Valganciclovir research paper - Jose Montoya & Andreas Kogelnik

[gbells]

That's true, but Lerner's is the only study which ran for a long time.

Lerner found that it takes 4 months before the benefits of Valcyte even begin to appear. So at 4 months you will only see the first small inklings of improvement. Thus for Montoya to terminate his Valcyte study at only 6 months was a mistake; he should have run the study for a least 18 months say.

Note also that in terms of antibody blood tests for herpesviruses, Montoya used different study inclusion criteria to Lerner's. Dr Lerner's theory is that ME/CFS is caused by an abortive herpesvirus infection, and thus the testing criteria he used were based on detecting such abortive infections.

A PR forum poll found Valcyte moved 50% of patients trying it up at least one level on the ME/CFS scale of: very severe, severe, moderate, mild, remission.

A study needs at least 30 people. The design of the PR poll doesn't show that it reached the threshold. It also was uncontrolled.

 

[godlovesatrier]

Did anyone manage to get valcyte in the UK on insurance? If so could you PM me any details, as last time I followed up on Dr Busnal, he was retiring and would only prescribe acloyvir.

 

[internetjoe]

Have there been any additional studies on valcyte for me/cfs patients?

 

[cfs since 1998]

Sorry to bump a very old thread, but I wanted to point out that this paper is no longer paywalled.

Something strange happened in this study. Blood tests showed a small amount of the drug was present in 3/10 of the placebo subjects. Could have definitely thrown the results off.

Other problems with the study, it was too small and too short. A non-statistically-significant association is inconclusive in a small sample size.

However, arguments against valganciclovir are toxicity and a poorly understood immune modulation (monocyte counts dropped a huge amount). Both of these things could make patients worse, masking any benefit.

Finally, multiple sclerosis is now widely believed to be caused by EBV, but antivirals have been of marginal benefit to MS patients. The reason for this is not known.

 

[Down but not out!]

Finally, multiple sclerosis is now widely believed to be caused by EBV, but antivirals have been of marginal benefit to MS patients. The reason for this is not known.

Hello,

I think one problem is that valcyte/valacyclovir (for example) only inhibits viral replication rather then eradicating the virus in the same way an antibiotic attacks a bacterium. I did find a paper that demonstrated a reduction in the viral load of EBV when taking 500mg of valacyclovir every day but it took a long time. They postulated that it would take something like 10 years to rid the body completely, and that hasn't been tried.

I suppose a second question might be as to how much of reduction of viral load is necessary before the associated immune activation and potential autoimmunity begins to 'stand down'. I think this is why the studies e.g. Lerner that showed some efficacy generally ran for 6 to 12 months at least, and why I'm not surprised that antivirals have made little difference to MS - they just aren't potent enough or long enough.

One further comment about Dr Lerner's research, he was a doctor working at the sharp end with patients and had real clinical experience. I think that is often undervalued nowadays. His hypothesis was consistent with the more recent research by the likes of Dr Bhupesh Prusty on latent herpes viruses driving a chronic inflammatory response.

 

[cfs since 1998]

Hello,

I think one problem is that valcyte/valacyclovir (for example) only inhibits viral replication rather then eradicating the virus in the same way an antibiotic attacks a bacterium. I did find a paper that demonstrated a reduction in the viral load of EBV when taking 500mg of valacyclovir every day but it took a long time. They postulated that it would take something like 10 years to rid the body completely, and that hasn't been tried.

I suppose a second question might be as to how much of reduction of viral load is necessary before the associated immune activation and potential autoimmunity begins to 'stand down'. I think this is why the studies e.g. Lerner that showed some efficacy generally ran for 6 to 12 months at least, and why I'm not surprised that antivirals have made little difference to MS - they just aren't potent enough or long enough.

One further comment about Dr Lerner's research, he was a doctor working at the sharp end with patients and had real clinical experience. I think that is often undervalued nowadays. His hypothesis was consistent with the more recent research by the likes of Dr Bhupesh Prusty on latent herpes viruses driving a chronic inflammatory response.

I mostly agree. Here are my thoughts.

Note the reduction in viral load at 500mg/day was in healthy volunteers (link). The authors estimated 99% of the latent EBV could be eliminated in 5 years, and maybe all of it in 11 years. One thing we don't know is if it works the same in patients. It's possible the decline in ME/CFS taking valacyclovir could be slower due to deficiency in the immune system, or it may not decline at all if we experience B-cell clonal expansion. (At least one of the study subjects had an increase in viral load during the trial, although the group as a whole declined on average).

Valacyclovir is a relatively weak inhibitor of EBV compared to HSV. Note people taking valacyclovir for HSV suppression can still have outbreaks, they are just much less frequent. Anyway, a higher dose should result in a faster decline--though since most of the virus is latent, there is a limit to how fast you can eliminate it. You could take a dose high enough to reach 100% inhibition and it still might take years to reduce that latent load >99%.

Ever since Fluge and Mella started looking at rituximab I've always thought they should combine it with an antiviral and this idea has been proposed by Dr. Klimas and her research partner. But Fluge and Mella seem to think it's autoimmune only.

Here's the problem with antivirals though, which that patient experiences don't seem to jive with Dr. Lerner and Dr. Montoya's clinical experience. There are a ton of patients that have tried antivirals and either they didn't work or it made them worse. I myself got dramatically worse after valacyclovir for only a few days and the worsening was seemingly permanent. Unfortunately there is no explanation for why this happens to some of us.

The other odd thing is the observation that a lot of people seem to be helped by sunlight. UV radiation has immune suppressant properties even independent of its effect on Vitamin D production. They've done mouse studies on this. In one they compared one group of mice getting UV and another being fed Vitamin D to reach similar levels, and the UV mice had greater immune suppression. In another study they used genetically modified mice with no ability to synthesize Vitamin D and these also experienced immune suppression upon UV exposure. Anyway, hypothetically UV would cause EBV to reactivate so why would it help some patients? I believe there has to be an autoimmune component.

I can't prove it and it doesn't make a lot of logical sense but I feel like antivirals can actually trigger an autoimmune reaction in some people, similar to IRIS in HIV patients.

There is still too much we don't know about ME/CFS but I feel like there is an interplay between chronic viral infection and autoimmunity that is more complicated than we realize and going to be difficult to treat.

One idea I had was to use a drug that interferes with antigen presentation (this is what UV radiation does). I asked ChatGPT and it suggested Abatacept, Belatacept, or Leflunomide.

 

[heapsreal]

Hello,

I think one problem is that valcyte/valacyclovir (for example) only inhibits viral replication rather then eradicating the virus in the same way an antibiotic attacks a bacterium. I did find a paper that demonstrated a reduction in the viral load of EBV when taking 500mg of valacyclovir every day but it took a long time. They postulated that it would take something like 10 years to rid the body completely, and that hasn't been tried.

I suppose a second question might be as to how much of reduction of viral load is necessary before the associated immune activation and potential autoimmunity begins to 'stand down'. I think this is why the studies e.g. Lerner that showed some efficacy generally ran for 6 to 12 months at least, and why I'm not surprised that antivirals have made little difference to MS - they just aren't potent enough or long enough.

One further comment about Dr Lerner's research, he was a doctor working at the sharp end with patients and had real clinical experience. I think that is often undervalued nowadays. His hypothesis was consistent with the more recent research by the likes of Dr Bhupesh Prusty on latent herpes viruses driving a chronic inflammatory response.

Something that might help avoid long term toxicity of valcyte is once the viral load has dropped from valcyte, replace valcyte with famvir/famcyclovir or maybe valtrex. Famvir and valtrex have been used to prevent cmv, ebv etc in organ transplants. They are alot safer to take long term.

 

[Treeman]

One idea I had was to use a drug that interferes with antigen presentation (this is what UV radiation does). I asked ChatGPT and it suggested Abatacept, Belatacept, or Leflunomide.

Did you use any of them? And how successful were they?

 

[cfs since 1998]

Did you use any of them? And how successful were they?

No and I don't plan to until there's at least a small clinical trial first. I am going to try to get more UV, though.