Monitoring for CMV-specific CMI in intermediate-risk KT recipients must be regular to reflect dynamic changes in overall immunosuppression and individual susceptibility. The early assessment at post-transplant day 15 remains particularly informative.

Background Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. The aim of this study was to evaluate whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy. Methods In this open-label, non-inferiority clinical trial, patients were randomized 1:1 to follow immunoguided strategy, receiving prophylaxis (valganciclovir 900 mg daily) until CMV-CMI recovery or to receive fixed-duration prophylaxis until day +90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed two deleterious events (CMV disease/replication and neutropenia). Results A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs. 2.7%; P = 0.149) and replication (17.1% vs. 13.5%; log-rank test, P = 0.422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs. 37.8%; OR, 6.0; P < 0.001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome. Conclusions Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed.

This cross-sectional study analyzes factors associated with the development of CMV-specific CD8þ response, measured by IFNg production after cytomegalovirus (CMV) peptide stimulation, in CMV-seropositive solid organ transplantation candidates. A total of 114 candidates were enrolled, of whom 22.8% (26/114) were nonreactive (IFNg < 0.2 IU/mL). Multivariate logistic regression analysis showed that age, HLA alleles and organ to be transplanted were associated with developing CMV-specific CD8þ immunity (reactive; IFNg ! 0.2 IU/mL). The probability of being reactive was higher in candidates over 50 than in those under 50 (OR 6.33,). Candidates with HLA-A1 and/or HLA-A2 alleles had a higher probability of being reactive than those with non-HLA-A1/non-HLA-A2 alleles (OR 10.97,. Renal candidates had a higher probability of being reactive than lung (adjusted OR 8.85,) and liver candidates (OR 4.87,). The AUC of this model was 0.84 (p < 0.001). Positive and negative predictive values were 84.8% and 76.9%, respectively. In renal candidates longer dialysis was associated with an increased frequency of reactive individuals (p ¼ 0.040). Therefore, although the assessment of CMV-specific CD8þ response is recommended in all Rþ candidates, it is essential in those with a lower probability of being reactive, such as non-renal candidates, candidates under 50 or those with non-HLA-A1/non-HLA-A2 alleles.