Analysis of spontaneous resolution of cytomegalovirus replication after transplantation in CMV-seropositive patients with pretransplant CD8+IFNG+ response

Abstract

This prospective study evaluates whether CMV-seropositive (R+) transplant patients with pretransplant CD8+IFNG+ T-cell response to cytomegalovirus (CMV) (CD8+IFNG+ response) can spontaneously clear the CMV viral load without requiring treatment. A total of 104 transplant patients (kidney/liver) with pretransplant CD8+IFNG+ response were evaluable. This response was determined using QuantiFERON-CMV assay. The incidence of CMV replication and disease was 45.2% (47/104) and 6.7% (7/104), respectively. Of the total patients, 77.9% (81/104) did not require antiviral treatment, either because they did not have CMV replication (n = 57) or because they had asymptomatic CMV replication that could be spontaneously cleared (n = 24). Both situations are likely related to the presence of CD8+IFNG+ response to CMV, which has a key role in controlling CMV infection. However, 22.1% of the patients (23/104) received antiviral treatment, although only 7 of them did so because they had symptomatic CMV replication. These patients developed symptoms in spite of having pretransplant CD8+IFNG+ response, thus suggesting that other immunological parameters might be involved, such as a dysfunctional CD4+ response or that they might have become QFNon-reactive due to the immunosuppression. In conclusion, around 80% of R+ patients with pretransplant CD8+IFNG+ response to CMV did not require antiviral treatment, although this percentage might be underestimated. Nevertheless, other strategies such as performing an additional CD8+IFNG+ response determination at posttransplant time might provide more reliable information regarding the patients who will be able to spontaneously clear the viremia.