Antiviral therapy of two patients with chromosomally-integrated human herpesvirus-6A presenting with cognitive dysfunction

Background: Human herpesvirus 6 (HHV-6) is a neurotropic virus implicated in central nervous system (CNS) dysfunction, multiple sclerosis, seizures and encephalitis. Inherited or chromosomally integrated HHV-6 (CIHHV-6) is a condition characterized by high DNA loads and germ line transmission of HHV-6 genomes, which are integrated into the telomere. Objectives: We previously reported that integrated HHV-6 can be reactivated by trichostatin A in vitro. Therefore, we hypothesized that a broad array of neurological symptoms of CIHHV-6 patients may respond to antiviral drug treatment. Study design: The patients have been treated with antiviral drugs and monitored for viral load, late mRNA, and clinical improvement. Results: Antiviral therapy of two CIHHV patients resulted in successful clinical resolution. However, both patients relapsed on multiple occasions within 4-6 months of cessation of antiviral therapy. Conclusions: Successful antiviral drug treatment suggests that clinical symptoms of these patients were due to symptomatic reactivation of CIHHV-6. Alternatively, some CIHHV-6 patients may have a reduced resistance to community-acquired HHV-6 strains due to tolerance leading to persistent infections. (C) 2012 Elsevier B. V. All rights reserved.