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Stanford Antiviral Chronic Fatigue Syndrome Trial Promises Hope, But More Study Needed

111512_0224_Valganicicl1.jpg


by Cort Johnson

Before XMRV was Kogelnik/Montoya…the 2006 unblinded Kogelnik/Montoya study, finding that 6 months of Valcyte use returned 75% of participants to full health, hit the community like a lightning bolt. Yes, the study was very small (12 people) and it was unblinded, but the stories of recovery were so dramatic that it was hard to imagine they hadn't hit gold. All that was left, it seemed, was to document the progress with a more rigorous, placebo-controlled study that appeared to be under way.
"These preliminary clinical and laboratory observations merit additional studies to establish whether this clinical response is mediated by an antiviral effect of the drug, indirectly via immunomodulation or by placebo effect." (Kogelnik et al, 2006)

Six years later that study has still not shown up. This latest study by Montoya, which did not involve controls, is simply a retrospective analysis which examined the effect of Valganciclovir treatment on 61 patients treated at the Stanford clinic from 2004-2009 using a chart analysis.
Heavily 'infected' patients....


All patients had above normal HHV6 (>1:320), EBV VCA (1:640), EBV VCA (1:640) and EBV EA (1:160) IgG titers. The early EBV antibodies (EBV NA IGG), that Dr. Lerner and others believe are tied to aborted but simmering infections in ME/CFS, were also measured. Note that because healthy people can have similarly high titers, none of these titers are considered diagnostic of an active infection by most practitioners in the medical community.

Montoya has proposed, however, that high titers in the presence of certain symptoms are suggestive of an active infection. The authors noted that, while high titers can be found in healthy people, most healthy people have quite low herpesvirus titers while higher titers are commonly found in people with chronic fatigue syndrome. Something must be pushing those herpesvirus antibody titers higher in ME/CFS and, of course, an active herpesvirus infection is the first thing that comes to mind.

A patient was deemed a responder if self reports of cognitive and physical functioning increased by 30% or more at some point in treatment. The average patient age was 47 and the average length of illness was a hearty 10 years. The average treatment period was about 6 months - much shorter than recommended by Dr. Lerner.
Results


Almost 60% of patients responded physically and fully 80% responded cognitively - a nice response. As a group, patients rose from an average of 34/100 to 53/100 physically (56% jump) and from 43/100 to 66/100 cognitively (50% jump). (Unfortunately from the way the study was written the percentage increase could have been interpreted as 19% and 23%. Thanks to Tom Kindlon for pointing this out). Put another way, the patients jumped from being a third of normal physically to about half normal and from about 40% of normal cognitively to two-thirds normal.

This was blunted to some extent by the fact that only the highest data point, not an average, was used to assess effects. That means we know that, at least at one point in their treatment, 80% of the participants reported that they were at least 50% better cognitively, and almost 60% were improved physically by at least 50%, but we don't know how long the effect lasted.

Teasing out the responders indicated that they improved an average of 34 and 37% respectively.

A look at the charts included in the paper indicated that there were some dramatic improvements. A couple of people went from a score of about 20-30 to 80-100 on physical functioning -meaning they were effectively well. Several others experienced dramatic improvements going from 0-20 to 50-60. (Two unfortunate people went from around 20 to less than 10). It was fairly easy to find 30-40 point gains - which equate to major improvements in functionality - but many people made smaller gains.

The most significant result may have been the quite strong finding (P<.0002) that longer treatment durations (7.4 months on average) resulted in improved benefits relative to shorter treatment durations (5.5 months). Long antiviral treatment regimes are a key feature of Dr. Lerner's antiviral treatment protocol.

The authors called the findings 'clinically striking' when placed in context of how difficult it was to treat ME/CFS, and indeed most doctors would probably be very happy to see responses like this in their patients. (Their patients would be happy as well :))
Antibodies Strike Out


111512_0224_Valganicicl2.png
The antibody results indicated how much researchers still have to learn. The researchers thought that higher antibodies would be indicative of poorer health, but they were not, and antibody levels did not drop significantly more in the responders than in the non-responders. (There was a 'trend' toward better response in patients with high baseline antibodies). Whatever the effects of the trial, it did not appear to happen at the antibody level.

Potentially obscuring the antibody results, however, was the possibility that some patients may have hypogammaglobulemia (low B-cell and antibody levels), while others may have overly strong antibody responses, and bigger studies would be needed to tease out these factors. It's possible that too many complicating factors were present for a finding of statistical significance to show up in a study of this size.

Figuring out why some people improve during antiviral treatment while others do not has been a key goal for Montoya, and he's reportedly been plowing through immune findings to see if he can pick up measurements that change significantly as people get well. Finding that would give him and the ME/CFS research community a strong biomarker to concentrate on. (Dr. Kogelnik is looking at patients for this as well). This was not that study, however, and hopefully that paper will appear in the future.
Conclusion


111512_0224_Valganicicl3.jpg
Valcyte has not gone the way of XMRV. As with XMRV, the promise of an early study - in this case the 2006 unblinded one with its remarkable success rate - did not hold up, but this study was positive and many patients did improve - in many cases, it appears, significantly.

The study, though, was underpowered in many ways; it was retrospective, it was not placebo-controlled, and patients' self-reports were rudimentary to say the least - they appear to have simply rated themselves on a scale from 0-100 on their physical and cognitive functioning and only the highest scores were used. The most intriguing result was the increased likelihood of benefit in patients with longer treatment duration - a key facet of Dr. Lerner's program.

Without a blinded control group, however, all the results can be challenged - it can be argued that the responders were simply due to placebo, the benefit was transient, and the increased benefit with duration was simply an indicator that time in combination with placebo really does heal somewhat with ME/CFS.

The road to understanding the role that pathogens play in ME/CFS has been long and crooked. With all the interest in antivirals, it's remarkable that we still do not have a single well-designed, rigorously controlled ME/CFS antiviral treatment trial. Every study, from Dr. Lerner's trials to Dr. Montoya's two studies, has had enough design flaws for skeptics to be able to discount the findings. There's still a great deal of work to be done to figure out how and why antivirals are working when they do work in this disorder.

One such study was underway. In Dec 2010 we were informed that two papers from Dr. Montoya's placebo-controlled, doubled blinded study - which involved extensive immune testing, exercise testing, etc - were in process. (We were also informed that the study we've just looked at would be published 'soon' :)). At a conference that year, Dr. Montoya reported that he was on the track of several immune biomarkers (IL-5, IL17F, ENA78, EOTAXN, IP10) that improved during treatment. He also reported that an early antigen marker usually associated with cancer may be a biomarker for this group.

The big EBV/HHV6 study is still to come…
View the Post on the Blog
 
it would be interesting to see a study where they also test nk and cd8 function in those patients as well as compare antivirals with combo of antiviral and immune mod with a placebo treatment and seeing the before and after results of viral titres , nk and cd8 function. Im suprised further sudies havent been done but then alot also depends on drug companies and patents for new indications etc.

cheers!!!
 
Given that there was no significant difference in serology between responders and non-responders, (either baseline or changes), it seems to me that any improvement,must have been due to other factors, perhaps due to other immune system changes as a result of reducing the level of infection, or side effects of the drug itself.
 
Thanks for another great piece, Cort: its thorough, fair and a little depressing.

It's extraordinary that six years after a highly promising finding we still don't have a decent placebo-controlled study to properly evaluate the treatment.

There is a separate thread on this study, including some excellent analysis by Dolphin. This highlights issues raised by the study itself that they used peak scores - which may have come a long time after treatment was discontinued, suggesting the treatment may not be related to the improvement. Worse, the use of peak scores means that any patients with fluctuating scores will appear to improve since the highest peak will be recorded, while troughs will be ignored.

Montoya['s] reportedly been plowing through immune findings to see if he can pick up measurements that change significantly as people get well
That sounds alarmingly like data mining: your main hypothesis (high antibody titres) flops so you search through data for until you find an association that looks significant. Except if you search through enough possibilities, you'll find several 'significant' associations just by chance. Surely, after so many years working on this, if there was a genuine strong association then Montoya would have already found it?

Maybe one of Montoya's oft-promised studies will finally materialise and lift my gloom.
 
Cort, I think you are making a mistake when you say:

The most significant result may have been the quite strong finding (P<.0002) that longer treatment durations (7.4 months on average) resulted in improved benefits relative to shorter treatment durations (5.5 months). Long antiviral treatment regimes are a key feature of Dr. Lerner's antiviral treatment protocol.


Here are two possible source for this "longer treatment means bigger improvements" result:

Trough vs Peak differences will get bigger (on average) for longer study duration, if you are reporting only on peak results. This result could easily be a direct effect of the reporting design, where only peak results are reported. Basically, the longer duration gives more time for a randomly higher peak to be seen and reported.

Placebo effects get stronger with duration. This result (especially when paired with the lack of immune changes) suggests a psychological/placebo effect is being seen. This is bad news, not good news.

Other random points:
I think it's pretty clear that this research has failed, or is in deep-deep trouble.
Why? Because successful research moves forward. If a researcher does a successful intervention study with 12 people and no placebo, then the next experiment will be an intervention study with more than 12 people and/or a placebo group, and almost certainly both.

This research program took several steps backward. First: The earlier study was intervention, and the later study was population based, that's a HUGE step backward. Second: While it is ok for the first study is a research program to be no-placebo, once you have good results from that, the follow on studies should have a control group of some kind.

Also, using "peak scores" results for a disease like ME/CFS where patients are known to go through better and worse phases, is a major design flaw. It completely negates any results (my opinion, of course). What possible motivation could there be for a design like that, in a disease like this?

Remember, the drug Drs. Kogelnik and Montoya are testing is produced by some Pharma company. That company would love to sell it to millions of ME/CFS sufferers. So there should be plenty of money available to fund a follow-on study to expand the use of a drug. So whatever the problem, it's not a lack of funding.

Joshua (not Jay) Levy
 
Cort, I think you are making a mistake when you say:

The most significant result may have been the quite strong finding (P<.0002) that longer treatment durations (7.4 months on average) resulted in improved benefits relative to shorter treatment durations (5.5 months). Long antiviral treatment regimes are a key feature of Dr. Lerner's antiviral treatment protocol.


Here are two possible source for this "longer treatment means bigger improvements" result:

Trough vs Peak differences will get bigger (on average) for longer study duration, if you are reporting only on peak results. This result could easily be a direct effect of the reporting design, where only peak results are reported. Basically, the longer duration gives more time for a randomly higher peak to be seen and reported.

Placebo effects get stronger with duration. This result (especially when paired with the lack of immune changes) suggests a psychological/placebo effect is being seen. This is bad news, not good news.

Other random points:
I think it's pretty clear that this research has failed, or is in deep-deep trouble.
Why? Because successful research moves forward. If a researcher does a successful intervention study with 12 people and no placebo, then the next experiment will be an intervention study with more than 12 people and/or a placebo group, and almost certainly both.

This research program took several steps backward. First: The earlier study was intervention, and the later study was population based, that's a HUGE step backward. Second: While it is ok for the first study is a research program to be no-placebo, once you have good results from that, the follow on studies should have a control group of some kind.

Also, using "peak scores" results for a disease like ME/CFS where patients are known to go through better and worse phases, is a major design flaw. It completely negates any results (my opinion, of course). What possible motivation could there be for a design like that, in a disease like this?

Remember, the drug Drs. Kogelnik and Montoya are testing is produced by some Pharma company. That company would love to sell it to millions of ME/CFS sufferers. So there should be plenty of money available to fund a follow-on study to expand the use of a drug. So whatever the problem, it's not a lack of funding.

Joshua (not Jay) Levy
"Placebo effects get stronger with duration. This result (especially when paired with the lack of immune changes) suggests a psychological/placebo effect is being seen. This is bad news, not good news."

False. Absolutely backwards. Look at the research on placebo vs active drug in conditions like depression that respond well to placebo. Placebo effects are mediated by expectations (and neurologically by release of endogenous opioids and other rewarding brain chemicals), and they are at their greatest strength early in the course of a treatment when the treatment is novel. (i.e. after you've been doing something for six months, and nothing has changed, its hard to particularly get your hopes up and change your behavior then..)

ME/CFS has a lower placebo response rate than most other medical conditions. It is very, very difficult to treat by any means.

I think "regression to the mean" is a more significant problem than placebo in ME/CFS treatment effects. This is because the illness has fluctuating symptoms. Patients may start a new therapy when they are feeling really desperate, then they "improve" over time but are really just going back to their average level of sickness. At some point they hit a wall again and the cycle repeats. This behavior pattern is what I see with a lot of the patient reports on forums. Patients are very prone to changing things when they are in a relapse, and not prone to change things when they are in remission. It's a problem.
 
I wrote this:
"Placebo effects get stronger with duration. This result (especially when paired with the lack of immune changes) suggests a psychological/placebo effect is being seen. This is bad news, not good news."

False. Absolutely backwards. Look at the research on placebo vs active drug in conditions like depression that respond well to placebo. Placebo effects are mediated by expectations (and neurologically by release of endogenous opioids and other rewarding brain chemicals), and they are at their greatest strength early in the course of a treatment when the treatment is novel. (i.e. after you've been doing something for six months, and nothing has changed, its hard to particularly get your hopes up and change your behavior then..)

i wouldnt think placebo effects would last. For what its worth my t cells improved with antivirals so placebo wouldnt affect that?

Well, there are different placebo effects based on the psychology of the patients involved. I'm sure that some patients have the effect Satoshikasumi describes, but others have a commitment based effect. The longer and harder they work at something, the more committed to it they become (so a stronger placebo effect). Some people call it "no pain, no gain". The more work, the bigger the expected result.

But since the research are reporting only peak response (not average response, or longest lasting response, or more recent response), they would mis-report both placebo effects.

Heapsreal: this is why it doesn't matter how long the effect lasts. If some thinks it worked great the day after, then that will be the peak response, and the only thing reported, even if they later come to believe it did nothing.

Cort, I had the following question: how did they report bad side effects? Did they report them? Did they provide more details than the PACE report, or less? Reporting peak good response sounds highly biased to me, so I'm a little interested in how they counted bad effects, although with no control group, it would be hard to tell how important these would be.

Joshua (not Jay) Levy

.
 
Thanks for another great piece, Cort: its thorough, fair and a little depressing.

It's extraordinary that six years after a highly promising finding we still don't have a decent placebo-controlled study to properly evaluate the treatment.

There is a separate thread on this study, including some excellent analysis by Dolphin. This highlights issues raised by the study itself that they used peak scores - which may have come a long time after treatment was discontinued, suggesting the treatment may not be related to the improvement. Worse, the use of peak scores means that any patients with fluctuating scores will appear to improve since the highest peak will be recorded, while troughs will be ignored.

Montoya['s] reportedly been plowing through immune findings to see if he can pick up measurements that change significantly as people get well
That sounds alarmingly like data mining: your main hypothesis (high antibody titres) flops so you search through data for until you find an association that looks significant. Except if you search through enough possibilities, you'll find several 'significant' associations just by chance. Surely, after so many years working on this, if there was a genuine strong association then Montoya would have already found it?

Maybe one of Montoya's oft-promised studies will finally materialise and lift my gloom.
Thanks Simon. It rather reminds me of the Ampligen last 'mining' episode. I can't imagine why - other than funding - a properly blinded study has not been forthcoming with acceptable representation of data before now.

Cort's piece is well-balanced - thankfully. When this latest was published back in October it was to the casual observer (i.e. me at the time) 'promising'. I do wish they wouldn't do this.

The headline and extract grabs the headline - the content gets assessed by others in the know - and then the 'hope' gets screwed.

I know the answer - but I can't help asking - is it only ME/CFS studies that do this?

Why-oh-why aren't these original findings built on properly using the funds that are available instead of them phaffing around like this.

It will only get cited by someone claiming it represents legitimacy only for them to be shot down by those who understand what this latest and former one means.

Depressing? Yes. Yet another small original study that I can only file away as 'interesting' along with several hundred others - never to see the light of day. [Sigh]
 
I wrote this:
"Placebo effects get stronger with duration. This result (especially when paired with the lack of immune changes) suggests a psychological/placebo effect is being seen. This is bad news, not good news."

False. Absolutely backwards. Look at the research on placebo vs active drug in conditions like depression that respond well to placebo. Placebo effects are mediated by expectations (and neurologically by release of endogenous opioids and other rewarding brain chemicals), and they are at their greatest strength early in the course of a treatment when the treatment is novel. (i.e. after you've been doing something for six months, and nothing has changed, its hard to particularly get your hopes up and change your behavior then..)

i wouldnt think placebo effects would last. For what its worth my t cells improved with antivirals so placebo wouldnt affect that?

Well, there are different placebo effects based on the psychology of the patients involved. I'm sure that some patients have the effect Satoshikasumi describes, but others have a commitment based effect. The longer and harder they work at something, the more committed to it they become (so a stronger placebo effect). Some people call it "no pain, no gain". The more work, the bigger the expected result.

But since the research are reporting only peak response (not average response, or longest lasting response, or more recent response), they would mis-report both placebo effects.

Heapsreal: this is why it doesn't matter how long the effect lasts. If some thinks it worked great the day after, then that will be the peak response, and the only thing reported, even if they later come to believe it did nothing.

Cort, I had the following question: how did they report bad side effects? Did they report them? Did they provide more details than the PACE report, or less? Reporting peak good response sounds highly biased to me, so I'm a little interested in how they counted bad effects, although with no control group, it would be hard to tell how important these would be.

Joshua (not Jay) Levy

.
"Well, there are different placebo effects based on the psychology of the patients involved. I’m sure that some patients have the effect Satoshikasumi describes, but others have a commitment based effect. The longer and harder they work at something, the more committed to it they become (so a stronger placebo effect). Some people call it "no pain, no gain". The more work, the bigger the expected result."

This argument contradicts the lived experience of every patient with bona-fide ME/CFS and requires the assumption that post-exertional malaise is not a real, biological phenomenon. It also contradicts the research on post-exertional malaise from the Pacific Fatigue Lab, the research on the long-term effects of CBT/GET that has come out of the Netherlands and other countries that had committed to a psychological approach, research on the extent of the disability in ME/CFS, research on the long-term outcome and recovery rate in ME/CFS, and the only study to estimate the placebo effect in ME/CFS.

I can't vouch for every patient on these forums, but my commitment, belief in a better future, optimism, trust in my doctor and the treatments; none of this was enough to improve my illness or allow me to live a normal life again.

Why didn't the placebos work for me in the first seven years of my illness? In the first two years, especially, I really believed I was going to get better soon.. I had that expectation and I thought I could figure out how to bring it under control, with the help of my doctor. In the first four years, I tried every permutation of exercise and psychotherapy known to man. I followed the official guidelines and tried long courses of biologically plausible treatments that made sense to me- drugs for orthostatic intolerance, sleep, stimulants, long-term antibiotics and antivirals, immune-boosting supplements. But none of this worked. Doing nothing didn't work either. I just kept getting more disabled over time. My anaerobic threshold and VO2 max scores kept falling.

Why was Ampligen the only "placebo" to work for me? I took it after being ill for seven years. After taking it, my anaerobic threshold and VO2 max came up. My neuropsychological test performance, attention span, and performance IQ rose.
 
If it was all about placebo then many of us would have been cured by the mountains of supps from iherb. Different treatments work for different people some of the time mainly because its guess work in which treatment is right for which patient. I dont think we are going to get away from sub groups, until someone can nail down the specific sub group one is in, then its an educated guess when we treat cfs/me.

There seems to be some people refusing to believe people get better with certain treatments but the fact is that some are getting better with certain treatments and i dont think its placebo and many have testing which correlates with their improvement. Theres no silver bullet for everyone and there is probably a certain number that wont improve with any type of treatments but there are also many that do improve if they have the right treatment for them.

In the early days of myself using antivirals, i stopped and started them as i couldnt quite believe it was helping, i thought maybe i was just naturally improving, but whenever i stopped i got worse and up went my lymphocytes. Back on antivirals down went my lymphocytes and i started to feel better.

If someone tells me they got better on vitamin c then good on them, pointless saying that they done have cfs/me etc maybe vit c was that one thing they needed. theres no way to really diagnose cfs/me but we can treat abnormalities found in testing and its a load of crap when they say testing incfs is normal, that just means your doctor isnt doing the right tests.
 
Why was Ampligen the only "placebo" to work for me? I took it after being ill for seven years. After taking it, my anaerobic threshold and VO2 max came up. My neuropsychological test performance, attention span, and performance IQ rose.

I'm curious, between the time you took Ampligen and the increase in your V02 max, had you done much additional exercise (more than you would do before Ampligen) prior to the test?

I don't mean to undermine anything, but I think a great test of treatment response would be the V02 max threshold increasing, after treatment with zero activity increase in between. This kind of evidence would make any reasonable level of improvement significant in my opinion.
 
Thanks for another great piece, Cort: its thorough, fair and a little depressing.

It's extraordinary that six years after a highly promising finding we still don't have a decent placebo-controlled study to properly evaluate the treatment.

There is a separate thread on this study, including some excellent analysis by Dolphin. This highlights issues raised by the study itself that they used peak scores - which may have come a long time after treatment was discontinued, suggesting the treatment may not be related to the improvement. Worse, the use of peak scores means that any patients with fluctuating scores will appear to improve since the highest peak will be recorded, while troughs will be ignored.

That sounds alarmingly like data mining: your main hypothesis (high antibody titres) flops so you search through data for until you find an association that looks significant. Except if you search through enough possibilities, you'll find several 'significant' associations just by chance. Surely, after so many years working on this, if there was a genuine strong association then Montoya would have already found it?

Maybe one of Montoya's oft-promised studies will finally materialise and lift my gloom.

I think it was in December of 2010 that Montoya promised several studies and that this one would be the first and the placebo-controlled one was in that package..My guess is that there is a strong association in there but in fewer patients than expected and ferreting them out may be difficult..

Yes, the time element is troubling but even this paper took about a year longer, if I have my dates right, than expected. Its possible that Montoya is balancing many plates and its going to take longer than expected for that second study to come out. I imagine it will come out at some point and then we'll see. I would not expect something earth shattering but I wouldn't expect a total loss either - I would expect some good news for some patients...just not as many as hoped for.

Everybody who studies this disorder ends up concluding its much more complex than they originally thought.
 
"Well, there are different placebo effects based on the psychology of the patients involved. I’m sure that some patients have the effect Satoshikasumi describes, but others have a commitment based effect. The longer and harder they work at something, the more committed to it they become (so a stronger placebo effect). Some people call it "no pain, no gain". The more work, the bigger the expected result."

This argument contradicts the lived experience of every patient with bona-fide ME/CFS and requires the assumption that post-exertional malaise is not a real, biological phenomenon. It also contradicts the research on post-exertional malaise from the Pacific Fatigue Lab, the research on the long-term effects of CBT/GET that has come out of the Netherlands and other countries that had committed to a psychological approach, research on the extent of the disability in ME/CFS, research on the long-term outcome and recovery rate in ME/CFS, and the only study to estimate the placebo effect in ME/CFS.

I can't vouch for every patient on these forums, but my commitment, belief in a better future, optimism, trust in my doctor and the treatments; none of this was enough to improve my illness or allow me to live a normal life again.

Why didn't the placebos work for me in the first seven years of my illness? In the first two years, especially, I really believed I was going to get better soon.. I had that expectation and I thought I could figure out how to bring it under control, with the help of my doctor. In the first four years, I tried every permutation of exercise and psychotherapy known to man. I followed the official guidelines and tried long courses of biologically plausible treatments that made sense to me- drugs for orthostatic intolerance, sleep, stimulants, long-term antibiotics and antivirals, immune-boosting supplements. But none of this worked. Doing nothing didn't work either. I just kept getting more disabled over time. My anaerobic threshold and VO2 max scores kept falling.

Why was Ampligen the only "placebo" to work for me? I took it after being ill for seven years. After taking it, my anaerobic threshold and VO2 max came up. My neuropsychological test performance, attention span, and performance IQ rose.
I took tried everything I could think of and had faith in many but had no effects from any treatments - bad or good for the first 10 years. That said I think I can harness the effects of placebo now....that is, for some reason, being relaxed and at ease and hopeful really do help now....I can see how stress really discombulates my system....

Until a rigorously designed blinded, placebo-controlled trial pops up though the placebo effect, particularly in this illness with all its controversy, will probably be highly entertained by many, even if past research suggests not. ..

I think we should keep in mind that Montoya is not primarily a researcher - he's a physician/researcher - his publication list is not that long or involved....so while I agree that six years is alarming and it must indicate that the results have not been straightforward, it'll probably take him longer to publish than straight researchers.
 
Dr. Lerner's protocol is a good example of the need to isolate factors. Dr. Lerner uses long term antiviral therapy but he is also adamant that his patients practice rigorous pacing.......which could lead some to posit that its the pacing that's doing it not the antiviral therapy.

Should antiviral therapy be able to work without pacing?..Does it require pacing or does not pacing just make it more difficult and take it longer for the antivirals to work?

It would take a separate pacing/placebo arm and a separate pacing/antiviral arm to ferret this out and that would be difficult because of the long time frames for his therapy and THAT is another problem...Doing a study of a year long or more length...

This is unusual stuff for the medical community. Herpesvirus antivirals are almost always taken short term not long term and certainly not the really long term, high dose protocols that Dr. Lerner uses. Those protocols have lead to him being characterized by some in the medical community as a quack. I've gotten several recovery/recovering stories from patients of his who said they were vigorously warned away from Dr. Lerner by other doctors only to find that his protocol worked for them.

Dr. Lerner's and Dr. Montoya's view of ME/CFS and herpesvirus infections bucks trends.........

The significance value of the long term duration benefits was rather high which was encouraging....the measurement of effects, however, was really poor - relying on a vague assessment and then they picked the highest values - obviously because the averages did not work out....