Antivirals as ME/CFS or Long Covid treatments (e.g. valacyclovir, valgancyclovir, amantadine)

[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.

 

[PageofME]

An update on my valacyclovir continuous trial:

I have been on acyclovir and after ten days on valacyclovir for about five weeks now. I take 1000mg/d. Since about two weeks the mild neurological problems that I witnessed since about two weeks in have further increased. When at the same time the I haven't developed the typical physical signs of neurotoxicity like tremor, slurred speech ect.

Because a situation yesterday when communication with others pointed to a decrease in executive control I am still going to get my renal function tested immediately at my GP's and have decided to go down on 3x250mg and add more rest to my daily routine.

It seems that I missed a very important point about the Lerner protocols: Dr. Lerner strictly advised his patients to rest in the first weeks of the treatment. I didn't completely miss that point but thought that because I was on a much lower dose (3-4g vs. 1g) it wasn't that important for me. On the other hand it's just so seductive to begin to follow a new life style immediately when you don't have an exertion intolerance anymore.

I am curious what my renal results will look like.

Being away from the forum was helpful. I researched on my own and found out that acyclovir has very good activity against EBV abortive lytic reactivation. Which is exactly why herpes theory of ALR was brought up in ME/CFS as playing a central or a causative role a long time ago. It was predicted in lab studies in 1980 and then confirmed clinically in AIDS patients with hairy leukoplasia.

I was somewhat shocked to realise that nobody here but also my ME/CFS specialist didn't know about this a bit paradoxical activity spectrum of acyclovir.

It made me realise that even though lots of people with medical degrees and a training in biomedicince are on this forum there is a big gap of information in basic knowledge about drugs and theories that aren't the darling theories of the most influential participants here and I can only encourage everyone to fact check everything that's said here on their own.

 

[Utsikt]

Being away from the forum was helpful. I researched on my own and found out that acyclovir has very good activity against EBV abortive lytic reactivation. Which is exactly why herpes theory of ALR was brought up in ME/CFS as playing a central or a causative role a long time ago. It was predicted in lab studies in 1980 and then confirmed clinically in AIDS patients with hairy leukoplasia.

I was somewhat shocked to realise that nobody here but also my ME/CFS specialist didn't know about this a bit paradoxical activity spectrum of acyclovir.

It made me realise that even though lots of people with medical degrees and a training in biomedicince are on this forum there is a big gap of information in basic knowledge about drugs and theories that aren't the darling theories of the most influential participants here and I can only encourage everyone to fact check everything that's said here on their own.

In the spirit of fact checking, would you be able to share the documentation for these claims?

 

[PageofME]

In the spirit of fact checking, would you be able to share the documentation for these claims?

I've researched it all with Gemini and haven't factchecked it all myself yet. Will do so with a friend who is a researcher and a pharmacologist as soon as my brain has restored itself from the mild drug toxification.

What I know already from a quick phone call with him: He broadly confirmed what Gemini claims and that he was aware of this somewhat paradoxical activity spectrum of acyclovir.

The most important papers Gemini pointed me towards that detected this paradoxical activity of acyclovir in EBV early stage replication:
Datta AK, Colby BM, Shaw JE, Pagano JS. Acyclovir inhibition of Epstein-Barr virus replication. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5163-6. doi: 10.1073/pnas.77.9.5163. PMID: 6254061; PMCID: PMC350017. doi.org/10.1073/pnas.77.9.5163
Colby BM, Shaw JE, Elion GB, Pagano JS. Effect of acyclovir [9-(2-hydroxyethoxymethyl)guanine] on Epstein-Barr virus DNA replication. J Virol. 1980 May;34(2):560-8. doi: 10.1128/JVI.34.2.560-568.1980. PMID: 6246281; PMCID: PMC288736. https://doi.org/10.1128/jvi.34.2.560-568.1980
The clinical proof in hairy oral leukoplasia:
Walling, D. M., Flaitz, C. M., & Nichols, C. M. (2003). Epstein‐Barr Virus Replication in Oral Hairy Leukoplakia: Response, Persistence, and Resistance to Treatment with Valacyclovir. The Journal of Infectious Diseases, 188(6), 883–890. https://doi.org/10.1086/378072

 

[PageofME]

I am off the drug since Friday now when I realised that the side effects had actually become intolerable. The shutting down of brain functions that are connected to the neocortex presumably which is theorised in the literature as a major side effect. What I observed was a mind that was numb, sluggish, and somewhat dissociated, and at the same time quick to react on conflictive emotions like fear and anger. It gave me a good grasp on what's going on in the birds or the cats around my apartment when they get into a fight. They don't overthink but get themselves right into it.


My brain now feels that it needs time to recover from that adverse effect when at the same time it doesn't feel as if there's a permanent damage.

Over all, I am very happy that I have made that trial at last and had the support of my GP to do so in order to find out whether it was feasible for me to go on the drug continually. And for the moment and given my ME/CFS upper moderate health level the benefits do not outweigh the adverse effects.

So that I have already decided to go back to a treatment regime that I have established in the first year of my experiments with only fighting flares when they present or doing a prophylactic cure when I realise I am to distressed to have a good control of my pacing because of inner or outer adverse experiences or the nurse within me needs a holiday for a couple of days.

My ME/CFS baseline seems to be quite strong after the trial. However, where it is exactly I of course have no idea yet. And that's certainly a lot of work after every time I am on the drug because it goes extremely fast that I lose not only an intuitive grasp of where my baseline lies but also pacing skills and the discipline to follow through every day unwaveringly.

 

[PageofME]

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.

Thank you for writing this. However, I don't know whether we can really be a support for each other. To be frank, I don't feel supported by someone telling me that the best explanation for my experience that acyclovir suppresses my flairs is that it is kind of a useless signal and that my fellow acyclovir responders over at Reddit are insignificant too.

What is this really about? My intuition tells me that you are looking for someone to support you. I feel that your current and past suffering with ME/CFS is much higher than mine. You are sicker than myself and for much longer for sure. Please just forget if I get you totally wrong. It's an intuition because on the conscious plane I can't understand why you have been writing to me several times; warning me that the drug that I have found that works for me again and again since many years both when I use it when acute or as a prophylaxis to prevent a flare and have fought hard to get prescribed off-label for years is actually not helping me.

Franky, I came on this platform and expected other patients to congratulate me for my sharp instincts and advocating skills and renew their interest in herpes research. However, the experience is quite different, and it's ok, I know how sick many patients are and for how long they have suffered, have had their hopes destroyed many times and are exhausted and traumatised. I of course have compassion for that. But I won't allow other patients to deny that this drug actually works for me and that I can be really happy and grateful that I have found something that I can turn to in an emergency situation and don't have to fear uncontrolled deterioration of my health levels.

I will have to move house soon and without that drug I would be already in a constant fear of deterioration because of the strain that comes with this. But now I am totally relaxed because I could tolerate another two weeks on the drug whenever necessary and stay without a flare even when I couldn't follow through with the required rest and pacing.

I am a bit puzzled. What could be your true message?

If you're angry that I have found a drug even before I was diagnosed and you haven't found anything since 35 years I'd completely understand and you have all my compassion – not pity – compassion! I can imagine what this means and how much strength and perseverance you had to bring up.

 

[PageofME]

My GP is now ready to support my decision to start a therapeutic trial of antivirals known to block early-phase EBV activity – specifically valacyclovir and famciclovir. Two key factors influenced this decision. First, my doctor noted that after five years of working together, she deeply trusts me to use the medication responsibly, meaning I will continue to prioritize adequate rest while on it.

Second, I suspect her change of heart was also driven by the massive body of evidence I provided showing that early-phase EBV activity is central for a major subset of ME/CFS patients, alongside the weight of new research projects recently launched at Ivy League universities in the US.

While we haven't finalized the exact protocol yet, my GP prefers a treatment regime where I maintain a low-stress lifestyle, careful energy management, and plenty of rest. Her initial thought was to use these virostatics to manage episodes as needed – acting as a prophylaxis during high-drain or emergency life situations, and, of course, to treat acute flares.

However, my goal now is to pursue a continuous trial for another six weeks to complete a full three-month course. I wouldn’t be particularly thrilled to do this with valacyclovir, but just yesterday, she wrote me a one-week trial prescription for Famvir (famciclovir), which makes a continuous course much more feasible. After just a day, I can already tell I tolerate it much better; the encephalitis-like side effects I experienced before are not an issue with this newer drug.

My experience with valacyclovir offered a major insight: because it had fewer initial negative effects compared to acyclovir, I ended up overdosing. It made me realize how common it is in medicine for patients to mistakenly believe that severe side effects prove a drug is working. I now recognize that I don’t need a massive prophylactic dose of 1000–1500 mg of valacyclovir; a much lower dose of 2x250 mg is sufficient for my current baseline and exertion threshold.

Because we ran out of time during my appointment to fully map out the transition, I used Gemini to calculate the equivalent dose for Famvir. Without diving into the complex pharmacology behind the recommendation, I landed on the exact same dosage: 2x250 mg of famciclovir. While it is too early to write an elaborate review after only 24 hours, I can safely say the side-effect profile is vastly more tolerable. To add to the good news, my kidney function lab results came back today showing that everything is functioning perfectly.

Last but not least, a shift is happening emotionally due to these changes in my medical situation. I have ongoing post-traumatic stress primarily tied to severe family and psychotherapeutic interpersonal abuse (betrayal trauma) that happened before I developed ME/CFS. These feelings are surfacing now because I have finally reached a much safer, less distressing environment compared to the last five years. During that time, I lived in constant fear of a deterioration in my health, trying to avoid flares at all costs by strictly pacing and striving to live as the "perfect" ME/CFS patient.

Between the new medication, the validation and support from my GP, and the highly promising research validating herpesvirus reactivation at the core of ME/CFS, my entire outlook and life situation have completely transformed in just a matter of weeks. Around that I experience a roller-coaster of intensive excitement looking at the positive changes and a much brighter future and complete exhaustion and even lethargy stemming from the overwhelming distress of the past years. I have restarted Chinese medicine treatments to help cope with this.

 

[PageofME]

The one-week trial of famciclovir is coming to an end and I am very satisfied. I experienced none of valacyclovir's brain-fogging side effects. Famciclovir has few side effects for me, the only one strong enough to notice at all is occasional dizziness. And overall, while I don't feel completely "sober," I don't feel impaired in any way. Valacyclovir, however, could induce massive, abnormal fatigue at times.

I informed my GP and have secured a prescription for three months, renewable as many times as I need it.

It's an absolute relief that I can check this task off my medical to-do list.