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From: 'Clinical & Patient Studies' <a href="http://www.treatmentcenterforcfs.com/clinical_patient_study/index.html">http://www.treatmentcenterforcfs.com/clinical_patient_study/index.html</a>

Subset-directed Antiviral Treatment of 142 Herpesvirus Patients with Chronic Fatigue Syndrome (<a href="http://www.treatmentcenterforcfs.com/clinical_patient_study/documents/Dr.A.MartinLerner-Subset-directed-antiviral-treatment-of-142-herpesvirus-patients-with-CFS.pdf">PDF</a>)

Virus Adaptation and Treatment, May 2010 Volume 2010:2

Dr. A. Martin Lerner, et al.

Purpose We hypothesized that chronic fatigue syndrome (CFS) may be caused by single or multiple Epstein–Barr virus (EBV), cytomegalovirus (HCMV), or human herpesvirus 6 (HHV6)infection. To determine if CFS life-altering fatigue and associated findings including muscle aches, tachycardia at rest, chest aches, left ventricular dysfunction, syncope, and elevated herpesvirus serum antibody titers are reversed by long-term subset-directed valacyclovir and/or valganciclovir.

Patients and methods Data were collected at physician visits every 4–6 weeks from 142 CFS patients at one clinic from 2001 to 2007. To be included in this study, patients had to be followed for at least six months. The data captured included over 7000 patient visits and over 35,000 fields of information. Severity of fatigue was monitored by a validated <a href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html" target="_blank">Energy Index Point Score</a>® (<a href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html">EIPS</a>®). Baseline and follow-up serum antibody titers to EBV, HCMV, and HHV6, as well as coinfections with Borrelia burgdorferi, Anaplasma phagocytophila, Babesia microti,and antistreptolysin O, 24-hour ECG Holter monitors, 2D echocardiograms, cardiac dynamic studies, symptoms, and toxicity were captured and monitored. International criteria for CFS plus a specifically designed CFS diagnostic panel were used.

Results and conclusions The Group A herpesvirus CFS patients (no coinfections) returned to a near-normal to normal life (P = 0.0001). The long-term <a href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html" target="_blank">EIPS</a>® value increased (primary endpoint, P < 0.0001) with subset-directed long-term valacyclovir and/or valganciclovir therapy. Secondary endpoints (cardiac, immunologic, and neurocognitive abnormalities) improved or disappeared. Group B CFS patients (herpesvirus plus coinfections) continued to have CFS.

Subset-Classification Directed Antiviral Therapy of Chronic Fatigue Syndrome:Phase I Clinical Trials

Presented at the 8th international IACFS Conference on Chronic Fatigue Syndrome, Fibromyalgia and other related Illnesses January 12-14, 2007, Fort Lauderdale, Fla.

Dr. A. Martin Lerner, et al.

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<a href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html"> Energy Index Point Score</a>®, Registered, U.S. Patent and Trademark Office, which depicts the capacity for physical activity of the CFS patient.<a href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html">EIPS</a>® units can be converted to Kcal/day expended. A CFS patient has an <a href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html">EIPS</a>® < 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 <a href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html">EIPS</a>® 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

<ol >

<li>The EBV initial subset <a href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html">EIPS</a>® mean scores inproved 1.12 units, val: 0.42 units (placebo) at 6 months: abd 3.2 units (open cal Rx) at 36 months</li>

<li>HCMV subset, initial<a href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html">EIPS</a>®, 3.5 u, final<a href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html">EIPS</a>®, 8.0 units, duration of gan, 3.5 years</li>

<li>EBV-HCMV subset, initial<a href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html">EIPS</a>®, 4.8u, final<a href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html">EIPS</a>®, 7.2 units</li>

</ol>

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.

From 'A Primer on ME/CFS (Myalgic Encephalomyelitis / Chronic Fatigue Syndrome)' <a href="http://www.treatmentcenterforcfs.com/documents/Dr.AMLerner-PrimeronMECFS.pdf">http://www.treatmentcenterforcfs.com/documents/Dr.AMLerner-PrimeronMECFS.pdf</a>

Conclusion:

1) Antiviral Nucleosides valacyclovir (EBV) and valganciclovir (HCMV, HHV6) inhibit Herpesvirus Host-cell necrosis (new virus replication) and Host-cell apoptosis (IE gene expression).

2) Causal relationship between CFS and EBV/HHV6/HCMV, specifically abortive lytic EBV/HHV6/HCMV replication producing hostcell apoptosis.

3) Previous research has not proven antiviral success due to limited timelines (6 months or less), and lack of subset classification of CFS patients. 47

4) Long term group and subset directed antiviral treatment is successful!

5) Conclusion ME/CFS patients return to more normal lives - work, raise families and socialize.

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