HHV-6 infection after allogeneic hematopoietic stem cell transplantation: From chromosomal integration to viral co-infections and T-cell reconstitution patterns

J Infect. 2016 Feb;72(2):214-22. doi: 10.1016/j.jinf.2015.09.039. Epub 2015 Oct 28.

Abstract

Objectives: Human herpes virus 6 (HHV-6) can reactivate after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and may be associated with significant clinical manifestations.

Methods: Case control study of HHV-6 infections after allo-HSCT. Chromosomal integration (ciHHV-6) for viral loads ≥ 5.5-log10 copies/mL was investigated. Viral co-infections, T-cell recovery, risk factors and outcome were compared in HHV-6- and non-HHV-6-infected patients. Antiviral treatment strategies were reviewed.

Results: Among 366 adult allo-HSCT recipients, 75 HHV-6 infections occurred. Three (4%) recipients were ciHHV-6. HHV-6 infections were associated with CMV (p = 0.05; sdHR 1.73, CI 0.99-3.02) and/or BKV infections (p < 0.0001; sdHR 4.63, CI 2.04-10.53) but not EBV reactivation (p = 0.34). A slower CD8+ T-cells recovery was observed until 6 months after allo-HSCT in the HHV-6-infected group (p < 0.001), independently of acute and/or chronic graft-versus-host disease. The overall probability of survival after allo-HSCT was diminished for active HHV-6-infected patients (p = 0.0326). Cord blood unit recipients had a higher risk of developing HHV-6 infection compared to bone marrow recipients (p = 0.0007; sdHR 3.82, CI 1.76-8.27). Anti-HHV-6 treatment achieved complete response in only 2/3 of the cases.

Conclusions: In this series of allo-HSCT recipients, 4% were ciHHV-6, active HHV-6 infection was likely associated with CMV and BKV co-reactivations, delayed CD8+ T-cell recovery and poorer outcome.

Keywords: BK virus; Chromosomally integrated HHV-6; Cytomegalovirus; Hematopoietic stem cell transplantation; Human herpes virus 6; T lymphocytes.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / immunology*
  • Case-Control Studies
  • Coinfection / epidemiology
  • Coinfection / pathology
  • Coinfection / virology
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Herpesvirus 6, Human / immunology
  • Herpesvirus 6, Human / physiology*
  • Humans
  • Male
  • Middle Aged
  • Roseolovirus Infections / epidemiology*
  • Roseolovirus Infections / pathology*
  • Roseolovirus Infections / virology
  • Transplantation, Homologous / adverse effects*
  • Virus Activation
  • Virus Integration*
  • Young Adult