppressing asymptomatic viremia and prevention of both direct and indirect effects of CMV infection. Meta analyses reveal decreased in mortality for patients receiving CMV prophylaxis. Costs associated with prophylaxis are less than for routine monitoring and pre-emptive therapy. The optimal duration of antiviral prophylaxis remains undefined. Extended prophylaxis may improve clinical outcomes in the highest-risk patient populations including donor-seropositive/recipient-seronegative renal transplants and in CMV-infected lung and heart transplantation.

Conclusions:  Prophylaxis is beneficial in preventing direct and indirect effects of CMV infection in transplant recipients, affecting both allograft and patient survival. More studies are necessary to define optimal prophylaxis regimens.