Dr Lerner

<p>From: 'Antiviral treatment creates improvement in a subset of ME/CFS patients' <a href="https://www.masscfids.org/research/recent-research/5-cfscfidsme/247-antiviral-treatment-creates-improvement-in-a-subset-of-cfscfidsme-patients">https://www.masscfids.org/research/recent-research/5-cfscfidsme/247-antiviral-treatment-creates-improvement-in-a-subset-of-cfscfidsme-patients</a>

A study on the use of antiviral agents in the treatment of ME/CFS for certain patients was published by Dr. A. Martin Lerner, <em >et al</em>. in <em >Virus Adaptation and Treatment</em> 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 <em >Borrelia</em> <em >burgdorferi</em>(i.e., the major form of Lyme Disease), <em >Babesia microti</em>,<em > </em><em >Anaplasma phagocytophila</em>, 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 <em >et al</em>.) 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."

<strong >WARNING:</strong><em > 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.</em>

<strong >Editorial note:</strong> It appears that this study pertains to those CFS patients who have<em > </em><em >known</em> non-latent herpes viral infections and who can tolerate antiviral and other treatments (Group B) for at least two years.

Additionally, this study was<em > </em><em >not</em> 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.<em > However, the improvement in the Group A subjects was quite robust—a greater improvement than normally seen in many CFS patients.</em>

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 <a href="https://www.masscfids.org/component/weblinks/weblink/47-me-cfs-web-links/77-subset-directed-antiviral-treatment-of-142-herpesvirus-patients-with-chronic-fatigue-syndrome?Itemid=267&task=weblink.go" target="blank" title="The Treatment Center for CFS. This link opens in a new window." ><strong >Treatment</strong></a><a href="https://www.masscfids.org/component/weblinks/weblink/47-me-cfs-web-links/77-subset-directed-antiviral-treatment-of-142-herpesvirus-patients-with-chronic-fatigue-syndrome?Itemid=267&task=weblink.go" target="blank" title="The Treatment Center for CFS. This link opens in a new window." > </a><a href="https://www.masscfids.org/component/weblinks/weblink/47-me-cfs-web-links/77-subset-directed-antiviral-treatment-of-142-herpesvirus-patients-with-chronic-fatigue-syndrome?Itemid=267&task=weblink.go" target="_blank" title="The Treatment Center for CFS. This link opens in a new window." ><strong >Center for CFS</strong></a>, 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.

From: 'Valacyclovir in the treatment of post viral fatigue syndrome' http://www.drmyhill.co.uk/wiki/Valacyclovir_in_the_treatment_of_post_viral_fatigue_syndrome</p>

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<p >Chronic Epstein-Barr virus and other human herpes viruses may be a cause of long term symptoms in chronic fatigue syndrome. Treatment with anti-virals is effective in restoring sufferers to health.<b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.dovepress.com/getfile.php?fileID=7766" >Lerner, A. Martin et al (2010). "An update on the management of glandular fever (infectious mononucleosis) and its sequelae caused by Epstein–Barr virus (HHV-4): new and emerging treatment strategies." <i>Virus adaptation and treatment</i> 2: 135 – 145.</a></b></p>

<h2 >Dr Lerner</h2>

<p >The Dr. A. Martin Lerner CFS Foundation was formed to ensure that Dr. Lerner’s past 25 years of CFS-specific work was recognised, and communicated to CFS sufferers and physicians worldwide. The Foundation, established in early 2007, conducted a major study, which documented his successful treatment. Investigators who had extensive backgrounds in information technology, application development, business processes and communications conducted the 18-month study. Data from the study produced significant findings and yielded peer-reviewed medical publications, global interest and presentations. The Foundation officially closed July 2011 after achieving its projected objectives. Dr. Lerner's work in CFS continues. Please see this website which provides very useful detail - <b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.treatmentcenterforcfs.com/CFS_Foundation/" >Dr Lerner CFS Foundation</a></b></p>

<h2 >Abstract of Dr Lerner's paper</h2>

<p >Please see <b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="https://www.dovepress.com/an-update-on-the-management-of-glandular-fever-infectious-mononucleosi-peer-reviewed-article-VAAT" >"An update on the management of glandular fever (infectious mononucleosis) and its sequelae caused by Epstein–Barr virus (HHV-4): new and emerging treatment strategies"</a></b>

“<b>Purpose</b>: Beginning in 1993 at a single chronic fatigue syndrome (CFS) treatment center, we began studies that demonstrate Epstein–Barr virus (EBV) nonpermissive replication. In the most recent study performed, EBV nonpermissive replication is the cause of 28.3% of 106 consecutive CFS cases, and is etiologic with human cytomegalovirus (HCMV) and/or human herpes virus 6 (HHV-6) as a coinfection in an additional 52.8% of CFS cases. Therefore, EBV is causally involved in 81% of cases of CFS. Further, EBV CFS is effectively treated with long-term valacyclovir. Coinfection HCMV and HHV-6 CFS requires valganciclovir with valacyclovir."

<b>Patients and results</b>: The validated Energy Index Point Score® (EIPS® ) (Please see here ' <b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html" >EIPS</a></b> and below) monitors severity of CFS illness and its recovery. A specific CFS diagnostic panel identifies EBV CFS subsets. Four separate EBV CFS therapeutic studies of several hundred CFS patients describe valacyclovir administration and long-term patient recovery. With valacyclovir, serum EBV titers (EBV, early antigen (diffuse); EBV, viral capsid antigen, immunoglobulin M); 24-hour electrocardiography Holter monitors; and cardiac dynamic studies improve.

<b>Conclusion</b>: Nonpermissive EBV infection is causal in a significant proportion of CFS cases. EBV CFS is safely and effectively treated with long-term valacyclovir.”</p>

<h2 >Post Viral CFS may be due to low level chronic infection with Epstein-Barr Virus or "Mono" and others</h2>

<p >Martin Lerner has been working since 1993 on the idea that many cases of chronic fatigue syndrome result from longstanding infection with herpes viruses. The most important of these is Epstein-Barr virus (glandular fever or “mono”), but he has also identified two other herpes viruses as a particular problem in CFS/ME sufferers, namely cytomegalovirus and human herpes virus 6 (HHV-6). He demonstrates that in CFS/MEs there is non-permissive replication of virus. By this he means that there is sufficient viral replication going on in cells to disrupt cellular metabolism and cause cell death, but not sufficient to result in a positive DNA polymerase test, or antigenemia with antibody response. This means that such chronic infection will not be picked up by standard virology tests including antibodies and PCR. This very much echoes the ideas of Dr John Chia, who believes that many patients with chronic fatigue syndrome have ongoing viral infection which he describes as being “under the radar”, i.e. the immune system does not seem to see it. This is a little bit like HIV infection, where the virus tucks itself away inside cells, again so the immune system cannot “see” it. See <b><a href="http://www.drmyhill.co.uk/wiki/Oxymatrine_in_the_treatment_of_post_viral_fatigue" title="Oxymatrine in the treatment of post viral fatigue" >Oxymatrine in the treatment of post viral fatigue</a></b></p>

<h2 >Four studies showing that long term antivirals work</h2>

<p >Lerner looked at 106 consecutive cases of CFS/ME and found the presence of Epstein-Barr virus alone in 28% of these cases, in a further 53% of cases there was Epstein-Barr virus combined with cytomegalovirus, or HHV-6, which means that Epstein-Barr virus was involved in a total of 81% of patients with CFS/ME.

Most importantly, he went on to show that the Epstein-Barr virus could be treated effectively with an anti-viral valacyclovir and if there is co-infection with HCMV or HH-V-6 then some trials used valganciclovir in addition to the valacyclovir. He reported good responses to treatment. Indeed, he reviewed four studies involving several hundred patients with CFS using this combination of drugs and reported long term patient recovery. This recovery was determined in terms of clinical improvement, improvement in serum EBV titres (with regard to EBV virus, early antigen (diffuse), EBV viral capsid antigen and immoglobulin-M), together with improvements in 24 hour ECG and improvement in cardiac dynamic studies.</p>

<h2 >So what are the criteria for initiating treatment with Valacyclovir and possibly also Valganciclovir?</h2>

<p >A high proportion of patients that I see with CFS/ME do very well on the standard regimes of diet, nutritional supplements, sleep, pacing, attention to mitochondrial dysfunction, thyroid and adrenal support. However, there is always a hard core of patients who, despite sticking to these regimes well, do not see the deserved improvements. These are the people for whom these drugs may be helpful. So what are the criteria?

An obvious initiating infection with Epstein-Barr virus and positive IgM tests and/or positive IgG tests shows that there has been exposure to Epstein-Barr in the past and there could well be ongoing non-permissive replication now.

If there is no IgG antibody to Epstein-Barr virus, then this indicates no prior infection and therefore no indication of the treatment.

Lerner also looks at other antigens, namely D (diffuse) and R (restricted) components of EVB early antigen (EA) to indicate non-permissive incomplete virus replication. I am not sure if this test is available and I will make enquiries. However, my view at this stage would be that anybody with a viral trigger, positive IgM and/or IgG antibodies and who has not responded to the above regime would be a candidate for a trial of Valacyclovir.

We then have to ask the question if there is any evidence of cytomegalovirus (CMV) or HHV-6 infection, which would require additional treatment with Valganciclovir. From his paper it does not appear that these two viruses are candidates for non-permissive replication and therefore it should be straightforward to diagnose these simply by doing IgG antibody studies for these two viruses.

As part of his work up, Lerner also does 24 hour ECG monitoring and the abnormalities he most commonly picks up are oscillating T-wave flats and inversions, together with tachycardia at rest. My guess here is that these cardiac abnormalities reflect mitochondrial dysfunction and poor energy delivery to the heart because of the cellular disruption resulting from chronic viral infection.

So to diagnose Epstein-Barr virus subset chronic fatigue syndrome requires the following positives:</p>

<ul >

<li >International criteria for CFS</li>

<li >24-hour ECG monitor, oscillating T-wave flats and inversions</li>

<li >Tachycardia at rest</li>

<li >Epstein-Barr virus, early antigen (diffuse) total antibody with or without viral capsid antigen IgM</li>

<li >Negative tests for acute co-infections such as Mycoplasma pneumoniae, Babesia microti, borrelia burgdorferi, Anaplasma phagocytophilic IgG, antistreptolysin O.</li>

</ul>

<h2 >Monitoring treatment</h2>

<p >Lerner monitors treatment using the Energy Index Point Score (EIPS - see table below) with patients visiting every four to six weeks and the score determined by agreement of patient and physician. A score of 0 – 5 is diagnostic of chronic fatigue syndrome, a score of 6 – 10 indicates patients no longer have CFS. This means a small change in the EIPS value is very clinically significant with an effect size of 0.8 being large. A CFS patient is considered to be a responder if the effect size is more than 1, or a non-responder if the effect size is less than 1 after one year of anti-viral therapy.</p>

<h2 >Treatment regimes</h2>

<p >Valacyclovir was prescribed at a dose rate of 1 gram every six hours (i.e. 4 grams per day). For overweight patients the dose was 1.5 grams every six hours and for small patients correspondingly less. A “Herxsheimer” response with worsening of symptoms and a worsening score continuing for two to six weeks after treatment began was a good prognostic omen. Increasing energy score and decreasing symptoms were apparent at the fifth to sixth month of continuing Valacyclovir. As the drug was continued, EIPS values of 7 and above were achieved and activities of normal living restored.

The above clinical improvements were accompanied by improvement in ECG monitoring.

Alcohol is forbidden. Exercise too early in CFS recovery may worsen CFS and so exercise was prohibited until EIPS 7 was achieved. At EIPS 8, light exercise is cautiously begun. The Valacyclovir dose is then decreased to 1 gram two times a day, continued for 6 to 12 weeks and then stopped. Approximately 20% of EBV CFS patients required maintenance Valacyclovir to prevent clinical relapse.

<b>The Energy Index Point Score</b></p>

<tr>

<th colspan="2"><b>CHRONIC FATIGUE SYNDROME</b></th>

</tr>

<tr>

<td>Bed-ridden, up to bathroom only</td>

</tr>

<tr>

<td>Out of bed 30-60 minutes a day (sitting in chair is out of bed)</td>

</tr>

<tr>

<td>Out of bed sitting, standing, walking 1-2 hours per day</td>

</tr>

<tr>

<td>Out of bed sitting, standing, walking 2-4 hours per day</td>

</tr>

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<td>Out of bed sitting, standing, walking 4-6 hours per day</td>

</tr>

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<td>Perform with difficulty sedentary job 40 hours a week, daily naps</td>

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<th colspan="2"><b>RECOVERY</b></th>

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<tr>

<td>Daily naps in bed, may maintain a 40 hour sedentary work week plus light,

<p >limited housekeeping and/or social activities</p>

</td>

</tr>

<tr>

<td>No naps in bed. Up 7.00am to 9.00pm. Able to work a sedentary job plus

<p >light housekeeping</p>

</td>

</tr>

<tr>

<td>Full sedentary workweek, no naps, some social activities plus light exercise</td>

</tr>

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<td>Same as 8 above plus exercise approximately ½ to 2/3 normal without excessive

<p >fatigue, awakens next morning refreshed</p>

</td>

</tr>

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<td>Normal</td>

</tr>

</tbody></table>

<p >

Lerner goes on to report on the outcomes of four studies using these regimes. The four studies involved 19, 11, 27 and 106 patients which give similarly good results. Energy consumption and physical activity both improved as did heart symptoms and ECG abnormalities.

In these groups between 10% and 25% required full dosage long term therapy to maintain an EIPS value of more than 7. Valacyclovir has been continued for seven years in patients without ill effects. He comments that patients appreciate the good prognostic omen of an early Herxsheimer response.

<b>Study 1:</b>“A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function.” Drugs Today. 2002;38(8):549–561 Lerner AM, Beqaj SH, Deeter RG, et al. Please see <b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.ncbi.nlm.nih.gov/pubmed/12582420" >“A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function.”</a></b>. This study concluded favourably on the use of valacyclovir in CFS patients.

<b>Study 2:</b> “A small randomized placebo controlled trial of the use of antiviral therapy for patients with chronic fatigue syndrome.” Clin Infect Dis. 2004;32:1657–1658 Lerner AM, Zervos M, Chang CH, et al. Please see <b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://cid.oxfordjournals.org/content/32/11/1657.full" >“A small randomized placebo controlled trial of the use of antiviral therapy for patients with chronic fatigue syndrome.”</a></b> Patients initially were treated with just valacyclovir, but after six months those patients with co-infection were also given intravenous ganciclovir. There is a slight confusion here because Lerner goes on to say that both valacyclovir and valganciclovir were necessary for these patients to recover without specifying when the valganciclovir was administered.

<b>Study 3:</b> “Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome: thirty-six months follow-up.” In Vivo. 2007 Sep-Oct;21(5):707-13. Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. Please see <b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.ncbi.nlm.nih.gov/pubmed/18019402" >“Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome: thirty-six months follow-up.”</a></b> Good results were achieved with just valacyclovir.

<b>Study 4:</b> "Subset-directed antiviral treatment of 142 herpesvirus patients with chronic fatigue syndrome." Virus Adapt Treat. 2010;2:1–11. Lerner AM, Beqaj S, Fitzgerald JT, et al. Please see <b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.treatmentcenterforcfs.com/pdf/Dr.A.MartinLerner-Subset-directed-antiviral-treatment-of-142-herpesvirus-patients-with-CFS.pdf" >"Subset-directed antiviral treatment of 142 herpesvirus patients with chronic fatigue syndrome." </a></b>Again good results were achieved with just valacyclovir.</p>

<h2 >Conclusions</h2>

<p >These regimes work well. Valacyclovir long term used to be an expensive therapy. Lerner’s costing for valacyclovir tablets for 1 gram every six hours was of the order 25-30 thousand dollars per year. The cost has recently come down a lot as the patent has run out. I can now obtain Valciclovir 500mg x 42 for £22.20, so around £133.20 for a month’s course. There is no doubt that valacyclovir is a very useful treatment for patients and my recommendation at present is to reserve this for those who do not respond to the standard nutritional work ups.</p>

<h2 >Related Article</h2>

<ul >

<li ><b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://drmyhill.co.uk/wiki/Chronic_viral_presence_in_CFS/ME" >Chronic Viral Presence in CFS/ME</a></b></li>

<li ><b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.doctormyhill.co.uk/wiki/Oxymatrine_in_the_treatment_of_post_viral_fatigue" >Oxymatrine in the treatment of post-viral-fatigue</a></b></li>

</ul>

<h2 >External Links</h2>

<ul >

<li ><b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.treatmentcenterforcfs.com/CFS_Foundation/" >Dr Lerner CFS Foundation</a></b></li>

<li ><b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.treatmentcenterforcfs.com/cfs_publications/index.html" >Complete list of Dr Lerner's published CFS papers and links</a></b></li>

<li ><b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.treatmentcenterforcfs.com/energy_index_score/index.html" >EIPS Index Score</a></b></li>

<li ><b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.dovepress.com/getfile.php?fileID=7766" >Lerner, A. Martin et al (2010). "An update on the management of glandular fever (infectious mononucleosis) and its sequelae caused by Epstein–Barr virus (HHV-4): new and emerging treatment strategies." <i>Virus adaptation and treatment</i> 2: 135 – 145.</a></b></li>

<li ><b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.ncbi.nlm.nih.gov/pubmed/12582420" >“A six-month trial of valacyclovir in the Epstein-Barr virus subset of chronic fatigue syndrome: improvement in left ventricular function.”</a></b></li>

<li ><b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://cid.oxfordjournals.org/content/32/11/1657.full" >“A small randomized placebo controlled trial of the use of antiviral therapy for patients with chronic fatigue syndrome.”</a></b></li>

<li ><b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.ncbi.nlm.nih.gov/pubmed/18019402" >“Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome: thirty-six months follow-up.”</a></b></li>

<li ><b><a target="_blank" rel="nofollow noreferrer noopener" class="external text" href="http://www.treatmentcenterforcfs.com/pdf/Dr.A.MartinLerner-Subset-directed-antiviral-treatment-of-142-herpesvirus-patients-with-CFS.pdf" >"Subset-directed antiviral treatment of 142 herpesvirus patients with chronic fatigue syndrome."</a></b></li>

</ul>

</td>

</tr>

</table>