Why did antivirals (valcyte, etc) for SEIDs fail?

[gbells]

I am trying to learn some theories as to why the antiviral drugs tried by Lehrner and Montoya failed to improve fatigue and mental fatigue significantly when tested by Montoya in a controlled study. Some possibilities are:

• Even if the viruses are inactivated by the drugs they can't fix the broken mitochondria which are stuck in a blocked apoptosis state and readily leak pro-inflammatory molecules instead of generating ATP (energy) from fat which is their normal function. This results in the fatigue and mental fatigue problems.
• Extended treatment triggers virus resistance or the strains a patient have may already be resistant (small percentage).

I reject the claim that Montoyas study was too short because its trend wasn't declining in a similar manner as Lehrner's study at six months.

 

[Wolfcub]

I often wonder about biofilm situations, that make the virus encapsulated, thus resistant.

Biofilms: Discovery of a new mechanism of virus propagation

 

[Wishful]

Another possibility is simply that viruses aren't a critical part of ME. They may trigger the ME state, but not be part of sustaining it.

Antivirals may help some PWME, by reducing the level of immune system activation. I know that viral infections make my ME symptoms more severe. However, when the viruses stop replicating, I'm still left with my baseline ME severity.

 

[Galixie]

I think Wishful is onto something.

Antivirals weren't helpful to me at all. I suspect that my immune system was initially triggered to start making antibodies many years ago. But the virus they are meant to fight is no longer detectable, so antivirals are useless to me because the real problem is an incorrectly triggered immune system, which antivirals don't fix.

 

[jstefl]

\While antivirals weren't helpful for some, Valcyte was extremely helpful for me. I took it for 10 months back in 2008 and had many improvements that have lasted more than 10 years now. Dr. Lerner had some successes, as did Dr Montoya. A study doesn't need a 0 % success rate to be a failure.

My mitochondria are not generating energy as they should, but that is easier to live with than all of the problems that I was living with previously. I have documented my improvements on this site previously and I believe that I would probably be dead by now if not for the Valcyte. I have gone from being mostly bed bound in great pain to being able to be up and about the entire day with only a short nap needed after lunch.

 

[Hip]

Valcyte was extremely helpful for me. I took it for 10 months back in 2008 and had many improvements that have lasted more than 10 years now.

I am always interested to hear ME/CFS treatment success stories. Can you say where you were on the ME/CFS scale of: very severe, severe, moderate, mild, remission before you took Valcyte, and where you ended up on this scale after the 10 month Valcyte treatment?

 

[Hip]

Antivirals weren't helpful to me at all.

Can I ask, what viral infections do you have (in terms of high antibody levels), what antivirals did you take, and for how long, and at what dosage?

 

[borko2100]

maybe because they arent all that effective and you need to be on them for years to get results

 

[Hip]

I am trying to learn some theories as to why the antiviral drugs tried by Lehrner and Montoya failed to improve fatigue and mental fatigue significantly when tested by Montoya in a controlled study.

Montoya did a number of things differently to Lerner: he used different viral blood test criteria (so Montoya may not have correctly identified the patients with active infection), he did not test for and treat co-infections (whereas Lerner did), and Montoya only ran his study for 6 months.

Also, I think a large flaw in Montoya's study was the ME/CFS severity scale he used to measure the outcome, which was the Multidimensional Fatigue Inventory (MFI‐20). This is a really bad scale, because it is purely subjective. It does not measure objective changes (like the number of hours you are able to be active each day), and so cannot accurately measure improvements in ME/CFS.

Whereas Lerner used a more objective severity scale, his Energy Index Point Score. So Lerner's study was much better at accurately quantifying the improvements.

Unfortunately Lerner's Valcyte study was not placebo controlled, but his Valtrex study was.

See this post for a summary of Lerner and Montoya's antiviral studies.

 

[Hip]

By the way, it's worth pointing out to any future readers who may be confused about the term "SEID": this term was once proposed as a replacement the name ME/CFS, but was never adopted. I suspect in a few years, people will see "SEID" and wonder what on Earth that means.

 

[Galixie]

Can I ask, what viral infections do you have (in terms of high antibody levels), what antivirals did you take, and for how long, and at what dosage?

I have perpetually high EBV antibodies, including the one that is only supposed to spike when you are first exposed to the virus. I took acyclovir in 2015. I can't remember for how long. I had zero symptom improvement and repeated antibody testing showed no reduction in antibodies.

I am in no way disparaging the use of antivirals, because there are some who benefit from them. I'm just speculating about why they didn't work for me.

 

[Hip]

I can't remember for how long.

Lerner's studies indicate that treatment for periods of a year or two can get results. So that's the time period that's often needed. That said, in spite of Lerner's good results with Valtrex, I don't think I've never come across anyone on this forum who did well on Valtrex. Whereas I've seen several success stories with Valcyte, when taken for around a year.

 

[Haley]

Valtrex has helped me immensely. I started off on 1.5 g a day for 3 months, then gradually dropped down to 500 mg a day (mainly due to financial reasons). I'm still on this dose. I've stopped taking it on several occasions, but I always ended up getting worse within a week (increased fatigue and brain fog, sore throat, increased pain - the usual mix of symptoms). After about 2 weeks and no signs of improvement, I start taking 500 mg a day again. It usually takes about 4 weeks to reach my previous level of function once I start the valtrex.

I would rather not take it, because I really don't like taking any medications, but it has made such a difference that I will take it while ever it has a positive effect. I plan to have another trial without it to see if it is still effective.

The valtrex got me from the mild/moderate border to mild.

 

[gbells]

Symptoms regress when you stop the meds though.

 

[jstefl]

@Hip When I started on Valcyte I was probably what I would classify as severe, or possibly worse. My blood pressure had dropped to 80/50 and my pulse slowed to 50. I was able to stand up only if I moved very slowly and was afraid to drive. My brain fog was severe and I suffered from a continuous extremely painful headache. I spent most of my day sleeping or in bed.

Within two weeks of starting Valcyte my headaches began to moderate. I was taking blood pressure medication to help maintain adequate pressure and took daily blood pressure readings and recorded them. I noticed that as time went by, my BP was increasing, so I began to taper off on the medication. By the time I finished the Valcyte I was completely off the medication and to this day, 11 years later my BP is in the ideal range.

I was tested for the Herpes viruses as well as the enteroviruses, and was positive for several. As I said, all of this has been documented in my previous posts, and I don't want to repeat in great detail again.

I was able to tolerate Valcyte with no problems. I tried Valtrex later and could not tolerate the doses that were recommended by Dr Lerner. I took the standard 450 mg dose of Valcyte twice a day for the 10 months. Remember that I did this back in 2008, the early days of Dr. Montoya talking about Valcyte and HHV-6. I was able to convince my doctor to keep me on Valcyte for only 10 months, with what I know today, I would use it for much longer. I attended the HHV-6 conference in Baltimore in 2008 and heard Dr. Lerner answer a question about how long you should take the Valcyte, and he replied that you should take it until you have recovered. He said that at that time he had one patient that had been taking it for 7 years!

Valcyte does seem to be difficult for many to tolerate, and I believe that one of the reasons that Valcyte therapy wasn't more successful was that patients weren't able to tolerate it. I had my blood monitored by my doctor as suggested, and had no adverse effects. I guess that makes me one of the lucky ones. I have been considering restarting Valcyte at a very low dose and staying there for the long run.

Today I would consider myself to be moderate on the scale. My brain fog has improved quite a bit and I am able to get out and about as long as I am careful. This summer, for instance, I attended the Experimental Aircraft Association fly-in. I drove 100 miles to get there, walked around from 9 AM until almost 4 PM and drove home. I had some moderate PEM and needed to walk slowly, but could never have done that pre Valcyte.

I didn't get any post Valcyte testing. I was attending the Mayo clinic at this time, and had a great deal of difficulty getting the Valcyte prescription from my doctor and getting proper testing from the Mayo lab. Again. I have detailed all of this in previous posts.

 

[Wishful]

From the ones here reporting benefits from antivirals, I'd guess that they were suffering from chronic viral infections while also suffering from ME, and the response to the virus was making the ME worse than it would have been otherwise.

I wonder if statistics would show that patients with ME and chronic viral infection tend to have more severe symptoms than average for ME.

 

[jstefl]

@Wishful
I don't believe that you can separate chronic viral infections from ME/CFS, I see them as interrelated. These viral infections are fairly common in the general population and often don't cause problems in healthy people. It is my sincere hope that once we find the cure for our problems, the importance of the viral infections will be greatly reduced by our immune systems.

 

[Wishful]

I certainly can't completely rule out viruses as having an influence in my ME, but my observations certainly don't support viruses as a major part of it. The rapid switching between ME state and healthy state doesn't seem to fit with the time frame for virus population change. I think it's more likely that some people have their ME made more severe by chronic virus infection, and some people might even be able to switch out of the ME state if they can destroy the virus that keeps their immune system activated. Likewise, some people may have a strong ME/microbiome connection, and some won't. It's not a homogeneous disease.

The doctors who had actual cures with antivirals should follow up with those patients to see if any return to the ME state when they get a regular viral infection, and leave the ME state when the infection passes.

 

[Hip]

The rapid switching between ME state and healthy state doesn't seem to fit with the time frame for virus population change.

Which rapid switching are you referring to? Do you mean the switch between healthy and getting ME/CFS?

When you catch a substantial infection, like the flu for example, you rapidly change from a healthy state to illness state (which is a state not unlike ME/CFS).

Also, many perfectly healthy people develop full-blown ME/CFS within days of catching an infection. One minute they are healthy, and the next they are immersed into full ME/CFS.

So I am not following why you say that doesn't seem to fit with the time frame for virus population change.

The doctors who had actual cures with antivirals should follow up with those patients to see if any return to the ME state when they get a regular viral infection, and leave the ME state when the infection passes.

I don't think antivirals have cured many ME/CFS patients, although there are some stories of cures. More often, a course of antivirals (usually lasting for a year or so) will improve the ME/CFS state, but not cure it. For example, antivirals may improve a severe ME/CFS patient such that they are now only moderate or mild.

Also, in some cases, the improvements are permanent (they remain after stopping the antiviral); in other cases, the ME/CFS soon returns once the antiviral is stopped.

I have not heard any stories of ME/CFS improved via antivirals returning or getting worse again after catching regular viral infection like a cold.

 

[gbells]

I don't think antivirals have cured many ME/CFS patients, although there are some stories of cures. More often, a course of antivirals (usually lasting for a year or so) will improve the ME/CFS state, but not cure it. For example, antivirals may improve a severe ME/CFS patient such that they are now only moderate or mild.

I agree. I think the smartest thing is to take the approach they use with cancer. For that they use methods to trigger apoptosis to kill the infected cells. Anti-virals don't kill them, they just suppress their function, either by stopping them from replicating or stopping protein production.

If you kill the infected cells they no longer drain energy through inflammation so you gain energy.