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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

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By AM Kogelnik, et al • • January 17, 2007

Journal: Journal of Clinical Virology, Vol. 37, Supplement I, December 2006, pp. S33-S38. [Funded by HHV-6 Foundation. E-Publication Jan 2007. Full text available for a fee at ] Authors and affiliations: Andreas M. Kogelnik, Kristin Loomis, Mette Hoegh-Petersen, Fernando Rosso, Courtney Hischier, Jose G. Montoya, Andreas M. Kogelnik, Kristin Loomis, Mette Hoegh-Petersen. Stanford University School of Medicine, Stanford, California, USA (Kogelnik, Rosso, Montoya); HHV-6 Foundation, Santa Barbara, California, USA (Loomis, Hischier); Palo Alto Medical Foundation Research Institute, Palo Alto, California, USA (Hoegh-Peterson, Rosso, Montoya). [Contact J.G. Montoya. E-mail: ]

Background: Twelve patients with long-standing symptoms of central nervous system (CNS) dysfunction were found to have elevated antibody titers 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.

Objectives: 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.

Study design: 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 activities. 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.

Conclusion: 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.

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