An assessment of the effect of human herpesvirus-6 replication on active cytomegalovirus infection after allogeneic stem cell transplantation

Abstract

Human herpesvirus-6 (HHV-6) may enhance cytomegalovirus (CMV) replication in allogeneic stem cell transplant (allo-SCT) recipients either through direct or indirect mechanisms. Definitive evidence supporting this hypothesis are lacking. We investigated the effect of HHV-6 replication on active CMV infection in 68 allo-SCT recipients. Analysis of plasma HHV-6 and CMV DNAemia was performed by real-time PCR. Enumeration of pp65 and IE-1 CMV-specific IFNgamma CD8(+) and CD4(+)T cells was performed by intracellular cytokine staining. HHV-6 DNAemia occurred in 39.8% of patients, and was significantly associated with subsequent CMV DNAemia in univariate (P=.01), but not in multivariate analysis (P=.65). The peak of HHV-6 DNAemia was not predictive of the development of CMV DNAemia. Timing and kinetics of active CMV infection were comparable in patients either with or without a preceding episode of HHV-6 DNAemia. The occurrence of HHV-6 DNAemia had no impact on CMV-specific T cell immunity reconstitution early after transplant. The receipt of a graft from an HLA-mismatched donor was independently associated with HHV-6 (P=.009) and CMV reactivation (P=.04). The data favor the hypothesis that a state of severe immunosuppression leads to HHV-6 and CMV coactivation, but argue against a role of HHV-6 in predisposing to the development of CMV DNAemia or influencing the course of active CMV infection.