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

[PageofME]

The timelines are a pretty good indication that any positive effect of aciclovir is from an off-target effect, not its action on herpesvirus replication

When I fight my ME flares with aciclovir I have just the same timeline as the infectiologists see in their patients fighting their HSV-1 or two brain inflammations.

Do you want to claim that aciclovir does not work as pharmacologists have figured out by directly stopping the virus to replicate but fights reactivation by side effects. You have funny ideas!

 

[PageofME]

Perhaps you could share which papers you think are the most interesting? There might be some threads already.

The leading researchers on the HHV-6b hypothesis are Cliff and Prusty. There aren't too many. They are all important.

 

[PageofME]

You may need to get a new textbook, or perhaps there is a new mechanism you can elaborate? HHV-6b does not have the same kinase as HSV-1 & HSV-2. Acyclovir only targets this specific kinase to HSV-1 and HSV-2. It is ineffective for HHV-6. An hour response time is quite interesting as people with full HSV-1 & HSV-2 outbreaks the acyclovir takes many days to clear their outbreaks and fully stop viral replication. This is in the perfect kinase match scenario too.

I am really glad I bumped into that textbook. I am aware of HHV-6b having a somewhat different shape and therefore doesn't seem to be a match with aciclovir because that was explained there too.

However, there was also claimed that even when aciclovir was not used clinically to fight HHV-6b because of this perveived mismatch and there being other herpes drugs like ganciclovir that fight HHV-6 really well it was still known from in vitro studies that aciclovir had good activity against HHV-6.

It is this information that I build my theory upon that I have HHV-6b reactivation that I can fight with aciclovir.

Response time: I can only repeat for the third time. I have a one hour response time not only when I use aciclovir orally (400mg every 3-4 hours, I weigh 66 kg) to fight my ME flares. When I have a mild flare or a flare is only upcoming then one day of aciclovir in combination with complete bedrest for another 1-2 days are enough to push my flares completely down.

When I could use it for the first time a couple of years ago I had a strong ME flare with brain inflammation involved (a hot, tingling feeling in my frontal lobe, a fever, and increased brain pressure were part of the picture. I stayed on the drug for one week, taking 2400mg every day, and then used it another week to stay on the safe side and prevent any flare-ups with 2x400mg every day.

My experience is just the same with cold sores lip cream. I feel an effect after one hour and then I have to reapply the lip cream every three hours the latest for about 2-3 days. I'm sure everyone would agree with me that symptom reduction can be sensed very fast after the first application (approx. one hour) but then needs to be continued continuously for several days.

I am HSV-2 negative.

This is consistent with what I read in that paper about how infectiologists apply aciclovir orally in their HSV brain inflammation patients. Aciclovir unfolds it's full fighting power after one hour and then gets metabolized really quickly. Therefore you ideally add a little bit every hour.

 

[Rick Sanchez]

I personally agree that if we theoretically assumed anti-virals worked on a subset of MECFS patients then the effect should occur fairly quickly. Although whether it would work within hours I have absolutely no idea. The other 2 patients who were certain that Acy / Vala worked for them claimed to have effects within 2 weeks too.

But I wonder. How do you square your theory with the fact that so many patients have tried Acy / Vala (at the required dose) and not had any effect?

If we accepted the idea that a HHV subgroup existed (which I sincerely doubt), then surely said subgroup would have to be tiny?

I hope you don't see our replies as needlessly arrogant. It's just that pretty much everyone here including myself considers the discussion as one that ended decades ago when no one could replicate results in placebo controlled studies.

 

[PageofME]

MECFS clinics who do antivirals already start off with a high dosis right away, and for long enough that IF it actually worked we would know by now. If I had to venture a guess I would say at least thousands of MECFS patients would have tried vala / acy by now (at the hypothetically required dosis)

The fact that more ppl say they had a positive effect from LDN or whatever supplement, than from antivirals says everything there is to say rly.

Here in continental Europe I haven't heard of anyone in the last years who was put on aciclovir with an ME/CFS diagnosis. It was done by some doctors back in the days I understand. That's the reason why several studies have been done.

The studies are inconclusive when at the same time researchers who have looked into this have said that aciclovir and other herpes drugs should be studied further, perferrably by seperating patients with PCR.

Antivirals? I think that there are so many of them with very different pharmacologies that we can't discuss them all together.

This is a thread on aciclovir and other herpes drugs with activity against HHV-6b. That's a specific question.

As I explained several times aciclovir develops its full potential within one hour and patients can feel this immediately. Whatever is done at these clinics – I doubt that it is done by well informed doctors.

Here in Switzerland it's almost impossible to get a prescription for a herpes drug without a proof of reactivation. And none of the ME/CFS specialists prescribe it.

My specialist was very interested when I brought him the HHV-6b research and the studies that were done on aciclovir. He's researched a drug against a retorvirus anti-body. So it's kind of his field. Still he wasn't at all up-to-date about the herpes research in ME/CFS. I doubt whether doctors at these clinics that you mention are.

I am actually reminded of the experimental poly-pharmacy that has developed in the US since the 1980ies in psychiatry when I hear what's being done at Long Covid clinics in the states. I agree with you. I also think that nothing will come of this.

On a personal note: Do you believe that you had a three months placebo effect that then faded away over another six months?

 

[ChronicallyOverIt]

I am really glad I bumped into that textbook. I am aware of HHV-6b having a somewhat different shape and therefore doesn't seem to be a match with aciclovir because that was explained there too.

However, there was also claimed that even when aciclovir was not used clinically to fight HHV-6b because of this perveived mismatch and there being other herpes drugs like ganciclovir that fight HHV-6 really well it was still known from in vitro studies that aciclovir had good activity against HHV-6.

It is this information that I build my theory upon that I have HHV-6b reactivation that I can fight with aciclovir.

Can you elaborate on what textbook this is and what claims they make on this? Or any research that shows this?

 

[PageofME]

I personally agree that if we theoretically assumed anti-virals worked on a subset of MECFS patients then the effect should occur fairly quickly.

But I wonder. How do you square your theory with the fact that so many patients have tried Acy / Vala (at the required dose) and not had any effect?

If we accepted the idea that a HHV subgroup existed, then surely said subgroup would have to be tiny?

I hope you don't see our replies as needlessly arrogant. It's just that many consider the discussion as one that ended over a decade(s) ago when no one could replicate results in larger studies.

I have chatted online or in person to five patients who have tried aciclovir. Four of them had the same positive effect as I had. Three of them told me that they went immediately back to work or planned to go back to uni.

Two of them described that after three-twelve months they had to increase dosage a lot-a little bit. One of them told me that after nine months the effect was gone. The others haven't tried it long enough to be able to tell anything about fading effects or I am not in touch with them anymore.

One friend of mine shows a very similiar ME symptom picture and has tried aciclovir as well with no effect.

So the immediate picture that I have is very different from what other's here are seeing. My impression – with a focus on the German speaking countries is – that very few patients have tried aciclovir.

 

[jnmaciuch]

Do you want to claim that aciclovir does not work as pharmacologists have figured out by directly stopping the virus to replicate but fights reactivation by side effects. You have funny ideas!

When aciclovir is used for several days, yes it would work by inhibiting viral replication. I'm saying you can't apply the same logic to the first hour.

You're right that the drug concentration peaks in the blood in one hour. What you're missing from the pharmacodynamic perspective is that this does not mean that viral load starts declining rapidly within one hour. A full cycle of HSV replication takes closer to 12 hours to complete, similar to other viruses in that family. The drug does not kill or clear the virus, just prevents further replication. So within the first hour, viral load will only be reduced by a small fraction at most (see this paper, figure 7). And that's assuming that the drug immediately gets to all the infected cells and binds to the right proteins to cease all viral replication immediately--which, if you know anything about pharmacodynamics, is a fantasy.

The vast majority of fully formed viral particles and immunogenic viral fragments are going to be sticking around and still triggering an infection response until they are all cleared out by the immune system (which takes hours/days). Basically all the symptoms that you feel from an infection, whether that is local inflammation of a cold sore or malaise/brain fog, are caused by immune signaling responding to that virus, not the virus itself. So even if there was a meaningful reduction in viral replication in the first hour--let's be generous and say something like 5%--the immune system would still be reacting to the leftover fragments and still causing symptoms as if there was no change in viral replication.

However, there is a possible explanation for why aciclovir could cause a symptom reduction within an hour besides placebo effect--in addition to inhibiting viral DNA polymerase, it also directly targets proteins in immune cells. Very simple experiments show that this is likely true (example). It's also possible it targets something directly in the nervous system that would alter the feelings of pain or brain fog or malaise. [Edit: what would need to be established in a clinical trial is whether this actually happens in-vivo and contributes to symptom relief more than random fluctuation.]

It seems like this is a theory you find really personally important, so I don't think further discussion will get anywhere. Though if you think people are disagreeing because they simply don't understand pharmacological or viral dynamics, I hope this might prompt you to reassess that assumption. If infectious disease experts are telling you differently, I think that is an indication that they don't understand those dynamics.

 

[PageofME]

Can you elaborate on what textbook this is and what claims they make on this? Or any research that shows this?

I don't have the energy to find it again now. But I will get back to you to let you know. It was in one of the two German medical school text books on infectiology. But I don't remember which number or publisher.

 

[Rick Sanchez]

Here in continental Europe I haven't heard of anyone in the last years who was put on aciclovir with an ME/CFS diagnosis. It was done by some doctors back in the days I understand. That's the reason why several studies have been done.

This is a thread on aciclovir and other herpes drugs with activity against HHV-6b. That's a specific question.

As I explained several times aciclovir develops its full potential within one hour and patients can feel this immediately. Whatever is done at these clinics – I doubt that it is done by well informed doctors.

Here in Switzerland it's almost impossible to get a prescription for a herpes drug without a proof of reactivation. And none of the ME/CFS specialists prescribe it.

On a personal note: Do you believe that you had a three months placebo effect that then faded away over another six m

I live in continental Europe and I know of at least two MECFS clinics who have treated patients with Aca / Vala (I won't mention them). How many patients at these clinics have tried in total I can not say. But if I had to guess I would say at least 50 patients just at these two clinics, and that's a conservative estimate! And yes, at the theoretically required dose.

My point is that a lot of patients have indeed tried these treatments, and a lot of patients still do... And yet even anecdotally the evidence that this treatment works is honestly terrible. In fact we have significantly more positive brain training ancedotes than when it comes to Acy / Vala. I mean, why aren't there success stories all over the place? Well probably because it doesn't work, which is also why we have no successful placebo controlled study for the treatment.

Gun to my head. I would say that something did happen as a result of Vala. However I just can't deny the very likely chance that it was merely due to placebo / random fluctuations, given what I know about the illness and the failed Rituximab studies.

Placebo controlled studies are the only way to figure out if something works with this illness. And I think that healthy scepticism is the only correct response to both our ancedotes.

 

[PageofME]

I live in continental Europe and I know of at least two MECFS clinics who have treated patients with Aca / Vala (I won't mention them). How many patients at these clinics have tried in total I can not say. But if I had to guess I would say at least 50 patients just at these two clinics, and that's a conservative estimate! And yes, at the theoretically required dose.

Gun to my head. I would say that something did happen as a result of Vala. However I just can't exclude placebo / random fluctuations, given what I know about the illness and the failed Rituximab studies.

Maybe you could tell me the names of these mysterious clinics in a personal message. Because I am still searching urgently for a doctor who prescribes aciclovir to me in continental Europe.

And please stay fair and don't redact my comments in a way that damages the strenghts of my arguments when you cite them above of your reply.

 

[PageofME]

When aciclovir is used for several days, yes it would work by inhibiting viral replication. I'm saying you can't apply the same logic to the first hour.

You're right that the drug concentration peaks in the blood in one hour. What you're missing from the pharmacodynamic perspective is that this does not mean that viral load starts declining rapidly within one hour. A full cycle of HSV replication takes closer to 12 hours to complete, similar to other viruses in that family. The drug does not kill or clear the virus, just prevents further replication. So within the first hour, viral load will only be reduced by a small fraction at most (see this paper, figure 7). And that's assuming that the drug immediately gets to all the infected cells and binds to the right proteins to cease all viral replication immediately--which, if you know anything about pharmacodynamics, is a fantasy.

The vast majority of fully formed viral particles and immunogenic viral fragments are going to be sticking around and still triggering an infection response until they are all cleared out by the immune system (which takes hours/days). Basically all the symptoms that you feel from an infection, whether that is local inflammation of a cold sore or malaise/brain fog, are caused by immune signaling responding to that virus, not the virus itself. So even if there was a meaningful reduction in viral replication in the first hour--let's be generous and say something like 5%--the immune system would still be reacting to the leftover fragments and still causing symptoms as if there was no change in viral replication.

However, there is a possible explanation for why aciclovir could possibly cause a symptom reduction within an hour besides placebo effect--in addition to inhibiting viral DNA polymerase, it also directly targets proteins in immune cells. Very simple experiments show that this is likely true (example). It's also possible it targets something directly in the nervous system that would alter the feelings of pain or brain fog or malaise. [Edit: what would need to be established in a clinical trial is whether this actually happens and contributes to symptom relief more than random fluctuation.]

It seems like this is a theory you find really personally important, so I don't think further discussion will get anywhere. Though if you think people are disagreeing because they simply don't understand pharmacological or viral dynamics, I hope this might prompt you to reassess that assumption. If infectious disease experts are telling you differently, I think that is an indication that they don't understand those dynamics.

I find theory interesting. But I started this discussion to learn more about what's a sensible practical use of aciclovir in ME/CFS with other patients who also have their flares fully suppressed by the drug.

I feel pretty alone and uncomfortable in dealing with self-medicating with a prescription drug that has not only long term kidney damage potential but can also foster the building of resistancies in herpes viruses.

But the message that I got from you and others here was that my direct experience with the drug was not accurate and couldn't be real because it contradicted the holy laws of immunology on an abstract level.

I feel that the sole reason to bring it up was to undermine my trust in my direct observations of the workings of the drug in my body and judge my and all the other cases of ME patients who respond to aciclovir as not real but a placebo effect.

I am sure you get that why I didn't find that helpful at all.

Yes, we can stop our discussion here.

 

[PageofME]

I want to thank you all for your comments. Your criticisms help me to put together the most important papers when I am going to see an infectioloigst in May regarding my symptoms and my use of aciclovir.