Low Dose vs High Dose Antivirals

[IreneF]

@used_to_race Dr Lerner writes in his papers that a worsening of symptoms in the first weeks of treatment is probably a Jarish-Herxheimer reaction and indicates good response. He said this reaction should be over by week 6.

I had it, too, but it lasted for only about 3-4 weeks. It felt a bit strange. I was clearly getting worse during that time, but it felt like it is part of the recovery, like when you have the flu in the final part of it when you still feel quite sick, but it feels like you're on your way to getting better.

I'm not saying you should continue high-dose treatment, I don't know what the right treatment is for you - just sharing my experience.

I think there's a lot of confusion about "herxing". It's a bodily reaction to an antibiotic treatment when the bacteria die and release toxins. So you would only experience it under those circumstances.
https://en.m.wikipedia.org/wiki/Jarisch–Herxheimer_reaction
I think feeling bad when you take antibiotics is often a side effect of the drugs themselves.

 

[Wonkmonk]

Dr Lerner calls it a Jarish-Herxheimer reaction, that's why I used the term. Dr Lerner always admitted he can't entirely prove why his treatment works (for some patients) and what exactly is going on, so it may not technically be a Herxheimer reaction.

 

[heapsreal]

Valtrex half-life is 2.5-3.6 hours, Famciclovir is 2.0-2.3 hours, so yes it is a bit shorter for Famciclovir, but Dr Lerner recommends the same dosing and frequency for both drugs (i.e. 1,000mg four times daily for patients <80kg).

Regarding the dosing, Valtrex bioavailability is lower for higher doses, i.e. if you take 1000mg at once, a smaller fraction is absorbed as if you take 500mg in two doses several hours apart. This effect is not observed with Famciclovir, absorption is almost entirely proportional to the dose.

I havent been able to find the answer to valtrex but famvir its said to have an intracellular half life of 18hrs.

https://www.ncbi.nlm.nih.gov/pubmed/8840412
Penciclovir-triphosphate has a prolonged in vitro intracellular half-life of 10 to 20 hours in HSV-1-and HSV-2-infected cells, respectively, and 9 to 14 hours in VZV-infected cells. In contrast, the in vitro intracellular half-life of acyclovir is substantially shorter at 0.7 and 1 hours in HSV-1- and HSV-2-infected cells, respectively, and 0.8 hours in VZV-infected cells.

Acyclovir is mentioned this link and that is how valtrex works ie converting to acyclovir. So famvir/penciclovir appears to last much longer going by the above link.

 

[used_to_race]

@used_to_race Dr Lerner writes in his papers that a worsening of symptoms in the first weeks of treatment is probably a Jarish-Herxheimer reaction and indicates good response. He said this reaction should be over by week 6.

I had it, too, but it lasted for only about 3-4 weeks. It felt a bit strange. I was clearly getting worse during that time, but it felt like it is part of the recovery, like when you have the flu in the final part of it when you still feel quite sick, but it feels like you're on your way to getting better.

I'm not saying you should continue high-dose treatment, I don't know what the right treatment is for you - just sharing my experience.

Yeah, I read those papers many times before starting treatment. He actually says in this paper that the herx reaction could happen for up to 10 weeks, and some people on other forums have complained about a worsening of symptoms for even longer on drugs like Valcyte. My experience was a little different though, because for the first 6 weeks I felt largely the same, maybe 5% worse. My normal daily functionality was like 6-8/10. Then suddenly, over a 2 day stretch, I went from 6-8/10 to like 3-4/10, with barely enough energy to go to the doctor's office. And because my doctor doesn't support me taking the antivirals and couldn't offer any useful feedback on what could be going on, I chose to stop. It's possible that someone like Lerner or Montoya would have seen this change as a big sign that I was going to improve later on, but I didn't want to risk anything myself. A week later, I'm back to "baseline sick", and I will be making an appointment with Dr. Chia pretty soon, so I think I made the right decision. Especially since my insurance is through my job and I'd lose it if I couldn't work for a long period of time.

 

[Wonkmonk]

As you know Dr Lerner's work very well, I assume you probably did all the test for co-infections, especially tick-born diseases, right? Just asking because in one paper I read that several bacterial co-infections - for some unknown reasons - can prevent antiviral treatment from being effective.

In another paper, he suggests that for those who do not respond for over 6 months, response rate can be improved by co-administering Cimetidine or Probenecid. But that's also probably not news to you

I think visiting a knowledgable physician who specializes in CFS antiviral treatment is the right course of action now.

 

[used_to_race]

@Wonkmonk it may surprise you but I haven't been tested for HHV6, tick-borne diseases, or many other things that may be a problem for folks like us. My current doc is an absolute nightmare and refuses to order these tests, repeatedly telling me I need psychiatric help. I'm going to switch insurance in November, at which point my plan is to see someone more competent at UCLA, along with Dr. Chia in January.

To be fair, I'm negative for CMV and I became sick in Colorado, which has the second-lowest incidence of Lyme in all 50 states. Chia's EV hypothesis really resonates with lots of details of my case, but I'm really looking forward to getting more extensive tests done soon. Moreso, I'm looking forward to having a doc who cares at all.

 

[Wonkmonk]

Ruling out psychology as a cause is important, but I find some physicians' focus on it very annoying, and in my case it went as far as trying to talk me into accepting my symptoms are from depression even though I insisted that's impossible.

Before my CFS diagnosis, when I visited a physician to ask what might be wrong, I told them at the very beginning, that I can definitely rule out depression. Some still tried, but it got much harder

I think now that my antiviral treatment was so successful, I take it as proof that I was right and that it didn't have anything to do with psychology or psychosomatics.

 

[Oberon]

Ruling out psychology as a cause is important, but I find some physicians' focus on it very annoying, and in my case it went as far as trying to talk me into accepting my symptoms are from depression even though I insisted that's impossible.

Before my CFS diagnosis, when I visited a physician to ask what might be wrong, I told them at the very beginning, that I can definitely rule out depression. Some still tried, but it got much harder

I think now that my antiviral treatment was so successful, I take it as proof that I was right and that it didn't have anything to do with psychology or psychosomatics.

I was accused multiple times by different doctors of my CFS being psychosomatic too. Eventually I actually went to a Psychiatrist and they told me I don't meet the profile of a psychomatic disorder. It's interesting how quickly doctors jumped to a psychosomatic cause, but the actual psychiatrist said it's very unlikely.

 

[heapsreal]

How many people have had pcr viral testing for the actual viruses versus testing for viral antibodies which is dependent on a healthy immune system??

 

[sb4]

Eventually I actually went to a Psychiatrist and they told me I don't meet the profile of a psychomatic disorder. It's interesting how quickly doctors jumped to a psychosomatic cause in my cause, but the actual psychiatrist said it's very unlikely.

Off topic but not even this has helped me. It was insisted I see a psychiatrist who then gave me the all clear, yet the very same doctor (and all those after him) who told me to see the psych then continued to tell me it was just anxiety.

 

[Wonkmonk]

I was tested for EBV PCR. No viral DNA detected.

I wasn't tested for the other herpes viruses, but I didn't have a cold sore in years, HHV6- IgG titer is low (1:32) and I never had shingles (VZV reactivation), so there is no evidence to suggest any complete HSV-1, VZV or HHV6 virus replication. CMV and HSV-2 is negative.

 

[2Cor.12:9]

Hi Everyone,

I was wondering if anyone's done research on the efficacy of lower doses of antivirals versus higher doses for CFS? Are there any studies out there?

I have one doctor recommending a lower dose of Famvir - 500mg, while another doctor is recommending 2000-3000mg Valtrex and I'm having trouble deciding on which approach to take.

I'm always hesitant to take more than is necessary due to potential toxicity issues, but I don't want to take away from the effectiveness of the treatment plan.

Thank you.

Thank you for asking this question! The answers have been really helpful as I navigate the antiviral dosage waters for the first time. I've been on 500 mg Valtrex 3 x daily for only 18 days and the added fatigue is brutal. Because so many here have still had a good response with just 2 pills a day, I'm going to cut back to see what happens. (I've had CFS for over 30 years and this is my first time trying an antiviral)

I appreciated this Valtrex/Famvir protocol by Dr. Podell -

http://www.drpodell.org/ValtrexConsent.pdf

 

[Wonkmonk]

Thanks for the interesting link. I think the following is important:

"Unfortunately, standard lab tests cannot definitely distinguish between latent, inactive versus active recurring infection."

Perhaps one could add that standard lab tests always test the blood only. What happens inside the cells and in the tissue and organs is totally a black box. For instance, there are studies that show that if presence of EBV in gum tissue correlates with the risk of periodontal disease:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312996/

I am wondering: What is going on in the organs? Could EBV be present in the heart, kidneys, brain etc. of (some) CFS patients and cause harm there?

If so, it likely won't ever be detected, because lab tests only check the blood.

Dr Lerner used to do heart biopsies and found the heart of CFS patients is damaged, but I am not aware he checked for the presence of EBV or other viruses in the heart tissue.

That would explain why recovery on antivirals is so slow (clearing the virus from organs and undoing organ damage occurs slowly) and also why recovery is incomplete in most cases and many patients relapse when they stop (virus reservoirs were not cleared completely).

That brings me to my favorite hypothesis: If EBV is the suspected cause of a CFS patient and s/he responds to Valtrex, could response be improved by using Rituximab plus Valtrex?

With respect to EBV, Rituximab is so to speak the Bazooka. Antivirals don't kill EBV, they just stop replication. Rituximab denies EBV access to its main reservoir: Memory B-Cells.

So combining Rituximab and antivirals would be much more effective in reducing viral load throughout the body.

I am surprised that no one seems to have tried this (or at least no study exists and no one reports in this forum so far).

 

[2Cor.12:9]

I am wondering: What is going on in the organs? Could EBV be present in the heart, kidneys, brain etc. of (some) CFS patients and cause harm there?
).

I wonder the same thing @Wonkmonk and don't know how it could not be , since every bodily system seems to be impacted in some way or another.

Dr.Pridgeon's accidental discovery that Herpes Simplex was found in gut biopsies of patients who "coincidentally" also had fibromyalgia, led him to believe that it is HSV rather than EBV that is the culprit in most of cases of fibromyalgia - He's had a good success rate with his antiviral and anti inflammatory protocol for his FM and also some of his CFS patients. If his hypothesis proves true, then perhaps we've been looking at the wrong herpes culprit - Where he found HSV is gut biopsies, he did not find EBV.

http://simmaronresearch.com/2016/10/pridgen-antiviral-treatment-fibromyaligia/

 

[Wonkmonk]

It's funny, I have (very low) positive EBV EA, so that's a red flag in Dr Lerner's protocol, but it's strange that I also have an extremely high HSV-1 IgG titer - it's reported as >1:20,000, so it's even outside the range that the lab reports (IgM is negative). No one could explain to me so far why HSV-1 IgG is so high.

So perhaps HSV-1 is indeed the culprit and not EBV, or perhaps they are both out of control.

 

[2Cor.12:9]

.

@Wonkmonk - just came across this. I also have Hashimoto's.

"A 2015 Polish study found the Epstein-Barr virus in the thyroid cells of 80% of people with Hashimoto’s and 62.5% of people with Graves’, while controls did not have EBV present in their thyroid cells. (1)

https://thyroidpharmacist.com/articles/epstein-barr-virus-and-hashimotos/

 

[Wonkmonk]

That's interesting. Of course, causality is so far unproven, but my first question would be: How is it that in some people, EBV is present in various tissues and organs and probably causes a lot of harm there, while in other people, it is not?

Regarding the latter group: Is their immune system more effective at keeping EBV out of the organs, and if so, why is that the case?

And I strongly suspect those who had EBV in their thyroid gland in the above study had no indication of active EBV in the blood in their standard lab tests.

 

[2Cor.12:9]

How is it that in some people, EBV is present in various tissues and organs and probably causes a lot of harm there, while in other people, it is not?

Regarding the latter group: Is their immune system more effective at keeping EBV out of the organs, and if so, why is that the case?
.

Cort Johnson has an interesting article regarding Michael Pender's EBV/autoimmunity hypothesis and a possible reason being that some people have a genetic defect that prevents them from keeping EBV in check - thus developing various kinds of autoimmune conditions.

"Pender and other researchers believe an inherited defect in cytotoxic T-cells that prevents them from controlling EBV may be behind a lot of autoimmunity. (A Simmaron Research Foundation project involves looking for inherited problems in T-cells, B-cells and NK cells killing capacity.) It turns out that a long list of autoimmune disorders are, in fact, characterized by low cytotoxic T-cell levels."

http://simmaronresearch.com/2014/05...nity-hypothesis-fit-chronic-fatigue-syndrome/

 

[heapsreal]

Cort Johnson has an interesting article regarding Michael Pender's EBV/autoimmunity hypothesis and a possible reason being that some people have a genetic defect that prevents them from keeping EBV in check - thus developing various kinds of autoimmune conditions.

"Pender and other researchers believe an inherited defect in cytotoxic T-cells that prevents them from controlling EBV may be behind a lot of autoimmunity. (A Simmaron Research Foundation project involves looking for inherited problems in T-cells, B-cells and NK cells killing capacity.) It turns out that a long list of autoimmune disorders are, in fact, characterized by low cytotoxic T-cell levels."

http://simmaronresearch.com/2014/05...nity-hypothesis-fit-chronic-fatigue-syndrome/

https://www.msaustralia.org.au/news...earchers-make-major-breakthrough-ms-treatment

 

[Janice Hargreaves]

Also there is Loebels et al ( PLoS One. 2017 Jun 12;12(6):e0179124. doi: 10.1371/journal.pone.0179124. eCollection 2017.) who believe that some people have problems with EBNA6 and so from my little understanding means these people cannot fully control EBV.

I'm on 400 mg Aciclovir 3 X a day plus weekly injections of B12 under directions of Dr Bansal. I am now At about 3 month mark and have dipped down in energy but many of long term symptoms have been vastly reduced.

So I'm hoping after 6 months if I carefully manage my use of energy ( I find that really difficult! )I can persuade my systems back into a more normal place? Who knows? I felt it's worth a shot.