Preemptive therapy best for preventing CMV after liver transplant

Last Updated: 2020-04-14

By Reuters Staff

NEW YORK (Reuters Health) - Preemptive therapy is more effective than antiviral prophylaxis for preventing cytomegalovirus (CMV) disease in CMV-seronegative liver-transplant recipients with seropositive donors, a randomized controlled trial shows.

Preemptive therapy involves monitoring patients for CMV viremia and starting antiviral therapy only after CMV replication is detected by PCR testing, whereas antiviral prophylaxis is started immediately.

Dr. Nina Singh of the University of Pittsburgh, in Pennsylvania, and colleagues compared the two options in 205 high-risk CMV-seronegative liver-transplant recipients with seropositive donors. Half were randomly assigned to preemptive therapy and half to antiviral prophylaxis.

Patients in the preemptive therapy group underwent weekly testing for CMV viremia for 100 days. When viremia was detected at any level, oral valganciclovir (900 mg twice daily) was administered until two consecutive negative tests resulted one week apart. Patients in the antiviral prophylaxis group received oral valganciclovir (900 mg daily) for 100 days.

The incidence of CMV disease by 12 months after transplant, the primary outcome, was significantly lower with preemptive therapy than antiviral prophylaxis (9% vs. 19%; P=0.04), largely due to a reduction in delayed-onset disease beyond 100 days (6% for preemptive therapy vs. 17% for antiviral prophylaxis; P=0.01).

There were no significant differences in acute allograft rejection, opportunistic infections, graft and patient survival.

In their JAMA report, the researchers also note, "T-cell responses (associated with protection against CMV replication or disease) and neutralizing antibodies (considered important in the context of primary CMV infection) were significantly increased with preemptive therapy compared with antiviral prophylaxis."

They caution, however, that "CMV-specific immune responses were exploratory end points and, therefore, all findings should be considered tentative and, at best, hypothesis-generating."

In an editor's note, Dr. Angel Desai and Dr. Preeti Malani of the University of Michigan, in Ann Arbor, write, "While these results provide some clarity regarding the use of preemptive therapy, several caveats remain. Preemptive therapy requires weekly monitoring by serum polymerase chain reaction and immediate initiation of antivirals when indicated. Transplant centers may differ in their capacity to support such frequent measures, and some patients may find these requirements costly, and logistically burdensome, especially if this specialized test is not easily available locally. The authors appropriately note that the decision to pursue preemptive therapy will ultimately depend on institutional capacity and available resources."

"Despite these limitations, preemptive therapy may be a viable option for preventing CMV infection among selected high-risk patients following liver transplant," Drs. Desai and Malani conclude.

The study was supported by the National Institutes of Health (NIH) and National Institute of Allergy and Infectious Diseases (NIAID).

SOURCE: https://bit.ly/34BzC6m and https://bit.ly/2wDyN0q JAMA, online April 14, 2020.