USE OF VALGANCICLOVIR IN PATIENTS WITH ELEVATED ANTIBODY TITERS AGAINST HUMAN HERPES 6 (HHV-6) & EPSTEIN-BARR VIRUS (EBV)
who were experiencing central nervous system dysfunction including long-standing fatigue
A Randomized, Placebo-Controlled and
Double Blind Study at Stanford University

Drs. Jose Montoya and Andreas Kogelnik of Stanford Hospital Infectious Disease Clinic are planning a double blinded placebo controlled clinical trial to determine whether patients with Viral Induced CNS Dysfunction, a subset of patients with Chronic Fatigue Syndrome, would benefit from valganciclovir treatment.

The trial will enroll 30 patients and is expected to start in the spring of 2007. The HHV-6 Foundation has supported this group to initiate and design the trial and Roche Pharmaceuticals, the manufacturer of valganciclovir, has agreed to fund the study in full. This trial was precipitated through a preliminary study conducted by Drs. Montoya and Kogelnik announced at the 2006 HHV-6 & HHV-7 Conference in Barcelona which reported the successful response to antiviral treatment experienced by nine out of 12 (75%) of patients chronically infected with human herpes virus 6 (HHV-6) and Epstein-Barr virus (EBV) and who were suffering from debilitating fatigue for more than one year (median 3 years, range 1 to 8 years). In these patients antibody titers dropped four fold suggesting (a) these patients had active infections (b) elevated antibody levels can be a useful indicator of active infection in some patients and (c) a subset of patients with CFS and elevated antibody levels to HHV-6 and EBV may have an illness that is caused by reactivation of these viruses, and that is responsive to valganciclovir therapy.

The successful results as well as the limitations of the preliminary study have warranted a larger, randomized controlled trial with long-term follow-up to confirm the possible value of antiviral therapy and exclude a placebo effect. Additionally, the study aims to establish a quantifiable biological marker in these patients that will facilitate the identification of those likely to respond to valganciclovir and will make it possible to assess response to treatment. The planned study will provide further definition of this subset of patients, with better and more standardized viral assays as well as immunologic, radiological, and genetic endpoints to determine whether there are objective and measurable changes in these parameters and whether they correlate with clinical improvement. Despite the fact that the improvements in physical activity and cognitive functions were dramatic and impressive in the

preliminary group, they were self-reported and not objective measurements. The planned study will utilize a more comprehensive evaluation of the functional status of subjects, using established and validated instruments. The resulting data from the trial will help to elucidate the possible role of EBV, HHV-6 (or a yet to be known virus) and/or an altered immune system as possible triggers for CFS.

The trial is now fully enrolled.