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Herpesvirus antivirals for ME/CFS linked to HSV-1 and VZV

Wonkmonk

Senior Member
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1,003
Location
Germany
Split from the thread 'Anatomy of an Enterovirus / Coxsackie B Virus Outbreak — Overt Illnesses and Subclinical Symptoms'

I'll probably still try the herpes virus route again. I think it is important to have tried everything, so you know that's probably not the problem. I think I'll do Valcyte plus Hydroxychloroquine for a while and see what happens.

And if herpes virus is not the cause, and it is instead enterovirus. Maybe if the herpes virus is better under control, the body has an easier time fighting the enterovirus. Or Valcyte has some activity against enterovirus as well. Or Valcyte in combination with Hydroxychloroquine (which Dr Montoya has been positive on). Or there is an immunomodulation effect that helps fight the enterovirus.

The herpes medications might be effect for a reason other than their antiviral potential. That would be consistent with the finding of I think Dr Montoya has made and also many on this forum including me, that the positive effects of antivirals don't seem to be dose-dependent or at least don't necessarily increase with a higher dose. If the antiviral effect was responsible, one would expect that a higher dose would have a better effect, but this is not what one observes.
 
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Hip

Senior Member
Messages
17,809
I'll probably still try the herpes virus route again.

For ME/CFS purposes, I think it is a good idea to treat any and every active ME/CFS-associated infection that you have, as indicated by chronically high IgG titers, as that's what the ME/CFS specialists usually do.
 
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Wonkmonk

Senior Member
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1,003
Location
Germany
The response pattern of patients with suspected herpes virus infections to antivirals would be entirely consistent with the hypothesis that they (or at least some of them) actually have enterovirus infection (or co-infection).

The herpes virus antivirals provide immunomodulation (stimulation?) and help keep the herpes viruses in check which in turn frees up immune system capacity to fight the enterovirus. Over time the immune system can grind it down, but it may take many years.

If the herpesvirus was the sole cause of the CFS, one would expect the antivirals to work much more quickly (this was also acknowledged by Dr Lerner). Dr Lerner said that's because there is an incomplete replication of the herpes virus that isn't inhibited by today's antivirals, but evidence for this theory is scant.

If you assume there is a co-infection of some sort (e.g., enterovirus) that is unaffected by the antiviral, but is better addressed by the immune system over time once the herpes viruses are under control, then the time-response relationship makes sense.
 

junkcrap50

Senior Member
Messages
1,325
The response pattern of patients with suspected herpes virus infections to antivirals would be entirely consistent with the hypothesis that they (or at least some of them) actually have enterovirus infection (or co-infection).

The herpes virus antivirals provide immunomodulation (stimulation?) and help keep the herpes viruses in check which in turn frees up immune system capacity to fight the enterovirus. Over time the immune system can grind it down, but it may take many years.

What is the minimum dosage for long term antivirals to grind down herpes virus? Learner used Valtrex 1,000mg 4x/day due to Valtrex's half-life. What do the other CFS docs use like Kaufman/Montoya/other well known ones use?

My cfs specialist who's also an infectious disease doc says that Valtrex 1,000mg 2x/day is probably enough (that's all my insurance will approve) for long term Learner-type treatment.
 

JES

Senior Member
Messages
1,318
The response pattern of patients with suspected herpes virus infections to antivirals would be entirely consistent with the hypothesis that they (or at least some of them) actually have enterovirus infection (or co-infection).

Yep, this is an intriguing possibility. I read some time ago from a random website (link) that acyclovir according to a study helped in shortening the illness duration in acute enterovirus infection. I think there's a lot that we don't yet know about the effects of these antiherpesvirals.
 

Wonkmonk

Senior Member
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1,003
Location
Germany
What is the minimum dosage for long term antivirals to grind down herpes virus? Learner used Valtrex 1,000mg 4x/day due to Valtrex's half-life. What do the other CFS docs use like Kaufman/Montoya/other well known ones use?

My cfs specialist who's also an infectious disease doc says that Valtrex 1,000mg 2x/day is probably enough (that's all my insurance will approve) for long term Learner-type treatment.

That's correct, Dr Lerner recommends Valtrey 1000mg 4x daily and 1500mg 4x daily for patients >80kg.

I think I read in this forum Dr Montoya is using lower doses for Valtrex in the 1000-2000mg per day range, because higher doses don't seem to be effective.

But on the other hand, @Learner1 was treated by Dr Montoya with 900mg 2x per day Valgancyclovir, which is a rather high dose. Dr Lerner recommends 900mg in the morning and 450mg in the evening (900mg in the evening for patients >90kg).

A great overview can be found in Hip's roadmap which you can find in the "General Treatment" subforum.

Needless to say, any treatment decision should be made together with a health care professional.
 

Wonkmonk

Senior Member
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1,003
Location
Germany
I read some time ago from a random website (link) that acyclovir according to a study helped in shortening the illness duration in acute enterovirus infection. I think there's a lot that we don't yet know about the effects of these antiherpesvirals.

My experience with Valacyclovir is entirely consistent with the hypothesis that it doesn't fight the virus responsible for CFS directly, but in some indirect way.

I had some good results in the first few months with Valacyclovir, but taking higher doses did not bring any further improvement at all. Adding another antiherpetic drug (brivudine) also didn't improve anything. If anything it made me worse because of additional side effects.

This is consistent with the idea that at some point, the herpes virus is kept in check and upping the dose further doesn't help much to help fight the pathogen that actually causes the CFS (e.g. enterovirus). It would also be consistent with an immunomodulation effect that is not dose dependent or for which higher doses have less additional benefit.

It is not consistent with the herpes virus being the cause of the CFS; because one would have expected the recovery to accelerate with higher doses of anti-herpetic drugs. That was not the case.
 

Wonkmonk

Senior Member
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1,003
Location
Germany
I also had highish titers to cytomegalovirus and herpes simplex 1

Same here with HSV-1 and VZV. It may be the case that enterovirus and herpes virus somehow act synergistically to produce the "normal" enterovirus-associated symptoms and CFS.

Only those of us where herpes virus and enterovirus is out of control get CFS, or they get a peculiar type of CFS with the characteristic symptoms you mentioned in addition to the usual fatigue etc.

Dr Lerner looked at multiple herpes virus co-infections and bacterial-herpes virus co-infection. In both cases he found that CFS cannot be successfully treated unless all involved pathogens are being treated.

But he did not look into herpes virus-enterovirus co-infection. That may be a similar case and it would explain why some patients don't respond to antiviral treatment at all.

Bad luck if that's the case, because enterovirus cannot be successfully treated so far.
 

Learner1

Senior Member
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6,305
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Pacific Northwest
But on the other hand, @Learner1 was treated by Dr Montoya with 900mg 2x per day Valgancyclovir, which is a rather high dose. Dr Lerner recommends 900mg in the morning and 450mg in the evening (900mg in the evening for patients >90kg).
Actually, I take 900mg twice a day, prescribed by Dr. Kaufman. I've never seen Montoya, but assume they talk occasionally.
 

Wonkmonk

Senior Member
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1,003
Location
Germany
Actually, I take 900mg twice a day, prescribed by Dr. Kaufman. I've never seen Montoya, but assume they talk occasionally.

Ahh, sorry, of course it was Dr Kaufman, I got that wrong. Brain not functioning well lately :rolleyes:

Are you still on Valcyte? I remember you plan to start antibiotics (hope I am not also getting this wrong), if you do, are you going to continue Valcyte plus start ABs?
 

Learner1

Senior Member
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Pacific Northwest
Yes, I've been on Valcyte 9 months. I hope I don't have to take it for me 5 years Montoya recommends. I think the idea is to beat back the viruses so they don't even think of reactivating.

I did 4 months of azithro/doxy/rifampin for chlamydia pneumoniae and mycoplasma pneumoniae.

Doing much better after all of it. My life is completely normal 40% of the time. The rest is a work on progress, dealing with all the collateral damage and POTS.
 

Wonkmonk

Senior Member
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1,003
Location
Germany
May I ask, if you know, what your titers were for chlamydia pneumoniae and mycoplasma pneumoniae?

I am also mycoplasma positive, but at the lower end just over the threshold.
 

Wonkmonk

Senior Member
Messages
1,003
Location
Germany
I myself, I read the papers from Dr Lerner and did the tests and I found the wildly elevated HSV-1, significantly elevated VZV and mildly elevated EBV EAD.

There are no doctors in Germany who do herpesvirus diagnostics and treatment for CFS.
 

Hip

Senior Member
Messages
17,809
I myself, I read the papers from Dr Lerner and did the tests and I found the wildly elevated HSV-1, significantly elevated VZV and mildly elevated EBV EAD.

If you have wildly elevated HSV-1, then by any standards you can assume it is a chronic active infection.

But HSV and VZV are not standard pathogens usually linked to ME/CFS; at least to my knowledge.

So high titers may not necessarily have any significance in the ME/CFS context. Although Dr Pridgen believes active HSV is involved in fibromyalgia, and he speculates maybe in ME/CFS too. The Pridgen Protocol uses two antivirals to target HSV: Famvir and Celebrex (Dr Pridgen believes COX-1/COX-2 inhibitors like Celebrex fight HSV).

But there are almost no studies showing a link between HSV or VZV and ME/CFS, so you might want to be cautious about your hypothesis that HSV and VZV are causing your ME/CFS.
 

JES

Senior Member
Messages
1,318
It sounds a bit complicated to me, so I probably won't send to Greece right now, also because my primary hypothesis is still that I have a herpes virus problem. As I wrote before, my HSV-1 IgG titer is ">1:20,000", so it is to be considered elevated by any standard. But when Valcyte fails to be effective, I might well seek the more sensitive test from Greece.

I suppose one way to establish a link between herpesvirus and CFS in your case would be to try one of the proven antivirals (like valtrex/valcyte/vitamin C IV) and while taking the drug, monitor changes in your antibody titer levels. Even if the absolute titer ranges are somewhat relative to each lab, if you perform the same test in the same lab, it should give a good indicator if these treatments actually have an effect on your levels.

If both your symptoms AND titers improve, then that's IMO pretty good evidence that a herpesvirus is involved in your case. I can't even find a doctor in my country to perform any kind of viral tests, so I'm always interested in hearing how these treatments work for others.
 

Wonkmonk

Senior Member
Messages
1,003
Location
Germany
I suppose one way to establish a link between herpesvirus and CFS in your case would be to try one of the proven antivirals (like valtrex/valcyte/vitamin C IV) and while taking the drug, monitor changes in your antibody titer levels.

If you have wildly elevated HSV-1, then by any standards you can assume it is a chronic active infection.

I'd say ">1:20,000" HSV-1 IgG qualifies as "wildly elevated". It's so high that it's even outside the range that the lab can report.

All your other caveats are of course correct, although I think a possible link between VZV and CFS has been pointed out (see the Montoya lecture that I posted elsewhere).

@JES What is puzzling is that even very high dose antiherpetic drugs (Valacyclovir 6 grams a day for several months plus 2000mg probenecid a day for 8 weeks plus Brivudine 125mg for several weeks) did not substantially improve the symptoms and did not lower the HSV-1 titers (at least not below 1:20,000 - maybe they went down from 1:100,000 to 1:50,000, but that doesn't show because it's all outside the labs range). VZV titers went down quite a bit, but are still >1:1000.

So I consider the use of these antiherpetic drugs to be a failure. It may be because I likely have some streptococcal activity (antistreptolysin O ~300 for a year, elevated >200) and Dr Lerner suggests that this can render antiviral CFS treatment ineffective. But he says that's only for titers >400 and my highest titer was 326.

It is currently my hope that the antiherpetic drugs were ineffective because of some bacterial activity, and that with my current antibiotic treatment, I can take care of that and the antivirals will be effective afterwards. I am going to try Valcyte because it's stronger and also going to try Hydroxychloroquine as mentioned by Dr Montoya.

But to be honest, I'm not optimistic. It's hard to see why antivirals should work now when so high doses for the past year were ineffective. But it remains to be seen.

But that's why I find the Enterovirus hypothesis is so interesting. It might be a plausible explanation for everything.
 

Hip

Senior Member
Messages
17,809
I'd say ">1:20,000" HSV-1 IgG qualifies as "wildly elevated". It's so high that it's even outside the range that the lab can report.

That's pretty high.

It might be worth looking at COX-2 inhibitors, as I think these work against HSV-1 not so much by an antiviral effect, but by preventing HSV-1 reactivation. See this study, which found that COX-2 inhibitor celecoxib suppressed HSV-1 reactivation in the trigeminal ganglia of mice. Celecoxib can cause severe stomach side effects, and is thus normally taken with proton pump inhibitors (although one study found that celecoxib can be taken transdermally, bypassing the stomach).

Glutamine also suppresses HSV reactivation. Ref: 1

I am thinking it is possible your high HSV titers might be due to constant reactivation of the virus from latency, rather than any significant ongoing systemic infection, which COX-2 inhibitors might help prevent.
 
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