Dr. Teitelbaum - When to use anti-virals

Cort

Founder of Health Rising and Phoenix Rising
Staff member
http://www.vitality101.com/health-a-z/when-to-use-antivirals-in-fibromyalgia-and-cfs
I've been meaning to post this very thorough reply to a question I sent to Dr. Teitelbaum - he's posted it to his newsletter today but wanted to post here as it answered many questions I had about the theory of giving anti- virals for high antibody counts. I realize it's controversial.
Nice that he gave you such a complete reply.. I'm going to copy it here - I hope that's OK. I think its a very well reasoned approach...


The visitor asked: "I recently read that antivirals for CFS can do more harm than good if there's no evidence of a current infection. I have a high early antigen EBV, but I'm confused if this is relevant since it's not an IgM antibody. My physician says she no longer checks for it because even healthy people can test positive. Can you clear this up for me?"
This is a bit complex, so please bear with me as I go through this...

It's true that IgG elevation reflects old infection, and most healthy people test IgG positive for EBV, CMV, HHV 6 and HSV1. Because of the immune dysfunction in fibromyalgia and CFS, viral reactivation is usually detected. This will not result in the standard IgM test for acute infection being positive, but has been shown to be associated with very high IgG titres in combination with a clinical picture that is suggestive. Though there is no set cutoff for the IgG to confirm viral reactivation, I consider titres of 4 (or 1:640) or higher to raise a suspicion for HHV 6, CMV, and perhaps HSV 1 reactivation.

For Epstein Barr (i.e., Mono), the EBV IgG antibody is positive in about95% of the healthy population. The EBNA is positive in 91% and the VCA IgG in 98%. Looking where they are relative to the median levels may add some information. For now, when checking for Epstein-Barr antibodies (EBV), the only test we really need is the EBV Early Antigen Ab, IgG. This test is positive in only about 52% of the population, where the other Epstein-Barr tests are positive in about 90 to 95%, making them not very meaningful. If the person wants a little more information, we can add the EBV VCA IgG antibody. The median level (half the population is less than this) is 186 AU/ML for the EBV VCA and 10.7 AU/ML for the EBV Early antigen, which gives us a reference point.

If titres are elevated and there is a history of flu-like onset (or symptoms) and the S.H.I.N.E.® protocol isn't adequately helping, or if the person is severely ill and showing strong signs of autonomic dysfunction (as is the case with the 25% of those with CFS/FMS), I consider a trial of antivirals and use the labs to then decide which antiviral to use.

If CMV IgG or HHV-6 IgG are over 4 (or 1:640 or higher), I go with the valcyte. If not, I treat with Valtrex 1 gm 3-4x day or Famvir 750 gm 3x day for 6 months. I also add Celebrex for it's antiviral effect (as long as their stomach is OK with it) along with ProBoost™ 3x day (under the tongue) and Zinc 20 mg a day. I give all these for 6 months, and continue beyond as long as their condition continues to improve and worsens if stopped. Improvement is usually seen at 4 months (though often sooner). Some peoples' symptoms may initially worsen on treatment. This is called a Herxheimer reaction. These folks are still most likely to improve over time, though they may need to start with much lower doses.

A large number of people also show immune dysfunction in the form of low IgG 3 or IgG1 antibody levels. In a small subset of the sickest of these people, especially those with autonomic dysfunction or a painful condition called small fiber neuropathy (common in FMS), IV gamma globulin can show marked benefit after 4 months. IV gamma globulin is expensive and needs to be insurance approved, which takes a lot of work. A simple quiz (validated in the Mayo Clinic Journal) to find if you have symptoms of orthostatic intolerance can help you determine if you may have autonomic dysfunction (OI is caused by autonomic dysfunction).

I know this is a complex discussion, but I believe it will be helpful to many of you (and your physicians). I consult with people worldwide on CFS and fibromyalgia, and if your doctor is interested and open, I'm happy to work with them as well.
 

weyland

Well-Known Member
I realize it's controversial.
The only thing that is controversial is assuming that serology alone proves herpes virus reactivation. But we have moved past this in CFS research. It has been shown that EBV viral load is higher in CFS patients.

But that study was more important for another reason. What it showed is that the EBV reactivation is not at a high level in CFS patients. In fact the reactivation is not to a level that would explain the deficient immune response to EBV. In primary chronic EBV infections, or other diseases like SLE that result in increased EBV activity, T cells will be continually exposed to viral antigen and will start to display cell surface markers of exhaustion. They did not find these markers on the CFS patients T cells. What this means is that these T cells are likely being exposed to inhibitory cytokines as a bystander effect, but that the inhibition is directed at other T cells. And we do know from several recent studies that CFS patients do have T cells that do display several exhaustion markers, and these are the likely target of the inhibitory signals.

That's basically just a long way of saying that in CFS, if you see elevated herpes titers, then you should be thinking less about treating those viruses and more about looking for the actual pathogen that is primarily causing the immune activation and likely the disease itself.
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member
The only thing that is controversial is assuming that serology alone proves herpes virus reactivation. But we have moved past this in CFS research. It has been shown that EBV viral load is higher in CFS patients.

But that study was more important for another reason. What it showed is that the EBV reactivation is not at a high level in CFS patients. In fact the reactivation is not to a level that would explain the deficient immune response to EBV. In primary chronic EBV infections, or other diseases like SLE that result in increased EBV activity, T cells will be continually exposed to viral antigen and will start to display cell surface markers of exhaustion. They did not find these markers on the CFS patients T cells. What this means is that these T cells are likely being exposed to inhibitory cytokines as a bystander effect, but that the inhibition is directed at other T cells. And we do know from several recent studies that CFS patients do have T cells that do display several exhaustion markers, and these are the likely target of the inhibitory signals.

That's basically just a long way of saying that in CFS, if you see elevated herpes titers, then you should be thinking less about treating those viruses and more about looking for the actual pathogen that is primarily causing the immune activation and likely the disease itself.
Interesting Weyland - thanks for that. Are you saying that ME/CFS T-cells do not show markers of exhaustion associated with EBV or viral exposure but show other markers of exhaustion?
 

Cort

Founder of Health Rising and Phoenix Rising
Staff member

weyland

Well-Known Member
Are you saying that ME/CFS T-cells do not show markers of exhaustion associated with EBV or viral exposure but show other markers of exhaustion?
The Charite study I linked above showed that EBV specific T cells in CFS patients do not display increased expression of PD-1, which is thought to be one of the main markers of functional T cell exhaustion. Recent studies, when looking at the global T cell pool, have found increased expression of PD-1 and CD95, loss of CD127 expression, etc. T cell exhaustion is driven specifically and primarily by continuous exposure to antigen. So I'm saying that CFS patients show signs of persistent immune activation, with signs of persistent viral antigen exposure via expected changes in exhaustion markers, but that this exhaustion is not being driven by EBV per the Charite evidence. The EBV specific T cells are likely being exposed to things like IL-10, TGF-β, and increased Treg activity as innocent bystanders. This will weaken their response somewhat but it will not cause full exhaustion as it would if they were being constantly exposed to EBV antigens.

I hope that researchers like Maureen Hanson have been paying attention to these recent findings. She has brought a T cell expert on board to her research projects and I think it's time someone looked specifically at exhaustion markers in ME patients. To my knowledge this has never been done before in ME beyond these few studies that have looked at PD-1, CD95, and CD127. There are a number of other markers that can be looked at, like CD160, CD244, CTLA-4, LAG-3, TIM-3, etc. Other findings are also compatible with a state of persistent infection and T cell exhaustion, such as the Lipkin/Hornig blood cytokine study, the Vernon study showing loss of IL-7, etc.
 

fdotx

Well-Known Member
The Charite study I linked above showed that EBV specific T cells in CFS patients do not display increased expression of PD-1, which is thought to be one of the main markers of functional T cell exhaustion. Recent studies, when looking at the global T cell pool, have found increased expression of PD-1 and CD95, loss of CD127 expression, etc. T cell exhaustion is driven specifically and primarily by continuous exposure to antigen. So I'm saying that CFS patients show signs of persistent immune activation, with signs of persistent viral antigen exposure via expected changes in exhaustion markers, but that this exhaustion is not being driven by EBV per the Charite evidence. The EBV specific T cells are likely being exposed to things like IL-10, TGF-β, and increased Treg activity as innocent bystanders. This will weaken their response somewhat but it will not cause full exhaustion as it would if they were being constantly exposed to EBV antigens.

I hope that researchers like Maureen Hanson have been paying attention to these recent findings. She has brought a T cell expert on board to her research projects and I think it's time someone looked specifically at exhaustion markers in ME patients. To my knowledge this has never been done before in ME beyond these few studies that have looked at PD-1, CD95, and CD127. There are a number of other markers that can be looked at, like CD160, CD244, CTLA-4, LAG-3, TIM-3, etc. Other findings are also compatible with a state of persistent infection and T cell exhaustion, such as the Lipkin/Hornig blood cytokine study, the Vernon study showing loss of IL-7, etc.
Hi Weyland, so do you think that taking anti- virals is safe or do you think they could make the situation worse given the immune system malfunction? I read that Dr.Naviaux in San Diego currently thinks taking anti-virals can make things worse if there's no sign of infection, and he doesn't think high antibody levels necessarily mean there is an ongoing infection. I heard that Dr.Klimas is also cautious about using them. I'm taking Famvir now but wish I could be more sure they wouldn't do more harm than good. My antibody levels to EBV and HHV6 are higher than what Dr.Teitelbaum would recommend giving them for.
 

fdotx

Well-Known Member
I put a link to it in the Resource section - thanks for posting.
Sure, I'd been looking for info like this for awhile so appreciate you putting where others have a better chance of seeing it. Betsy
 

weyland

Well-Known Member
do you think that taking anti- virals is safe or do you think they could make the situation worse given the immune system malfunction?
Personally I don't believe the underlying cause of ME is the proposed hypometabolic dauer state. I don't believe any of the most serious symptoms, signs, or abnormalities are caused by this state. Naviaux I feel has an overly simplistic view of the disease, that being ME = fatigue, and that the hypometabolic state is the cause of that fatigue, so therefore anything that further inhibits the mitochondria (such as antivirals) will make the disease worse or prevent recovery. I don't believe any of this is true.

I also don't believe that antiviral drugs will make the immune system changes worse. I believe they will either have no major effect or might actually have a slight beneficial effect. Besides their antiviral effects, people like Dr. Montoya believe that drugs like Valcyte might actually be having a beneficial immune modulating effect.
 

fdotx

Well-Known Member
Personally I don't believe the underlying cause of ME is the proposed hypometabolic dauer state. I don't believe any of the most serious symptoms, signs, or abnormalities are caused by this state. Naviaux I feel has an overly simplistic view of the disease, that being ME = fatigue, and that the hypometabolic state is the cause of that fatigue, so therefore anything that further inhibits the mitochondria (such as antivirals) will make the disease worse or prevent recovery. I don't believe any of this is true.

I also don't believe that antiviral drugs will make the immune system changes worse. I believe they will either have no major effect or might actually have a slight beneficial effect. Besides their antiviral effects, people like Dr. Montoya believe that drugs like Valcyte might actually be having a beneficial immune modulating effect.
Interesting - thanks for your input.
 

Remy

Administrator
Personally I don't believe the underlying cause of ME is the proposed hypometabolic dauer state. I don't believe any of the most serious symptoms, signs, or abnormalities are caused by this state. Naviaux I feel has an overly simplistic view of the disease, that being ME = fatigue, and that the hypometabolic state is the cause of that fatigue, so therefore anything that further inhibits the mitochondria (such as antivirals) will make the disease worse or prevent recovery. I don't believe any of this is true.

I also don't believe that antiviral drugs will make the immune system changes worse. I believe they will either have no major effect or might actually have a slight beneficial effect. Besides their antiviral effects, people like Dr. Montoya believe that drugs like Valcyte might actually be having a beneficial immune modulating effect.
I totally agree.
 

Forum Tips

Support Our Work

DO IT MONTHLY

HEALTH RISING IS NOT A 501 (c) 3 NON-PROFIT

Shopping on Amazon.com For HR

Latest Resources

Top