- Last Updated: 25 November 2015 25 November 2015
A study on the use of antiviral agents in the treatment of ME/CFS for certain patients was published by Dr. A. Martin Lerner, et al. in Virus Adaptation and Treatment 2 (2010): 47-57.
The paper is titled, “Subset-directed antiviral treatment of 142 herpesvirus patients with chronic fatigue syndrome.” What is particularly important about this study is the level of improvement achieved by a subset of patients. Furthermore, these patients had been followed very closely by Dr. Lerner for an extensive length of time (i.e., data was collected from the study group every 4-6 weeks, at one clinic, from 2001 to 2007).
Dr. Lerner is an infectious disease specialist who became ill with ME/CFS in 1986. Prior to this, he had completed decades of research of various infectious diseases. Over the subsequent decades his research has concentrated on the viral aspects of ME/CFS, the use of antivirals in its treatment, and the effects of viral infections on cardiac activity in ME/CFS patients.
In the current study, Dr. Lerner looked at a randomly selected group of ME/CFS patients who met the 1994 CDC case definition of CFS, had an Energy Index Point Score (EIPS) (explained below) of less than or equal to 5, and who had taken antiviral medication under the direction of his clinic for at least 6 months between May 2001 and December 2007.
These patients were then screened for high enough antibody titers to Epstein-Barr virus (EBV), cytomegalovirus (HCMV), or human herpes virus-6 (HHV-6) to indicate the existence of a continuing non-latent infection with one or more of these viruses.
Only those CFS patients with demonstrated non-latent infections with one or more of the viruses were included in the study. The sizes of the original patient group and of the original randomly selected patient group were not specified. 142 patients were in the final study group.
The study makes a number of major points:
(1) The research found that patients might have pathological activity of EBV, HCMV, or HHV-6 either separately or in various combinations. In his study, Dr. Lerner put CFS patients with non-latent infections of one or more of these viruses but no concurrent “other” infections of a limited type (described below) into Group A. There were 106 patients in Group A.
A second group, Group B, had non-latent infections of these viruses, either separately or in combination; but also had co-infections of Borrelia burgdorferi (i.e., the major form of Lyme Disease), Babesia microti, Anaplasma phagocytophila, and/or antistreptolysin O (i.e., adult rheumatic fever that is linked to a certain strain of streptococcal infection). There were 36 patients in Group B. This was too small to allow for separate statistical analyses of this group.
Dr. Lerner did not include in this study any CFS patients who did not have non-latent infections with EBV, HCMV or HHV-6 and who hadn’t already tolerated antivirals for at least six months.
(2) Group A patients with EBV only were given valacyclovir or famciclovir and those patients with HCMV and/or HHV-6 were given valganciclovir. Patients with EBV, and one or more of HCMV and HHV-6 were given both antivirals.
Group B patients (those with herpes virus infection plus the co-infections) were treated with the same antivirals as Group A, but were also treated with the currently indicated medications for the co-infection(s).
(3) Patients underwent lab tests, at 4-6 week intervals, in order to be checked for signs of toxicity (i.e, abnormal white blood cells, platelet counts, etc.). Close monitoring assisted with adjustments in the dosages of these antivirals and/or substitutions from one medication to another (e.g. famciclovir for valacyclovir). Cardiac symptoms and activity (e.g. changes in heart rhythm and/or T-wave patterns) were evaluated by way of qualitative Holter Monitors (HM) and 2D echocardiograms, and cardiac dynamic studies, at baseline and repeated at specific intervals.
(4) Improvement was measured by a validated Energy Index Point Score (EIPS). This scale measured a patient’s sickness state and activity capability from a score of 0 - “Bedridden, up to bathroom only”; to 4 - “Out of bed sitting, standing, walking 4-6 hours per day”; to 5 - “Performing with difficulty sedentary job 40 hours a week, daily naps.” Recovery starts at 6 - “Daily naps in bed, may maintain a 40-hour sedentary work week, plus light, limited housekeeping and/or social activities.” The remaining EIPS values describe levels of continued improvement, from 7 to 10. (10 is “Normal”.)
Improvement was also measured by a decrease in viral loads and improvement in cardiac symptoms.
(5) Dr. Lerner found that in these CFS patients, the herpesvirus infections were both “permissive” and “non-permissive.” In non-permissive infections, the herpes virus does not replicate a complete virus, but rather reproduces only viral fragments that then disrupt normal cellular machinery. He postulates that normal viral testing can miss the presence of these viral fragments. Other research (Glaser et al.) has also found that EBV viral fragments are present in some CFS patients.
(6) The study found that “Long-term valacyclovir and/or valgancyclovir subset-directed administration improved or eliminated CFS symptoms in Group A CFS patients. Single and multiple infected Group A patients responded. An initial Jarisch-Herxheimer response at the start of the antiviral medication initiates successful treatment…” (This response entails a temporary worsening in the patient’s condition.) Group A patients had been ill on average of 4.8 years before their first clinic visit and inclusion in the study. “The [average] duration of antiviral therapy was 2.8 years.”
Of the 106 patients in Group A, 79 (74.5%) had EIPS increases of equal to or greater than 1.0. (In other words, 27 Group A patients had less than a 1.0 EIPS treatment response.) For these 79 “responders,” the average EIPS baseline was approximately 4.36 with the two-year average EIPS improved to 6.35 (53 responders remaining). “The delta [change] for responders was 2.54 (P<0.0001). EIPS improved in both single and multiple herpes virus CFS patients.” Twenty-one Group A single and multiple herpes virus patients had EIPS values 7-9.
Dr. Lerner wrote in the Discussion section: “The long-term recovery of Group A CFS patients reported in this study is unprecedented.”
Group B consisted of 36 patients with various combinations of herpes viruses and co-infections. These subgroups’ beginning EIPS values were similar (3.78). Improvement in EIPS score on average for the different groups was from 1-2 points. All the CFS subgroups in Group B at study completion continued within the CFS diagnosis range.
A recap of Dr. Lerner’s research, according to the “Discussion” section, provides a definite theory that about why long-term antiviral therapy might work successfully against herpes viruses in CFS. The EBV, CMV, and HHV-6 viruses are constantly attempting to produce complete virus in host cells; if successful, this process leads to the spread of the virus and infection of other cells. At the same time, the body attempts to suppress this process and return the virus to latency—meaning that remaining virus is no longer active. In CFS, the herpes viruses can be active "permissively" and "non-permissively" (see item 5 above). Often, the process is non-permissive, that is, the viruses produce new viruses only part-way, but the early and intermediate products are sufficient to cause severe disruption to normal cell functioning, ultimately ending in the death of specific cells (apoptosis).
Thus for some CFS patients, their immune systems cannot completely stop this process and cause the herpes viruses to go into latency. Valacyclovir (for EBV) and valganciclovir (for HCMV, HHV-6) inhibit active viral production. The long-term antiviral therapy slowly assists the body's immune system to actually suppress viral activity into a latent, non-active state. During treatment, the patient will undergo specific tests at fixed intervals. Success is measured by specific viral antibodies returning to normal or turning negative, and finding that cardiac T-waves (either flat or inverted) have normalized and tachycardias have disappeared. Treatment is continued until the EIPS is equal to or greater than 7. If no further treatment is necessary, then the CFS patient independently will maintain herpesvirus latency.
"The thesis predicts that mRNA [a viral gene product] to intermediate/early herpesvirus genes is circulating in mononuclear cells [a specific immune cell] in the blood of CFS patients, but this mRNA is not present in healthy subjects."
WARNING: ME/CFS patients should be aware that the antiviral medications used in the study can be highly toxic and only some people will be able to safely tolerate them for a long period of time. The patients in this study had already tolerated them for six months before the study start. Patients who take these medications must be under the direct supervision of a knowledgeable physician who can test for toxicity at specified intervals to prevent critical and permanent organ damage.
Editorial note: It appears that this study pertains to those CFS patients who have known non-latent herpes viral infections and who can tolerate antiviral and other treatments (Group B) for at least two years.
Additionally, this study was not a controlled study that included subgroups of Group A and Group B that received no treatment—to determine, possibly, the difference in EIPS increases between treated subjects and controls. Such a study would at least partially demonstrate how much of the improvement was due to the antivirals as opposed to normal improvement in CFS patients over time. However, the improvement in the Group A subjects was quite robust—a greater improvement than normally seen in many CFS patients.
We are saddened that Dr. Martin Lerner died on October 5, 2015. Requiescat in pace.
The source of information used for this summary was the full text of the paper. This research paper is available, for free, by going to the Treatment Center for CFS, the clinic founded and run by Dr. Lerner.
This website offers additional data about Dr. Lerner, including his professional profile, an extensive listing of his professional publications, and videos from several presentations made by Dr. Lerner.
Notice about names
The Massachusetts ME/CFS & FM Association would like to clarify the use of the various acronyms for Chronic Fatigue Syndrome (CFS), Chronic Fatigue & Immune Dysfunction Syndrome (CFIDS) and Myalgic Encephalomyelitis (ME) on this site. When we generate our own articles on the illness, we will refer to it as ME/CFS, the term now generally used in the United States. When we are reporting on someone else’s report, we will use the term they use. The National Institutes of Health (NIH) and other federal agencies, including the CDC, are currently using ME/CFS.
Massachusetts ME/CFS & FM Association changed its name in July, 2018, to reflect this consensus.