Tenofovir Alafenamide anyone?

[heapsreal]

Almost a month for me on Tenofovir Alafenamide at 25mg a day. I can't say I've noticed much at all positive or negative. At the cross roads of doing another month and see if things improve or stopping and see if I notice things getting worse.

It's crossing my mind to just save up some money and get 6 months worth of generic valcyte. It seemed to help straight away

 

[godlovesatrier]

Hey heaps,

Maybe cmv and hhv6 are bigger issues for you. Or the valcyte immune modulation is much stronger than it is with TAF. Either way no harm saving up for it. Shame it's so expensive.

I do feel like I'm mainly benefitting from the immune modulation but it's really very hard to tell and if the sore throat is from ebv then I'm surprised the taf isn't hitting it harder. Or maybe it is.

 

[Shanti1]

I do feel like I'm mainly benefitting from the immune modulation but it's really very hard to tell and if the sore throat is from ebv then I'm surprised the taf isn't hitting it harder. Or maybe it is.

My understanding is that we get a flair because, as viral DNA transcription to RNA is inhibited, the viral proteins that inhibit our immune response are decreased, increasing immune recognition and destruction of virally infected cells, which further exposes the immune system to viral particles, in turn increasing the immune response even more. Nonetheless, at some point, the flair should stop and the symptoms should decrease to below baseline as a much larger percentage of viruses are pushed into their dormant phases.

I guess there is some information out there that TAF can also cause a TH2 to TH1 shift, although I was not able to find it myself. I suppose that in HIV treatment, it may cause an increase in TH1 simply by working in conjunction with other HIV anti-virials to increase the CD4 count.

I wonder how much of a leap of faith with TAF because we only have in vitro studies on its effectiveness against EBV. Knowing that TAF does get into our cells, I don't see why the in vitro wouldn't translate well into in vivo, which is why think it is worth trying.

I am sure I read recently that Dr Chia advises patients to take Inosine to draw out entereoviruses to expose them so that certain drugs can then get rid of them. Off topic but I am wondering if these drugs are enough by themselves.

I am not sure what Chia means by "drawing the virus out so that certain drugs can get rid of them". We can't get rid of a virus by causing it to replicate and then using an antiviral that inhibits replication because that only prevents the new virus from forming, but the "mother template" remains untouched. I just may not be understanding the context or the drugs involved.

As we know, with viruses that establish latency in cells, unfortunately, all antivirals can do is keep them in the latent phase. This is because their mechanisms only work on actively dividing viruses, but don't get rid of the viral reservoir.

The exception to this would be the immune activating medications because they may increase immune recognition of infected cells and facilitate the actual destruction of the cell and the viral DNA/RNA it is hosting. I think of Inosine and Oxymatrine in this category. This is also why people are interested in interferons, because they can strongly activate viral recognition by the Th1 side of immunity. Of course, that can come with scary side-effects from immune over activation. Apparently, peginterferon lambda is only active in the mucus membranes, which has generated great interest.

 

[hapl808]

@godlovesatrier Funny thing is that brain fog used to be my worst and most debilitating symptom. I worried I was getting early dementia and hoped that no one at work would notice. Now, after, a year on valac and using some off label meds that I think helped regulate my neural pathways, I almost never have brain fog.

I do still get mental fatigue, but not that feeling that my brain is working in slow motion and I can't grasp simple concepts. My main symptom now is orthostatic intolerance (something I only developed in April) leading to fatigue and poor cognition.

I get mental fatigue and constant brain fog. Unfortunately it was frustrating when I was more moderate, but being more severe it's totally debilitating. Work is pretty impossible. What things helped you most? Every time I try things like artemisinin, allicin, monolaurin, andrographis, oregano oil, etc - it feels like I get worse, then when I stop I can't tell if I returned to baseline which feels better because I've felt like shit for so long, or if I'm actually doing anything.

Yes it does feel like dementia, even though I have it milder than some when I get an attack of brain fog, I can't take in any new information, form memories or retrieve information. It's an absolute nightmare at work, but generally it's only when doing treatments that are new or antiviral or immune modulating that I experience this kind of issue.

Good description - I can't take in any new information or form new memories. I've found myself trying treatments that later I find in my journal I already tried and failed but I had no memory of attempting.

The frustrating part is a lot of things that worked when I was more moderate just stopped working when I became more severe. I haven't had a 'good' day in over five years.

 

[godlovesatrier]

That's a good summary Shanti.

Also I remember now he was talking about oxymatrine and Inosine. Sorry for going off topic there got my wires crossed but you explained it all much better than I could have

I forgot to say I'm experiencing quote bad arthralgia on the TAF. For example today I sat down for about 2 hours on the floor on a very comfy pillow and when I tried to get up my joints had totally locked up. It actually hurt to walk to be honest and I hobbled around for awhile until they have eased up. So yeah the viral immune modulation really seems potent with this.

I won't lie I'm excited to see this drug through and be rid of the brainfog and flu like symptoms it induces post dose. As that may then confer long term stability/improvement to (I hope) a stable 80% level of function. If I hit 90% I'd be excststic.

Oh and I forgot to mention this too. Yesterday summer bumps appeared on the sides of my fingers. I had the exact same thing happen last July when I started Josh's immune modulators. So it must be some sort of viral thing. Doctors don't know what causes it and have no treatment for it. It's a benign thing it's just weird! It tends to last as long as the primary immune response lasts.

Also you mwntion things like lambda that expose viruses. Whilst lamba is probably the only potent thing that can perform this function. Joshua Leisk did mass spectrometry on reishi products and found that only life extension reishi contains triterpenic acid. All the other reishi products don't contain any.
Anyway this acid causes viruses like ebv to be exposed to the immune system. I'm not sure if it works for other viruses though. But I'm taking that too. So even though the effect is rather slow and mild assuming it works it should very gradually lift tissue viral load over months/years. I hope anyway. This seemed to be the case for me last year as I went from strength to strength and then after the flu vaccine felt significantly worse.
I still react badly to vaccines.

 

[Shanti1]

I get mental fatigue and constant brain fog. Unfortunately it was frustrating when I was more moderate, but being more severe it's totally debilitating. Work is pretty impossible. What things helped you most? Every time I try things like artemisinin, allicin, monolaurin, andrographis, oregano oil, etc - it feels like I get worse, then when I stop I can't tell if I returned to baseline which feels better because I've felt like shit for so long, or if I'm actually doing anything.

I used to have a panic moment when someone would ask my phone number or address because there were moments I couldn't!
I think I was fortunate in that I was able to identify EVB and Candida as my triggering infections. Clearing the candida and pushing the EBV into latency made a big difference. Identifying my food triggers (sugar and starches) was also critical. Removing these obstacles it possible for other therapies to be effective. High-dose B1 and correcting B12 deficiency also seems to have played an important role.

I then read Reviving the Broken Marionette and Chronic Fatigue Syndrome: A Treatment Guide, both books on the use of off-label meds in ME treatment, based, in part on Dr. Jay Goldstein's work. I selected about 30 meds that I thought best addressed my symptoms and constitution and, to my surprise, found that I responded to well to 10 or so, all of them geared toward impacting cognition in some way. Since my ME/CFS tends to adapt to any med I use, I took them on a rotating basis, trying not to take anything more than once in a week. I do not have an explanation, but somehow the brain fog lifted over a two month period. If it starts to return, I can usually clear it pretty quickly with one of the meds. To me it seemed that with the EBV and candida out of the way, I could manipulate my dysfunctional circuitry and reset it to some degree.

Unfortunately, I either have residual damage or the EBV or something else is still causing me problems as when I attempted a bike ride in the over exuberance of my new found energy, I developed orthostatic intolerance overnight. Now I feel ok.... as long as I am lying down. Can only sit or stand with compression and meds, and even that is limited.

 

[Shanti1]

@godlovesatrier With valac, because of the low toxicity profile, I felt pretty comfortable that most of my "side-effects" were herx type reactions. With TAF I'm feeling more of a need to distinguish between the two because of TAFs ability to mess with mitochondria and kidney (although not as much as TDF). Not sure if you have any method you are using to distinguish between the two, sometimes it is tricky.

I watched this interesting video from Nija Nerd today on antiviral mechanisms and side effects, it is a bit long, but I thought you might find it interesting: https://www.ninjanerd.org/lecture/antivirals-hiv-hepatitis-influenza-herpes-treatment

That is interesting about the LE Reshi mushrooms. I do think botanicals and other more "natural" substances can modulate our immune systems to help with viral control, and I know from your prior posts that you have directly experienced that. For me, oxymatrine has been helpful in that way, but I may try adding the Reshi. Thanks!

 

[Shanti1]

@hapl808 I moved us over to the Jay Goldstein thread so as not to derail here. I hope you don't mind.

 

[godlovesatrier]

Something I found out today reading old PR threads. Baikal is apparently an anti retroviral too. However I've never been able to tolerate it. The herb dries my mouth out and causes a quote fierce brainfog with other immune based symptoms. So maybe it makes sense now that I have this response to TAF as it's acting in some of the same exact ways.


Brainfog has been pretty bad today. Today is day 5. But I haven't had any TAF since last night. Anyway I felt better for taking some 2 hours ago. But still got brainfog. It does raise my body temp but doesn't induce a fever. So can only assume that's a good thing.

 

[godlovesatrier]

TAF shouldn't effect the kidneys much becuass of the lower extracellular levels? Even so if I take it with my supplements I do get lower back ache. I don't if I don't.

As for my mitos that is a bit of a concern. I take glutathione and nac and a load of other things Inc some potassium sodium and plenty of magnesium. And I take it 3 x a day so they've got support. So far I have experienced some profound tiredness (starting yesterday) which makes me think they've stared to effect my mitochondria. I get a similair crash from famvir and I'm not sure if that's due to the same thing but it could be. I'm not really sure what we can do about this. It seems most patients either don't have this issue or they have it for a few months and then it goes away. I don't see how that's easily explained.

I'd love to know more if you have anymore information.

 

[Shanti1]

TAF shouldn't effect the kidneys much becuass of the lower extracellular levels? Even so if I take it with my supplements I do get lower back ache. I don't if I don't.

Yes, it should be much less!

As for my mitos that is a bit of a concern. I take glutathione and nac and a load of other things Inc some potassium sodium and plenty of magnesium. And I take it 3 x a day so they've got support. So far I have experienced some profound tiredness (starting yesterday) which makes me think they've stared to effect my mitochondria. I get a similair crash from famvir and I'm not sure if that's due to the same thing but it could be. I'm not really sure what we can do about this. It seems most patients either don't have this issue or they have it for a few months and then it goes away. I don't see how that's easily explained.

I should have done some more research before brining up the mitochondrial concerns. It appears that both forms of Tenofovir do not impact mitochondria as much as other meds in the Nucleoside/Nucleotide Reverse Transcriptase Inhibitor class:

Li M, Zhou L et al. Tenofovir alafenamide does not inhibit mitochondrial function and cholesterol biosynthesis in human T lymphoblastoid cell line. Antiviral Res. 2020 Nov;183:104948.

Stray KM, et al. Tenofovir alafenamide (TAF) does not deplete mitochondrial DNA in human T-cell lines at intracellular concentrations exceeding clinically relevant drug exposures. Antiviral Res. 2017

TAF is most certainly less toxic to kidney and bone marrow, but it is a relatively new. Oddly, this study found that TAF had significantly more adverse events reported per patient than TDF.
https://link.springer.com/article/10.1007/s00535-020-01680-0/figures/2

Probably still prudent to do mito support supplements as neurotoxicity from tenofovir is reported in studies and the proposed mechanism of action is mito toxicity. I didn't see any data on neuropathy for TAF. Also, I think it is hard to isolate the neuropathy to tenofovir because people are typically on multiple antivirals, but there you have it.

I'd love to know more if you have anymore information.

That is always the rub isn't it, side effect or Herx?
My thought on this is that is it very difficult to distinguish between the two, but I would think that an increase in symptoms that are within our typical symptom complex of EBV (swollen lymph, brain fog, fever, fatigue) may be the increased immune activity, while we should be suspicious of symptoms not within the EBV symptom complex, especially if it is listed as a TAF side effect (flank pain, nausea, changes in appetite). For me joint pain would be on the latter list, but that it because I never had it as an EBV symptom and didn't have it as a symptom with the flair I got on valac.
Here is a side effect list:
https://www.webmd.com/drugs/2/drug-172868/tenofovir-alafenamide-oral/details/list-sideeffects

 

[heapsreal]

That is always the rub isn't it, side effect or Herx?

Or an IRIS/Immune reconstitution inflammatory response. So freeing up the immune system and it then starts to go after other chronic infections you may have.

The herb astragalus is one of the few treatments that are effective for kidney health. It can help lower creatinine levels and increase your eGFR which can indicate how well your kidney function is. Personal experience I've seen it lower my creatinine and increase my eGFR levels.

 

[godlovesatrier]

Hi both,

Thanks for the links Shanti.

Re nausea etc that's meant to be a responder symptom. Less so with the loss of appetite though and the cough is meant to be an issue with toxicity or an IRIS symptom. Arthralgia is very common with this drug and I've been getting that really badly.

I've woken up today feeling a bit more normal. I did start to feel a bit better but hyper last night. I did get 9 and a half hours sleep which helped. Anyway I'm hoping that brutsl tirednes was a crash from exertion. I've been doing little jobs now for a few days and all I've experienced is brutal tiredness. Haven't had any lymph node pain, fatigue or anything. I get fatigue from TAF after dosing though for a few hours which I assume is productive.

But I agree with your symptom grouping. Thanks also for the study links. So I must be right the profound tiredness like I need to sleep all day must be due to a bad crash. I did 5 hours of reorganizing on Saturday and I did about 2 hours on Sunday. That was obviously a lot and my body needed to recover.
The same response on famvir to a crash would have been brutal fatigue, very bad brainfog and general difficulty in function. Which might confer that penciclovir is indeed far less potent hence the easy reactivation of viruses.

Interesting!

 

[godlovesatrier]

Just a thought I had thismorning. I wonder if tenofovir works best for subgroups where the patient has ebv reactivated in whatever state and they often get sick. That is they get sick very easily and the sickness can drag on for weeks. This describes me.

Whereas a lot of patients never get sick or are possibly not constantly unwell with what feels like a cold or stomach bug. So maybe that is more predictive of response. Just a thought I might be way off.

 

[godlovesatrier]

Day 6 today. Felt great all day then had the following symptoms from the tfa: brainfog, some muscle fatigue, joint pain (mild), pretty extreme tiredness on exertion but not instant takes like half an hour to come on, tiredness round the eyes is really bad (same as famvir). But it's not remotely over stimulating and doesn't make me angry. I am however a tad hyper in the evenings and not in a good way. Though valtrex used to make me feel like this too from memory and it doesn't anymore. So did egcg and so did famvir. Again those three no longer do that.

I'm also sleeping well. Getting about 9 hours. But my energy envelope is smaller I'd say thank it was before I started. Just got to be patient and see if the drug gradually improves me. But a the moment if I continue to have this extemee tiredness on exertion with photosensitivity which is indicative of neurological inflamation then this is probably not worthit.

Oh and I've had a headache for two days after taking it. I'm sure Dr Myhill said that was a good response and I'm hoping it's due to immune effect or modulation effecting pathogens in the brain but I could be way off.

 

[Shanti1]

Just a thought I had thismorning. I wonder if tenofovir works best for subgroups where the patient has ebv reactivated in whatever state and they often get sick. That is they get sick very easily and the sickness can drag on for weeks. This describes me.

Whereas a lot of patients never get sick or are possibly not constantly unwell with what feels like a cold or stomach bug. So maybe that is more predictive of response. Just a thought I might be way off.

These are good questions! When I looked into TAF mechanism of action on EBV it acts as a adenosine nucleotide analog and inhibits viral DNA polymerase. Valacyclovir does the same, but as a guanosine analog. Theoretically, it should be helpful in any situation where the virus is actively dividing.

But a the moment if I continue to have this extemee tiredness on exertion with photosensitivity which is indicative of neurological inflamation then this is probably not worthit.

I hear you, neurological symptoms are always very disconcerting for me.

 

[godlovesatrier]

Today's was horrible. Profound tiredness round the eyes ALLL day...so so hard to concentrate. They feel sore, dry and extemely tired.

But sore throat has gone and myalgia and aches and pains post dosing isn't worse.

I felt fantastic yesterday and crashed last night. So the sore eyes and generally brutally tired state are due to the crash

 

[godlovesatrier]

Oh and when I do crash I seem to be sleeping better. Which might be an important clue.

 

[Shanti1]

@godlovesatrier Sorry to hear you had such a rough day. Have you decided if you are going to continue on? Lower the dose? Stop?

 

[godlovesatrier]

Hello,

I may have to stop. But I can't help but feel it's made a huge difference to my viral load. It's bizzare how I felt fine two days ago. I just think that when I crash the symptoms are worse becuase the TAF is hitting the viruses so I feel pretty bad. It was like this with famvir. If I had a bad crash I'd experience brutal ME symptoms. Whereas with TAF I just experience brutal tiredness and some muscle fatigue.

I have been doing a lot though this last week so I may be doing too much. But the lack of larger energy envelope is quite annoying.

I'm going to take sodium benzoate and glycine today every hour and see if I can recover more quickly from my crash. That might stop a lot of the symptoms. But I woke up at 8 after 9 or 10 hours sleep and I'm still really tired. But the tiredness has moved to my body now not my eyes.

I'll have to decide whether to continue at some point. On a plus note I haven't crashed on this stuff like I do on valtrex. Crashes on that were a hell of a lot worse. Which makes me think the combined broad spectrum effect of immune modulation and antiviral action with TAF is actually very wide. Time to get up...