*Purpose: Cytomegalovirus (CMV) infections cause significant morbidity and mortality among all solid organ transplant recipients. CMV discordant (D+/R-) recipients are at higher risk of developing CMV viremia after cessation of prophylaxis. CMV specific T cell immunity has been shown in many publications to predict those at highest risk for CMV associated events. However it is unknown if changes in maintenance immunosuppression guided by CMV T cell immunity may lead to fewer CMV events as a result of improved immunity.

*Methods: This is a retrospective single center analysis of 38 CMV discordant recipients between October 2018 and June 2020 that received a CMV T cell immunity assay prior to cessation of universal prophylaxis. 32 (84%) were kidney recipients, 3 (8%) liver, 3 (8%) simultaneous liver-kidney and 1 (3%) simultaneous pancreas-kidney. CMV viremia was defined by positive CMV PCR (>137 U/mL) and/or symptomatic disease. Recipients who had low T cell immunity (CMV CD4/CD8 < 0.20) on initial testing underwent reduction of antimetabolite (MMF) dose if deemed appropriate based on immunological and hematological parameters. Subsequent CMV T cell immunity was tested after reduction of immunosuppression.

*Results: The majority of CMV discordant recipients were male (N=26, 68%), African American (N=22, 58%), and received rabbit anti-thymocyte globulin induction (N=32, 84%). At a median follow-up of 9 months (IQR 4, 24), six (16%) episodes of CMV viremia were observed. Those who developed viremia had significantly lower CMV CD8 specific T cell immunity compared to those who did not develop viremia (0.14±0.20 vs. 1.54±4.09, p=0.03) with a similar though non-statistically significant CD4 specific T cell immunity (0.057±0.03 vs. 0.33±1.07, p=0.08). Thirteen (34%) recipients underwent repeat testing at an average of 78±44 days after initial test. Of the 13, nine (69%) had a median MMF dose reduction of 500 mg (IQR 500,750) while four (31%) had no dose reduction. On subsequent testing those with reduction of MMF had an improvement in both CD8 [0.01 (IQR 0, 0.04) to 0.05 (IQR 0, 1.17) p=0.07] and CD4 [0.04 (IQR 0.02, 0.09) to 0.1 (IQR 0.06, 0.25) p=0.007] specific T cell immunity. Conversely, those with no change in MMF dose had no discernable improvement in both CD4 [0.02 (IQR 0, 0.09) to 0.06 (IQR 0.01, 0.25), p=0.11] and CD8 [0.03 (IQR 0.02, 0.04) to 0.04 (IQR 0.02, 0.12) p=0.17] specific T cell immunity. No significant difference in acute rejection episodes occurred between groups.

*Conclusions: This single center study confirms previous findings that CMV high-risk recipients with low CMV T cell immunity had higher rates of CMV viremia. More importantly, we demonstrated that CMV specific T cell immunity may improve with changes to maintenance immunosuppression. Further studies are required to see if serial T cell immunity assays may be used as adjunctive data to adjust maintenance immunosuppression to reduce the risk of CMV events.

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