title: Early HHV-6 replication is associated with morbidity non-related to CMV infection after kidney transplantation.
abstract: Human herpesvirus type 6-(HHV-6) has been associated with morbidity after liver transplantation.
  
  
  OBJECTIVE
  The aim of this study was to determine the HHV-6 seroprevalence among donor-recipient 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  Pre-transplant HHV-6 seroprevalence was significantly higher among kidney recipients compared to their donors (82.6x54.8%; 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Complexo Hospitalar Santa Casa de Misericórdia de Porto Alegre, Universidade Federal de Ciências Médicas de Porto Alegre, Porto Alegre, RS, Brazil. rbs_schroeder@hotmail.com
authors.forename: Regina Barbosa
authors.initials: RB
authors.lastname: Schroeder
authors.forename: Tatiana Ferreira
authors.initials: TF
authors.lastname: Michelon
authors.forename: Gabriela
authors.initials: G
authors.lastname: Garbin
authors.forename: Valter
authors.initials: V
authors.lastname: Garcia
authors.forename: Janaina Gomes da
authors.initials: JG
authors.lastname: Silveira
authors.forename: Luciano
authors.initials: L
authors.lastname: Santos
authors.forename: Jorge
authors.initials: J
authors.lastname: Neumann
authors.forename: Elizete
authors.initials: E
authors.lastname: Keitel
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000821:virology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D019349:Roseolovirus Infections / Q000821:virology*; D016036:Seroepidemiologic Studies; D019562:Viral Load; D014779:Virus Replication / Q000502:physiology*
chemical_list: D007074:Immunoglobulin G