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Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome
Article first published online: 19 AUG 2013
© 2013 Wiley Periodicals, Inc.
Journal of Medical Virology
Volume 85, Issue 12, pages 2101–2109, December 2013
How to Cite
Montoya, J. G., Kogelnik, A. M., Bhangoo, M., Lunn, M. R., Flamand, L., Merrihew, L. E., Watt, T., Kubo, J. T., Paik, J. and Desai, M. (2013), Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome. J. Med. Virol., 85: 2101–2109. doi: 10.1002/jmv.23713
- Issue published online: 1 OCT 2013
- Article first published online: 19 AUG 2013
- Manuscript Accepted: 18 JUN 2013
- F. Hoffmann–La Roche (Basel, Switzerland)
- Stanford University School of Medicine Molecular Basis of Medicine Scholarly Concentration
- Stanford University School of Medicine Medical Scholars Fellowship Program
- chronic fatigue syndrome;
- human herpesvirus 6;
- Epstein–Barr virus;
- randomized clinical trial
There is no known treatment for chronic fatigue syndrome (CFS). Little is known about its pathogenesis. Human herpesvirus 6 (HHV-6) and Epstein–Barr virus (EBV) have been proposed as infectious triggers. Thirty CFS patients with elevated IgG antibody titers against HHV-6 and EBV were randomized 2:1 to receive valganciclovir (VGCV) or placebo for 6 months in a double-blind, placebo-controlled trial. Clinical endpoints aimed at measuring physical and mental fatigue included the Multidimensional Fatigue Inventory (MFI-20) and Fatigue Severity Scale (FSS) scores, self-reported cognitive function, and physician-determined responder status. Biological endpoints included monocyte and neutrophil counts and cytokine levels. VGCV patients experienced a greater improvement by MFI-20 at 9 months from baseline compared to placebo patients but this difference was not statistically significant. However, statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P = 0.039), FSS score (P = 0.006), and cognitive function (P = 0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months. Patients in the VGCV arm were 7.4 times more likely to be classified as responders (P = 0.029). In the VGCV arm, monocyte counts decreased (P < 0.001), neutrophil counts increased (P = 0.037) and cytokines were more likely to evolve towards a Th1-profile (P < 0.001). Viral IgG antibody titers did not differ between arms. VGCV may have clinical benefit in a subset of CFS patients independent of placebo effect, possibly mediated by immunomodulation and/or antiviral effect. Further investigation with longer treatment duration and a larger sample size is warranted. J. Med. Virol. 85:2101–2109, 2013. © 2013 Wiley Periodicals, Inc.