Early HHV-6 replication is associated with morbidity non-related to CMV infection after kidney transplantation

Human herpesvirus type 6-(HHV-6) has been associated with morbidity after liver transplantation. The aim of this study was to determine the HHV-6 seroprevalence among donorrecipient pairs, analyze the incidence of early active infection, its clinical manifestation, interaction with CMV, and the related morbidity in the first year after kidney transplantation. 46 donor-recipient pairs had IgG evaluated by ELISA before transplantation: HHV-6-(Pambio – USA) and CMV-(Roche – USA). A frozen whole blood sample collected weekly (from the 1st to the 6th week) was retrospectively tested for HHV-6 viral load (VL) determination by real time quantitative PCR (qPCR, Nanogen – Italy). Patients were preemptively surveyed for CMV by pp65 antigenemia (Ag, APAAP, immunohistochemistry, Biotest – Germany) from the 4th to the 12th week after transplantation. Active infection was defined as qPCR-HHV6+ (viral-load/mL-VL) and Ag+ (+cells/100.000 granulocytes), for HHV-6 and CMV, respectively. DCMV was defined as simultaneous positive antigenemia and suggestive signs/symptoms. Concerning +qPCR-HHV6, associated factors, clinical manifestation, interaction with CMV and morbidity were searched. Pre-transplant HHV-6 seroprevalence was significantly higher among kidney recipients compared to their donors (82.6×54.8%; p=0.005 [3.9 (1.4–10.4)]). Active infection by this virus occurred in 26.1% (12/46), with no association with previous IgG (p=0.412). Median VL was 125 copies/mL (53–11.264), and the median Ag was 21 +cells (2–740). There was no association between HHV-6 and CMV activation after transplantation (p=0.441), neither concerning DCMV (p=0.596). Median highest Ag+ and days of ganciclovir treatment were similar between qPCR-HHV6 + or − (p=0.206 and p=0.124, respectively). qPCR-HHV6+ was associated with higher incidence of bacterial (p=0.009) and fungal (p = 0.001) infections, and higher number (p=0.001) of hospital admission and longer duration of hospitalization over the first 6 and 12 months post-transplantation (p=0.033 and p=0.001). Latent HHV-6 infection is more common among recipients than donors before transplantation. Early active infection by this pathogen after transplantation does not increase DCMV incidence or severity during the first 3 months of follow-up. However, early HHV-6 replication is associated with other infections and hospitalizations in the first year.