“The FDA and NIH have independently confirmed the XMRV findings as published in Science, October last.” mmdnewswire

Celebrating today’s press release from the Netherlands, I would like to report that I am quite sure that the antiretroviral drugs are having a beneficial effect. My daughter and I are a little under and over fifteen weeks of treatment respectively. She started tenofovir as a third drug six weeks ago and I started it two weeks after she did.

We are on a definite uphill trajectory, she more clearly than I. She has been more and more functional and much less miserable for a month. She has gone out for fun socially four of the last five days. Much more time upright. She is planning her life. In the last three weeks, she had one three day dip with a sore throat (not a usual symptom for her). Otherwise lots of pretty good time. I would like to say that she is very balanced about all of this. She is an extremely informed, sophisticated patient. After what she’s been through at the hands of the medical profession, she is pretty much of a skeptic. She is quite sure this real.

I also am better in many ways. I have, however, had mild progression of neurological disease (new sensory radiculopathy which is a recurrent problem). For me, each of the drugs flared my neurological symptoms and then things settled after a couple of weeks. I remain almost free of malaise, a miracle to me after fifteen years of living with it. Reduced symptoms related to vasospasm. In the last week my sleep has normalized. Very big.

For the record, I would like to state publicly that I am not prescribing for myself or my daughter.

Not science. Clinical medicine. There are other factors beyond the antiretrovirals for both of us, though not enough to explain what we are experiencing, in my opinion as a doctor, patient and mother. We are being treated for XMRV. And the paradigm shift that came with finally knowing what is wrong with us has helped in many ways, including choice of pharmaceuticals. No controlled study here. But lots of clinical improvement.

Addendum April 4, 2012. I wrote this post when I was coming to terms with my own mistakes. I’m not proud of the writing now, kind of a rant, though I still agree with it in substance. If you’ve reached this page as part of a search for ILADS, please also read yesterday’s post, Integrity, which discusses a new paper that addresses the persistence of Borrelia burgdoreri in Rhesus Macaques, despite long term antibiotics. The clinical implications of this paper support my conclusions. Shortly after I wrote this open letter, I was reassured by the president of ILADS that their guidelines were about to be revised. However, the same guidelines from 2004 are still on their website today. Their approach is dangerous and unsupportable.

The following article was recently published by two of your members, one a physician whose name appears on the ILADS Lyme treatment guidelines list of authors. The pot calling the kettle black!

http://www.peh-med.com/content/5/1/9/abstract

The IDSA has recently reviewed their document because of legal action brought by Attorney General Blumenthal of Connecticut. Their review committee decided to leave their guidelines unchanged. ILADS refuses to even consider that anything their guidelines say might be misleading to physicians untrained in treating infectious diseases or patients without access to adequate medical care.

IDSA:  Lyme Disease 2006 Guidelines

ILADS:  Guidelines for the management of Lyme disease

In my opinion, both of these documents are ridiculous. Patients are trapped in the middle, collateral damage in a war that is all about politics, self-interest, money, insurance companies, medical licenses. One side says not to treat, other than an irresponsible recommendation for inadequate prophylaxis. The other treat ad infinitum, even if you’re not sure what you’re treating and the patient seems worse. Nothing here about the medical reality of treating a real disease. Seems pretty obvious that the truth is somewhere in the middle.

The ILADS treatment guidelines are a failure in my opinion. They need to be revised to stop harming patients. All these antibiotics you have been fighting so hard for are not the answer. This has been my opinion for a long time and I have written many times to the group before quitting ILADS recently, but was largely ignored. There is a groupthink that has occurred which does not allow a threat to the status quo in my opinion. Because of my blog, I am receiving many, many letters from people who have failed treatment or are failing treatment for TBDs. These letters are only confirming my original conclusions. It is completely heartbreaking to see how seriously people, whole families, have been harmed, physically, emotionally, financially by an incorrect construct. It is a complete and utter disaster. People on both sides of the Atlantic are trying to treat themselves and their children without guidance according to a completely unsupported document filled with dangerous misinformation. It is incumbent upon the organization, which calls itself a medical society, not a political organization or a support group, to reconsider its recommendations. Past time.When I was in private practice, I justified my lack of supporting data for what I was doing by observing clinical results. I expected to see a clinical response in a reasonable amount of time. Also the therapies I was offering were relatively innocuous. I fully believed that with informed consent, it was a decision reached between patient and doctor to depart from conventional treatment. But this is not the same thing. Antibiotics are not jelly beans. They are being handed out to this patient group in a completely indiscriminate manner often to the detriment of those taking them. Even the lucky ones who get a partial remission generally relapse after a while. And at that point escalating antibiotics does not seem effective for most. Also the patients who consider their treatment successful are often not really so healthy if you inquire more deeply. And that goes for a lot of the treating doctors too, not just patients and advocates. Why are there so many sick doctors in the group if the ILADS guidelines work so well?The reason that this has happened is that for many, antibiotics work. This group generally respond in a pretty straight forward manner when first treated. For another group, antibiotics do move the illness, but are at best a bandaid, especially if they need to be continued long term. Not that bandaids aren’t useful sometimes. But judgement seems to have been lost in the treating physician group. That’s the biggest problem as I see it. Kill, kill, kill, something. It hasn’t worked. Will never work. Patients should save their money and go to the beach. They’d do better.The disease is a relapsing remitting process all on it’s own. If you give absolutely no pharmaceutical treatment, just lots of good food, fresh air, reduced stress, supportive therapies, many get better. Incompletely, but I got better results with biofeedback and oxygen therapy than I am seeing in the antibiotic group now. I am not in practice, but fate seems to be providing me with a “clinic without walls” of a sort and my message today is that these patients have been worse than neglected. They have been completely screwed by their doctors, conventional, LLMDs, alternative. It is truly pathetic!I appreciate fully how difficult it is to do clinical research in private practice. And that practicing medicine by adhering to any protocol is unrealistic. But in this case, I think it is incumbent upon the physicians choosing to depart from conventional wisdom to come up with some evidence. It’s been years. Not enough to say it works when so many patients are still sick. And it seems pretty clear at this point that it has little or nothing to do with finding the correct antibiotic protocol. Each doc is out there trying something a little different, and ALL have failed with a growing subset of patients. The more aggressive LLMDs have done the most damage. And they’re not even interested in follow-up in my experience. Time for patients to move on.I have never said that I didn’t believe that some people with missed Lyme Disease respond to longer treatment than a month of Rocephin. However, I do not believe that clinical judgment is worthless to tell who will benefit from longer term treatment and who will not. There is an idea in the treating physician group that if you keep pounding away at it, a large number of people will get better because of years of treatment. There is not a shred of evidence to support this idea. Complete myth. It is just as likely or more likely that those patients who did improve did so slowly on their own, despite their treatment. Also, this improvement rarely means a return to former health and function. It is much less clear cut than that.

I have no problem with a few months trial of antibiotics for a patient who has been chronically ill and undiagnosed for years who has positive Bb serology or some other evidence for an active TBD. If there is a clear clinical response, then treatment for that person must be individualized. Probably that patient should be maintained on some regimen if they relapse and respond a second time, because it is harder to regain control after each relapse. By the way, in six or seven years of reading the ILADS elist, I have only seen this mentioned once, with respect to analysis of a small number of one pediatrician’s patients. This piece of information might have saved the quality of my daughter’s life, when her antibiotics were stopped the third time, had I known this before a couple of years ago.

Hurting some of your patients because you think you are helping the others is unacceptable. Even if most are really being helped, which is not at all clear. And I think it is not anywhere near most over the long haul. The treating physicians are looking at too small a window of time. Where are all these patients who needed years of antibiotics in order to recover and are now all better? It looks to me like part of the problem is that at one point, Lyme treatment worked better than it seems to now. Maybe those patients are mostly treated by now.Undoubtedly, there has been more XMRV involvement over time. With a few exceptions, everyone I know about is still sick, including most of the sick doctors. And the recovered people I know still have sick family members, especially young people. Preselected group for treatment failure, but if the ILADS approach worked so well, wouldn’t the sick doctors who are members of the group be better? In fact, everyone I know who underwent years of shotgun treatment is sicker than they were five years ago, including people treated by almost every well known LLMD. So how am I supposed to know it works so well? Because of all the pooh-poohing of the mainstream opinion that long term antibiotics do not generally improve the long term outcome? Show me some data. It’s way past time. That’s the elephant in the room.A recent paper by ILADS physicians Stricker and Green, co-authored by an NP and two attorneys, strangely, argues that long term antibiotics and indwelling central lines don’t kill people, so it’s OK to do it. A couple of hundred people were treated for a long time and complications tracked. But no efficacy data was revealed. I wonder why? Bet the statistician had a few problems. With the exception of Brian Fallon’s work, nobody has published anything of significance that I can recall in a decade! I’m sure I’m forgetting something, but precious little. What literature does the term LLMD refer to?Then there’s the money… Holding a life preserver just out of reach to a drowning person while charging them $250-$600 per hour uncovered by insurance is a rather questionable practice for a service you are representing as life saving with no proof. There are very few ILADS physicians who take insurance. Most of the drugs, once you resort to IVs, which can cost thousands per week, are not covered. Patients can’t afford to keep coming back and paying to tell doctors what happened to them. Not that most are interested in follow-up anyway in my experience. Also, almost none of these physicians are available to their patients in anyway when they are really in trouble medically. Maybe that’s worse than no help.The politics and medicine of all of this have clearly been affected by a small number of evil, self-serving IDSA doctors who continue to spout their nonsense. And doctors have a hard time accepting what they don’t understand and a bad habit for blaming the patient when things don’t go well. ILADS should be the side of the good guys. The patients are trapped in the middle and more than a few are being damaged by friendly fire. When you don’t know, it’s a good idea to tell a patient, “I don’t know”. Not there’s a good chance I can cure you. That’s what patients think they are being told when they embark on years of potentially life threatening treatment. Completely misleading.

Again, I am not against the use of antibiotics if they work. My concern is that there are lots of antibiotics being prescribed long term based on faith rather than clinical response. It’s not trying them that is the problem for the most part, though personally I was immediately harmed by antibiotics, but that’s rare. The problem is continuing them out of desperation. Also over time, it appears that most relapse anyway, so that needs to be factored into the equation. You can’t maintain patients on multiple IV drugs indefinitely. And when they come off, the drugs have no doubt done lots of damage in terms of floral disturbance, colonization with resistant organisms, GI damage, etc. Sometimes drug toxicity causes direct damage. I know people who have been permanently damages by quinolones and aminoglycosides that didn’t help their situations. Very poor cost benefit ratio in my opinion. But of course patients should be able to decide for themselves. That decision should be based on something more than impressions. There is not really even a coherent rationale to the guidelines as they now stand in my opinion.

I was disabled for a year with my first big time crash. I recovered enough to have a private practice for most of a decade with no treatment at all except for ARB’s, neurofeedback and bioidentical hormones. If I’d been blasted with antibiotics then, I might not have gotten those good years. Perhaps if nothing had changed in my environment I wouldn’t have recovered at all. Many have found improvement with avoidance of triggers.Without any long term follow-up, it is impossible to say what is the best way to go with antibiotics for any person at any given time. But I believe that the current ILADS guidelines, as they are being put forth and used, are hurting as many people as they are helping. One advocate wrote to me that it was necessary to sacrifice the few for the many. I don’t think it’s so few, but even if many more are helped than harmed, I don’t believe that anyone needs to be sacrificed. It’s the paradigm that needs to change so that the doctors are thinking about the correct disease process.

I would like to respond to the cautions that ended yesterday’s Chicago Tribune article by Trine Tsouderos. http://www.chicagotribune.com/health/ct-met-chronic-fatigue–20100607,0,6405426,full.story

There are dozens of antiretroviral drugs that have been brought to market for HIV. Unfortunately, only three have been shown to inhibit XMRV in vitro. The risk of taking these drugs is not that great over the short term. The only real potential dangers from the drugs are picked up with simple safety labs. Muscle wasting can occur from AZT, but it takes YEARS to develop. I know of patients who have been on AZT for 15 years who are fine. The doses of AZT used in the early days of AIDS were much higher than what is used now, leading to the scary side effect profile, but the reality is that our current regimen is quite easy to take. In my opinion the magnitude of the risk, with minimal monitoring labs, is small. It sounds to me like Dr. Sax, quoted in the article, is trying to frighten people from getting the help they need to get himself off the hook. His AIDS patients have a much better quality of life than CFS patients do. Has he ever treated even one CFS patient? I bet not. What he said is inaccurate fear mongering. He says it’s worth it with HIV because without treatment there is a horrible death. With CFS there is a horrible life. There is no playing it safe for us. This is a calculated risk, a small one at that, considering the certain alternative. If the drugs cause a significant problem, stop them. I really don’t understand the overabundance of caution. This patient group is routinely prescribed all kinds of dangerous drugs that don’t even attempt to address the cause of the illness, only aiming for symptomatic relief. I can’t tell you how many patients I have heard from who have been injured by their psychiatric medications. My daughter has had NO SIDE EFFECTS from antiretrovirals after three months. I had initial symptom flares with each drug that settled after a week or two. We are doing regular safety labs, more often than is routinely done to monitor AIDS patients, and we are just fine.

Easy for a doctor who doesn’t have a sick daughter to say this isn’t the way to proceed. If he did, he would probably be finding a friend of his to prescribe for her, not telling her she should wait for double blind placebo controlled studies and clinical trials that will take years. Every day is intolerable. There is already vast experience with the drugs. You can grow a healthy baby on AZT. Tenofovir is being studied by the CDC for prophylaxis in healthy individuals at high risk for HIV (cdc link). How toxic could it be? We are currently being monitored for problems and there are none. All drugs have potential side effects. So what? Suicide is a leading cause of death in the CFS patient group. What if the drugs work? They work for HIV, the closest human model we have.

No matter, the patients will find out the truth. All the ID docs who have refused to consider an infectious etiology for CFS will be shown to have been wrong. They have consistently refused to care for these patients, even though a viral etiology should have been obvious from the epidemiology. The CDC failed in its primary mandate. There has been a retrovirus loose in the general population for over forty years and the technology has been there to find it for a couple of decades. It is a multigenerational infectious disease that is contaminating the blood supply. New incurable XMRV infections are occurring every day while scientists and doctors play it safe. It may be much easier to develop a vaccine for this one than it has been for HIV, but that work hasn’t even begun, five years after XMRV was discovered. It is a miracle that safe drugs already exist. In my opinion, it’s crazy not to try them.

For fun, letʼs look at Kochʼs postulates with respect to XMRV and CFS.

1. Isolate the organism from every case. The WPI has verified XMRV in 99 of 101 of the original samples from the Science paper.
2. Propagate in pure culture in vitro. Done.
3. Reproduce disease by injecting the organism into a suitable recipient. Accomplished in tissue culture. Also lots of epidemiological evidence for vertical transmission.
4. Re-isolate the organism. Accomplished in tissue culture.

I don’t think that the outcome depends on finding the cause of CFS or autism. The prostate cancer research and the fact that the blood supply is contaminated will carry it forward. The in vitro testing was done for prostate cancer patients. If the drugs work, it will be patient driven. Causation may be proven clinically before the science happens. The WPI’s study hasn’t even been replicated yet!

As I have said, I don’t think the drugs we are taking are particularly dangerous. Patients all over the world are taking much more dangerous drugs that are just bandaids. The evolving treatment regimen involving the three drugs identified in the Singh paper is the first thing that ever presented itself to me that might actually arrest the disease process at its foundation. A bottom up, rather than a top down approach. Unfortunately, it’s not going to be a slam dunk. We need specific drugs. But it’s a miracle to me that there are three safe drugs already on the market that work in vitro. It is stunning to me that the government isn’t funding clinical trials nine months after the Science paper was published. In the meantime a whole new crop of sick people will continue to do the same things that don’t work or even harm. And the band played on…

In hindsight, it was obviously an infectious disease all along. It should have been apparent from the epidemiology. It will be a phenomenal teacher of the pathophysiology of human disease. It will illuminate genomics and evolutionary theory.

I see many commonalities between CFS and ASD. Autistic children have the IBS, food and chemical sensitivities, problems with heightened sensory systems and disordered processing. Also there seem to be far too many patients with CFS who have autistic children. Why aren’t the epidemiologists looking at this? For clinicians, I think ASD will be very satisfying to treat in light of this new paradigm. In my private practice, I found that autistic kids were responsive to the relatively gentle therapies I offered. I am hopeful that the ASD community will help move things along for all X+ patients. The parents that I knew in practice would have moved heaven and earth had they known what to do. I believe that this is it. Time will tell.

There have always been a few chronically ill people. But in the thirty years since I finished school, there has been an enormous increase in chronic neuroimmune illnesses. The alternative medical community has identified many of the clinical associations, metabolic and hormonal deficits, but I think most of them will turn out to be downstream effects of X. When I was a student I was taught to always look for one cause of a patient’s clinical presentation. I think X is it for so many, though it is possible that it is not the only unrecognized retrovirus out there. ME/CFS, Lyme Disease, ASD, GWS, MCS, atypical MS, various cancers, others. Disease expression is due to many factors, age of infection, genetics, concurrent infections, immunologic stressors. The scope of it is truly breathtaking.

Never forget, medicine is an art. Good science and good medicine are not at all the same thing. Inspired medicine does sometimes require a leap of faith.

 
I think we are both getting better. There has been an incremental improvement. Still a long way to go, but things are definitely looking up.

My daughter started tenofovir 300mg once daily as a third drug four weeks ago. She improved noticeably after two weeks and has stayed better for another two weeks, with a three day dip in the middle, but not a severe one. All of her symptoms are more stable than before starting treatment three months ago. She still has awful moments, but they don’t last long compared to before. There is one confounder. She started Actos for hypoglycemia shortly before starting antiretrovirals and it was immediately helpful. However, her dysautonomia is improved and I can’t attribute that to Actos. The other change for her was stopping long term antibiotics.

I restarted tenofovir at half dose 2 weeks ago and went up to full dose 5 days ago. I again had a small flare of neurological symptoms that is almost resolved now. Other symptoms are much improved, e.g. cardiac and GI symptoms. I am still having episodes of instability, but they are less frequent, less severe and not as long lasting as previously. I’m hard to evaluate however, because I was already on an uphill course for the six months prior to starting antiretrovirals, since discontinuing Lyme treatment last summer.

Our current regimen is:
AZT or zidovudine 300mg BID
Isentress or raltegravir 400mg BID
Viread or tenofovir 300mg once daily

I can’t tell yet whether C4a and TGF beta-1 will be good markers of recovery or not. So far it appears that we both had an inflammatory flare after beginning treatment that was partially resolved a month ago. New specimens from this week are pending. They take a couple of weeks to come back.

It is certainly much too soon for celebration. Things don’t look that different from the outside. She’s not ready for school and I’m not ready for work. But less suffering overall at our house. Signs of life. Each day lately I feel more and more optimistic.

I drafted the above last night. After a very active day yesterday, my daughter woke up feeling very poorly today and is having a harder day than any in the last couple of weeks, with symptoms of inflammation and dysautonomia. However, she bounced quickly with supportive care. So I think it is a good time to post. To communicate the hope and the uncertainty…