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Learning CFS: the Lerner Antiviral Treatment Trial Succeeds

Discussion in 'Phoenix Rising Articles' started by Phoenix Rising Team, May 24, 2010.

  1. hvs

    hvs Senior Member

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    Fascinating possibilities. What kind of relationship does XMRV have to all the secondary infections? And Lerner argues that we have special kinds of infections from herpes-famly viruses.

    The good news is that I think we'll learn it all in time, thanks to the prostate cancer link and, one would expect, links to other illnesses that aren't "cfs".
     
  2. Cort

    Cort Phoenix Rising Founder

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    Honestly, I think you're missing the forest for the trees

    No scientific difference between groups - that's true; there was no statistically scientific difference in the outcomes between Group A and B and that's a good point. I don't think based on this paper, at least as far as I read it, Dr. Lerner can say he has statistical evidence indicating that you must treat other infections as well as herpes infections in order for your treatment of herpes infections to be effective.

    Big Difference in Treatment Overall - the main thrust of the paper, however, was not to demonstrate that fact - the main test of the paper was to demonstrate that long-term antiviral treatment in patients with nonpermissive herpesvirus infections is effective and statistically it accomplished that in spades. The p value for the difference between baseline EIPS and Last EPIS was <.00001 - which is n incredible outcome for a treatment trial. I imagine it was so robust as there was so much data in the study - there was no way that that finding was going to be due to chance.


    Again I think you're missing the forest for the trees. Yes, you can argue that one element of the scales could be described differently and decide because of that that the entire scale is no good but on the whole the scale presents a clear trajectory from poor health to better health, and it has been validated in a prior study against standard fatigue scales and it worked as well as they did or better.

    Nobody doubts that but the EIPS it's scale isn't a measure of fatigue - its a measure of functionality - which, of course, is CFS patients big goal. This study shows CFS patients going from spending most of their time in bed on average to spending most of their time out of bed and even working. It's much more than a fatigue scale.

    Most studies have not looked for nonpermissive infections ie the early antigens to EBV. In fact the few studies that have looked for them - have found them. Check out Lerner's previous studies as well as a Natelson study. Dr. Glaser also believes these kinds of infections play a key role in CFS. I believe he has a small study out.
    Yes, if its an the arbitrary choice - but then again, while the EIPS scale may not be perfect -its hardly arbitrary! You're suggesting that there is basically no difference between the points on the scale - I think most people who look at it can quickly see that there is a significant difference between the points on the scale; this isn't rocket science - you go from 0 bedridden to 3 in bed 22-24 hours a day to five in working. I think a lot of people think that the jump from 4 to 5 is way too high; you go from 18-24 hours a day to working a sedentary job with difficulty. But that only buttresses the study's findings because most of the people in the study took that leap - it is that leap which people are looking for. That is the fundamental finding of the study - the average patient went from mostly bedridden to working and with enough energy left over to engage in other activities. Questions about the individual scales can't hide that fact.

    You're suggesting that these people did not have CFS. That's an interesting argument we usually see associated with the Oxford definition and CBT - the patients got better on CBT because they did not have CFS. I don't think that applies here. Dr. Lerner is a well known CFS physician -most of the people who see him presumably know they have CFS - on average they've been going to doctors for 4-7 years as I remember. Again, Dr. Lerner is not testing for typical EBV infections; he is looking for a certain type of infection that few physicians look for.

    I think the patients in Dr. Lerner's practice would strongly disagree that they would naturally get better over time - as would CFS patients in any doctors office. Are you suggesting at the fourth year that people with EBV infections are suddenly prone to get better?

    I agree that placebo would be helpful altho I would note that the metanalysis study Wessely et al did found that rates of placebo in CFS were actually lower than normal. Lerner was working without federal funding (and honestly I wonder how you're going to do a year long placebo controlled trial).
     
  3. Gerwyn

    Gerwyn Guest

    The decision to call a change of 1 point on the(subjective) EIPS scale significant is entirely arbitary.

    All learners study shows from a scientific point of view that people with pathogenic infections are ill.They get better.No one knows whether they got better with the drugs or naturally.

    There is no placebo arm so no conclusion is scientifically possible.

    There is no statistically significant differences between any of the groups in outcomes.

    the point is that a value of 5 gives a diagnosis of CFS (entirely arbitary) and six does not.

    There is no clinical difference between 5 and 6.

    People with EBV infections are ill they do get better with or without antvirals.

    The assumption is that these patients had CFS in the first place.


    It is easy for a patient with EBV to make a fukuda definition of CFS.This is especially true if the doctor making the diagnosis believes the virus is cauative.

    He has not come anywhere near to demonstrating that that in this study.

    The study was carried out to test his hypothesis that EBV caused CFS.

    I really cant see how it could be called a successful study when there is no way of distinguishing cause from effect or any objective method of evaluating treatment efficacy.

    The EIFS scale has never been independently validated in any way. P values are not a measure of treatment effectiveness but merely whether the result has been achieved by chance or not

    According to Jasons studies the majority of patients diagnosed according to the Fukuda dont have the illness which has PEM as mandatory>Epstein Barr does not cause PEM.EBV does not cause the Neuroendocrine manifestations associated with CCC ME,cfs in the latent phase. There are only two kinds of EBV infection acute and chronic.The same applies for herpes
     
  4. cfs since 1998

    cfs since 1998 *****

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    http://www.forums.aboutmecfs.org/sh...reatment-in-EBV-Subset-CFS-36-months-followup
     
  5. Gerwyn

    Gerwyn Guest

  6. cfs since 1998

    cfs since 1998 *****

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    The study I posted above did have a placebo arm, the patients were diagnosed according to the CDC Fukuda criteria and had been sick more than 3 years. EBV is present in 90 percent of the population. I don't understand why you are saying "they only were sick with EBV, not CFS" when there is no such diagnosis as chronic EBV--that's what CFS used to be called.
     
  7. Gerwyn

    Gerwyn Guest


    what i am essentially saying is that correlation is not causation.he is labelling a subset with CFS assuming causation when chronic infection with epstein Barr is asymptomatic.If someone has glandular fever then they do have all the symptom of CFS.it does not mean they have the illness.the only way of distinguishing the two is PEM.Most physicians would test for Epstein Barr.if that is positive then that is an exclusion criteria for diagnosing CFS.So by definition active epstein Barr precludes a diagnosis of CFS even under Fukuda. i hope I was clearer that time.sorry for any confusion

    This is the relevant part of the FUKUDA paper


    Background
    The chronic fatigue syndrome is a clinically defined condition (1-4) characterized by severe disabling fatigue and a combination of symptoms that prominently features self-reported impairments in concentration and short-term memory, sleep disturbances, and musculoskeletal pain. Diagnosis of the chronic fatigue syndrome can be made only after alternative medical and psychiatric causes of chronic fatiguing illness have been excluded.

    If patients have Epstein Barr virus then they cannot receive a diagnosis of CFS because Epstein Barr is a recognised medical cause of fatigue.Thus a Epstein Barr subset of CFS is impossible.
     
  8. dannybex

    dannybex Senior Member

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    I'm with you Jackie. I know a half dozen people who have recovered -- and maybe 2-3 that are steadily improving -- and that gives me hope and inspiration. Dr. Klimas has also mentioned that she's had patients with 'COMPLETE RESOLUTION' -- so it does happen, albeit rarely. I think it would be a lot less rare if we all had access -- and funds -- to get the testing and treatments that have helped and are helping patients get better.
     
  9. jackie

    jackie Senior Member

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    thanks cort! As someone that is using av's... my "take-away" (what I personally find so useful in this study) is that it's showing that LONG TERM treatment can make a difference! If you look at Chia's work and what he says..."emerging evidence shows that a number of infections can trigger and possibly perpetuate the symptoms of ME/CFS. The INITIAL INFECTION can create an IMBALANCE in the IMMUNE SYSTEM which allows the PERSISTANCE of the offending virus AND may also REACTIVATE pre-existing DNA VIRUSES, such as VZV (shingles), EBV, CMV, HHV-6, Chlamydia Pneumoniae, Parvo Virus B-19, Q Fever, Brucella Species, Toxoplasma, Borrelia Burgdoferi...(all having been reported to cause me/cfs.)

    Enteroviruses (EV, Coxsackie B, and Echo) are also CLEARLY IMPLICATED triggers/causes of ME/CFS. Viral Genome (RNA) was found in the blood and muscle of PWC's by several researchers - (although when a NIH investigator couldn't produce the same results - this discrepancy led to a shift in the paradigm in the mid '90's. NO more investigation, no more funding, case closed!) Until now (thanks to dr. chias persistance)...the focus is back on! (if you can FIND the affecting pathogen - treat it! You wouldn't believe the places he's found EV's!)

    There are NO FDA approved Antivirals against EV's (although Ive heard that a new drug may be ready soon, ...can't remember the name) But the Lerner study SHOWS (what some patients have long been aware of)...that LONG TERM AVS CAN treat non-permissive Herpes (at least) effectively....IF taken in higher doses and for long enough....reducing the viral load on the overall system.

    As for "naturally getting better anyway"...I beg to differ! There is evidence that I may have contracted MY me/cfs while in the womb (my mothers 7th month of pregnancy). Extremely ill from the time of my birth, ill as a young child, early teens...intermittent/sporadic remissions for young adulthood, then relapsing for my 30's,40's, 50's!!...and moving into my 60's.

    The improvements I have made (granted they are mostly in cognitive/memory etc. - but quite significant - AND I am no longer bedridden/but still housebound - which I'm very greatful for - no complaints here!) are entirely due to my AV use.

    I purposefully took NO OTHER TREATMENT, staying at 3200mg. per day (other than meds for Hypertension, and atenolol for OI). With my history I guarantee that it's no coincidence that I'm improving while on the AV's (even though acyclovir has NOT shown impressive results in some "studies"...remember the 30 day acyclovir study?!)...I don't believe that I'm "just naturally getting better"!
    What "we" NEED are drugs targeting these viruses specifically....and funded research/studies (chia gets no money for research/studies and was turned down by the cfids, for example...dont know why)

    (just saw your post, danny...HI! the costs are a problem, i know.
    I'll be honest...acyclovir wasn't the FIRST choice for me, BUT acyclovir (which is MUCH cheaper AND was covered by my HMO INS. and Valtrex was NOT) was offered as an alternative...and I jumped at the chance! It requires frequent dosing (I take 8 pills per day - 2 at a time to get my 3200mgs)...but at least I can afford it, i have my liver/kidney function tests done regularly - so far, so good!...drink lots of water..and although it can be tough on one's stomach for some (like me!)...i cant complain.

    I wanted (asked for) interferon..but my ins. said No. I'll try just about anything (if I can find the money to do it!)...i figure that at my age and because I've been ill for so long I have nothing to lose! I realise that it's much harder for a younger person to want to "experiment"....without impressive "studies" to back one's decision.

    Oh..and i just had my Tcells checked recently as well...cd8=normal now!, cd4=surprisingly high...which does MEAN something as I do have severe chronic shingles(vzv)/reactivation of hsv1 (and as I'm not the only one this is happening to on AVs') and could be an important piece of the puzzle.

    jackie
     
  10. Enid

    Enid Senior Member

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    It seems to me we should encourage all those who have devoted against impossible odds their research and time into this and not criticise (except the Psychos) More pleasure at the advance of understanding of this awful disease should be welcomed for all.
     
  11. Cloud

    Cloud Guest

    The report is a bit much for my concentration ability this past few days, therefore it's highly likely I'm missing some important facts that would address my questions. I will have to read it again when more clear. But for now, there are a few things that come to mind immediately for me with this study....

    First of all this is good news for many pwc's and great news as another contribution to unraveling the puzzle of ME/CFS. It also lends to solidifying the infectious cause position. One concern I have is the difference in responsiveness between groups A & B. The reported high rate of responsiveness is with group A, those with Herpes infections only. The responsiveness is much lower for group B, those with Herpes & co-infections. Well, I have been of the belief that most pwc's DO have Herpes & co-infections, and according to this studies conclusion, would therefore fall into the less likely to respond category. But the study does suggest that those fitting the group A criteria have a really good chance of recovery with this treatment, and that's good news for that group at least.

    My own experience as a person with highly reactivated CMV and non herpes co-infections is that treating any of the re-activated infections decreases the symptoms of illness significantly. My experience of treating CMV with Vistide is a great example....The drug is only effective for the CMV and not the co-infections, yet I made dramatic improvements with Tx. Of course relapse is a concern if I don't get the co-infections dealt with and that's been my focus since going off the Vistide in December.

    This study at the very least puts many more pieces of the puzzle into place. Soon the xmrv story will add more to the puzzle. I think that Dr Lerner is a man of Integrity and, I feel we are extremely fortunate to have him on our side. I'm thankful for his devotion and years of work on our behalf.
     
  12. Hope123

    Hope123 Senior Member

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    RE: Dr. Lerner's fatigue scale

    It's been a long while since I read this paper and I don't have the energy at the moment to pull it up but it's published out there. The scale was part of a study he did with Valtrex I believe a few years ago.

    Patient and physician-reported scales are used in many areas of medicine but usually they have undergone some process of evaluation before they are accepted as useful and I did not see some of the critical factors used to evaluate scales in Lerner's paper.

    Two important factors are:
    1. Validity - does the scale actually reflect what it is suppose to measure? does it reflect patient experience? This ties into the point made by Gerwyn to this scale and also by others in regards to Dr. Bell's scale. Some people have a hard time seeing how movement in one point equates to actual significance in their lives and others think mental/ physical function is lumped too much together (e.g. you can be better mentally but not physically or vice-versa) I think this is where the calorie comparisons came into play.

    2. Reliability - if you give the scale to the same person twice in one day or if you had two different MDs rate the same person on the same day, would the scale fluctuate much merely due to different interpretation rather than true changes?

    3. Response - this ties in with #2 above to some degree. How sensitive is the scale to true clinical changes? Would it pick it up? And how well does it pick it up?

    I understand that Lerner and his team are limited by funds and resources but these above matters should be considered when using a new scale. One alternate possibility would have been to use an established functional scale (many out there) concurrent with their own scale to compare.

    Also, I agree having no controls is an issue and Kati's point about treating patients slightly later would have been one way to have controls. Another way would have been to follow those folks who dropped out of Lerner's clinic and see how they are doing. As the study stands, it only tells us about the people who continued to see him so it's self-reinforcing. (You improve, you stay in the clinic, you get counted.) We don't know the denominator -- e.g. all the people who went to see him but dropped out due to not improving or developing drug adverse effects or were improving but ran out of $.

    With a retrospective study, you can't do the above but maybe they can do some of this with current and future patients.
     
  13. julius

    julius Watchoo lookin' at?

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    Gerwyn,

    When you say that EBV is exclusionary for CFS, do you mean that basically, if you have EBV you can't have CFS?

    I'm totally confused....I thought EBV was very common in CFS patients. Isn't it similar to the other herpesviruses, parvovirus, etc. that tend to show up often in CFS patients?

    Also, if you could just clarify how your statement in post #51;
    "A person with an EBV infection will easily qualify for a diagnosis of CFS under the FUKUDA criteria"

    agrees with your statement in post #62;
    "So by definition active epstein Barr precludes a diagnosis of CFS even under Fukuda."
     
  14. jackie

    jackie Senior Member

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    Wonderful stories, sickofcfs! great news re your uncle (if I can do four years I can certainly do eight - or more! as he has done!) Often...all we have to hang on to ARE the anecdotes of others fighting this disease! And yours and others stories help so much!

    The sometimes subtle improvements "we" report, are difficult to convey to others not experiencing them! We are talking about improvements that may take place over months to YEARS! When you're living through the process you do question yourself as to what you are REALLY feeling (...how much better do I consistantly FEEL?)...but after a time, you generaly know the difference in overall improvement.

    I try to be as "self-analytical" as I can be (without taking the sheer joy out of feeling better!). I look for "other" answers for the differences...such as have I improved my surroundings to make my life easier? am I limiting situations that make me feel worse? but in the end I always come back to the AV's as the cause - for me, anyway. And, like you and your daughter...I wouldn't give them up for all the world (I DO hope to be able to reduce my dosage at some point...but am in no hurry for that right now).

    I'm not expecting a CURE (that's not possible at this point, imo - and we still have the spectre of XMRV to contend with - I would imagine I'd test pos. but don't know yet)....but moving forward (even an inch at a time..and any reduction of PEM - which I forgot to mention is ALSO improving for me)....is a big deal.

    Some might think that because I still experience shingles (and chronically so AND on both sides of my body at once) means that I'm not improving in important ways...but I don't agree. In fact, I sort of feel "lucky" that I have them - as they are irrefutable evidence that I am riddled with herpes!...and at the same time I have these wonky tcell counts and yet a clear-cut improvement (and those around me have judged this as well) in my ability to read/write/comprehend/memorize.

    I scored so badly on some diagnostic neuro/physchiatric tests with my neuro that I was actually dx'd with MCI, and given a script for Aricept/Namenda (which I didn't take), and told that I might be "pre-dementia/alzheimers...and yet some time later (after continuing and raising my AV dosage)... he reversed his dx! How many times does THAT occur?

    These are very nasty and persistant viruses we are dealing with (they are referred to as "Stealth" and "Smoldering" viruses for good reason - they actually "talk" to each other - as they are taking over!), and as such, are incredibly difficult to track down and to treat! Although I haven't had this tested yet...my doc said that if he tested my DNA TODAY...he felt sure that he would find VZV in it! Genetics play a HUGE role, imo. (I have several blood relatives with me/cfs...and this may have gone back several generations in my family)

    (BTW: chronic EV's, CMV, HHV-6, EBV, VZV, HSV1, that's me!) thanks again for the stories and so happy for you and your daughter's improvements...the big ones are great but even the "little ones" add up!

    jackie
     
  15. anciendaze

    anciendaze Senior Member

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    We know there are apparently healthy people who test positive for XMRV. We know retroviruses generally affect immune response. It is possible that 75% of those with such problems have coinfections. It is even possible that if you excluded all those with coinfections the carefully-defined clinical disease would disappear.

    Healthy people do not spend a lot of time consulting doctors. This negative selection effect makes it hard to determine actual onset of a disease which does not appear immediately life-threatening. My current working hypothesis is that the first reported signs and symptoms may not mark the onset of XMRV infection. They may correspond to coinfections.

    After decades of watching enthusiasts for different possible causes at war with each other, I'm not interested in watching replays. When you come right down to it, we've had the knowledge for a long time that most people with EBV infection either recover without treatment or respond to treatment quickly. We now know that some people who do not respond quickly will respond to longer treatment. What is missing is an explanation for why they are different.

    There are similar patterns of infection by HCMV, HHV-6 or even HSV. We have had no clue as to why, in a very few cases, a common virus can result in encephalitis or myocarditis, just to name two serious consequences.

    I'm guessing XMRV makes the difference.
     
  16. Lesley

    Lesley Senior Member

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    XMRV perhaps?
     
  17. Cort

    Cort Phoenix Rising Founder

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    Here's what I got about that Group B; they started off sicker and they actually improved quite substantially (which is why they couldn't be differentiated from Group A significantly) but they still had CFS by Dr. Lerner's definition - which is why he called their progress 'bleak'. But I didn't think their progress was bleak at all - I thought it was pretty good. I'm not sure how he treated them differently after he got this data but apparently he did start treating them differently and he said their numbers were better than the report indicated.
     
  18. Cort

    Cort Phoenix Rising Founder

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    Dr. Lerner is not testing his patients for classic signs of active EBV infection. The importance of high antibody levels to early antigens is a real grey area in Science - there is no agreement that this finding denotes disease and therefore it could not be excluded under Fukuda. This type of infection is not going to exclude anyone from being diagnosed with CFS under Fukuda because this type of EBV is not a 'recognized medical cause of fatigue' - Dr. Lerner is trying to make it one. Dr. Lerner is attempting to say that nonpermissive herpesvirus infections do cause disease and that disease happens to be called CFS.

    If this kind of infection was an accepted cause of fatigue than physicians would be doing the tests and treating it like they would hepatitis or HIV but they're obviously not doing that. These patients come from all over the country and the world to see Dr. Lerner because he's doing these tests that pick up their abnormalities.

    I don't think you're suggesting that we call people with CFS whose illness was triggered by granular fever or infectious mononucleosis and who never recovered - infectious mononucleosis patients - instead of CFS patients? That would out a nice chunk of CFS patients.

    I would love to have PEM in there - for sure, that would have been nice - but I'm just not worried about that. Their functionality was in the pits. I'll assume that these peoples inability to function in a pre-treatment and Dr. Lerner's admonitions to them not to exercise was an indication of their PEM.
     
  19. Bob

    Bob

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    This is really fascinating, and possibly very significant science for the CFS/ME community...
    There seem to be a few significant, and potentially groundbreaking, studies coming out at the moment, such as Huber's work on HERV.

    Here is a PDF link to Lerner's published paper...

    Subset-directed antiviral treatment of 142 herpesvirus patients with chronic fatigue syndrome
    http://www.treatmentcenterforcfs.co...ment-of-142-herpesvirus-patients-with-CFS.pdf

    (at least I think it's the same paper as this thread is referring to)
    (I can't see this posted anywhere else, so apologies if it has already been posted)...
     
  20. Gerwyn

    Gerwyn Guest

    sure epstein barr symptoms mirror the symptoms of CFS as defined by FUKUDA as long as PEM is not used.in reality however if there is a medical reason for the fatigue such as epstein Barr infection then a formal diagnosis of CFS cannot be given
     

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