The experiment in progress

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.

It is unfortunate that the way this is playing out, the people least likely to respond fully are the ones most likely to be trying antiretrovirals. It is turning into a quiet revolution of mostly old, sick ladies. For a patient population too sick and too individually isolated to ACT UP (link), maybe insisting on treatment now is a form of civil disobedience. But if age and duration of illness are negative prognosticators for a full response to treatment, which is likely, disappointment in the responses of a few sick grandmothers could be misleading to many who have recently become clinically ill and therefore might benefit more quickly or fully.
That said, we are about the same as the last time I reported. It would seem that at four and a half months of treatment, our gains are continuing, or at least holding, but the rate of change is slow. At this moment, it looks like improvement will have to be judged in months or years, not weeks. For me, the almost complete absence of malaise makes taking the drugs worth it (“malaise” for me is the feeling of a viral prodrome). It has been one of my most unrelenting and difficult to live with symptoms. Manifestations of vascular spasm are improved for both of us. The energy deficit is better, but persists. Push/crash unfortunately persists, though the crashes are less severe and of shorter duration.

But AIDS patients get better in weeks, so what’s happening? HIV+ patients are treated early in their illnesses, when their CD4 count goes too low or their viral load reaches a certain point. If they present after they have progressed to AIDS, they are treated pretty quickly or they die. The X+ patients trying antiretrovirals have had smoldering infections for many years. It seems to me that the inflammation and autoimmunity that becomes established as the illness progresses is the body doing what it is supposed to. It knows the virus is there and responds accordingly. The confusion with invader and self isn’t going to just go away, when the virus is integrated into the DNA of existing cells, even if we stop it from replicating. Also neurodegeneration that has already happened would be expected to improve slowly, if at all. 

It did seem that tenofovir had a positive effect for both of us. There is of course no way for me to know if it was the tenofovir by itself or tenofovir as a third drug. I started it once and went off due to a flare of symptoms, then back on at half dose for a week, before going up to full dose without problems. It may be that with this patient population, it will be necessary to finesse the drugs. Start low and increase as tolerated.

I would like to take this opportunity to state that my daughter is twenty years old and makes her own medical decisions. I would also like to repeat that I am not prescribing for myself or my daughter. We have an excellent family practitioner who cares for us. We are very fortunate. From my mail, it would seem that most are not so lucky.
Many people are writing to me who are trying to make decisions about how to proceed in the treatment maze. My advice is to tread lightly if you can and carefully consider a retroviral etiology. The people who are better have generally gotten there by the rational treatment of an opportunistic infection, e.g. Borrelia burgdorferi or one of the herpesviruses. If you are in a successful holding pattern, I’d not rock the boat until we know more. There is a significant subset of patients who have done well with trigger avoidance, including avoidance of what doctors have to offer. Less is often more.

There is a narrow-mindedness in the scientific community, insisting on an orderly progression through a stepwise scientific process with which everybody should be patient while it unfolds in some proper way. To that I say, we’ve been incredibly patient, some for as long as twenty-five years already, while the epidemiologists have ignored the obvious epidemic in our midst. If this many chickens had been getting sick due to a new retrovirus, they would have figured it out. In the future, I’ll write about some of the work that has been done in the world of animal retroviruses in the last few decades. The level of metabolic detail as to transmission, restriction factors and pathogenesis that has already been elucidated there is both hopeful and dismaying at the same time. While the humans with a new retroviral infection languished and transmitted it to others, animals have gotten quite a bit of attention. Of course they euthanize cats. At any rate, many clues for us there.

These are not new drugs. We have twenty-three years of experience with them in HIV.  We know the side effects pretty well by now (several million patients have taken them).  We are simply using them in an attempt to treat a newly discovered retrovirus.  We do that in medicine every single day – try an existing drug for a condition for which the drug was not originally intended.  It still seems common sense to me to do what we can to shut off the virus, until we know more, which looks like it will be quite a while. We have a right to try treatment in the meantime. Happens everyday in the real world practice of medicine. The reasons for resistance now, have more to do with politics, money, self-interest and inertia, than what is in the best interest of patients. As usual.

If it is possible to treat it even partially now, think how much suffering could be averted. Already another year is gone. The lost potential in my inbox alone is staggering. Reclaiming that potential should be a national priority. We don’t even know the magnitude of the problem. We have the technology. But even if all resources were brought immediately to bear, it would likely still be a bitch to treat. As things are, it appears progress will depend on people being afraid of catching something. Worked for HIV. And then, when the testing is together, the drug companies will smell the money. With any luck. We are so overdue.

Connecting the dots

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.

End of 4th month of antiretroviral Rx for X infection

We continue to improve. Still underwater, but just under the surface. I don’t want to turn this into a Twitter type report, but do want to respond publicly to the many inquiries and good wishes I have received. I especially don’t want to talk about specific symptoms, though many people have asked for that kind of detail. I’m looking at rating scales as a way to report. But increasingly, as I learn from the science, my characterization of the disease becomes simpler and simpler. To a large extent it boils down to symptoms of inflammation and vasospastic events, as well as symptoms of neurodegeneration for a subset with more advanced disease. There are many questions, but thinking about it in those terms works for me. Within that framework we are better, but I can’t quantify it. Best to look at function.

The Karnofsky performance scale (link) is the most basic of the rating scales commonly used for CFS. We were both about 40% a year ago and had gained maybe 10 KPS points by the time we started antiretrovirals. We have gained about 20 KPS points since then. So 70%. 10 more points to function. 20 for my daughter, because at her age it takes more to get a life. I just want to be able to sit in a chair all day and see patients:).

The reduction in malaise has been obvious to me and definite for her as well, though she didn’t have it all the time as I did. The energy deficit seems a bit better, but not enough for a normal life as yet. Push/crash is still there, but the crash is less severe and less long lasting. The worst downhill excursions are less often and much less severe than before, but not gone. We are both flirting with exercise, but there is some payback. Still it was impossible before. So what was impossible, isn’t. Still a ways to go, but seems pretty amazing to me considering how grim things were a year ago when we quit Lyme treatment.

My daughter continues to be able to go out socially, but not every day. She has been talking about taking a few courses at community college in the fall. I continue to be able to drive, go to town and do errands. Four months ago, a trip to the grocery store once a week was a herculean effort. Running to town is now no big deal most days. Four months ago, I needed a laptop to write from the sofa. Now I sit at the desk most of the time or use my iPad outside. I enjoy going to an internet cafe and having a latte (I’m a coffee lover), whereas before there was no energy for anything inessential. I didn’t drive for four years and a year ago my husband was my caregiver. I drove for the first time about six months ago.

I know of another dozen or so people who have started antiretrovirals, one or two drugs. A few stopped after days, because of intensification of their symptoms. The others are a little better or definitely not worse. And more are starting. I know of no one that feels they’ve been harmed.