Tenofovir Alafenamide anyone?

[godlovesatrier]

Mines due to arrive in 3 weeks. Very long shipping for some odd reason.

Bizzarely since my virus I've been able to tolerate more valtrex than usual. If I take benzoate and glycine with the valtrex that seems to help my kidneys filtrate the calculi better. I think I have slow but not compromised kidney function. Getting more kidney and liver tests soon.

But very excited about the taf. 1g valtrex isn't enough. My sore throat and pharangeal symptoms are there all the time if I can control the fatigue symptoms enough to do more than I could a month ago. But the valtrex will only work for a few hours. I'd say 4 or 5 before sore throat returns. As for fatigue and PEM I respond better to Josh's energy supplements for that than I do anything else (so far). But that's not to say the underlying cause isn't pathogenic.

Stress is now no longer a factor so my hpa has returned to baseline.

 

[Shanti1]

Keep us updated on how you go with it all too

I certainly will!

If I take benzoate and glycine with the valtrex that seems to help my kidneys filtrate the calculi better.

I wonder if it has to do with the pH of your urine? Benzoate can cause the urine to be quite acidic. Certain stones form more readily in alkaline pH and other in acidic.

 

[godlovesatrier]

Interesting. Yes that could definitely be it. I had no luck whatsoever with lemon juice.

 

[godlovesatrier]

Noticed any startup effects or any neurological worsening @Shanti1 ? Dr Myhill talks about TAF on her website and she says responders should experience worsening neurological symptoms if it's hitting the right things. This is extremely subjective though and even Myhill says nobody is entirely sure who the responders are until they take and do well with the drug.

 

[Shanti1]

@godlovesatrier Thanks for the info on Myhill. I have taken two full 25mg doses over two days and noticed increased fatigue, brain fog, hyperacusis and worsening of my OI. I also got an increased temperature feeling, but didn't actually take my temp. I consider the latter a good sign. Despite the increase in brain-fog, I also got a that same brain stimulation, noticeable at night, that I had with the valacyclovir. I skipped my dose yesterday and feel better today. I am going to start back up again at a quarter tablet and ease into it like I did with the valacyclovir (which I am continuing to take).

 

[Shanti1]

Interesting. Yes that could definitely be it. I had no luck whatsoever with lemon juice.

On a side note, whether a substance creates acidity or alkalinity in the body oddly has little to do with the original pH of the substance. The contribution of most high-acid foods is minimal compared to the acid already in the stomach.

What is thought to determine a food's contribution to an acidic or alkaline state (which is then ultimately adjusted for by the kidney), is its protein and mineral content, which can be plugged into a calculation to come up with the Potential Renal Acid Load (PRAL).

The paper below gives the PRAL value for various foods, with values with a positive PRAL being more "acidic" and those with a negative PRAL being more "alkaline".

Potential renal acid load of foods and its influence on urine pH
https://www.direct-ms.org/wp-content/uploads/2018/01/Remer-and-Manz-Acid-Base.pdf

Potential renal acid load (PRAL) was calculated according to Remer (15) using the following formula: (0.49 * total protein intake) + (0.037 * phosphorus intake) – (0.021 * potassium intake) – (0.026 * magnesium intake) – (0.013 * calcium intake).(Ref)

 

[godlovesatrier]

I'm fairly sure that unlike some medication myhill says you can actually titrate up on this stuff. Which is exactly what I need so I was quite pleased to read that. She definitely suggest 12.5mg a day if experiencing the symptoms you do. Also your symptoms are responder symptkms so maybe your the one third that respond to the drug. Details are very sketchy from Dr Chia.

Anyway fingers crossed for you.

As for renal capacity that's really very interesting. I do wonder if there's a lag on the supps I take and that unless I cleared my kidneys for say 10 days and then restarted valtrex I wouldn't notice any diff.

To be clear I get pain in the uretor I think this called which is the pipe travelling from kidney to bladder. The pain used to be sharp lasting say ten seconds but very painful. Now I don't really feel any until I take some supps and I can feel some very mild pain.

 

[Shanti1]

Also your symptoms are responder symptkms so maybe your the one third that respond to the drug.

After improvements with vala and oxy, I'm hoping to move the needle a bit more. We'll see what the next month brings. Good to know that Myhill doesn't think titration is an issue, I don't feel I have a choice. Same with val, starting at the full dose would have been intolerable.

As for renal capacity that's really very interesting. I do wonder if there's a lag on the supps I take and that unless I cleared my kidneys for say 10 days and then restarted valtrex I wouldn't notice any diff.

As far as the ability of a food to impact the pH of the urine, or it's PRAL value, that happens soon after the food is absorbed from the intestine and should pass within 24 hours. There are lots of PRAL food charts out there if you Google them. What is interesting is that lemons and oranges are considered alkaline. I'm not a proponent of the "alkaline diet", except that fruits and veggies are generally healthy, but I find it interesting that there is a scientific measurement behind the acid capacity of foods.

As far as the ureter pain you get after sups, I doubt that is related to PRAL, could be so many things.

 

[godlovesatrier]

From Myhills site:

According to all present knowledge, for ME patients gradually introducing the drug is sensible when using Vemlidy as well. There are, however, hardly any experiences available so far. Some few more severely ill patients have had positive experiences with an initial dose between 2 - 3mg. For the most severely affected, perhaps even as little as 1 mg is sufficient for the start.
Nevertheless, immune reactions are to be expected in these cases as well. Unfortunately, there are no guarantees as to whether no resistancies will develop at such a low initial dose. On the other hand, there is also no guarantee that a severe IRIS will not develop when starting at a higher dose, which has unfortunately already been reported by relatives of most severely ill patients as well.

--

i think the issue here is that as she says there might be some antiviral resistance at very low doses. But I guess starting at a quarter would be ok.

anyway food for thought.

 

[heapsreal]

From Myhills site:

According to all present knowledge, for ME patients gradually introducing the drug is sensible when using Vemlidy as well. There are, however, hardly any experiences available so far. Some few more severely ill patients have had positive experiences with an initial dose between 2 - 3mg. For the most severely affected, perhaps even as little as 1 mg is sufficient for the start.
Nevertheless, immune reactions are to be expected in these cases as well. Unfortunately, there are no guarantees as to whether no resistancies will develop at such a low initial dose. On the other hand, there is also no guarantee that a severe IRIS will not develop when starting at a higher dose, which has unfortunately already been reported by relatives of most severely ill patients as well.

--

i think the issue here is that as she says there might be some antiviral resistance at very low doses. But I guess starting at a quarter would be ok.

anyway food for thought.

Tough going cutting them into 1mg pieces.
Been 3 weeks for me and I think one side effect I may be getting is dry eyes.

 

[godlovesatrier]

Haha yep. Probably a crush and measure job. Even so that would be hard work!

 

[MartinK]

I'm under the impression that Tenofovir can't penetrate the CNS so if the virus is there it won't work?
Can anyone disprove this?
Maybe it doesn't apply to Tenofovir Alafenamide... it would be interesting to discuss it.

 

[godlovesatrier]

If I'm reading this right it penetrates the cns but at incredibly low concentrations.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428394/

The paper does mention it that CNS penetration is more potent when tenofovir (taf) is combined with
elvitegravir that this has a stable concentration in CNS. But it's very unclear if that is just elvitegravir. Plus I have no idea what that is I need to look it up.

But I wonder if any of the other things I take would increase CNS concentration. I haven't got anything to base my theory on.

I take 1g NAC 3 x a day but would grapeseed extract increase CNS concentrations. Or maybe Tempol. Pure guess work on my part. Maybe someone else can confirm. @Hip @dreamydays

 

[Shanti1]

i think the issue here is that as she says there might be some antiviral resistance at very low doses. But I guess starting at a quarter would be ok.

Took a quarter last night and still had increased fatigue, hyperacusis, and irritability. The irritability issue can actually be quite impactful to my relationships. My poor husband hums when he is happy and I shoot him dagger eyes and have to leave the room or I might lose it.

I'm under the impression that Tenofovir can't penetrate the CNS so if the virus is there it won't work?
Can anyone disprove this?
Maybe it doesn't apply to Tenofovir Alafenamide... it would be interesting to discuss it.

I'm afraid you are right about this. I am finding the same issue with tenofovir alfenamide. In fact it may be even worse at penetrating the CNS than tenofovir fumarate. That is disappointing, but given my lymph node issues (now much better since valacyclovir) I'm sure I have plenty of EBV outside of my CNS as well.

If I'm reading this right it penetrates the cns but at incredibly low concentrations.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428394/

Looking at the abstract, it looks like tenofovir disoproxil fumarate yielded detectable tenofovir in the CNS, but, after switching to tenofovir alafenamide CNS tenofovir concentrations declined, becoming undetectable by 24 weeks.

At week 24, median TAF plasma concentration was 11.05 ng/mL (range, 2.84–147.1 ng/mL) 2 hours post dose but was below assay sensitivity 6 hours after dosing. TAF was below assay sensitivity in all CSF specimens.

 

[godlovesatrier]

Ah so it's non existent then. As we thought.

I'm just reading Byron Hyde's book. Yes I think if it's not going to penetrate the CNS then thats likely not very helpful. Yet it's effective in 33% of ME patients as proven of Dr Weir and Dr Chia. I'm still amazed by this high percentage. So I wonder what that's all about...maybe they have chronic ebv instead and all they need to do is shift that and the bodys immune system can mop up in the cns by itself?

 

[Shanti1]

Yet it's effective in 33% of ME patients as proven of Dr Weir and Dr Chia.

I'm not so familiar with Dr. Weir's philosophy, but Dr. Chia is very enterovirus focused, so perhaps that 33% is more relative to his patient base with known/suspected enterovirus?

 

[godlovesatrier]

I'm not convinced that Dr chia doesn't test for herpes viruses too. Maybe someone can tell me if they know thats wrong. I say this because he will add in anti herpes virus drugs for some patients. I can only surmise that this is becuSe when taking oxymatrine those viruses reactivate meaning the patient can't continue to the Equilibrant.

This is just a guess though. Without asking him it's hard to say if he's ever seen this displayed in a subset of patients or not.

At the same time some of the drugs he uses alongside Equilibrant have dual or triple function so that's another factor.

As for the 33% it seems Myhill, Weir and Chia have no idea at all why those 33% responded well to the drug. They also can't differentiate who will do well on the drug beforehand. Myhill has I believe a lot less experience prescribing it than the other two but I reckon she did prescribe it briefly in the past. Dr Weir no longer prescribes it because he has no ide which patients will react favourably.

 

[heapsreal]

I wouldn't stress about it if it cross the bbb or not. Trial and error and see how you feel is more important as there probably isn't any research of cfsme pts. If it lowers the viral load and or lowers inflammatory cytokines, your going to feel alot better for it. Give it a good 3 months and see what happens.

 

[godlovesatrier]

I agree Heaps. It's the only way to go. No way to know what's going to work if even the doctors don't know.

 

[MartinK]

have you also looked into whether there is also a sefe profile difference in Alafenamide and other Tenofovir forms?