Photo Credit: Dr Microbe

Immune monitoring post-solid-organ transplant reduces the duration of antiviral prophylaxis without having a higher risk for developing CMV infection.

The development of cytomegalovirus (CMV) infection has been shown to decrease allograft survival in patients who have received a solid-organ transplant. It has been shown that patients at immediate risk for CMV infection are CMV-seropositive and have received antithymocyte globulins. Although the conventional course of treatment to prevent CMV in these patients is prophylaxis with an antiviral drug, this approach has been associated with toxicity and increased healthcare costs.

Immune Monitoring

The use of assays to gage CMV-targeted T cell-mediated immunity has only received limited study. Oriol Manuel, MD, and colleagues developed an open-label, non-inferiority, randomized clinical trial focusing on kidney and liver transplant recipients to address this knowledge gap. When asked about the need for this type of clinical study, Dr. Manuel explained, “CMV infection remains a significant opportunistic infection in solid-organ transplant recipients. There are few biomarkers to determine the risk for infection after transplant. We wanted to use a novel assay that measures the immunity against CMV to decide the duration of the antiviral preventive drugs, a strategy called immune monitoring.”

The study team enrolled participants in the trial from six healthcare centers in Switzerland after having undergone a kidney or liver transplant; the study included 193 patients. These transplant recipients were CMV-seronegative with seropositive donors, which put them at high risk for CMV complications, or CMV-seropositive receiving antithymocyte globulins, which put them at immediate risk for CMV complications.

The researchers randomly separated participants into two cohorts: the intervention cohort (n=92), which received antiviral prophylaxis based on immune monitoring, and the control cohort (n=101), which received a fixed duration of antiviral prophylaxis. The control cohort was subsequently divided into two groups—patients who were CMV-seronegative and were scheduled to receive 180 days of valganciclovir and patients who were CMV-seropositive and received 90 days of valganciclovir.

Assay Applied

During the study, the participants were monitored once a month using the CMV ELISpot assay (T-Track CMV) based on the highly sensitive ELISpot technique (enzyme-linked immunosorbent spot). This method enables the detection of CMV-specific protein-reactive effector cells. The researchers found that the length of time the prophylaxis was administered was significantly shorter in the immune-monitoring group (adjusted difference, −26.0 days; 95%, CI, −41.1 to −10.8 days; P<0.001).

“We found that by using immune monitoring, we were able to reduce the duration of antiviral prophylaxis without having a higher risk for developing CMV infection,” Dr. Manuel shared. Furthermore, Dr. Manuel and his colleagues are exploring the potential application of immune monitoring in practice. He said, “Immune monitoring allows [the practitioner] to individualize the duration of antiviral prophylaxis in a given patient, so reducing costs and drug toxicity. We are now evaluating whether the use of these assays is feasible in the routine clinical practice.”

Dr. Manuel hopes that the findings of this study can be applied to further research, “We only evaluated the assays in kidney and liver transplant recipients. This strategy would need to be evaluated in larger trials, including other organ transplant recipients.”