Antivirals as an ME/CFS treatment (e.g. valacyclovir, valgancyclovir, amantadine)

[PageofME]

Can you please provide a translation?

I will provide one as soon as possible.

But she's basically saying the same as I from her personal experience. Acyclovir suppresses flares fully or if not acute causes a dissolution of exertion intolerance.

She's saying something along the lines of: No matter how much I go over my exertion threshold (she's been a mild/moderate patient for 25 years and knows pacing very well) I don't have PEM.

 

[PageofME]

I switched from aciclovir to valaciclovir ten days ago. I am experiencing it just as I could expect it from the information available on the differences between the two drugs. Valaciclovir is more effective and it lasts longer in the body.

It was a bit tricky to find the right dosage and I experimented a bit. I started with 500mg twice daily. I experienced two very strong peaks where I felt really drugged and after ten hours I felt sober again which I thought might be ok with shingles or HSV prevention but not with ME/CFS.

If the theory is true that ME of the flu-like lead symptom group who respond to aciclovir represents a smoldering abortive type of herpes reactivation that the immune system can't control anymore (Maria Ariza, Ohio State) I think you don't want to be sober. Not even for a couple of hours.

I chatted with a friend who is a researcher and a pharmacolcogist and knows (val)aciclovir well because they use it at the children's hospital where he works to prepare the kids against CMV reactivation before immune therapy. He looked it up for me and yes, at the hospital valaciclovir is given every eight hours.

I have decided on a regime of 4x250. I am taking two doses within three hours in the morning to push the drug mirror higher up during the day while I am active and take the third dose in the late afternoon. I don't exert myself in the evening and I take the last dose when I go to bed.

I have been pretty active when at the same time I continue to rest for one or two hours during the day. I feel that if I wanted to do more I needed to take a higher dose of the drug and that's not feasible for me at the moment.

I will go off the drug in a couple of days – I prefer to do it in a cold turkey fashion because I really don't want to be active while not on a high enough dose of the drug and risk the building of resistancies. And it is only when I'm sober that I can return to listen to my body to find out about my exertion threshold.

I hope I find a good specialist soon who will help me to find out what's sensible for me to do. Is it to go continually on the drug and start work rehabilitation like some patients do it. Is it to continue to just take valacyclovir in emergency situation and from time to time to give the nurse and super pacer part of me a holiday as I have been doing it for the first year of experimenting with the drug?

I am really curious what time will bring!

 

[Evergreen]

Can you please provide a translation?

Here's a summary:

The slides start with some research. She says some specialists prescribe (val)acylovir based on a hypotheses that persistent or reactivated herpes infections contribute to symptoms for a subset of ME/CFS patients. She summarises this study - placebo-controlled - which concluded:

We conclude that acyclovir, as used in this study, does not ameliorate the chronic fatigue syndrome. We believe that the clinical improvement observed in most patients reflected either spontaneous remission of the syndrome or a placebo effect.

She then talks about Lerner's studies, with reported good response and lasting recovery.

Then on to her experience:

She was doing better - in what she calls a remission - and then got chicken pox [edit: shingles], covid and staph aureus infections, one after the other. She had a big crash. That was two years ago.

Since then she has been trying to support her immune system, first with herbal tinctures which weren't effective enough. She asked her doctor for acyclovir and got it, but the next day saw an immunologist who independently prescribed acyclovir, presumably on the basis of lab results for herpes simplex I (shown on slide but unclear where those results are from, and no column labels, nor what they mean, but the immunologist clearly picked out herpes simplex as warranting treatment).

Day by day she felt better and steps went up. No matter how much she went over her baseline, no PENE.

However, other things she measures look worse "Body Battery", resting heart rate (higher), heart rate variability (lower).

Then she tried another drug and it seems that didn't end well - her next update will be about that.

 

[Evergreen]

Here's the abstract of the placebo-controlled study [formatted with gaps for ease of reading]:

Acyclovir Treatment of the Chronic Fatigue Syndrome​

Authors: Stephen E. Straus, M.D., Janet K. Dale, R.N., Martin Tobi, M.B., Ch.B., Thomas Lawley, M.D., Olivia Preble, Ph.D., R. Michael Blaese, M.D., Claire Hallahan, M.S., and Werner Henle, M.D.Author Info & Affiliations
Published December 29, 1988
N Engl J Med 1988;319:1692-1698
DOI: 10.1056/NEJM198812293192602
VOL. 319 NO. 26
Twenty-seven adults with a diagnosis of the chronic fatigue syndrome were enrolled in a double-blind, placebo-controlled study of acyclovir therapy.

The patients had had debilitating fatigue for an average of 6.8 years, accompanied by persisting antibodies to Epstein–Barr virus early antigens (titers ≥1:40) or undetectable levels of antibodies to Epstein–Barr virus nuclear antigens (titers <1:2) or both. Each course of treatment consisted of intravenous placebo or acyclovir (500 mg per square meter of body-surface area) administered every eight hours for seven days. The same drug was then given orally for 30 days (acyclovir, 800 mg four times daily). There were six-week observation periods before, between, and after the treatments.

Three patients had acyclovir-induced nephrotoxicity and were withdrawn from the study.

Of the 24 patients who completed the trial, similar numbers improved with acyclovir therapy and with placebo (11 and 10, respectively). Neither acyclovir treatment nor clinical improvement correlated with alterations in laboratory findings, including titers of antibody to Epstein–Barr virus or levels of circulating immune complexes or of leukocyte 2′,5′-oligoadenylate synthetase. Subjective improvement correlated with various measures of mood.

We conclude that acyclovir, as used in this study, does not ameliorate the chronic fatigue syndrome. We believe that the clinical improvement observed in most patients reflected either spontaneous remission of the syndrome or a placebo effect. (N Engl J Med 1988; 319: 1692–8.)

 

[PageofME]

Here's a summary:

The slides start with some research. She says some specialists prescribe (val)acylovir based on a hypotheses that persistent or reactivated herpes infections contribute to symptoms for a subset of ME/CFS patients. She summarises this study - placebo-controlled - which concluded:

She then talks about Lerner's (uncontrolled) studies, with reported good response and lasting recovery.

Then on to her experience:

She was doing better - in what she calls a remission - and then got chicken pox, covid and staph aureus infections, one after the other. She had a big crash. That was two years ago.

Since then she has been trying to support her immune system, first with herbal tinctures which weren't effective enough. She asked her doctor for acyclovir and got it, but the next day saw an immunologist who independently prescribed acyclovir, presumably on the basis of lab results for herpes simplex I (shown on slide but unclear where those results are from, and no column labels, nor what they mean, but the immunologist clearly picked out herpes simplex as warranting treatment).

Day by day she felt better and steps went up. No matter how much she went over her baseline, no PENE.

However, other things she measures look worse "Body Battery", resting heart rate (higher), heart rate variability (lower).

Then she tried another drug and it seems that didn't end well - her next update will be about that.

Thanks for this summary. I would like to add what the insta poster is saying about dosage:

Because she and her immunologist believe that there is an ordinary problem with herpes as a comorbidity to ME/CFS and the doctor is not prescribing it in the fashion of Dr. Lerner against ME/CFS directly dosage seems to be inspired by fighting ordinary herpes flares.

It's interesting what you @Evergreen write about the idea of the doctor that she's tackling HSV with the drug. Because the dosage of acyclovir is rather similar to fighting a shingles episode where the drug is prescribed in a higher dose and over a longer time.

To fight an ordinary HSV reactivation acyclovir is prescribed for five days at 200mg every three hours. The insta poster had instead the double amount of 400 mg daily for two weeks. She does write something about the rationale behind this. She says that in Germany there is the idea evolving that some (ME/CFS?) patients can't control herpes well and should therefore be put on an aciclovir for several weeks and that that was on off-label use. It's quite confusing, actually.

Because it is on the contrary a standard practice that low dose aciclovir or rather valaciclovir because of its longer endurance is used when people have regular HSV or shingles outbreaks in a preventative way.

What I think is maybe the most important point of the insta poster's account is that instructed by her doctor after two weeks she went down on a "preventative" dosage of 2x400mg of acyclovir and that now she's experiencing that she's becoming acute again, in the language of most ME/CFS patients she develops PEM again.

And this is so important: Why, because we acyclovir responders do not get a little bit or a lot better in certain symptoms like fatigue or cognitive issues but we don't relapse anymore at all. Similarly when we go off thr drug we're not just a little bit less well again but we simply experience ME/CFS coming back again. I feel that this is difficult for people to understand because from what I've seen the efficacy of a drug for ME/CFS is always discussed as a matter of a bettering/worsening of certain symptoms.

But what acyclovir responders all have in common is something different: We don't have "crashes", PEM, or how I like to call it flares or episodes anymore. And when we go off the drug we're relapsing again and have to pace again to stay stable. While we don't have to pace on the drug – but are in my case instead tired because of the side effects.

I am not surprised to hear that the insta poster states that she's relapsing on that low "preventative* dose of acyclovir because from my experience and from what other acyclovir responders write on Reddit and elsewhere 2x400mg of acyclovir is not a high enough dose for moderate ME/CFS. I needed 1600-2400mg of acyclovir a day to prevent relapsing continually and are now without flares on 1000mg of valacyclovir a day. I don't think that I could go down on 500mg of valacyclovir and certainly not on 800mg of acylovir – because it's metabolized really fast.

In Switzerland I know that aciclovir is not even used for prevention but only valacyclovir because of its slower metabolisation.

I'm concerned that low doses might be just the perfect regime to allow the hypothesised atypically reactivated virus or viruses (EBV? VZV? HHV6b?) at the root of ME/CFS flares to develop resistances against herpes antivirals.

Thinking this all through I think that I am going to write to my ME/CFS specialist that other ME/CFS specialists prescribe acyclovir to ME/CFS patients in this risky fashion because they think of herpes as a comorbidity and don't know that it is hypothesised in an atypical reactivation pattern as a possible root cause of ME/CFS.

 

[Evergreen]

It's interesting what you @Evergreen write about the idea of the doctor that she's tackling HSV with the drug. Because the dosage of acyclovir is rather similar to fighting a shingles episode where the drug is prescribed in a higher dose and over a longer time.

To fight an ordinary HSV reactivation acyclovir is prescribed for five days at 200mg every three hours. The insta poster had instead the double amount of 400 mg daily for two weeks. She does write something about the rationale behind this. She says that in Germany there is the idea evolving that some (ME/CFS?) patients can't control herpes well and should therefore be put on an aciclovir for several weeks and that that was on off-label use. It's quite confusing, actually.

The immunologist put her on 400mg every 3 hours, 5 times a day. She was to feed back after a week, which she did, and she was told to continue the same for another week. Then from week 3, she was to take 400mg twice a day.

There is no indication that the immunologist was trying to treat her ME/CFS. My understanding is that the dose of 400mg every 3 hours is used for immunocompromised people.

What I think is maybe the most important point of the insta account is that instructed by her doctor she went down on a "preventative" dosage of 2x400mg and that now she's experiencing that she's becoming acute again, in the language of most ME/CFS patients she develops PEM again.

Except that she doesn't write that. [Edit: she does! She writes, 3 days after reducing the dose, I notice the exhaustion increasing again.]

Edit: Note the very next sentence on the same slide translates to: "But what is really fascinating is that no matter what I did beyond my baseline, no PENE!"

 

[PageofME]

The immunologist put her on 400mg every 3 hours, 5 times a day. Molly was to feed back after a week, which she did, and she was told to continue the same for another week. Then from week 3, she was to take 400mg twice a day.

There is no indication that the immunologist was trying to treat her ME/CFS. My understanding is that the dose of 400mg every 3 hours is used for immunocompromised people.


Except that she doesn't write that. She writes that she was so fed up being limited again for 2 years without concrete help that she tried another drug at the same time as the acyclovir, and that she should have known better. She does not write that when she reduced her dose she started developing PEM again. She implies that something went wrong when she tried another drug at the same time as acyclovir.

On the third to last sheet she writes: Seit drei Tagen sollte ich die Dosis auf zweimal täglich reduzieren, und ich merke, wie die Erschöpfung wieder zunimmt.

It is formulated a bit sloppy but I think that she means: Seit drei Tagen habe ich wie verordnet die Dosis auf zweimal täglich reduziert, und ich merke wie die Erschöpfung...

In English: For the past three days, I have reduced the dose to twice a day as prescribed, and I am noticing the increasing exhaustion again. (Google)

I belive that when speaking of exhaustion she's pointing to her experience of becoming mildly acute with an ME/CFS flare (PEM) again. What do you think that this means?

It's only on the second to last slide that she begins discussing this other drug. After she's finished discussing aciclovir.

I was also wondering whether she's discussing ME/CFS patients with herpes comorbidities or problems with herpes in general. And actually I conclude that she's discussing that there's this emerging idea in Germany that ME/CFS patients have often comorbid problems with herpes and yes, as you say, they might think that because of an immune defect ME/CFS patients then need higher dosage and to be put on longer therapies to fight herpes flares.

And it makes so much sense because in the new German Konsenus Statement and also in the older Long Covid and ME/CFS guide for clinicians that was created by Carmen Scheibenbogen there are everytime explicitly mentioned that in a group of patients there are herpes reactivations that should then be treated with herpes drugs to help patients stabilise their ME/CFS and not getting worse because of additional chronic infections.

I think what makes her account difficult to understand is that she's not well read into herpes reactivation causative theories of ME/CFS and thus hasn't fully grasped the difference of these two understandings of the role of herpes in ME/CFS. On the one hand she's summarizing Lerner's ideas – full recovery on herpes drugs because herpes is at the root of ME/CFS – and then again the emerging German leading clinicians' idea of the role of herpes in ME/CFS as a comorbitiy that is a important and more difficult to treat compared to non-ME/CFS patients because of immunity issues.

I will end again by stating that I think this is really stupid, and it's so good to realise what's going on. Even though top researchers from the US who are researching Long Covid cohorts with ME/CFS are saying that herpes reactivation is one of the most important hypotheses for explainig ME/CFS pathomechanism in Germany everyone seems to follow Prof. Scheibenbogen and autoimmunity theory. And this is now leading them to treat patients with these potentially risky herpes drug therapies.

 

[Evergreen]

On the third to last sheet she writes: Seit drei Tagen sollte ich die Dosis auf zweimal täglich reduzieren, und ich merke, wie die Erschöpfung wieder zunimmt.

It is formulated a bit sloppy but I think that she means: Seit drei Tagen habe ich wie verordnet die Dosis auf zweimal täglich reduziert, und ich merke wie die Erschöpfung...

In English: For the past three days, I have reduced the dose to twice a day as prescribed, and I am noticing the increasing exhaustion again. (Google)

I belive that when speaking of exhaustion she's pointing to her experience of becoming mildly acute with an ME/CFS flare (PEM) again. What do you think that this means?

It's only on the second to last slide that she begins discussing this other drug. After she's finished discussing aciclovir.

You are right that she says that 3 days after reducing her dose, she started feeling exhausted again, @PageofME, I missed that line when flicking through. I'll go back and fix my post.

I was also wondering whether she's discussing ME/CFS patients with herpes comorbidities or problems with herpes in general. And actually I conclude that she's discussing that there's this emerging idea in Germany that ME/CFS patients have often comorbid problems with herpes and yes, as you say, they might think that because of an immune defect ME/CFS patients then need higher dosage and to be put on longer therapies to fight herpes flares.

I don't think the immunologist necessarily thinks that ME/CFS patients in general are immunodeficient. But it sounds reasonable to consider her immunodeficient, given that she was having one infection after another and had lab results that (presumably) showed she had an active infection.

I will end again by stating that I think this is really stupid, and it's so good to realise what's going on. Even though top researchers from the US who are researching Long Covid cohorts with ME/CFS are saying that herpes reactivation is one of the most important hypotheses for explainig ME/CFS pathomechanism in Germany everyone seems to follow Prof. Scheibenbogen and autoimmunity theory. And this is now leading them to treat patients with these potentially risky herpes drug therapies.

I'm not sure I follow. Are you saying you think that the immunologist treating her herpes simplex infection as she did was stupid and risky, and instead should have treated her with an untested regimen based on a hypothesis? If so, I do not agree at all.

 

[PageofME]

I'm not sure I follow. Are you saying you think that the immunologist treating her herpes simplex infection as she did was stupid and risky, and instead should have treated her with an untested regimen based on a hypothesis? If so, I do not agree at all.

I am saying that given that we have all this anecdotal evidence of patients mostly self-medicating with aciclovir who write that they have to be on high doses continually in order not to relapse and that we have all the research and theories pointing to herpes playing a central role as the cause of ME7CFS doctors should be careful with prescribing herpes drugs to ME/CFS patients.

I especially think that the regimes that are aimed at preventing standard herpes reactivation with low doses are maybe the perfect conditions to foster the building of resistances of herpes against the standard herpes drugs in ME/CFS.

I didn't say that doctors of ME/CFS patients shouldn't fight their herpes flares with herpes drugs but they should urgently be trained on the current evidence and hypotheses including anecdotal experiences of ME/CFS patients who are aciclovir responders to become aware that standard preventative herpes regimes are potentially not suitable in the aciclovir responder group of ME/CFS patients because this dosage might be directly messing with what's going on in patients.

I am not a doctor but I find it weird that they are – as you suggest – fighting herpes flares that are not presenting with the typical outer symptoms of HSV or VZV reactivation but with a rationale that is based on fuzzy lab results (acute lytic herpes reactivation can't be determined via antibodies in blood tests but only via PCR).

 

[Evergreen]

I didn't say that doctors of ME/CFS patients shouldn't fight their herpes flares with herpes drugs but they should urgently be trained on the current evidence and hypotheses including anecdotal experiences of ME/CFS patients who are aciclovir responders to become aware that standard preventative herpes regimes are potentially not suitable in the aciclovir responder group of ME/CFS patients because this dosage might be directly messing with what's going on in patients.

I disagree. I have not seen any evidence yet that would warrant clinicians changing their practice. What evidence have you seen that suggests pwME and herpes infections deteriorate more than the wider population of people with herpes infections following standard treatment for those herpes infections?

I'm frustrated with the lack of science in this discussion, so I've tried to find placebo-controlled trials of anti-virals.

Richman et al. 2019 (including Klimas) discuss 3 papers that look at either acyclovir, valacyclovir or valgancyclovir:

1. Straus et al. 1988 - negative trial of acyclovir

2. Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. Valacyclovir Treatment in Epstein-Barr Virus Subset Chronic Fatigue Syndrome: Thirty-six Months Follow-up. In Vivo. 2007;21(5):707–713.

3. Montoya et al. 2013

In Straus et al. 1988's trial of acyclovir, 87.5% (21/24) of those who completed the trial were "responders". The problem is that the responders were evenly split between those who got the drug and those who got the placebo. While many people improved, no-one was responding to acyclovir. It's unlikely that the dose was too low, since 3 of the 27 who started the trial had to withdraw due to nephrotoxicity from acylovir. @PageofME, why do you think Straus et al. 1988 found that acyclovir was not effective if acyclovir is, indeed, effective for some?

I've started a thread for Lerner et al. 2007's trial of valacylovir and a thread for Montoya et al. 2013's trial of valgancyclovir.

 

[PageofME]

I disagree. I have not seen any evidence yet that would warrant clinicians changing their practice. What evidence have you seen that suggests pwME and herpes infections deteriorate more than the wider population of people with herpes infections following standard treatment for those herpes infections?

I'm frustrated with the lack of science in this discussion, so I've tried to find placebo-controlled trials of anti-virals.

Richman et al. 2019 (including Klimas) discuss 3 papers that look at either acyclovir, valacyclovir or valgancyclovir:

1. Straus et al. 1988 - negative trial of acyclovir

2. Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT. Valacyclovir Treatment in Epstein-Barr Virus Subset Chronic Fatigue Syndrome: Thirty-six Months Follow-up. In Vivo. 2007;21(5):707–713.

3. Montoya et al. 2013

In Straus et al. 1988's trial of acyclovir, 87.5% (21/24) of those who completed the trial were "responders". The problem is that the responders were evenly split between those who got the drug and those who got the placebo. While many people improved, no-one was responding to acyclovir. It's unlikely that the dose was too low, since 3 of the 27 who started the trial had to withdraw due to nephrotoxicity from acylovir. @PageofME, why do you think Straus et al. 1988 found that acyclovir was not effective if acyclovir is, indeed, effective for some?

I've started a thread for Lerner et al. 2007's trial of valacylovir and a thread for Montoya et al. 2013's trial of valgancyclovir.

Thank you for your post and questions, @Evergreen.

I am super interested to go on in this discussion.

My priority in the next days, however, will be to taper off of valacyclovir and begin to take back the full responsibility of my energy management. I can't therefore start it right now. But I am really glad that you're interested at having a discussion on herpes drugs and hopefully also herpes reactivation hypotheses in ME/CFS.

 

[PageofME]

What evidence have you seen that suggests pwME and herpes infections deteriorate more than the wider population of people with herpes infections following standard treatment for those herpes infections?

Just a quick answer to that one. Maybe there's a misunderstanding. I am not saying I am afraid poeple deteriorate in their ME/CFS illness level. I am saying that this treatment regime that the insta poster is on, and maybe a forum member who posted about this was on too, is risky because if you take herpes reactivation causative theories (Ariza, Prusty, Cliff) and the experiences of ME/CFS acyclovir responders seriously (see Reddit: Continual high doses are necessary) the established low dose preventative herpes drug regimes seem like the perfect set of conditions in ME/CFS to foster resistances of the herpes viruses against the drug. I mean by this the reduction in her regime to 2x400mg of aciclovir after two week.

She describes herself that on the high dose she had no PEM, and on the low dose it was coming back. If herpes reactivation is the cause of ME/CFS then that regime is too weak to supress her reactivation fully and that's what you don't want with a virostatic, that you fight flares only with half force, because this is the perfect condition for the building of resistances of the viruses.

Maybe this is all perfectly clear for you? I am stating it because I am not sure whether these facts are known to you and it's the facts that my argumentation is based on.

Are you aware of herpes reactivation being hypothesised by the above researchers as playing a central role in the pathomechanism of ME/CFS?

There are two theories: one is the abortive latent virus reactivation theory that is mainly postulated theoretically by Maria Ariza. The other is Jacqueline Cliff's HHV-6b theory. If you don't know them it would be important that you gain a basic understanding of them.

 

[Jonathan Edwards]

I am saying that this treatment regime that the insta poster is on, and maybe a forum member who posted about this was on too, is risky because if you take herpes reactivation causative theories

I don't think it is reasonable to make statements about medical risks absed on highly speculative theories. You may have a firm belief in certain theories but I worry that members will take this as medical advice. It has no evidence base.

 

[PageofME]

You might get Stevens Johnson syndrome and go blind, or die of agranulocytosis or whatever.

Why is it that I dearly have to laugh at you criticising me giving patients medical advice?

What I am not doing btw.

 

[forestglip]

Moderator note: We are allowing the discussion of anecdotal accounts, including an anonymized social media poster's account of the treatment with anti-herpes medication at relatively high doses. We think that if this idea is becoming popular, it is useful to examine the evidence for and against it and also, importantly, to consider the risks of the treatment.

Please try to keep any future discussion focused on the science and avoid speculation about which treatment regimens an individual is using. If you think a post breaks the no medical advice rule, please report it to moderators.

 

[Evergreen]

But I am really glad that you're interested at having a discussion on herpes drugs and hopefully also herpes reactivation hypotheses in ME/CFS.

The rituximab rollercoaster and the GET/CBT debacle taught me a lot of lessons. As a result, I'm just not interested in anecdotes or hypotheses, only in data testing those hypotheses. So I'm happy to discuss Straus et al. 1988 or thread for Lerner et al. 2007's trial of valacylovir and a thread for Montoya et al. 2013's trial of valgancyclovir.

Similarly, happy to discuss Jackie Cliff's team's - in their own words - "preliminary evidence of enhanced reactivation of some human herpesviruses" from "a small pilot study" in a subgroup of those with ME/CFS (Lee et al. 2021, thread here). I will be interested to see what their next study shows:

We are asking our study participants to record their symptom severity frequently, so that we can determine whether changes in HHV-6B concentration in saliva occur before or after changes in ME/CFS symptoms.

In this way, we aim to determine whether HHV-6B causes the symptom changes or if these occur after the disease gets worse.

Until I see that data, I don't see any point in discussing theoretical risks.

If herpes reactivation is the cause of ME/CFS then that regime is too weak to supress her reactivation fully and that's what you don't want with a virostatic, that you fight flares only with half force, because this is the perfect condition for the building of resistances of the viruses.

Too many ifs there for me.

That's why I asked if you had seen evidence of pwME deteriorating below their baseline after treatment - that's what your hypothesis would predict, right?

Are you aware of herpes reactivation being hypothesised by the above researchers as playing a central role in the pathomechanism of ME/CFS?

There are two theories: one is the abortive latent virus reactivation theory that is mainly postulated theoretically by Maria Ariza. The other is Jacqueline Cliff's HHV-6b theory. If you don't know them it would be important that you gain a basic understanding of them.

Yes, and I'm aware that they are hypotheses, not facts, so I'll watch out for their publications testing those hypotheses.

If I were getting infections all the time, I would hope that an immunologist would be able to help based on observing how I responded to treatments, both in terms of lab results and symptoms, given all their experience working with people with immune systems that are dysfunctional in a myriad of ways, without having to know how Cliff's research pans out.

 

[PageofME]

Thanks for your statements and questions. I resonate a lot with folks who are careful to jump on hypes.

As I already mentioned I am going to take a break from the forum for some time.

Just a quick answer to that one:

That's why I asked if you had seen evidence of pwME deteriorating below their baseline after treatment - that's what your hypothesis would predict, right?

No, that's not what I am saying. I am saying that low doses of (val-)acyclovir in patients who are without PEM on high doses – like me and many more patients whose accounts are being shared here or on Reddit great numbers – might stop working for people after a couple of months because of the building of resistances.

Add: And yes, I have seen such accounts here and on Reddit.

I look forward to going through the few studies that have been done on acyclovir one by one with you and seeing what we can learn from them! As a historian making reasonable interpretations where there is a lack of information is exactly what I was trained at.

 

[Evergreen]

What I think is maybe the most important point of the insta poster's account is that instructed by her doctor after two weeks she went down on a "preventative" dosage of 2x400mg of acyclovir and that now she's experiencing that she's becoming acute again, in the language of most ME/CFS patients she develops PEM again.

We need to come back to this sentence again, because this is not what the insta-poster says. She describes:

• Going on an anti-viral and experiencing less PEM and increasing her steps
• But noticing other things she measures looking worse (resting heart rate, heart rate variability)
• Reducing her dose and noticing exhaustion increasing again
• The very next sentence on the same slide translates to: "But what is really fascinating is that no matter what I did beyond my baseline, no PENE!"

So while it's true that she describes an increase in exhaustion coinciding with reducing her dose, she explicitly points out that she still did not have PEM.

And if the other things she measures capture something real, then the worsening began before she reduced her dose.

I think this is important to clarify, because most people on the forum will not able to read the anecdote for themselves as it is in German.

 

[Mij]

No, that's not what I am saying. I am saying that low doses of (val-)acyclovir in patients who are without PEM on high doses – like me and many more patients whose accounts are being shared here or on Reddit great numbers – might stop working for people after a couple of months because of the building of resistances.

I'm not sure what 'without PEM on high doses' actually means considering PEM is used in general terms, but I understand what pwME are feeling b/c I'm in the subgroup of reactivation of viruses. I don't feel that I have a chronic infection, my immune system feels like it's locked in a persistent, energy-draining state that mimics a chronic infection. That's how I describe it, but I do get reactivations every few years, and more often now that I'm older.

I'm not going to my GP to get tested over and over again. Went grocery shopping yesterday, I was swaying, I wanted to lie down on the floor- it's not PEM, this is a reactivation of a virus that I've been dealing with for the last month. and taking antivirals will only temporarily help me feel better.

You will see 'great numbers' on reddit b/c it fits their own personal experience with ME, that doesn't mean there are great numbers out there.

I'm not trying to stress you with this. I'm just sharing my own experience with ME for the last 35 years.

 

[PageofME]

A quick update on my first longer term use of acyclovir/valacyclovir.

10 days on 2000mg of acyclovir a day every three-four hours.
18 days on 750-1000mg of acyclovir a day 3-4x250mg whereas I take one or two doses of 250mg within a few hours after waking (depending on the activities I have planned) and then the other two doses after another 6-7hours respectively.

Please note: I won't reply to comments immediately because I need some time of from forum discusssions.

A couple of observations stand out:

I tolerate the medication better and better. So there's obviously a (German habituation effect. I am dlad!

With the only serious side effect of headaches or a headachy feel but not very painful or intolerable but a bit unpleasant for sure.

I understand now that up to three mg/a day as some more severe patients describe their dosage might be tolerable – not really in the first weeks but afterwards.

The combination of the drug and the eating of a lot of rather fast sugars leads to a feeling of being pretty drugged for some time. So I try to avoid that. But does not always work around Swiss chocolate

I guess that the sugars speed up the break down of the drug in the kidneys.

I experience massive fatigue in the afternoon – which is something very different from mitochondrially mediated exhaustion while acute with ME flares!

I suppose that it is partly because the drug helps me to not stress myself out anymore with pacing and a constant worry in the background of doing too much and brings a lot of relief – especially that I managed after years to convince my GP to help me with a regular prescription at least for a trial of valacyclovir. Because I haven't managed yet to organise it myself.

The fatigue feels as if the psychological/physical exhaustion that has built over the past years since I became a moderate is being set free.

Also I could imagine – I am aware that this is all guess work – that there might be some fatigue that is induced when the brain shuts down to do self-repair as described in this article:

Das Gehirn heilt sich selber

Mittlerweile kann die Medizin vieles reparieren: Knochen werden verlängert, Herzklappen eingesetzt, Gelenke geschmirgelt. Nur die Nervenzellen entziehen sich der mechanischen Wiederherstellung. Der ärztliche Eingriff ins Gehirn kann zwar Krankes entfernen. Doch es ist unmöglich, die Nervenzellen...

www.nzz.ch

Lastly, my dementia signs have strongly gone up. I am for example a lot worse at English at the moment compared to normal. I have experienced this before some time after I had been able to stabilize ME/CFS flares and being not acute anymore for many months. After some more months the dementia signs went down again.

I am speculating that it might have to do with a lot of cell death at the same moment in the frontal lobe where I experience smoldering brain inflammation signs when acute with ME/CFS. Maybe the immune system is capable of detecting and destroying cells where aciclovirtriphosphat has stopped viral activity?

Add: Pronounced fatigue (a classic tiredness that has nothing to do with ME/CFS "fatigue" that I can tell apart from acute ME exhaustion easily with my 20 years of intensive yoga and mindfulness training) might have two more causes:

1) Low ferritin, I was at 43 microgramme/l three weeks ago and falling because of a gynaecological problem where I felt already the typical tired legs and arms in the last weeks.

2) Direct effect of acyclovir that shows up in the package insert as well.

It is impossible to tell which reason is responsible for what amount of the total fatigue. The fatigue feels good, rest feels restorative, and the experience is insync with my situation. So I guess that brain healing fatigue and psychological fatigue because of discharging of stored up distress play an important part.