DNAemia Thresholds to Discontinue Antivirals in Preemptive Management for Cytomegalovirus Seropositive Recipients After Kidney Transplantation

BACKGROUND: Treatment of cytomegalovirus (CMV) after kidney transplantation aims to achieve cessation of viral replication; however, the use of highly sensitive DNA assays creates uncertainty regarding the optimal DNAemia threshold for safely discontinuing antiviral therapy. We evaluated the safety and efficacy of ending antiviral therapy at a lower DNAemia cutoff (<log10 2.30; 200 IU/mL), compared with undetectable DNAemia (<log10 1.49; 31 IU/mL). METHODS: This retrospective cohort study included 1048 CMV IgG-positive kidney transplant recipients under a preemptive strategy for CMV prevention: 664 in the undetectable DNAemia period (March 2018-July 2019) and 384 in the low DNAemia period (August 2019-July 2020), with 1-y follow-up. The primary outcome was CMV recurrence. Secondary outcomes included antiviral duration, refractory CMV, and time to recurrence. RESULTS: A total of 515 patients (49.1%) met the DNAemia threshold for antiviral treatment, of whom 195 (18.6%) presented with CMV-related symptoms. The low DNAemia period required less time to achieve the DNAemia threshold for treatment withdrawal (23 versus 27 d; P < 0.001). CMV recurrence was similar (12.2% versus 10.8%), as were rates of recurrent CMV disease, refractory CMV, acute rejection, and graft function. Recurrence tended to occur earlier in the low DNAemia period (37 versus 44 d; P = 0.08). In multivariate analysis, only older donor age (hazard ratio, 1.024; P = 0.004) and earlier CMV onset (hazard ratio, 0.968; P < 0.001) were associated with recurrence. CONCLUSIONS: Setting the DNAemia threshold at <200 IU/mL to end antiviral therapy was safe, shortened treatment, and did not increase CMV recurrence. These real-life results support a new threshold for stopping treatment in CMV-IgG-positive patients under a preemptive strategy.