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Presented at the 8th international IACFS Conference on Chronic Fatigue Syndrome, Fibromyalgia and other related Illnesses January 12-14, 2007, Fort Lauderdale, Fla.
Subset-Classification Directed Antiviral Therapy of Chronic Fatigue Syndrome:
Phase I Clinical Trials
A. Martin Lerner, (1) Safedin H. Beqaj, (1) Robert G. Deeter, (2) and James T. Fitzgeral (3) Department of Medicine, William Beaumont Hospital and Wayne State University School of Medicine, (1) Glaxo Wellcome Co., (2) and Department of Medical Education, University of Michigan, Ann Arbor, Michigan (3)
Objectives (1) Patients with CFS frequently have serologic evidence of Epstein-Barr virus (EBV) and/or cytomegalovirus (HCMV) infection. The paradigm guiding this research is that persisting infection with one or both of these viruses may be etiologically related to CFS. Therefore, at least 3 subsets of CFS are present. (2) Our previous work indicates that CFS is associated with abnormal electrical repolarization (recovery) after cardiac contraction which is recognized by abnormal recurrent T-wave flattering or inversions at 24-Hr. ECG Holter monitoring. The absence of these Holter monitoring changes excluded CDC- defined CFS (96% sensitivity, p 0.01). (3) A uniformly present “intolerance" to exercise: defines CFS. We determine the severity of CFS by the Energy Index Point Score®, Registered, U.S. Patent and Trademark Office, which depicts the capacity for physical activity of the CFS patient.EIPS® units can be converted to Kcal/day expended. A CFS patient has an EIPS® < 5 units.
Methods Three CFS subsets were studied in Phase I Clinical Trials: A) placebo controlled, randomized 6 month trial of valacyclovir (val) in EBV subset (27 patients): a further 27 patients were treated with open val for 36 months B) One 36 year-old patient with HCMV subset treated with valganciclovir (gan) for 42 months, and C) nine patients with EBV/HCMV co-infection CFS treated for 30 months with both val and gan. Patients met CDC criteria for CFS, had positive T-wave findings at Holter monitor and appropriate serologic (ELISA) titers for EBV (EBV, viral capsid antigen VCA, IGM; EBV, Early antigen, diffuse, HCMV(V), Igm, IgG). Lyme disease, rheumatic fever, chronic sinusitis and IgG subclass deficiency were specifically excluded. Patients were seen every 4 – 6 weeks and EIPS® assessed as well as possible toxicities to administered antivirals, CBC, AST, ALT, creatinine and urinalysis. Valacyclovir was given 14.3mn/kg p.o. q 6 h. Patients drank 6 eight-ounce glasses water/day to avoid renal stones. Valganciclovir was given 12.9mg/kg q AM and 6.5mg/kg q PM.
Results
- The EBV initial subset EIPS® mean scores inproved 1.12 units, val: 0.42 units (placebo) at 6 months: abd 3.2 units (open cal Rx) at 36 months
- HCMV subset, initialEIPS®, 3.5 u, finalEIPS®, 8.0 units, duration of gan, 3.5 years
- EBV-HCMV subset, initialEIPS®, 4.8u, finalEIPS®, 7.2 units
With valacyclovir and/or valganciclovir, sinus tachycardias at rest lessened, abnormal cardiac wall motion improved and EBV, VCA, IgM serum antibody titers diminished. Symptoms, sore throats, fevers, lymphadenopathy, syncope, cheat pain, palpitations and muscle aches decreased, or more often disappeared.
Conclusion Subset directed pharmacokinetically administered valacyclovir and/or valganciclovir long-term was effective in treatment of 37 CFS patients in these phase 1 clinical trials. No serious side effects were seen.
Energy Index Point Score® (EIPS®) is a registered trademark, U.S. Patent and Trademark Office.
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