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Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein

Discussion in 'Latest ME/CFS Research' started by heapsreal, Oct 16, 2012.

  1. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Abstract

    Valganciclovir has been reported to improve physical and cognitive symptoms in patients with chronic fatigue syndrome (CFS) with elevated human herpesvirus 6 (HHV-6) and Epstein–Barr virus (EBV) IgG antibody titers. This study investigated whether antibody titers against HHV-6 and EBV were associated with clinical response to valganciclovir in a subset of CFS patients. An uncontrolled, unblinded retrospective chart review was performed on 61 CFS patients treated with 900 mg valganciclovir daily (55 of whom took an induction dose of 1,800 mg daily for the first 3 weeks). Antibody titers were considered high if HHV-6 IgG ≥1:320, EBV viral capsid antigen (VCA) IgG ≥1:640, and EBV early antigen (EA) IgG ≥1:160. Patients self-rated physical and cognitive functioning as a percentage of their functioning prior to illness. Patients were categorized as responders if they experienced at least 30% improvement in physical and/or cognitive functioning. Thirty-two patients (52%) were categorized as responders. Among these, 19 patients (59%) responded physically and 26 patients (81%) responded cognitively. Baseline antibody titers showed no significant association with response. After treatment, the average change in physical and cognitive functioning levels for all patients was +19% and +23%, respectively (P < 0.0001). Longer treatment was associated with improved response (P = 0.0002). No significant difference was found between responders and non-responders among other variables analyzed. Valganciclovir treatment, independent of the baseline antibody titers, was associated with self-rated improvement in physical and cognitive functioning for CFS patients who had positive HHV-6 and/or EBV serologies. Longer valganciclovir treatment correlated with an improved response. J. Med. Virol. 84:1967–1974, 2012. © 2012 Wiley Periodicals, Inc.

    http://onlinelibrary.wiley.com/doi/10.1002/jmv.23411/abstract

    anyone has access to the full article for free, a link would be good.

    cheers!!!
    justy, merylg, Ecoclimber and 3 others like this.
  2. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    It states longer treatments were associated with improved response. Be nice to know the treatment length but i also take it that its longer then montoya's initial study length of 6 months?

    cheers!!!
  3. dmbaken

    dmbaken

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    Valganciclovir Treatment
    Patients followed one of two valganciclovir treatment
    regimens based on clinical judgment (e.g., history
    of side effects to antimicrobials). Fifty-eight
    patients took 900 mg of valganciclovir twice daily (induction
    dose) for 3 weeks, followed by 900 mg of valganciclovir
    once daily (maintenance dose). Six
    patients only took the maintenance dose for the duration
    of their treatment.
    The length of treatment varied among patients
    according to the treating physician’s clinical judgment.
    If patients were treated with valganciclovir
    more than once and the two treatment regimens were
    more than 1 month apart, then the first treatment
    regimen was used for analysis as well as for establishing
    baseline and final functioning levels and antibody
    titers. If, however, multiple treatments with valganciclovir
    were

    <
    1 month apart, these were considered a
    single treatment course for analysis purposes.
  4. dmbaken

    dmbaken

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    mean treatment in months was 6.5 (SD = 2.0)
  5. anniekim

    anniekim Senior Member

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    Apologies if this has been posted elsewhere on here. Are the HHV6 titres mentioned 1 :336 lower than Montoya has used before?

    Also sorry for my ignorance but does this study say response could not be predicted by how high titres were just if one had positive serology?

    http://www.meassociation.org.uk/?p=13221

    EDIT

    Sorry see this has been posted elsewhere so moderators please feel free to delete this. (threads have been merged)
  6. anniekim

    anniekim Senior Member

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    Were the titre numbers for HHV6 that were considered high in this study 1 :360 lower than other studies Montoya has done?

    Also sorry for my ignorance but is this piece of work saying response to valcyte couldn't be predicted by higher titres but purely if there was positive serology?

    Sorry I don't understand what this means, 'mean treatment in months was 6.5 (SD = 2.0)'. What is it in months? Many thanks
  7. hmnr asg

    hmnr asg

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    here is the full article.

    H

    Attached Files:

  8. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    I think its saying higher the tires doesnt mean a better response to treatment or the worse the condition is eg someone with lower titres could be more ill then someone with higher titres and the one with lower titres could respond better then the person with higher titres and vice versa. I suppose theyare saying its not an indication if they will respond or not. I think theyare saying if u have titres above the minimum then these viruses can be an issue for you??
    anniekim likes this.
  9. anciendaze

    anciendaze Senior Member

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    Notice that improvements were associated with reduced viral titers. This points to a useful therapeutic goal, even if valgancyclovir is not the drug used. They failed to validate their hypothesis about patients with high titers being more likely to respond.

    The problem which seems to have turned up is that a high titer may be either the result of an especially active infection or an especially active immune response to a lesser infection. Both these and other viruses in the herpes group are immunotropic, and have immunomodulatory characteristics. It seems very likely that there is damage to the immune system over time. If immune response does not decline, the result may be an autoimmune disease. On the other hand, if it does, you have a situation where you can't tell if you are looking at a serious infection. Simply looking at the numbers doesn't tell you.

    This kind of problem is common in chronic infectious diseases.

    We know that long-term infection with some strains of EBV is associated with several cancers. We have also seen that HHV-8 is associated with Kaposi's sarcoma. We don't have a "smoking gun" for HHV-6, but it is looking like this is only a matter of time. Association between CMV and a number of cancers is also under investigation. All these are human herpes viruses.

    It is no longer safe to assume that active infections by these common viruses are harmless. If your immune system is holding them latent you are probably in good shape. If they are reactivated something should be done to change the situation.
    Dolphin, anniekim, vli and 1 other person like this.
  10. SOC

    SOC Moderator and Senior Member

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    These results are consistent with what my daughter and I saw with our valganciclovir treatment. I had been continuously sick longer than she had, I was sicker, but she had higher HHV-6 and EBV titres. We both responded well to valganciclovir. My daughter is now in remission. I'm improved, but still significantly impaired.

    It appears that my immune system was damaged by the illness and was not producing sufficient antibodies, so my titres weren't very high. My daughter's immune system seemed to be still fighting and she recovered faster, but I still got a huge improvement.

    So, I can easily see why titres are not directly related to response. Antibody titres don't tell the full story for patients with immune impairment.
    Dolphin, anniekim and vli like this.
  11. anciendaze

    anciendaze Senior Member

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    I want to add that these problems with tests are not peculiar to weird conditions easily confused with mental illness. Even though tuberculin testing for TB infection was suggested (by A. Conan Doyle!) soon after tuberculin was discovered as an antigen provoking immune response to those bacteria it was not used as a test for many years. (During this time it was the basis of attempted treatments, most of which failed.) After the incidence of TB was reduced various tests with tuberculin became standard for diagnosis. It worked well for cases of recent onset TB.

    I know of at least one much later case in which a tuberculin test was administered, and failed, though an autopsy later revealed extensive TB which was hard to see on X-rays. The patient's immune system was simply too far gone, and the doctors involved were not familiar with long-standing TB infections.

    Our whole healthcare system has problems coping with chronic infectious disease.
    SOC and Dolphin like this.
  12. Dolphin

    Dolphin Senior Member

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    The percentages reported could be reported in another way.



    As the figures show, this means the final scores were 53%* and 66%* (i.e. a 19-point increase from 34 to 53 would be described usually as a 56% increase and a 23-point increase from 43 to 66 would be described usually as a 53% increase).

    [*Dolphin: because of rounding, the figures could actually be anywhere between 52-54% and 65-67% respectively]

    One point to note is that the analysis is slightly unusual:


    ---------

    Also, as the authors say,
    ---------
    ---------
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  13. Bob

    Bob

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  14. Stukindawski

    Stukindawski

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    One part of this study I'd like to commend is in this simple quote:-

    "in patients with chronic fatigue syndrome (CFS) with elevated human herpesvirus 6 (HHV-6) and Epstein–Barr virus (EBV) IgG antibody titers."

    Ok, the CFS part is still there but, I am desperate to see more research that focuses in on biological abnormalities previously discovered in patients and using them to refine a cohort.

    I've read some pretty heavy debates about the virtues of lumping and splitting, but I think you have to commit to a lot of the splitting type of research before you can actually answer that question anyway.
    Bob likes this.
  15. Simon

    Simon

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    It's worth pointing out that this study failed to find any difference in response between high-anitbody titre and low-antibody titre patients.

    Very little can be read into the improvements since, as the authors say, there was no placebo control group. Also, as Dolphin points out, they used PEAK scores to measure improvements, not mean or final scores; this means that even if there was no overall improvement across patients they would still appear to be one if fatigue scores fluctuated over time (above average scores give the peaks, below average scores are ignored). As Dolphin also points out, they reported the improvements in a conservative way so the results do actually look interesting, but without a control group its impossible to draw any conclusions. Does anyone know if they plan to publish a controlled trial?

    ps I think the Research1st report on this has it about right:
    I should point out that I haven't read the full text, just the abstract and Dolphin's analysis - but that's surely at least as good? :)
    Dolphin likes this.
  16. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    There was a significant improvement in a significant number of patients, however was this due to treatment? Also was the treatment affecting some other biological agent, if herpesvirus 6 (HHV-6) and Epstein–Barr virus (EBV) titres were not significantly changed. Have I got this wrong, lol? To me it seems that the treatment was very helpful, just not for the reasons he thought it would be. Also, it's possible I guess that the titres may not change because of other factors, including dysfunctional immune system. In other words it might seem that HHV-6 and EBV are a problem in these patients, but that might be a false reading.
  17. Dolphin

    Dolphin Senior Member

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    The titers did change:

    and

    If one looks at the paragraph in the discussion that starts:
    they give possible reasons for the lack of association with baseline titers. I have no idea if some are plausible or not (e.g. some with reactivated virus may have borderline
    hypogammaglobulinemia).
    Bob likes this.
  18. RustyJ

    RustyJ Contaminated Cell Line 'RustyJ'

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    Oh sorry, I have completely misread it. Too tired.
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  19. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Non responders could be apart of the non responders dr lerner found, they were the ones with bacterial co-infections like lyme,mycoplasma etc but he does get improvement with this group when he treats with abx as well.

    Also i think whats being misunderstood is that the titre levels didnt neccessarly correspond with patient severity ie some with low titres were sicker then those with high titres.

    Antibody titres are also dependent on a healthy(to a degree) immune system being able to pump out alot of these titres as well.
    RustyJ likes this.
  20. satoshikasumi

    satoshikasumi Senior Member

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    This means the average treatment was 6 and a half months
    67% of the study population were treated from 4-8 months
    95% of the study population were treated from 2-10 months.

    anniekim likes this.

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