title: Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue.
abstract: BACKGROUND
  Twelve patients with long-standing symptoms of central nervous system (CNS) dysfunction were found to have elevated antibody titres to human herpesvirus-6 (HHV-6) and Epstein-Barr virus (EBV). All patients had four or more of the following neurocognitive symptoms: impaired cognitive functioning, slowed processing speed, sleep disturbance, short-term memory deficit, fatigue and symptoms consistent with depression.
  
  
  OBJECTIVE
  We sought to determine whether elevated antibodies to EBV and HHV-6 indicated chronic viral activation in patients with CNS dysfunction and if their symptoms could be improved by suppressing viral activity with oral valganciclovir.
  
  
  METHODS
  Patients with high IgG antibody titers against HHV-6 and EBV who were suffering from central nervous system dysfunction and debilitating fatigue for more than one year (median 3 years, range 1-8 years) were treated with 6 months of valganciclovir in an open label study.
  
  
  RESULTS
  Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activites. In the nine patients with a symptomatic response to treatment, EBV VCA IgG titers dropped from 1:2560 to 1:640 (p = 0.008) and HHV-6 IgG titers dropped from a median value of 1:1280 to 1:320 (p = 0.271). Clinically significant hematological toxicity or serious adverse events were not observed among the 12 patients.
  
  
  CONCLUSIONS
  These preliminary clinical and laboratory observations merit additional studies to establish whether this clinical response is mediated by an antiviral effect of the drug, indirectly via immunomodulation or by placebo effect.
authors.affiliation: Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Kogelnik
authors.forename: Kristin
authors.initials: K
authors.lastname: Loomis
authors.forename: Mette
authors.initials: M
authors.lastname: Hoegh-Petersen
authors.forename: Fernando
authors.initials: F
authors.lastname: Rosso
authors.forename: Courtney
authors.initials: C
authors.lastname: Hischier
authors.forename: Jose G
authors.initials: JG
authors.lastname: Montoya
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy*; D015673:Fatigue Syndrome, Chronic / Q000188:drug therapy* / Q000821:virology; D005260:Female; D015774:Ganciclovir / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D019349:Roseolovirus Infections / Q000188:drug therapy*; D000077562:Valganciclovir
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D007074:Immunoglobulin G; D000077562:Valganciclovir; D015774:Ganciclovir