Preemptive monitoring and treatment of cytomegalovirus infections in CMV-seronegative liver transplant recipients who receive organs from CMV-positive donors appears to be better at preventing infections than a viral prophylaxis strategy, according to infectious disease and organ transplant specialists.
In a study published in JAMA that may have gotten scant notice because of its publication during the early days of the COVID-19 pandemic, investigators at the University of Pittsburgh and other transplant centers reported results of a randomized clinical trial comparing the two CMV management strategies, and found that the incidence of CMV disease was significantly lower for patients who were started on valganciclovir when asymptomatic CMV viremia was detected, compared with patients on antiviral prophylaxis with valganciclovir.
The study “is a significant game changer for the field of transplantation,” commented Michael G. Ison, MD, professor of infectious diseases and organ transplantation at Northwestern University, Chicago.
Dr. Ison discussed the study and its implications during a session on potentially practice-changing clinical trials presented virtually during IDWeek 2020, an annual scientific meeting on infectious diseases.
In the trial, Nina Singh, MD, and colleagues randomly assigned 100 CMV-seronegative liver transplant recipients to receive preemptive therapy, in which patients underwent weekly testing for 100 days with a highly sensitive real-time plasma polymerase chain reaction assay for CMV. If viremia at any level was detected, the patients received oral valganciclovir 900 mg twice daily until two consecutive tests performed 1 week apart came back negative.
The remaining 105 patients were randomly assigned to 100 days of oral prophylaxis with 900 mg valganciclovir twice daily, started within 10 days of transplant.
CMV disease incidence lower
The incidence of CMV disease within 12 months of transplants, the primary outcome, was 9% in the preemptive therapy group, compared with 19% in the prophylaxis group (P = .04)
The difference between the groups was largely accounted for by a reduction in disease onset beyond 100 days in the preemptive therapy group (6% vs. 17%, respectively, P = .01)
There were no significant differences in secondary endpoints of rejection, opportunistic infections, graft loss because of retransplantation, neutropenia, or receipt of one or more doses of granulocyte colony–stimulating factor for the management of neutropenia.
At 1-year follow-up, the incidence of all-cause mortality was 15% in the preemptive therapy group, and 19% in the prophylaxis group; the difference was not statistically significant.
“While most transplant centers utilize universal prophylaxis, I think that this study really suggests that preemptive monitoring, if it can be safely accomplished at your center, may be of the greatest benefit to your patients,” Dr. Ison said.
He noted that Singh et al. also looked in an exploratory analysis at CMV-specific immunity and observed that patients assigned to preemptive therapy “clearly had better CMV-specific immunity, whether CD4 or CD8 cells, and had higher lymphocyte numbers than those patients that had received universal prophylaxis.”
In a comment, Sarah Doernberg, MD, from the division of infectious diseases at the University of California, San Francisco, agreed that “exploratory analysis of CMV-specific immune responses suggested increased CMV-specific immunity in those in the preemptive group, a finding that warrants further study. The feasibility of adopting reliable preemptive monitoring must be considered as individual centers ponder adopting this approach.”
Dr. Doernberg moderated the session where Dr. Ison discussed the data, but was not involved in the research.
The study by Singh et al. was supported by the National Institutes of Health. Dr. Singh reported research grants from NIH. Dr. Ison disclosed research support and paid consultation for several companies. Dr. Doernberg disclosed consulting for Basilea and Genentech.