Report on protease inhibitor trial

Ali stopped Lexiva also. After two weeks, she hadn’t experienced any benefit. The only thing she noticed, besides a little GI upset, was a very minor CNS effect, which she experienced as similar to “a little too much Cymbalta”. I am SSRI intolerant and had a similar experience, though it wasn’t subtle and took a week to clear. Very strange. No obvious explanation.

There is of course no way to know if taking it for longer would have made a difference for Ali, but with so little to go on, continuing without clear benefit didn’t seem like a good idea. Someday we will look back on our Lexiva trial and understand the biology of what happened. For now, we have three drugs that have been shown to be effective in vitro, in more than one study: AZT, tenofovir and raltegravir. Three drugs work for HIV. So we’ll stay the course. We are tremendously better, though recovery is so far incomplete.

Report from Michael Snyderman MD

Michael Snyderman presented his updated poster at MD Anderson last week for a conference on hematologic malignancies. Dr. Snyderman is an oncologist with CLL and CFS who believes that existing antiretrovirals should be fully investigated for the treatment of XMRV infection. His pioneering research should have significant overspill for understanding how to approach the treatment of CFS. He is exploring something which, even if partially successful, sheds light into the pathogenesis of human gammaretroviral infection. His early evidence that it is possible to effect the disease process even after neoplastic transformation has already occurred, is nothing short of astonishing.

Link to the most current ppt.
Link to presentation as a pdf.

Dr. Snyderman’s comments:

The CFS symptoms continue to be improved. The CD19 cells continue to decrease which means that the majority of the leukemia cells are responding. Thus some of the cancer measurements are favorable even if the trisomy12 story is incomplete. Cancer may be more difficult to treat than CFS but what we learn with cancer will help CFS. Several important scientists have become interested in XMRV and cancer and may sponsor studies that would benefit CFS patients.

Thank you, Dr. Snyderman.

Coverage of the weekend’s events by the CFS Patient Advocate

The author of the excellent blog, CFS Patient Advocate, attended the ILADS and NJCFS conferences this weekend, and I want to publicly thank him for his continued lucid coverage of the important events. I encourage everyone to read thees informative posts from an experienced observer:

ILADS conference 2010 – Dr. Marcus Conant
ILADS conference 2010 – Dr. Jose Montoya
ILADS conference 2010 – Dr. Joseph Brewer
NJCFS conference day – Dr. Judy Mikovits

More Lyme Disease

This weekend is ILADS’ annual meeting. Many people have written to me about their failed Lyme treatments. Please see earlier posts here and here for my thoughts on chronic Lyme Disease and the disastrous treatments still being pushed by ILADS. If you take a look at their agenda for this meeting, it’s pretty clear that they’re still advocating the same old, same old. There is one talk on XMRV, one on HIV and one on CFS, so there’s a little progress, but the rest of the agenda indicates that they are unable to incorporate anything new into their thinking at all.  They don’t know anything about viruses and it would seem they are unwilling to learn. Deplorable. Months before I wrote my open letter to ILADS, I was very vocal with the powers that be in that organization and was told that their guidelines were being revised. But I’ve seen or heard nothing that indicates that it is happening. Why change it? It’s working out pretty well for them. Completely irresponsible!

Here’s a case for you. Adolescent female who didn’t recover when treated for Lyme the way her siblings did. Has been treated for Lyme several times with no results for over a year. Lives in Europe and can’t get any treatment there at all. They had to travel to the US to see an LLMD to get a prescription for an antibiotic and a SPECT scan. The antibiotic didn’t work and the scan is not relevant to anything. Wouldn’t change anything no matter what it shows. The mother of this girl requested an XMRV test and was refused. So he orders tests at Igenex, but won’t order a test from VIP Dx, even for a patient who has traveled from Europe and can’t get tested there. I think there’s steam coming out of my ears while I write this. I know these guys. I knew them when I was in practice and some of them were my doctors. I can list all the reasons why they are behaving like ostriches for as long as they can get away with, but the reality is, I don’t understand. They aren’t dumb, though you couldn’t tell from their behavior. So I can only conclude that they are self-serving. Poor patients.

The current ILADS guidelines should be an embarrassment to every member. In my opinion, this document is contributing to tremendous ongoing unnecessary patient suffering. Exempli gratia, chosen at random: 27. Sequential treatment
“Clinicians increasingly use the sequence of an intravenous antibiotic followed by an oral or intramuscular antibiotic [19,37,101,47,48]. In two recent case series that employed combination therapy and sequential therapy, most patients were successfully treated [19,47]. A logical and attractive sequence would be to use intravenous therapy first (e.g., intravenous ceftriaxone), at least until disease progression is arrested and then follow with oral therapy for persistent and recurrent Lyme disease.”
Let’s take a look at the references. 19, 37 and 47 are from the J Spiro Tick Dis, so not retrievable on PubMed. 101 is a lecture by Joe Burrascano MD, an ILADS member. 48 is a paper that says that clinicians don’t follow the IDSA guidelines. Nothing about efficacy. And no references after 2003 in the entire document. For that alone I would think someone would want to update. Just for credibility. Though I don’t know why you’d want credibility without a clue of what to do.

When you put out a document like that, it is also necessary to look at the effect the document has on the real world. Obviously something the IDSA has never done. But two wrongs don’t make a right. ILADS is supposed to be the good guys.

One thing is increasingly clear to me, chronic Lyme burns itself out to be indistinguishable from CFS. LLMD’s are generally not knowledgeable with respect to CFS. None of my Lyme doctors suggested that I had CFS. Nothing about the end-point of what is being called chronic Lyme fits with an active bacterial or protozoan infection. All the antibiotics in the world, even paid for ones, won’t fix it. 

The cytokine storm that occurs when chronic Lyme patients are given antibiotics, called a “herx” by LLMD’s, is not a good thing in my opinion, if it persists beyond a short time. The idea that it means that you are killing Borrelia burgdorferii is, I believe, a complete myth.

Lyme Disease responds to treatment. If it’s going to respond, almost any broad spectrum antibiotic you throw at it will work. Tetracyclines, macrolides, penicillins, cephalosporins work. Patients who do not respond to antibiotics in an obvious way clinically will not respond no matter how long they are blasted. The patients who do not respond likely have a retrovirus or more than one retrovirus. They need specific treatment for the underlying cause of their disease.  I am hopeful that all this deviant treatment, on both sides of the fence, will eventually become an anachronism. But for now, a word to the wise. Don’t do what I did.

Patients who do respond to antibiotics, relapse and respond again may need to be maintained on long-term antibiotics. I want to say this very clearly, because I am being cast as anti-antibiotic and I am not. I am against persisting when it is a losing battle. I fully acknowledge how difficult these decisions are at this time. They need to be made individually within the context of the physician patient relationship, but they must be informed by what is known. And what is known is changing very quickly.

We don’t know what part tick-borne disease plays in the total picture. Any good doctor knows what he doesn’t know and acknowledges it. There is obviously a place for antibiotics in this patient population, but the fact that some respond doesn’t justify the huge iatrogenic injuries that are occurring. I’ve heard of quite a few gall bladders lost to Rocephin and a couple of people who still have their gall bladders, but have chronic right upper quadrant pain. And untold losses to the Bartonella witch hunt. People permanently harmed by quinolones and aminoglycosides.

Most of the patients who write to me are clearly hyperimmune or autoimmune. They do not get opportunistic infections in the way that AIDS, transplant or other immunosuppressed patients do. Borrelia burgdorferi and certain activated viruses probably play a part in pathogenesis, but are not opportunistic in the same way that happens with HIV. They do not overwhelm and kill the host.

Of course, if current HIV drugs control the disease, LLMD’s and CFS doctors will quickly become irrelevant. So why would they want to try them? Even if the patients are X+ and are begging for prescriptions. They’d lose their captive audiences. People traveling from all over to pay outrageous amounts of out-of pocket cash, which the doctors can justify to themselves, since they can’t get paid adequately for what they do under the current system, as the patients aren’t covered for what they have. Eventually ID doctors will treat it.

My husband was diagnosed with cardiac Lyme and treated with antibiotics twice for persistent arrhythmias, dysautonomia and the usual TBD suspects. Oral antibiotics made him worse. IV antibiotics gave him C. diff. He is now much better, having refused treatment for almost three years, other than a 5 day course of Alinia a couple of years ago that helped. Ali, who I once considered antibiotic dependent, has had no antibiotics since last fall. Her case actually supports ILADS’ conclusions more than most, and even she is proving them wrong.

Protease inhibitor trial

We’re about the same as the last times we posted. Much better than when we started, but not quite as good as we were a month ago. It’s so hard to tell, even week to week. Month to month is more useful when thinking about what’s happened. We are not quite as functional as were at one point, but hugely more stable than even a few months ago. The descents into hell aren’t happening, but there have been no very recent great shows of physical activity.

A little discouraged and impatient, Ali and I decided to start a protease inhibitor nine days ago. Feeling that we do not have complete control of the virus, and knowing that a PI is often necessary for control of HIV, we decided that the potential benefit/cost ratio of a trial was good. The two papers to which I linked in my last post, identified amprenavir and indinavir as possible candidates. Postulating that the disease requires active replication of more than one virus, it is possible that a PI that affects MLV’s, might affect the disease process, even if X is not susceptible to it. Another involved HMRV might be. Due mostly to the difficulty of complying with indinavir, which is an every 8 hour drug that should be taken on an empty stomach, we chose Lexiva, fosamprenavir, an every 12 hour drug that can be taken with our other drugs.

As has been her modus operandi with her antiretroviral trial, Ali has had no significant difficulties with the drug. I, however, only tolerated it for a week. The effects were purely neuropsychiatric. Doesn’t happen with HIV. The drug has very little in the way of CNS effect. Two days on, two days off, six days off kilter altogether, definite cause and effect. Intriguing, but away from function, which is my goal. Still, depending upon how Ali does, I may try again at half dose, the way I did with Viread. The effect of Lexiva was not like the inflammatory flare that occurred with the other drugs. It’s very hard to describe in words, but, for me, it is more proof of concept, even if the clinical effect was not immediately acceptable. More evidence of retroviral drugs interacting with retroviruses in novel ways.

I would like to take this opportunity to say something that I think is much needed for all of us to think about. In our need to fight the prevailing medical impression that it is a somatoform disorder, the very real neuropsychiatric manifestations of the disease have been denied, even sometimes to ourselves. The brain is just an organ like any other. When it gets sick, it looks different than when the heart or gut get sick. It is much more threatening, because it touches on who we are at the deepest levels. The need to keep it private is very damaging. Goes hand in hand with the disbelief. Psychiatrists have done more damage to this group patients than almost any other specialty. My own psychiatric care was truly abysmal. Whores all to the drug companies. Paid at least in part, to witness their patients’ pain, they push drugs that are often harmful.

In some ways, I think the choice to start antiretrovirals now is an even tougher one than when we started. Early experience is that it is hard for most people to get on the drugs. There are positive signs that antiretroviral therapy will be the way the disease is treated in the future.

There are patients writing to me who are subjects in a funded clinical trial of XMRV positive patients. My understanding is that there is no antiretroviral arm in this study. It involves Valcyte I believe. While there may be a place for treating activated herpesviruses in this disease, in my opinion, at the end of the day, Valcyte, Valtrex, etc. will be after-thoughts. How pathetic that there’s a chance to study something that could actually control the underlying cause of the disease and instead money is being spent to find out again what we already know. Results I can figure out from my email. While individuals undertake antiretroviral trials on their own. Begging to be lab mice. Voluntary biological experiments, with no assurance at all of success. Forced to try the only real treatment possibility available, in a completely uncontrolled fashion. It’s an outrage.

7 months

It feels like we’ve dipped a little and then plateaued. Not in any way crashed, but our physical resources are more limited than we would like. It still feels like HAART is working for us, but may not be enough for full function. We are vastly improved from 7 months ago when we started treatment, but are not fully recovered, though I had similar thoughts a couple of months ago and then we started uphill again. So it would appear that progress is not entirely linear.

We have both had to back off a bit because of physical limitations and a desire to work with the drugs and not against them. The absence of relentless pain and a little energy can really go your head, let me tell you. It is easy to forget that it is necessary to take care. The disease still rears its ugly head with unfortunate regularity, but its power is significantly blunted.

Ali will tell her own story soon I’m sure. A couple of weeks ago, I started having more sleep problems again. Sleep disruption is a sentinel symptom for me. A bad night’s sleep is generally followed by a sick day. Chicken or egg. A few days into it, I realized that I had let myself run out of Deplin by mistake. When I restarted it, things improved again. In my excitement to have discovered how potent it is for me, since I didn’t notice much going on it, and because it has been so obviously important for Ali, a trial of higher dose, 15mg, seemed like a good idea. It disrupted my sleep completely, so I went back down, but things have not yet settled down all the way. The other possible contributing factor was a change from a brand Estrasorb to a compounded estradiol cream. My sleep is completely dependent upon adequate estradiol, so I’ve switched back to what I was using before. The last couple of nights have been better, but not yet good again. My symptoms are subsiding as the sleep issue improves.

My recent experience with Deplin has led me to read more deeply about the methylation cycle to try to understand why l-methylfolate supplementation might be so important. Our current drug regimen can do nothing about existing integrated virus, which can be transcriptional or silent. It is unlikely we will be well unless the virus can be silenced. Take a look at this paper: (Blaskova/Hirsch). They found that the latent reservoir in HIV infected individuals without viremia had hypermethylated HIV-1 promoters that are resistant to reactivation in vitro, as opposed to viremic patients with hypomethylated 5′ LTR.

We have both begun weekly injections of B12 (hydroxocobalamin), 10mg IM, and a multi which includes B complex. The vital cellular functions that are dependent on the B vitamins require an adequate supply of the complex.

I am having an exacerbation of muscle weakness and a feeling of lactate build-up that could be related to adverse effects of AZT, though it goes up and down with all my other symptoms; if it were an adverse drug effect, I would expect it to get steadily worse, not wax and wane. In addition, there are a couple of patients who write to me who are having problems that could be AZT related or exacerbated. It is unfortunate that drug choices are so limited. Ali still has not experienced any problems at all attributable to the drugs. I would like to point out that I do not feel in any danger. If I have to, I’ll stop the drug, but I want to stay on it and will push through if I can until I know more.

Presumably integrated virus is still transcriptional. The negative testing for the protease inhibitors against X is unfortunate. The PIs interfere with the assembly of new viral product. A PI is necessary for complete blockade. There is a tiny amount of evidence in the literature that MLVs are inhibited by the PIs amprenavir and indinavir (Powell/Otto, Feher/Tozser). It is possible that XMRV protease differs from that of HIV too much for the drugs to have an effect. It is also possible that there is a problem with the testing of the entire class of drugs to date. In addition, one might speculate that even if X is not inhibited by the existing PIs, P might be, given that there is apparently activity against MLVs. We are considering our options.

For me, being better enough to enjoy myself is almost an ecstatic experience. I really didn’t expect to get better. Nothing in my years as a doctor had led me to believe that my illness would do anything other than continue on a downhill course. The story of HIV, at least in this country, is a hopeful one for us. The AIDS patients who died in the early years missed the benefits of the unfolding science, but most of us will still be around to see it, our disease is so slow. The trick for us will be to go on with the time we have left and not be anchored by anger and loss. There is redemption in forgiveness. Much has been lost, but there have been gains as well. Many of the people writing to me are struggling with or have mastered acceptance of very difficult realities. When released from the prison of illness, that wisdom and compassion will be a force to be reckoned with.

I have set up an elist for patients who are taking antiretrovirals and prescribing physicians to share treatment experiences. Caregivers are also welcome. If you have started or prescribed treatment, please contact me if you would like to be included:

“Time for Action” Campaign

For ME/CFS Patients, Their Families and Friends

Organizers:  Robert Miller, Rivka Solomon, Charlotte von Salis

On the heels of the September 7, 2010, historic NIH meeting with ME/CFS patients and their families, now is the time to let our federal health agencies know we are expecting big changes. The more they hear from us now, the more they’ll listen to us next time we meet. Our “Time for Action” campaign is advocacy made easy — yet it will have a huge impact. We ask patients, their families and friends to email, call and/or fax NIH Director Collins and NIAID Director Fauci with this simple question every day, starting today. (Please Cc: emails to Robert Miller at:

Dear Directors Collins and Fauci,

What have you done for ME/CFS today? Patients and their families are waiting.

Name: John Doe (or John)
Location: Miami, FL
Time: Sick 12 years

Contact info:
1)  National Institutes of Health
Director Francis Collins
     Cc to:
Phone: 301-496-2433
Fax:  301-402-2700

2)  National Institutes of Allergy and Infectious Disease
Director Anthony Fauci
     Cc to:
Phone: 301-496-2263
Fax: 301-402-3573

For inspiration, here’s their “How To” video.