Antiviral treatment creates improvement in a subset of ME/CFS patients

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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.

Books about Pain and Pain Management

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Last Updated: 20 November 2015 20 November 2015

The Massachusetts CFIDS/ME & FM Association does not assume any responsibility for the outcome of treatments or other self-care strategies described in any of the listed books, that might be undertaken by readers and we recommend individuals always consult with their healthcare providers before trying any new treatment, supplement, or healthcare product.

 Pain Free 1-2-3: A Proven Program for Eliminating Chronic Pain Now, by Jacob Teitelbaum, MD, 2005, ISBN: 0071464573.   

Pain Free 1-2-3 is another informative and engaging book to come from Dr. Jacob Teitelbaum, author of the well-known guide for ME/CFS and Fibromyalgia (FM), From Fatigued to Fantastic (now in its 3rd edition). The target audience for this particular book consists of individuals with FM, myofascial pain or chronic pain. Though Dr. Teitelbaum touched on the importance of decreasing or eliminating pain when someone has ME/CFS and/or FM in all the editions of his first book, this book allows him to expand on this topic and it nicely complements the first series. 

Dr. Teitelbaum starts out by explaining what sorts of things can help to promote healing and repair tissues as well as what sort of things may put stress on one’s body and cause pain. The treatment strategy formulated by Dr. Teitelbaum (which he claims can eliminate chronic pain) includes recommendations such as: striving to get the best possible nutrition and quality sleep, correcting one’s hormonal deficiencies, learning how to identify and eliminate pain triggers (including getting treated for any persistent infections since they put a strain on the immune system), and learning about the many types of pain and how to deal with each of these. [N.B. There is no solution to the pain from lactic acid build-up due to mitochondrial dysfunction except time and bed rest. Your body has to break down the lactic acid to dispel the pain.—Ed.]

The second half of the book summarizes numerous treatment options, including herbal /natural remedies and alternative therapies, prescription therapies, and/or a combination of both approaches. He also states the best order in which to try these and how they will be most beneficial. (It is understood that treatments should be pursued while under the care of one’s doctor.)       

Though this book offers a lot of practical information, the way it is marketed (i.e., the flashy titles, making things sound so easy to do, or making rather incredible claims) is a negative and may actually discourage interest in this book. It is not clear why Dr. Teitelbaum has chosen this type of delivery style considering his extensive knowledge about ME/CFS and FM and chronic pain as the medical director of the Center for Effective CFS/Fibromyalgia Therapies in Maryland. On the positive side, if readers can get past the packaging, they will appreciate the value of the information in this book and will sense the author’s optimism and desire to enlighten readers.

Trigger Point Therapy for Low Back Pain: A Self-treatment Workbook (New Harbinger Self-Help Workbook), by Sharon Sauer, CMTPT, LMT and Mary Biancalana, MS, CMTPT, LMT, 2009, ISBN: 1572245638.   

As the title implies, this book is intended for individuals who suffer from low back pain and who would like to learn more about what is causing their pain and find out what they could do to alleviate some of the pain. The type of pain discussed in this book is muscle pain, more specifically, pain coming from the tightening of the myofascia—the thin, fibrous tissue that encloses layers of muscles and supports the musculature of the body. Changes within this tissue present as “trigger points” which are painful knots that develop in the muscle fiber and cause constriction of nerves and blood vessels and this in turn, causes pain and referred pain.

Myofascial trigger point therapy is a type of bodywork done by medical practitioners and/or trained therapists using manual and physical techniques to find (through palpation) and reduce these knots and myofascial constriction, but considerable relief can be also achieved at home though various self-applied methods. Therefore, this book contains what two knowledgeable therapists in this field and members of the International Myopain Society, Sharon Sauer and Mary Biancalana, want to share with readers.

The authors write from personal and professional experience and are very careful and sensible in how they communicate with readers. Their first recommendation is that anyone with low back pain be thoroughly evaluated by a primary care physician and/or specialist for all possible causes. Patients are also urged to get their doctors’ approval before participating in any of the home exercises and/or seeking therapy from licensed practitioners using this discipline.

This is a very user-friendly book, which is not overly long (as it concentrates only on muscle groups involved in lower back muscle pain), and in which the information is conveniently broken down into 17 small chapters. Once the basics are covered, a chapter is devoted to each of the ten specific muscle groups associated with low back and/or buttock pain, as well as trigger points that are activated and causing pain.

Symptoms and patterns of muscle pain/referred pain for each group are well explained and in many cases, accompanied by illustrations and diagrams. One chapter, in particular, seems very helpful because it provides a reference chart listing general problems and the muscle groups associated with these, including a notation as to which chapter discusses this particular muscle group.

Treatment recommendations, within each chapter for each muscle group, consist mainly of helpful stretches, ways to apply pressure against painful areas and promote release of knots, range of motion exercises with easy to follow diagrams, and instructions for how to use self-care tools and other therapies (i.e., backnobber, therapy balls, pillows, use of heat, etc.).

This book is effective in enlightening readers about myofascial pain and trigger point therapy. As mentioned before, content is limited to the lower back muscle groups.  It is important to note this book solely concentrates on trigger point therapy and this type of pain and it does not include any information on fibromyalgia in particular. We do not think this is a problem because the at-home techniques and tips could be beneficial and this type of intervention has been included in recent fibromyalgia publications.

 Sciatica Solutions: Diagnosis, Treatment, and Cure of Spinal and Piriformis Problems, by Loren Fishman, MD and Carol Ardman, 2006, ISBN: 0393330419.

Dr. Loren Fishman, a specialist in rehabilitation medicine, researcher and professor at Columbia College of Physicians and Surgeons, and his wife, Carol Ardman, a freelance writer and editor, wrote this book because of the misunderstanding that surrounds sciatica and associated problems. This is a genuine problem noticed by Dr. Fishman himself, who has over thirty years of clinical experience. Therefore, they wanted to provide a book which clarifies this type of pain, explains how to better recognize it, reviews the kind of tests or care one might consider getting for it, and explains the wide range of treatment options, both conventional and alternative.

This is not a book about general back pain, which is often muscular in nature, but one that focuses on sciatica—a pain, neurological in origin, that typically runs along the sciatic nerve and causes distinct set of symptoms and pain patterns in the buttocks and the legs (i.e., numbness, “electric shocks”, and other peculiar sensations).

The book is divided into two parts. In the first part, Dr. Fishman goes over the multiple causes of sciatic-type pain and describes how it feels, but also differentiates it from other conditions which are often mistaken for it.

One chapter reviews basic components and functions of the nervous system (i.e., the interaction of the brain, spinal cord, the nerve fibers and nerve roots). Of particular interest are the illustrations of the spine, nerve root patterns and diagnostic diagrams.

Another chapter is dedicated to the diagnostic and nerve function tests used to diagnose sciatica-related problems or to evaluate nerve damage.

The last chapter in the first part offers an extensive review of the conditions associated with sciatica. Here too, the in-depth explanation of the Piriformis Syndrome—a condition affecting the buttocks when the sciatic nerve becomes entrapped and compressed, was found to be especially informative and unique to this book.

The second part of the book deals with treatment options and many things that patients can do on their own. It is understood that patients will have first sought appropriate medical care and evaluation from their primary care providers or specialists.

Recommendations include such things as strengthening abdominal, torso and core muscles, becoming educated about different exercise/movement techniques, and paying attention to daily routines, posture, and even one’s clothing, handbags and footwear.

Medical treatments, such as physical therapy, medical devices, and various mechanical techniques are reviewed.

An overview is provided on frequently used medications, injections and other invasive treatments, as well as various surgical procedures (including brief descriptions and reasons for these surgeries).

The book concludes with many types of nonmedical alternative techniques and the importance of nutrition and lifestyle changes. Dr. Fishman is a strong proponent of alternative treatments, like yoga, and promoting patient education.

This book is easy to read and comprehend, even though it contains some technical information. The authors have done a good job in how they have explained or illustrated this information. Their writing style is friendly and speaks to the readers.

This book would be especially beneficial for individuals who are just starting out with sciatica, because it provides them with the knowledge they need to make informed decisions. Individuals who might already be receiving medical care for this problem will find parts of this book helpful because it provides a better understanding about the mechanisms driving the pain and offers additional ways to manage it.