Has anyone here tried methotrexate with tenofovir/truvada?

[Katt]

I just recently had some auto-antibodies pop back up in my bloodwork shortly after having some unplesant POTS-like symptoms return.

My thought is that if latent viruses are causing auto-antibody production then targeting the virus (EBV in this case) with tenofovir should, in the long run, reduce viral levels and the low dose methotrexate (5-10mg) should hopefully speed up that process. I think someone was studying low dose methotrexate with Valtrex but Valtrex is not very effective against EBV so tenofovir seems like a better option.

My doctor is willing to give it a try, I'm just cusrious to know if anyone here has tried that combination.

And yes I am aware of all the dangers of methotrexate, I am just sick of my body attacking itself! I was doing so well and had all my autoimmune symptoms go into remission for awhile but recently made the stupid mistake of trying out some "immune activating" supplements because I was concerned about my previous lyme infections not being fully gone. It could simply be a coincidence but I feel like anything that is labled as an immune activating/stimulating herb ends up making me feel awful so at this point it really seems like my symptoms are related to an autoimmune process.

 

[cfs since 1998]

I have not heard of anyone trying that, Katt. Apparently, the Norweigans have seen ME/CFS patients react very poorly to methotrexate.

This recent post from @dankeen suggests that anti-CD38 (plasma cell) drugs might be the way to go. Drs. Fluge and Mella were using cyclophosphamide for this, but are switching to other drugs, as described in the post.

Ofatumumab is an anti-CD20 drug that can be given as a subcutaneous injection (Kesimpta). I think it's interesting because it is apparently better able to deplete B cells in lymph tissue than rituximab.

A lot of ME/CFS patients have reported severe side effects from tenofovir despite it being a relatively safe and tolerable drug when used in healthy people for HIV prevention. Even 1/10th or 1/20th tablet has provoked reactions in some. Just be careful and start slow.

 

[Tammy]

And yes I am aware of all the dangers of methotrexate, I am just sick of my body attacking itself!

I am curious why you think the body is attacking itself vs the anti-bodies are going after the virus? The auto-immune theory or body attacking itself has never made sense to me.

 

[cfs since 1998]

I am curious why you think the body is attacking itself vs the anti-bodies are going after the virus? The auto-immune theory or body attacking itself has never made sense to me.

Circumstantial evidence that ME/CFS is an autoimmune disease: female to male ratio, age of onset, symptom overlap, comorbidity with rhemuatoid arthritis, Sjogren's syndrome, and psoriasis, family history of autoimmune disease, increased rate of B cell lymphoma, and the EBV connection (evidence is building that EBV might be involved in most autoimmune diseases).

Microbiological circumstantial evidence that ME/CFS is an autoimmune disease includes B-cell clonal expansion, T-cell activation and exhaustion (also seen in other autoimmune diseases), increased EBV detection in plasma, detection of autoantibodies by Scheibenbogen's group, Prusty's experiment where ME/CFS IgG damaged healthy mitochondria in vitro.

Genetic circumstantial evidence that ME/CFS is an autoimmune diseases: association with HLA genes and a high rate of autoimmune conditions in blood relatives.

I am working on a comprehensive essay on this topic with citations.

 

[Tammy]

@cfs since 1998 , In the very simplest of terms can you explain why the body would attack itself?

 

[cfs since 1998]

@cfs since 1998 , In the very simplest of terms can you explain why the body would attack itself?

There are a few. The most popular explanation is molecular mimicry, where part of a virus looks like the body.

Another explanation is a breakdown in self-tolerance due to immune dysregulation or inflammation. In other words, even in healthy people, there is always a balance between immune activation that's too low to fight pathogens and too high such that the body's own tissues are attacked. This balance could be upset in autoimmune conditions.

A third is that tissues could be infected by the virus itself, for example, there is one hypothesis paper that says ME/CFS could be due to direct infection of endothelial cells by EBV.

 

[wabi-sabi]

In the very simplest of terms can you explain why the body would attack itself?

The body gets confused and mistakes itself for a germ.

Think of the way animals try to camouflage themselves from predators by blending into the environment. The better it works, the less they get eaten. Viruses (maybe bacteria too?) try to camouflage themselves by looking like art of your own body. Because the immune system can learn, metaphorically speaking, it learns what each virus look like and remembers to attack it where ever the immune system sees it. If a virus camouflages itself well enough, your immune system can't tell the difference between it and you. It attacks everything that looks dangerous, including yourself.

A stick insect tries to look like a stick so it doesn't get eaten by birds. If the bird knows that the stick sort of thing is really tasty meal, it might make a mistake and try to eat a stick once in a while. This is autoimmunity.

 

[Katt]

I am curious why you think the body is attacking itself vs the anti-bodies are going after the virus? The auto-immune theory or body attacking itself has never made sense to me.

My blood work showed auto-antibodies. That means they are dysfunctional anti-bodies that attack the tissue of the body instead of infected cells. Doctors are not able to detect all types of auto-antibodies due to testing limitions so theoretically you could still have them without it showing up on regular bloodwork. But when they do show up on your bloodwork that is a clear indication of immune dysfunction. I hope that made sense, not sure if I am being clear enough.

This post has more info: https://forums.phoenixrising.me/thr...ing-the-acetylcholine-antibodies-thing.58168/

 

[Katt]

I have not heard of anyone trying that, Katt. Apparently, the Norweigans have seen ME/CFS patients react very poorly to methotrexate.

This recent post from @dankeen suggests that anti-CD38 (plasma cell) drugs might be the way to go. Drs. Fluge and Mella were using cyclophosphamide for this, but are switching to other drugs, as described in the post.

Ofatumumab is an anti-CD20 drug that can be given as a subcutaneous injection (Kesimpta). I think it's interesting because it is apparently better able to deplete B cells in lymph tissue than rituximab.

A lot of ME/CFS patients have reported severe side effects from tenofovir despite it being a relatively safe and tolerable drug when used in healthy people for HIV prevention. Even 1/10th or 1/20th tablet has provoked reactions in some. Just be careful and start slow.

Thanks for the info! I have taken tenofovir before and had amazing results with it. Zero side effects and it gave me more energy. To be fair I was very mild at that point and after being on it for 6ish months my doctor told me I no longer had ME/CFS because I no longer had any type of sleep dysfunction and most of my other symptoms were gone. The methotrexate I am on the fence about but the tenofovir I really want to go back on.

I was diagnoised with Sjogren's syndrome in the past and had one of the 2 Sjogren's auto-antibodies come back up in my bloodwork. I was on one of those injectables (Enbrel which is a TNF blocker) in the past but it didn't seem to do anything for me. However, I tried it when I had fairly severve ME/CFS & POTS & Sjogren's syndrome so maybe I was just too sick to get any benefit. Also a TNF blocker may just not have been the right drug for me.

I'm not surprised to see the some people with ME/CFS reacted poorly to methotrexate. It seems to me that there are very different types of immune dysfunction between people with this illness. It's unfortunet that we cannot do a better job of testing to see who will respond well to what meds. I have a feeling that in the future ME/CFS will no longer be a diagnosis and will instead be broken up into more specific groups.

I typically respond well to anti-inflammitories like steroids but those drugs frighten me more because of how much they mess up my blood sugar. This might end up being a total mistake but my doctor seems pretty confident that I will get some benefits from the methotrexate based on my blood work and the fact that multiple close relatives of mine have serious autoimmune illnessess. It seems like a reasonable risk but I'm still giving it some more thought before filling my script.

 

[cfs since 1998]

Thanks for the info! I have taken tenofovir before and had amazing results with it. Zero side effects and it gave me more energy. To be fair I was very mild at that point and after being on it for 6ish months my doctor told me I no longer had ME/CFS because I no longer had any type of sleep dysfunction and most of my other symptoms were gone. The methotrexate I am on the fence about but the tenofovir I really want to go back on.

I was diagnoised with Sjogren's syndrome in the past and had one of the 2 Sjogren's auto-antibodies come back up in my bloodwork. I was on one of those injectables (Enbrel which is a TNF blocker) in the past but it didn't seem to do anything for me. However, I tried it when I had fairly severve ME/CFS & POTS & Sjogren's syndrome so maybe I was just too sick to get any benefit. Also a TNF blocker may just not have been the right drug for me.

I'm not surprised to see the some people with ME/CFS reacted poorly to methotrexate. It seems to me that there are very different types of immune dysfunction between people with this illness. It's unfortunet that we cannot do a better job of testing to see who will respond well to what meds. I have a feeling that in the future ME/CFS will no longer be a diagnosis and will instead be broken up into more specific groups.

I typically respond well to anti-inflammitories like steroids but those drugs frighten me more because of how much they mess up my blood sugar. This might end up being a total mistake but my doctor seems pretty confident that I will get some benefits from the methotrexate based on my blood work and the fact that multiple close relatives of mine have serious autoimmune illnessess. It seems like a reasonable risk but I'm still giving it some more thought before filling my script.

Fluge and Mella also started a trial of Enbrel (etanercept) but they stopped the trial due to poor response. I don't know if they stopped for lack of response or side effects, they never published anything on it, but you can still find the record on clinicaltrials.gov.

Glad to hear tenofovir helped you in the past and you didn't have side effects. However, over 10 years ago I took valacyclovir (valtrex) with minor side effects that were reversed when I stopped. I recently tried it again and it took me from mild to severe. This disease is like a casino where you might hit the jackpot with a particular drug or it might bankrupt you.

Methotrexate is certainly a cheap and easily administered drug and it is tempting to try it for those reasons alone. I have been tempted myself but the side effects sound awful. Maybe it would work better if combined with an antiviral.

 

[Tammy]

A third is that tissues could be infected by the virus itself, for example, there is one hypothesis paper that says ME/CFS could be due to direct infection of endothelial cells by EBV.

IF I were to believe that the body attacks itself this would be the closest explanation that I might entertain. If a virus were embedded in tissues wouldn't the anti-bodies have to get through the tissues to get to the virus? But I still don't see this as the body attacking it's own tissues ...........just trying to get to the virus.

 

[Katt]

Fluge and Mella also started a trial of Enbrel (etanercept) but they stopped the trial due to poor response. I don't know if they stopped for lack of response or side effects, they never published anything on it, but you can still find the record on clinicaltrials.gov.

Glad to hear tenofovir helped you in the past and you didn't have side effects. However, over 10 years ago I took valacyclovir (valtrex) with minor side effects that were reversed when I stopped. I recently tried it again and it took me from mild to severe. This disease is like a casino where you might hit the jackpot with a particular drug or it might bankrupt you.

Methotrexate is certainly a cheap and easily administered drug and it is tempting to try it for those reasons alone. I have been tempted myself but the side effects sound awful. Maybe it would work better if combined with an antiviral.

Sorry to hear Valtrex made you worse It really does feel like taking anything (or doing anything) is a gamble when you have ME/CFS. Valtrex is pretty harsh on the kidneys & liver and I suspect that a bad responce to it could indicate issue with one of those organs. For example if liver enzymatic detoxification is slowed down for any reason (like high levels of yeast/ethanol producing bacteria) then Valtrex would slow that down even more creating a very high toxic burden on the body. Since the liver is so important not only for clearing toxins but also maintaining hormonal balance it does seem possible that any drug that affects the liver could tip the scales significantly in the wrong way.

And if I remember correctly Enbrel does not pass the BBB so it doesn't get into the nervous system. Since headaches & pain in my spinal cord were one of the first symptoms I developed and the last to go way (also the ones that came back first), I have a good feeling that most, if not all, of my issues are in my nervous system. So maybe that's why Enbrel was a failure.

Taking methotrexate alone scares the crap out of me because it has been associated with increased viral reactivation (at least it seems to increase EBV reactivation). Since taking antivirals helped me so much in the past it only seems logial that increasing viral activity would make me much worse. But like you said, all of this is a gamble because we know so little. Doing a treatment based on minimal science and a lot of guessing isn't a great way to do treatment, it all feels very medieval. Logically, I should just be happy with my progress and stop poking the bear. That's the advice I would give someone else in my position. But at this point my curiosity is winning...