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Antiretrovirals

Discussion in 'Antivirals, Antibiotics and Immune Modulators' started by Hutan, Jun 11, 2018.

  1. brf

    brf Established Member (Voting Rights)

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    We're really excited to see that he's so open.
    Thanks so much @Hip for commenting already and including a link.
     
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  2. deboruth

    deboruth Established Member (Voting Rights)

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    Dr. Edwards, Dr. Lipkin's lab has been doing quite extensive immune profiles. What I've seen must be considered preliminary; there appear to be marked immune abnormalities that characterise the ME/cfs population. He also has broken out somewhat differing abnormal data for ME/cfs samples with IBS. Caligiuri et al, with Komaroff last author, studied samples from Tahoe outbreak patients and concluded abnormalities in NK cell data; 1986 or 87. Unger found abnormalities in perforin in a study, which she hypothesized could relate to NK function. Marshall-Gradsniak et al in Australia reported findings of abnormal NK. Are there reasons for these to be considered unreliable?
     
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  3. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Yes. None of them have been consistently confirmed. When real abnormalities are found in a given disease they are usually confirmed by dozens of labs within a year or two. When new autoantibodies are described in a particular condition the finding is usually confirmed by every routine lab in the Western world pretty soon.

    Mady Hornig in Ian Lipkin's group has found some statistical differences in cytokine levels in early and late disease but they are not very big and it is hard to know if they are chance findings or something real. Unconfirmed findings of this sort are commonplace in other diseases. Hundreds of different immune findings have been reported in rheumatoid arthritis, the vast majority of which turned out not to mean anything much.
     
  4. deboruth

    deboruth Established Member (Voting Rights)

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    Dr. Edwards, I believe Dr. Lipkin's involvement in ME pre-dated events surrounding XMRV. His participation in ME research (or "cfs") originated with the "CFS Initiative" funded by a private foundation. It is based at Columbia but operates with participation from Harvard (Komaroff et alia.) Not a big deal, but I thought you would like to know.
     
  5. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Yes, I suspect that the idea of a link between retroviruses and ME went back before xmrv, which came out of that idea - someone finding what they wanted to find. Klimas was in this area before too. AIDS vastly expanded the dying specialty of virology and then all the extra virologists had to find something else to discover.
     
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  6. leokitten

    leokitten Senior Member (Voting Rights)

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    Don’t most if not all ARVs exhibit significant mitochondrial toxicity? That’s my big worry taking them for ME, since we most certainly have dysfunction in cellular metabolism and do not want to create yet another problem.
     
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  7. chrisb

    chrisb Senior Member (Voting Rights)

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    Most will already be familiar with this but the idea of retroviruses went back at least as far as De Freitas and her patent application in about 1991. There may or may not have been something in this but it undoubtedly fuelled the suspicions about the official view of the illness when attempts to replicate the findings appeared to be obstructed by refusal to follow her precise protocols, or so it was alleged.
     
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  8. deboruth

    deboruth Established Member (Voting Rights)

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    eThis subject is very well covered in Osler's Web by Hillary Johnson as is much more every ME patient needs to know. Can buy on line.
     
  9. Hip

    Hip Senior Member (Voting Rights)

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    I speculated here that Elaine DeFrietas may have actually found bovine leukemia virus — a retrovirus that was recently demonstrated to live in the tissues of around 1 in 3 humans (detected by breast tissue PCR in women).

    BLV has a whole set of effects on the immune system in its natural host the cow. What it might do to the immune systems of the ~33% of humans that have BLV remains to be elucidated.
     
    Last edited: Feb 26, 2019
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  10. Susan K

    Susan K Established Member

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    @Jonathan Edwards or anyone else on this forum, do you think that the benefits that some pwme have using antivirals or antiretrovirals are due to anti-inflammatory effects?
    I find ibuprofen beneficial but don't take more than 400mg per day in an attempt to stave off kidney problems.
     
  11. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I don't think antivirals have any significant anti-inflammatory activity.

    I also don't think that inflammation is a significant aspect of ME - as far as we know there is no inflammation.
     
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  12. Susan K

    Susan K Established Member

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    @Jonathan Edwards Thanks very much for your response.
    Do you think the folks that report improvement are improving for some other reason? We never have a control for comparison.
    I understand that there is not evidence in the primary literature for inflammation in this disease. Yes, some very severe ME patients have elevated pro-inflammatory cytokines (and maybe even elevated anti-inflammatory cytokines - I may remember incorrectly). Also I know there are efforts to try to measure inflammatory signals/molecules using the latest imaging techniques.
    But, NSAIDs really make a difference, so how else could they be acting to alleviate malaise or "sickness behavior" or the "flu-like feeling"? I don't happen to have pain like a lot of pwme have.
    These and all drugs have complex and unknown mechanism or action (prostaglandin(s) inhibition, etc, ?)
     
    Last edited: Jun 15, 2019
  13. Amw66

    Amw66 Senior Member (Voting Rights)

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    is there not pro inflammatory cytokines expressed/ post mortem inflammation in dorsal ganglia?
     
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  14. Susan K

    Susan K Established Member

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    @Hip, @Jonathan Edwards, or others on this forum, it's my impression from reading the scientific literature over the past 30 years, that we don't really know how to measure inflammation unless its extreme/acute. Measuring CRP is a poor surrogate for the detection of inflammatory processes, esp in chronic illness. One of the most sensitive cellular markers of inflammation is the nuclear localization of the NF-kappaB transcription factors (as dimers) and the binding to their target (inflammatory) genes to regulate expression. We have no clinical test for such cellular activity that I know of.
    Any thing I am missing?
     
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  15. duncan

    duncan Senior Member (Voting Rights)

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    I think you covered it like a pro. :)
     
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  16. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    I had not heard that in general people with ME found NSAID helpful for ME symptoms. It is hard to draw a conclusion from one case. Maybe there is another cause.

    CRP is a reasonably good indicator of even quite limited inflammation. It does not need to be extreme or acute. It is essentially a sensitive internal bioassay that the liver performs detecting interleukin 6. If NF kB goes up TNF goes up, hepatocyte IL-6 goes up and CRP goes up. So yes we do have a test for NFkB transcription in that sense. That may not be detectable in serum if the process is very local but ME does not seem to be a local problem, unless it is entirely hidden away in the brain, which it might be.

    I don't think we have good reason to think that the isolated cases of dorsal root ganglion pathology found at autopsy are relevant more generally to ME. Dorsal root ganglion pathology would be expected to produce symptoms different from those PWME report.

    Clearly something is going on in terms of signalling in ME but 'inflammation' seems to me to be unlikely to be a useful way of describing it.
     
  17. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    As far as I know in the few controlled trials of anti-virals there was no difference in response from placebo. That is really the only way to assess these things.
     
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  18. Hutan

    Hutan Moderator Staff Member

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    Going off topic a bit - but I have found that ibuprofen helps. I noticed that when I took it for migraines I was quite a bit better, and then I experimented taking it when I didn't have a migraine, and found the same. I have tracked quite a lot of things for two periods of a few months and there was enough of a correlation between improved symptoms (including objective things like resting heart rate in the morning, POTS and shock index) when I took ibuprofen to convince my doctor to let me try Mobic (which didn't help).

    Given it's so widely used, it would be great if there was a blinded trial done. I've discussed this before on the forum somewhere. Edit - Found it here, we could continue any discussion about this on that thread.

    That said, I have constantly mildly elevated CRP, so maybe I am a special case.
     
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  19. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

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    Interesting. I guess the difficulty is that everyone gets intercurrent pains and sore throats from this and that and it may be that if everyone took ibuprofen they would feel a bit better. I have constant sciatica and often 'viral' symptoms in my throat and I always sleep better after ibuprofen. A trial could come out statistically significantly positive just because of that
     
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  20. obeat

    obeat Senior Member (Voting Rights)

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    Ibuprofen no use to me!
     
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