Testimony of Jamie Deckoff-Jones MD
CFSAC
September 17, 2010

To whom it may concern:

I am a 56 year old emergency physician. I have been diagnosed with CFS, chronic Lyme Disease and atypical MS. My 20 year old daughter has been diagnosed with CFS and chronic Lyme Disease. I have been ill for 16 years and disabled for 6. My daughter has been ill for 7 years and disabled for 4. In the last few years, I have almost died twice and my daughter has been hospitalized for cerebral vasculitis. My husband has been ill for 7 years and is functional. My 15 year old son is clinically healthy.

In October of last year, I read the Mikovits paper in Science. It was immediately apparent to me that our illness was of retroviral origin. In February, my daughter and I tested positive for XMRV by culture. We were both almost housebound at that time. With the help of a compassionate family doctor and the guidance of an experienced AIDS doctor, we started the three antiretroviral drugs that tested in vitro against XMRV in the Singh study. Six months later, my daughter has started community college and I am planning a return to part-time practice. As always with clinical medicine, there are confounders, but I do not think it possible that we have not been helped by antiretroviral therapy.

Because the patients have no help, I started a blog to share our experiences with treatment and my clinical ideas. The response has been enormous. My email is filled with stories of unbelievable pain, neglect and abuse. The wasted lives and wasted talent are a national disaster. Instead of contributing, a staggering number of people are unable or almost unable to care for themselves.

Since CFS patients don’t die from their disease for a very long time, there is a tendency to feel that there is no hurry. Good science takes time after all. But it is a progressive disease. There are a staggering number of patients who are too sick to wait. They need compassionate care. They’ve been denied basic care, even common decency, for decades. It’s been a year since the association between XMRV and CFS was elucidated. Scientists say causation has not yet been demonstrated. I say it should be a clinical assumption at this point. As a physician, it’s obvious from the stories and family histories of the patients contacting me. Where have the epidemiologists been all this time? I am an emergency doctor and this is an emergency!

To me, it’s a miracle that existing safe drugs may be effective. It is a travesty that clinical trials have not yet begun. It brings shame on the medical profession that doctors are unable to connect the dots. If there was a hurricane or an earthquake, everybody would be rushing to help. Even if all resources are immediately mobilized, many will be lost. The patients have very advanced disease. It is beyond a disaster.

New babies are being born with it every day. Is it possible that AZT in pregnancy will prevent it, as it does HIV? Why is nobody trying to find out?

The WPI has single-handedly made things happen for patients. Why are they not funded? They are a tiny non-profit. They have handed the world the answer on a silver platter. Is our government ever going to step up to the plate?

Sincerely,
Jamie Deckoff-Jones MD
Santa Fe, NM

Lots of people are speculating as to why we might be better, other than HAART, including me of course. Maybe it’s our genetics. Maybe Lyme treatment worked:). Maybe quitting Lyme and other palliative treatments worked. Maybe we’re taking something else that did it.

All the drugs cause an intensification reaction in most patients. It generally subsides in weeks, but is persisting in a few patients. Except for us and a 16 year old that hasn’t been ill for long whose mother reported on this blog, results are so far not as encouraging as hoped. The most obvious difference between us and the others is that we have been on all three drugs for a few months. Also Deplin may be a factor for us, as discussed later in this post. Actos has helped Ali and may have made it easier to get on the drugs, which haven’t bothered her at all, clearly an exception to the rule. I had a hard time getting on them, but was very motivated. It wasn’t worse in any way than where I’ve been before, but it required a willingness to suffer.

AZT seems to be the easiest to start, but may have the least clinical effect. I haven’t seen or heard any indication that all the fear about AZT exacerbating the existing mitochondrial defect has any basis in clinical reality. It is the broadest spectrum drug we have; it inhibits transcription of HIV, HTLV, FeLV, MLV’s and XMRV. It also has the best CNS penetration of the three available drugs. There are some potential long-term consequences of taking it that hopefully we will be able to avoid when new, specific drugs are developed. This happened with HIV disease, in which AZT is generally not needed anymore for effective treatment, at least in the developed world.

The inflammatory flare that follows starting the drugs may have to do with an increase in unintegrated viral DNA exacerbating the existing pathological response. It is an intensification of existing symptoms. I will resist the impulse to call it a ‘herx’. We don’t have a handle on the pathogenesis of X related disease yet, so we can’t know what the drugs are doing specifically with respect to this virus. With HIV, patients stay healthy until the virus activates, then die pretty quickly if not treated. X smolders without killing. Many of us are very far down the road and it isn’t surprising to me that the established pathological processes don’t just turn themselves off, since provirus is present in existing cells and probably still doing damage. Recovery likely depends upon the formation of new, uninfected cells, so it is a slow process.

The biggest reason I can think of not to try these drugs now is the potentially serious consequence of exposing drug naive virus to a regimen that doesn’t really do it. It’s possible that it will be better in the long run to wait. It’s a very personal decision that has to do with quality of life now and ability to temporize, or not. It should be made in consultation with a knowledgeable physician. But as things are, many patients are unable to find help and a few are trying antiretrovirals without supervision. This is of great concern, given that the drugs are not easy to take and need to be managed. There is so little information to go on that anyone who chooses to go ahead now must know that they are taking a big chance. Each person’s assessment of risk to potential benefit is going to be different. The risk of doing nothing needs to be carefully evaluated in light of the information available, as our understanding of what’s going on medically is changing all the time right now. Unfortunately, clinical medicine is all we have. It doesn’t look like science is going to save us for a while. Also I think one should probably not start antiretrovirals without a willingness to take them forever.

Although it goes a bit against the grain to post this information publicly, some have asked and my intention is to inform about what seems relevant. So, in addition to HAART, here are our current daily meds, once a day unless otherwise noted.

Me:
Cozaar 100mg
     switched from Benicar 6 months ago; have been taking an ARB for 15
     years
Norvasc 5mg prn severe hypertension
Deplin 7.5mg x 6 months
Low dose aspirin x 6 months
Armour thyroid 30mg for years
High dose cyclical topical estradiol and estriol
    since menopause two years ago
High dose topical testosterone
     have been taking testosterone since ’97
Prometrium 200-400mg (since ’97)
Topical selegilene .5mg x 8 months
Topical D3 10,000 units x 6 months
     had to slowly increase dose; didn’t tolerate previously due to
     increased pain
Meriva SR (curcumin extract) 2 capsules BID, added recently

Ali:
Actos 7.5mg BID x 6 months
Fortamet 500mg BID x 4 months
Cortef 5mg for years
Deplin 15mg x 1 year
Topical progesterone 200mg 12 days per month during luteal phase
Topical D3 10,000 units x 6 months
Meriva SR 2 capsules BID, added recently

There are also many things we are not taking anymore, including antibiotics, Klonopin, pain medicine, anticonvulsants, psychoactive drugs and truckloads of supplements.

Ali has PCOS, as do more than a few second generation women in my ‘clinic without walls’. PCOS is a very common, though under-diagnosed syndrome characterized by LH and insulin insensitivity. The LH insensitivity interferes with normal ovulation and there is impaired formation of the corpus luteum cyst and therefore, inadequate progesterone. PMS in this group looks like an exacerbation of the illness. Atypical reactive hypoglycemia is seen in male patients as well, as are hormone deficiencies.

Actos has been quality of life changing for Ali. The treatment for PCOS is usually metformin, sometimes with Actos. Treatment encourages normal ovulation. In addition to the luteal phase defect, PCOS is associated with insulin insensitivity. Ali became so sugar sensitive that she didn’t tolerate any carbs at all. Two physician friends suggested Actos at the same moment for her, for completely different reasons, so the lightbulb went on for me. Actos (a TZD or thiazolidinedione, like Avandia) works by binding to PPARγ which are receptors on the membrane of the cell nucleus. TZDs enter the cell, bind to the nuclear receptors, and affect the expression of DNA. Activating PPARγ decreases insulin resistance, inhibits VEGF (vascular permeability factor), dropping levels of certain cytokines. Here are links to a few Medscape articles and pertinent papers:
Medscape: Insulin–sensitising drugs for Polycystic Ovary Syndrome
Medscape: Antidiabetic Agents for Treatment of PCOS
Medscape: Pharmacologic Treatment of Polycystic Ovary Syndrome
Treat Endocrinol. 2006;5(3):171-87.
PPAR Res. 2006; 2006: 73986. 
J Endocrinol Invest. 2005 Dec;28(11):1003-8.
Reprod Toxicol. 2007; 23(3): 438–448.

As for the fear of exposing the virus to a hormone activator with physiologic progesterone, testosterone or hydrocortisone replacement, nothing new is being added. My gut says it is safer to cover young women for progesterone deficiency to prevent an estrogen dominant state, especially given the concern with respect to X and oncogenesis, but we cannot know at this time. All the steroid hormones, including sex hormones, cortisol and the mineralocorticoids are metabolized via common pathways link; note that progesterone is metabolized to androgens and aldosterone, and that there are bidirectional pathways. Replacement tries only to tip the ratios. It’s nothing like taking birth control pills, which is how the gynecologists treat PCOS. Birth control pills are synthetic estrogen and progesterone-like drugs (that may or may not activate virus, time will tell). With bioidentical hormones (same molecular structure as the hormones the body makes on it’s own), you are not taking over the cycle, but supporting it, normalizing it. You’re not exposing the virus to anything that isn’t there anyway. A menstruating woman’s body makes some progesterone, but women with PCOS don’t make enough. Unless you want to take out ovaries, the virus is going to see some progesterone. They use ablation for hormone dependent cancers, but it’s extremely destructive to quality of life. So, for the record, Ali and I have both improved despite taking hormones, in my case full bioidentical HRT, including testosterone.

Endocrinologists as a group seem to be particularly clueless with respect to managing CFS/Lyme patients, even though hormone depletion is probably pretty universal. Because the ‘bioidentical’ hormones are naturally occurring substances, they can’t be patented. Therefore they have not been studied and doctors generally don’t know how to use them.

Deplin is L-methylfolate, a medical food, the only active form of folate that crosses the blood brain barrier. It is a regulator of synthesis of monoamines (serotonin, norepinephrine and dopamine). In the face of deficiency, it is useful for depression. Ali added it to potentiate Cymbalta about a year ago, and it allowed her to wean from the drug. I tried Deplin because it had such a profound effect for Ali. I didn’t notice anything going on it, but have tried to stop it a few times and had difficulty with irritability and sleep disruption, so continue to take it. Because sufficient levels of all B-complex vitamins is important, B12 supplementation (sublingual or parenteral) is worth considering with Deplin, hydroxocobalamin probably being the preferred form.

People have questioned me as to whether Ali and I really have CFS. We meet the Canadian criteria for CFS, but not the ridiculously inadequate CDC case definition. In my experience, most chronic Lyme patients meet Canadian criteria for the disease. My early symptoms, in hindsight, were related to sensory and cranial nerve dysfunction, and vasospasm – classic, atypical and intestinal migraines, hypertensive crises, sensory disturbances. We are both hyper, not hypo, immune. Ali has had vasculitis. I was diagnosed with Crohn’s on surgical path. I am more of an atypical MS picture (radiculopathies, +Rhomberg, +Babinski). Ali is more classic CFS with POTS being a big part of her symptom complex. My orthostatic intolerance is superimposed on hypertension, so I don’t get tachycardic unless I’m over-medicated and hypotensive, but gravity is still an obstacle for me for more obscure reasons. Neither of us is particularly MCS or drug intolerant.

Ali has persistent IgM specific bands for Borrelia burgdorferi. I have fleeting IgG specific bands. We both had positive FISH test for Babesia microti. We both had postive PCR’s for Mycoplasma fermentans and high IgG titers for Bartonella henselae. I had high titers for Bartonella quintana.

One of my few positive tests, besides the usual TBD suspects, is a low positive nucleolar ANA and very high circulating immune complexes. Also very low alpha MSH and mildly elevated VEGF. I have never been tested for HHV-6, etc. I tend to run a borderline high white count with normal differential and I have slightly low globulins. Ali has elevated IgG titers for EBV, but hasn’t been extensively tested for other activated viruses. She has had a low IgG subunit.

As for the genetic component, Dr. Shoemaker says we have HLA profiles that put us at risk. I am an Ashkenazi Jew, a group which has a variety of genetic diseases, including Familial Dysautonomia. I am probably an Ehlers-Danlos variant, becoming more flexible with age and exacerbations of illness. My husband has Marfan’s Syndrome. My husband and Ali are positive for the V Leiden gene. So a genetic hodgepodge.

Historically, Ali and I go up and down together, but I think that has to do with stress and cortisol activation. Our triggers have been hormonal shifts (puberty and childbirth), sustained stress and a concussion once for me. That fits with X having glucocorticoid and androgen receptor elements. 

All I really know for sure is that we are X+, we’ve been on antiretroviral treatment since March, on three drugs since May and we are a lot better. Lyme Disease was a big piece for Ali, probably not for me. We’ve each gone up at least 30 KPS points since starting HAART. I don’t think it’s possible that antiretrovirals haven’t helped us. Nothing else we’ve tried in the last few years has worked, except for Deplin and Ali’s Actos, and I think we can all agree that we were unlikely to get this kind of improvement from those interventions. But it is possible that the other things we are taking are potentiating the effects of the drugs or ameliorating the side effects of treatment. Neither of us feels completely well, especially me. But we are both hugely more functional. We can only hope it continues.

P.S. Ali wants me to disclose the things about her in this post, because she thinks they are so important.

Still going uphill. Ali has surpassed me physically, to my great joy. There are moments when we both find it hard to contain the new found energy. We are also each having our own difficulties reintegrating into life again. There has been so much lost; in moments it is very hard to come to terms with where we are now, rather than dwelling on what might have been. But I can tell you with certainty that all of these lazy, crazy, faking patients will get up at the first possible moment with a burning desire to do something, anything that has a positive effect on the world. Nobody wants to be a burden. I can remember a time, not so long ago, when I thought that my husband would be better off if I died. It is going to be breathtaking to behold so many chronically ill people recover, whether it’s now with these three drugs, which I think is likely to be the case for at least some patients, or a little later, when the drug companies finally get to work on it.

The disease is a relapsing, remitting process on it’s own. Many people who get sick for the first time, get well within a year or two. However, it is rare for patients who have been sick for several years unremittingly, to get better enough to return to nearly full function. We are both now over 80 KPS points; we were at about 40 points when we quit Lyme treatment a year ago and at about 50 points when we started HAART 6 months ago. (Karnofsky performance status). It is unlikely that we are some kind of rare exceptions. We are the only patients I know of so far on three drugs for any length of time (since May). There are a few who have been taking one or two drugs for several months who are somewhat better or not better. There is a single case report on this blog of a teenager who is much better on two drugs (comments in HAART post of Aug 22). I encourage anyone else trying antiretrovirals to get in touch with me or share here.

I read things suggesting that we are the tip of the iceberg, but as far as I can tell, we are only a small handful of people. Only a very few doctors brave and compassionate enough to help. There’s an attitude that these patients don’t die, so what’s the hurry? It took fifteen years with HIV, so everyone should be patient now. But since something has been learned in the last twenty-five years, it seems to me that this time, all that experience could be brought to bear to speed up the process a bit.

I just watched a YouTube video of Dr. John Coffin at the XMRV conference yesterday, expressing his opinions about off-label use of antiretrovirals. The only thing that he said of importance was that the disease remits on it’s own, but that only makes clinical trials all the more pressing, so that we don’t rely on anecdotes. Now! Not in a couple of years when the scientists say that they have proven causation. The patients are so willing to be part of the experiment, trapped in purgatory. But the scientists are worried. Don’t mean to single out Dr. Coffin; he’s in good company. But what a bunch of fuddy duddies, practicing medicine without licenses. And their basis for opinion is what? Wish they could all spend a few hours in a CFS body. Bet they’d take a few pills and see what happens. Spend a day living with the agony of a child you can’t help, can’t comfort. It’s intolerable. So many people. While these scientists pontificate. It’s an emergency!

It’s amazing to me how respectful the patients are as a whole. There is a certain wisdom and acceptance of reality not seen in most patient groups. Nobody expects a thing. It’s been too long. We’ve become too patient. No one knows better than I do the meaning of the word can’t. It will be incumbent on those of us who recover some measure of function to fight for the others.

Tonight is the WPI fundraiser. Please donate whatever you can.

The murine leukemia viruses (MuLVs) are gammaretroviruses that have been important in the study of retroviral pathogenesis, oncogenesis, viral integration, transcriptional regulation and gene therapy. Now they are important in the study of the MuLV related human retroviruses, including XMRV and the newly identified polytropic variants. 

Sandra Ruscetti, a collaborator on the Science paper, has been studying mouse retroviruses for more than thirty years. She is the head of the Retroviral Pathogenesis Section, Laboratory of Cancer Prevention at the NCI. Her work is now highly relevant to the study of gammaretroviral disease in humans. Dr. Ruscetti is an author on over 120 papers listed on PubMed. From her NCI profile webpage (link):

“The focus of our research is devoted to understanding the molecular basis for the pathogenesis of retrovirus-induced diseases. We have been studying retroviruses that cause leukemia or neurological disease in rodents to obtain basic information on how molecular changes in normal cells can result in pathological consequences. Our current studies are focused on determining whether similar mechanisms may be utilized by the human retrovirus XMRV to cause cancer and neuroimmune diseases in man. Overall, we hope to use the information gained from our studies to design and test rational strategies to counteract the retrovirus-induced molecular events that are responsible for these diseases.”

PVC-211 MuLV models neuroimmune disease in rats. It was derived by passage of the Friend virus complex (both F-MuLV and SFFV) through rats. It is an ecotropic virus that contains point mutations in its envelope gene which allow it, unlike Friend MuLV,  to infect brain capillary endothelial cells and to cause neurodegeneration in rats. Microglia are activated macrophages in the CNS recruited from peripheral monocytes. They are activated by vascular damage, leakage of vessels, causing elevation of VEGF, a vascular permeability factor, in the rat cerebellum. Activated microglia cause upregulation of proinflammatory cytokines and chemokines, e.g. MIP-1a. There is an increase in iNOS, an enzyme involved in response to oxidative stress, increasing NO. So the result of activation of microglia, not a direct result of the virus. The cascade damages neurons indirectly. This paper also reports the use of clondrate-containing liposomes, which kill microglia, to block the neurogenerative effects of the virus.

J Virol. 2009 May;83(10):4912-22. Epub 2009 Mar 11. Neurodegeneration induced by PVC-211 murine leukemia virus is associated with increased levels of vascular endothelial growth factor and macrophage inflammatory protein 1 alpha and is inhibited by blocking activation of microglia. Li X, Hanson C, Cmarik JL, Ruscetti S. (full text pdf)

Another important murine model for human disease, SFFV has been studied for it’s oncogenic effects in mice. It was derived by recombination of the ecotropic Friend MuLV with endogenous polytropic envelope gene sequences and then underwent specific deletions throughout its genome to generate a replication defective MLV that encodes a unique envelope protein that is responsible for its pathogenicity.  The unique SFFV envelope protein is responsible for the Epo-independent erythroid hyperplasia caused by the virus. It does this by activating a cellular tyrosine kinase (sf-Stk) that activates proliferative signals in erythroid cells.  Because these proliferating SFFV-infected erythroid cells can still differentiate into red blood cells, they become immortal (transformed) only if SFFV has activated (by insertional mutagenesis) a cellular gene that blocks this differentiation.  Inactivation of tumor suppressor genes in SFFV-infected erythroid cells also favors the outgrowth of transformed cells.

Int J Biochem Cell Biol. 1999 Oct;31(10):1089-109. Deregulation of erythropoiesis by the Friend spleen focus-forming virus. Ruscetti SK. (abstract)

Here are links to more light reading:), highly relevant papers about the neuropathogenic retrovirus, PVC-211 MuLV, by Dr. Ruscetti, going back in time:

J Virol. 2002 February; 76(3): 1527–1532.

J Virol. 2003 May; 77(9): 5145–5151.

Leukemia. 1997 Apr;11 Suppl 3:233-5.

J Virol. 1996 December; 70(12): 8534–8539. 

Cell lines from wild mice (wild mice themselves apparently have not been studied much) are susceptible to exogenous xenotropic and polytropic MuLVs. Although cell lines from lab mice are not susceptible to xenotropic MuLVs, they are susceptible to polytropic MuLVs, as are the lab mice themselves. This is because lab mice carry a mutant Xpr1 receptor that doesn’t facilitate entry of xenotropic MuLVs but will allow entry of polytropic MuLVs.

A xenotropic virus may cause disease in a non-mouse species, but to qualify as a xenotropic virus, the virus need only use a particular receptor. So it may complete early events (cell entry and integration) in cultured cells but not be able to assemble new, infectious particles, much less pass from host to host. These issues seem very case-specific to a newbie like myself. If you want to know what a particular strain of MuLV does, you have to consult the published literature on that particular strain. There are many different strains and mutants, and they have their idiosyncrasies.

Here’s a mouthful that helped me understand, from the background section of a paper on an amphotropic MuLV that discusses the different designations of murine retroviruses according to their host ranges:
A large number of genetically transmitted endogenous murine leukemia viruses (MuLVs) and non-genetically acquired exogenous retroviruses have been classified on the basis of their in vitro host range, interference and neutralization properties. Regardless of their origin, the gammaretroviruses isolated from a wide variety of inbred or feral mouse strains have been designated as ecotropic (MuLV-E), xenotropic (MuLV-X), amphotropic (MuLV-A), polytropic, mink cell focus forming (MCF) and ‘modified polytropic’ viruses. The MuLV-E’s are the most common endogenous or exogenously acquired retroviruses of mice and they grow well in mouse or rat cells but not in cells derived from higher primates, humans or other mammals. All MuLV-E strains induce syncytia in a Rous Sarcoma virus transformed, non-producer XC rat cells. The xenotropic viruses (MuLV-X) are the genetically transmitted endogenous retroviruses of mice that do not replicate well in mouse cells which produce these viruses, but they grow preferentially in cells of heterologous species, including human and other primate cells. The polytropic and ‘modified polytropic’ viruses are endogenous nonecotropic MuLVs that grow in mouse, human and other mammalian cell types. Most of the polytropic viruses are expressed during leukemogenesis in various inoculated mice and they are called mink cell focus forming (MCF) as they induce syncytia in the replication defective Kirsten mouse sarcoma virus transformed non-producer, mink cells. In contrast, the amphotropic retroviruses do not induce foci in transformed mink cells (i.e. not related to MCF viruses) and they display distinct interference, host range and neutralization patterns from all other endogenous or exogenously acquired, ecotropic, nonecotropic, xenotropic, polytropic or MCF MuLV strains. (Virology Journal 2006, 3:101)

Most studies on MuLVs are carried out by injecting mice with ecotropic MuLVs (another class of exogenous MuLVs), which recombine with endogenous polytropic envelope gene sequences to generate pathogenic polytropic MuLVs, or by infecting mice with a virus like SFFV, which carries its own pathogenic envelope gene.

Yes folks, it is harder than rocket science. But I think it is important for us, trying to understand what is wrong with us and what to do about it, to consider the science and learn the terminology. If things take off as they should with the research, understanding these concepts will be necessary to integrate the scientific literature into our clinical thinking going forward. The uninitiated might think that this post is completely over the heads of most readers. But, due to extreme neglect by the medical profession, the patients in this group have been forced to read difficult science before. 

Look at how far science has come in characterizing retroviral diseases in mice! Bodes well for us for the future, now that they finally know what they are looking for.

This post is an attempt to answer the most common questions I am receiving. I’d like to take this opportunity to thank everyone who has written and shared. There is a thoughtfulness and deep intelligence in your letters. So much wasted talent to be reclaimed if the disease can be ameliorated. The unbelievable suffering I am witnessing through my correspondence keeps my hands in the fire, even as we improve, with an urgency for the work to move along as quickly as humanly possible.

The doctors are being incredibly slow on the uptake. Infectious disease specialists should be stepping up to the plate instead of waiting for it to hit them on the heads. But, they are so beaten down by what they already have to do each day and the system they have to function in, that they can’t yet see the greatest opportunity they’ve ever had to be healers. In the end they will treat it nevertheless. For now, shame on the IDSA for not even noticing. The last news on their website is from 2009.

The drugs are hard to get on for most. AIDS patients do not have the same problem getting started that CFS patients seem to. It appears to be an inflammatory flare and all three drugs can cause it, rather than direct drug toxicity, since the side effects of the drugs are well known. It may have to do with a build-up of viral products in the cell cytoplasm when the virus is first shut down. The presumption is that it could be in any cell in the body, so the widespread change in what has been homeostasis of a sort is likely involved. I am tempted to say, if you have to, try: start low, go slow, but that approach is a complete no-no with HIV because of mutagenesis. We do not have enough information to know whether it matters with X, P, Y or Z if we expose the viruses to the drugs at low dose for a short time or not.

Not everyone who has been taking antiretrovirals for several months has improved. We are the only X+ people on all three drugs that I know of. I have been corresponding with one X- patient on all three drugs that is not better. It is possible that there are pathogenic variants that are not susceptible to the protocol we are taking.

For me, the inflammatory flare caused by the drugs subsided in a couple of weeks and it didn’t send me anywhere I haven’t been before. I’m not at all happy about having to say that the drugs may make you sicker for a while and it may take months before you know if they are helping or not. Sounds a lot like Lyme treatment. But there it is. We desperately need quantitative measures.

The main risk that I see to a trial of the drugs, other than time, money and the possibility of feeling worse for a while, is the exposure of virgin virions to antiretrovirals that may not be as good as what we’ll have in a few years. And it is always possible to die or be damaged from a drug. I pray every day that that won’t happen to anyone choosing the experiment; with proper supervision, the risk of permanent harm is most likely low. Lower than the risk of leaving the disease untreated for some.

Our best hope now is that the entire group of human gamma retroviruses can be treated as a whole, rather than requiring identification and separate testing of drugs for each variant. Maybe it will break down to X and the polytropic variants. It seems likely that a recombination event is involved in pathogenesis. Ruscetti J Virol. 2009

We are taking AZT 300mg twice daily, Viread 300mg once daily and Isentress 400mg twice daily, standard adult HIV doses. We are having monthly blood counts and metabolic panels. The only abnormal labs have been the inconsequential macrocytosis caused by AZT. Neither one of us can tell that we are taking the drugs.

Lots of concern has been expressed about the mitochondrial defect in the disease and AZT. I was short of breath at rest when I started AZT and not at all now, so I guess my mitochondria are tolerating the AZT. I don’t mean to be sarcastic; it’s just that this kind of backwards thinking is holding us back. To me, it is common sense that the problems caused by the virus can only be affected by turning it off, including the cellular hypoxia.

Many are thinking about how to pay for the drugs. With positive testing from a CLIA certified lab and documented improvement, the meds should be covered by insurance. Time will tell how much of a fight that becomes. VIP Dx is currently the only commercial lab testing for human gamma retroviruses. AZT and generic tenofovir are fairly inexpensive in Canada, very roughly $100 and $150 respectively per month. Isentress is expensive everywhere, about $1000/month; Merck has a compassionate use program.

Considering the various ways to go about trying to inhibit NFkB, a simple, safe approach is to supplement with curcumin.

Actos addresses several problems seen commonly in this patient population. My daughter’s antiretroviral trial was preceded by the addition of Actos. I knew that we were mucking up the experiment, but she was having horrible reactive hypoglycemia, even with severe sugar restriction, and needed an intervention at that point. As it turns out, she had no problems getting on the drugs at all, which seems to be an exception, so I am wondering if the Actos assisted with the cytokine flare that seems to occur when starting the drugs. It activates PPARγ, decreasing insulin resistance, inhibiting VEGF, dropping levels of certain cytokines.

Low-flow supplemental oxygen by nasal cannula during the worst moments is helpful for many.

I have no personal experience with Ampligen. My impression from my mail is that some have experienced a partial remission from it that generally doesn’t last. It is an intravenous drug which is a serious obstacle. Same comments for IVIG; also it is a blood product…

I traveled to Reno last weekend. Without a caregiver. Twelve hour day Monday. Fifteen hour day Tuesday. Lots of standing. Walking. Meeting my heroes. Got stuck at the Dallas airport for many hours on Wednesday. Walked miles because they kept moving the gate. Reasonably active days since. No significant crash. Astonishing!

A year ago, I existed from the bed to the couch. When I started HAART, I could be up for short periods, fifteen to thirty minutes at a time. I could go to town now and then, but it was an enormous struggle. I could push it for something important, but it would level me for significant periods of time. My pattern then was a sine wave, roughly five days above water, five days below.

I just functioned for several consecutive days at a level that would have been taxing even before I got sick. With very little payback. I’m still having dips, but they are brief, measured in minutes and hours, not days, and don’t go to helplessness.

My daughter is also doing extremely well, but I’m afraid to jinx it by saying too much:). Suffice it to say, that she proves that I am not the only one. We are both deeply grateful for all of the good wishes we have received.

Reno was a once in a lifetime experience for me. It was my first time away in over five years that didn’t involve seeing doctors for treatment. That alone made it a personal miracle. The WPI has accomplished so much in such a short time. David to the Goliath of ignorance and disbelief we’ve faced for decades living with this diabolical disease. The spirit of interdisciplinary sharing that they are encouraging from inception signals a new era for patients. They are changing the playing field for us completely. Each alone and unrepresented no longer. Uncared for no longer.

Please visit this wonderful coverage of the event and photos of the facility: CFS Patient Advocate blog

At this point, I still do not see a better course of action on the horizon for the sickest X+ patients than the protocol we are following. We are only two patients, but talk to any experienced CFS or Lyme doctor and they will tell you how unlikely a return to function is for patients as far down the road as we were. We are both progressing steadily towards that goal. It seems tangibly within reach as I write this.

Clinical trials are essential. It is an outrage that we are getting better while a staggering number of people languish in isolation without meaningful treatment. Our antiretroviral trial to date is tremendously encouraging and urgently needs formal follow-up.

Since my last post, several people have written to say that I sounded discouraged. I don’t feel discouraged. I feel realistic. It’s too bad that it didn’t turn out to be a fairy tale, but I really didn’t expect it to. We are improved. Relief is relief. For now, I’m thrilled to have a finger in the dyke.

I didn’t report more specifically about responses to treatment other than ours, because the information available to me is spotty and some of it is hearsay. It is really only fair for me to talk about us. But since I did attempt to summarize very generally, I would like to add that when I said that some people on treatment aren’t better, length of time since starting is variable as is the choice of drugs. When I said people hadn’t tolerated the drugs, I was talking about very abortive attempts to get started. Also these people haven’t given up. False starts are to be expected under the circumstances. It was my intention to report only in the most general terms, in an attempt to give an impression of what it is like to get started. It’s ridiculous that we all have to try to figure it out this way. We need a real clinical study!

So I’m not discouraged. I’m angry. My disappointment in my colleagues is profound, with pathetically few exceptions. People write to me asking if they should go to this one or that one, try this protocol or that. To the doctors I say: It’s the virus stupid. You’re not going to stop a retrovirus with the wrong antivirals, ever more sophisticated combinations of antibiotics or any amount of supplements. I understand the reasons why it became this way, but I don’t understand any longer.

We’ve been given the answer and almost nobody is running with it. Why are these doctors still telling their patients that it’s better for them to adhere to the same old half-baked ideas that haven’t worked than try specific treatment for what they have? Better to keep their captive audience. If these drugs work, patients will be able to be treated through normal channels. They won’t have to travel and spend ridiculous amounts of money on uncovered treatments that are often worthless or dangerous. I’ve never seen a group of people so invested in their own ideas as the doctors caring for these patients. It’s like they’ve been in the dark so long, they can’t stand the light.

Why has mainstream medicine abandoned us? It’s because of doctor discomfort with not knowing what to do with a patient that doesn’t fit. Easier to blame the patient. Also the disease makes the patients “crazy”, but still smart enough to read, thus knowing more than the doctors. All worsened by the insurance companies practicing medicine, the loss of the doctor-patient relationship which is essential to the treatment of chronic illness and, of course, the government not doing its job to inform the doctors of what they should have known long ago.

To my colleagues: You are sleeping with the enemy. Here’s your chance to be a hero. There are still people out there who believe that HIV doesn’t cause AIDS. What are you planning to do? Wait for the government to tell you the obvious? Wait for the insurance companies to tell you it’s a good idea to treat? Some of us will be dead by then. Get a clue and help your patients!

Coming up on eleven months after publication of the Science paper, sadly my email (which includes treating physicians) is still my only source of clinical information besides what’s happening in my own household. It would appear that fewer than twenty people have tried antiretrovirals for X infection. Of those, about a third are at least some better (on one to three drugs), about a third are not better (on one or two drugs) and about a third didn’t tolerate the drugs long enough to learn anything. As far as I know, no one has been harmed.

When I decided to write publicly about my experiences, I already knew that the drugs were having an impact on my illness. But I also knew that it didn’t mean that in the long run this would be the way CFS or any other X related illness would be treated. I believed that reporting the experience had value whatever the outcome.

Due to decades of ignorance as to the causative organism, there is a strong tendency for patients to identify with symptom groups. My first friend to be felled by CFS visited me for a month in early ’97. I already knew that I was ill, but didn’t recognize that we had the same disease because we fall into different symptom subsets. In the end, the association between X and CFS will be irrelevant. If you are X+ you will be able to go to an ID doc and he or she won’t glaze over when listening to your history. They will ask you how you are doing on your drugs and measure your viral load.

In my opinion, the sickest patients have a right to try the drugs. There is a coherent rationale for a new approach to treatment of a horrible debilitating disease with existing, safe drugs.

It is unbelievable to me that clinical trials have not yet begun, ten months after the Science paper was published. It is completely outrageous that it is business as usual with a few twists in the scientific and medical worlds. New people, new babies, are being infected every day with an incurable retrovirus like HIV. The blood supply is contaminated. We have no idea how it’s transmitted. This one may be easier to vaccinate against than HIV has proven to be, but nobody has even begun to work on it.

With HIV, patients waited years for drugs and viral load measures. We have a road map this time. The science has lagged so far behind that there are millions of people with very advanced disease. It is an emergency.

The doctors aren’t doing any more for the patients than the scientific world has. There are over a thousand people out there with positive cultures. Many of them want to be treated. It is perfectly legal to prescribe drugs off-label and the doctors caring for these patients have been prescribing them more dangerous drugs than these for decades. But the absence of a replicative study has made most doctors unwilling to consider treatment with antiretrovirals. Patients have written to me that they can’t even get their doctors to order a test!

The scientists with whom I correspond believe that it is safer if patients wait until the science runs it’s course. They believe that there is an orderly sequence that needs to happen before anyone rushes for treatment. I am obviously an early adopter and it is true that in the case of treatment for chronic Lyme, I bought into the ILADS hypothesis, so buyer beware. I am reporting here, including my mistakes, in the hope that others will have more clarity than I did with respect to the use of antibiotics in this patient population. When we were diagnosed with Lyme nothing fit, but there were intelligent, well intentioned doctors offering what sounded like meaningful treatment. And it worked for my daughter for several years, so there is value in properly used antibiotics, but it needs to be tempered with what we now “know”. It’s only with time that the truth is finally being revealed. This time there is considerable clarity, if one allows the skipping of a few admittedly very important steps in the scientific process. But let’s look at what we’ve got to work with.

There are many commonalities with HIV disease: sensory and autonomic neuropathy, dementia, opportunistic infections, susceptibility to certain cancers, metabolic problems involving vitamin D, detox problems, abnormalities of glucose metabolism, vertical transmission.

It is worth noting here that the “fatigue” is not seen clinically in HIV disease in patients treated with HAART. It is therefore tempting to speculate, that XMRV is being inhibited by treatment as well, since there must be patients who have both. Epidemiologic studies should be very illuminating.

Commonalities between CFS and  ASD: sensory disturbances, cognitive issues, IBS, mitochondrial defect, detox problems, opportunistic infections, susceptibility to vaccine inury.

GWS: Very similar picture to CFS, inluding high prevalence of PTSD in the patient population. Similar stress response is particularly noteworthy.

XMRV is an exogenous human retrovirus. All the other known human exogenous retroviruses cause disease in humans. XMRV is a gammaretrovirus. Other examples of the same genus are the MLV’s and FeLV. MLV’s cause a variety of diseases including cancer and neurodegenerative diseases in mice. FeLV causes disease in cats not unlike CFS in humans, fatigue, adenopathy, GI disturbance, neuropathies, abnormalities of serum osmolarity.

Here are a few little loose dots, but ones I find particularly tantalizing because they reflect on the neuropsychiatric piece. Some autistic children have PANDAS (Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus) in which they have difficulty clearing the organism and OCD symptoms are prominent. Avian leukemia virus is an alpharetrovirus. Parrots in captivity get a form of trichotillomania, aptly called feather-picking, that responds to Prozac. Trichotillomania is a form of OCD. Here is an article suggesting that compulsive behavior can be transplanted from one mouse to another. link Lab mice lack the XPR1 receptor (required for XMLV and XMRV entry into cells) and are therefore resistant to the xenotropic strains of MLV, but have ERV’s. There is evidence that endogenous retroviruses which have been thought not to cause disease, probably do sometimes. And a fascinating presentation suggesting ERV involvement in schizophrenia. link

It seems to me from my email that there is a peak in the patient population around age 55 or 56 in both the CFS and Lyme groups, regardless of when they first became ill. Perhaps a bell curve? I suppose it could be chance, but it seems too frequent to me for chance. It suggests to me that there was a horizontal transmission event, like a vaccine that went out in the mid or late 1950’s. And this sobering paper. link There also seems to be an increased incidence of other likely X related neuroimmune diseases, particularly ASD and MS, in family members of CFS patients. Any epidemiologists out there want to take on these important questions? Sure doesn’t seem like we can count on the CDC to help us.