More random thoughts

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.

Cozaar 100mg
     switched from Benicar 6 months ago; have been taking an ARB for 15
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

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. 

I have attempted to monitor therapy by following our TGF beta-1’s, which were severely elevated for both of us at baseline, and C4a’s, which were normal. It may still prove interesting, but doesn’t seem useful as a guide to clinical decision making. It looks like the numbers reflect the inflammatory flare and possibly slow resolution, but it is still too soon to tell. So far, it seems the numbers do not reflect our clinical improvement.

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.

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13 thoughts on “More random thoughts

  1. >I am XMRV+, have been on Depline 7.5mg for a few months on top of heavy Lyme treatment, and see little to no difference. So I can say Depline has had no effect on me. I have seen some data to suggest some people see improvement on 15mg of Deplin.

  2. >Jamie- I want to thank you for your continued honest and cogent reports on yor and Ali's HAART experiences. You have an uncommon sense in your sorting out of symptoms and reactions. Your discussion of what goes into assessing the personal and medical issues in choosing to try an experimental therapy, with so little known about the organism/illness relationship, are an appropriate warning to a desperate group of people, while at the same time a challenge to your medical colleagues to get off tier asses and not over-estimate the risks.

    I'm very much with you personally in that I'm not getting any younger and have had this illness for twenty-five plus years. If I come up X positive it would be a continued cruelty to waste an iota of precious time waiting years for clinical trials to churn out.

    In another odd mirror, I also have a daughter Ali's age who is completely disabled by fatigue and severe, chronic, all over pain. Although our symptoms diverge from each other in the severity of her pain vs my fatigue and cognitive fogging, if my test comes back positive I'd be shocked if she did not also have X. Ali's reports have therefore been both very helpful and hopeful for me to hear in regards to possibilities for my own daughter to be able to return to life. As angry as I am about what I have had to endure from the neglect and ignorance of our medical system, I become completely enraged with what our daughters have had to go through, before their lives even got much of a start.

  3. >You and Ali remain in my thoughts and prayers. Thanks for all you have done and God bless you both.


  4. >Jamie and Ali, thank you so much for sharing this very personal information of yourselves. I feel that it is good for us to share the details that we may or may not have in common.

    I also think you both are extremely lucky to have access to good medical care with doctors that are willing to dig deeper. Unfortunately I don't have such luck here in Vancouver BC- but keep on hoping and looking.

    Take good care and I hope that your healths continue to improve.

  5. >Very useful, I'm sure it will help many others understand the complexity of treatment–all facets. A bit mind-boggling, too.

    I'm worried about the Vitamin D–that's 10,000 IU daily? Maybe I had that wrong. That will most definitely deplete Vitamin A reserves functionally as they share a secondary receptor and cross-talk.

  6. >Thank-you so much for sharing your thoughts and current regime.

    I have found Vitamin D to be helpful for some of my symptoms – I take a spray form. I have been intolerant of pill form. I am curious what the name of your topical form is…my doctor recently recommnded topical Vitamin D – but I was unsure if it was over-the- counter or prescription?

    Also, thanks again for your words and thoughts – it gives me something to look forward to…being this sick is no fun and so isolating. But I am hopeful someday it will change.


  7. >Thanks for your thoughts and in depth review of what you and Ali are taking. The hardest part of all this for most of us is to find the "knowledgeable physician" to consult with!

  8. >Jamie and Ali, I am so, so grateful to you both. I came back from an AT through-hike with Lyme 10 years ago. Relapses were part of my life but mostly I was pretty functional. In early January, CFS moved in and my life moved out. My position for 2010 has been 90% supine. Thank goodness I can read!

    And thank goodness, thanks to the NYTimes, I've become a regular reader of your blog. I so appreciate your coming out about your experiences. You give me great hope and reduce the isolation. It is helpful to know that I am not alone. It is also helpful that you share your insights and expertise, Jamie. I'm sure it's not the medicine you want to practice, but you are helping many of us heal.

  9. >Speculating here….I've recently read gammaretroviruses spend the majority of their lifecycle in the post integrative latent phase. This may be the reason why HAART is not a totally effective treatment.
    Could the reason Dr Deckoff-Jones and Ali are responding well to HAART due to the fact that the gammaretrovirus is being stimulated out of the postintegrative phase by the use of hormone therapy? It is accepted hormones stimulate the activation of XMRV.

  10. >Let me add my voice loudly to the chorus of those praising you and your daughter for what you are doing here!

    I am in the process of obtaining a diagnosis. I am sending my XMRV test in next week. My doctor has ordered the HHV-6 test and I noticed that you mentioned that you never bothered with that one. Do you feel that one is a red herring?

    Thank You!

  11. >Thank you both for your transparency! I especially appreciate the input on hormones in this post. I am 38, have a long history of multiple female complications (including endometrisosis, PCO with multiple ER trips for ruptured ovarian cysts, both primary and secondary infertility, recurrent miscarriages, LPD…) and was on Metformin for the better part of 10 years. Metformin at the time of conception is the only medical common denominator between my three pregnancies I carried to live birth while every baby we miscarried was conceived on non-Metformin cycles.

    After a significant CFS relapse 3 1/2 years ago, about three years ago my endometriosis pain started getting out of control again and my doctor tried me on YAZ. I cannot tolerate most BCPs (full blown panic attacks being the primary reason) but seemed to handle these better than most and they did help manage pain.

    After several seemingly helpful months I began bleeding heavily along with growing pain. As the bleeding could not be brought under control after 10 solid weeks, I opted for a hysterectomy, leaving my cervix and my left ovary to avoid HRT. Unfortunately my trusted ob/gyn moved out of town the week my bleeding crisis started, so this decision and surgery had to be made through a doctor I had never even met prior to my first appointment about the bleeding.

    After surgery I was told, "Since you are no longer trying to conceive, there is no reason for you to remain on Metformin." I fought back saying, "As long as I have an ovary, I still have PCO" but my argument fell on deaf ears. In less than 2 years since I stopped Metformin I have gained nearly 50 pounds and feel all the effects of IR.

    My PCP is compassionate and has been willing to let me give Metformin another try, but has been waiting to prescribe it as we worked through several other issues such as gal bladder, significant allergic reactions and relentlessly recurrent opportunistic infections. I hope to see her sometime this next week without any other "crisis" to address and will be sure to mention Actos as well.

    jenni, living with CFS since 1990 (XMRV+)

  12. >jamie and ali, you two are so generous with your personal information. it is clear how dedicated you are to helping people with cfs.

    i am very grateful.


  13. >Hi Jaime,

    Thanks for all the info you post here – you seem to be providing a lot of the pieces for this bamboozling cfs/m.e. jigsaw puzzle, lol.

    As far as your hormone supplements go, what kind of dosages are you on, re: Estradiol and Estriol, and Testosterone?

    My levels are low, but my (non-M.E. interested… in the UK, what else would you expect) Gyn person is loathe to prescribe as high as nec. to deal with my symptoms – when the supplements work, my serum levels show up 'too' high.
    Recent test shows my Androstenedione level is low, so maybe my Andro level should be boosted rather than testosterone, Estradiol and Estriol separately. Do you have any thoughts on this?



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