Personal report

I have been reluctant to report anything publicly with respect to the effects of antiretrovirals. It is my belief that without the benefit of clinical trials to guide us, each person who chooses to go down this road at this time should decide on their own with the scientific information currently available. I didn’t want to influence that decision with a single positive report. But I’ve changed my mind about reporting, as, incredibly, my response to treatment is a significant fraction of the clinical information currently at hand for those trying to decide how to proceed.
I am Harvard/Einstein educated. My medical school training took place mostly in county hospitals in the Bronx. My father was a brilliant surgeon and I wanted to follow in his footsteps, but wanted a life too. Things weren’t too great for women in surgical training back then. So I became an emergency physician, before there was such a thing, and a surgical first assistant in a community hospital where I was the director of the ER.
From ’86-’96 I worked at Santa Clara Valley Medical Center in San Jose, CA. It is the Stanford affiliated county hospital, regional burn, spinal cord injury and neonatal intensive care units. During that time I became the assistant director of the ED and director of Urgent Care. Before becoming a mother, I flew a few shifts a month for Stanford LifeFlight. I was the queen of stress.
I never saw a doctor until I was 41, including two home births. I had my first neurological symptom (sensory) when my second baby was four months old and nursing. It came and went for four days. I thought I had MS, then it went away entirely and I forgot about it. In the year that followed, I experienced several recurring seemingly unrelated problems. In hindsight, they were all different manifestations of vascular instability and dysautonomia. About a year after my first overt symptom, I experienced a series of personal tragedies in quick succession. Shortly, thereafter, I developed symptoms that precluded working.
When I stabilized from the crash, I didn’t seek treatment. As a doctor, I intuitively knew that there was no help. I recovered enough with no treatment to have a private practice. In my practice, I treated the after effects of brain injury alternatively, predominantly with HBOT and neurofeedback, including patients with ASD, Lyme Disease and ME/CFS (not always identified as such). In ’03, my entire family was diagnosed with Lyme Disease. My daughter had had acute Lyme in ’00 that was successfully treated, but in ’03 became ill without another known tick bite. She was antibiotic responsive, leading us to six years of treatment by LLMD’s with disastrous results. I have been critically ill twice since then. Last summer, I fired my doctors and went off all treatment. I have been on an up-hill trajectory since then.
Even though I treated patients, I never identified with ME/CFS though I now meet all sets of diagnostic criteria. Until I was treated for Lyme, I didn’t consider myself fatigued. I was still very athletic. My “fatigue” consisted of an inability to tolerate sustained mental activity. I had symptoms of vascular instability related to working, and in my last two years of practice, I had to shorten my work day. Depression and brain fog are not part of my symptom complex (except medication induced). I have had a sleep disturbance since working 36 hours on/12 off for months at a time as an intern and I worked 24 hour shifts in the ER for years followed by many years of night shifts. I have had malaise most of the time since my first crash in ’96. I’m not interested in sharing my long list of symptoms. All CFS/Lyme patients have such a list. Vascular instability and a relapsing, remitting very slow degenerative neurological process define my illness, with almost autoimmunity.

When I first saw the Science paper a few days after it was published, it was an ah-ha experience for me. I knew very little about viruses and almost nothing about retroviruses. But what little I did know enabled a fusion of everything I’d learned as a doctor and a patient. So much so, that as I sent my daughter’s and my blood for culture, I thought, if it isn’t this one, there’s another one out there. Here was the fundamental cause of all the subtle and not so subtle things that had gone wrong with my entire family, including the opportunistic infections, the genetic piece, an explanation for vertical transmission and even the activation by stress that matched my direct experience (the virus has a glucocorticoid receptor element in it’s promotor region). I also saw X in my family of origin, members of whom have had aggressive prostate cancer, autistic spectrum disorder and Lyme Disease. So I had a lot of clues.

For me, understanding is everything. I finally know what I am fighting. I expected that it would be years before there was meaningful treatment. But when the Sakuma paper was published, even though only one drug was inhibitory, I became more hopeful for the near future. I have been sailing around in the fog without a navigator for so long, that the Singh paper seems like a having GPS to me.
I had a mild neurotoxic reaction to starting AZT, that has subsided incompletely (still have peripheral paresthesias increased from baseline). Cheap stuff. Easy to tolerate. About a week after starting Isentress, so during the third week of treatment, I experienced a noticeable reduction in malaise, always a prominent symptom for me. During the beginning of the sixth week, I experienced an increase in energy and ability to be semi-functional for several hours a day. Previously, I was essentially couchbound and going to town was a monumental effort. I can now run to town for a few errands and it’s not a big deal. Other symptoms are better as well. Neurologically, I think I am a little worse, but it is manageable.
I posted that I had started tenofovir a few days ago. The last day and a half have been very bad for me. Definitely toxic. I am reporting now because I believe that this is how it’s going to be. This is NOT going to be a bed of roses. I have been sick a very long time. I am a canary in the coal mine. We have no way of knowing what immune reconstitution might look like. There isn’t much science to follow, except for what has been learned from managing AIDS, a very different bug. It’s going to be a long time before the scientific community helps us. Even our own doctors seem to be slow on the uptake. I don’t know of a single clinical trial that is in the works. Testing even seems to be controversial in some circles.

I am an ER doctor by nature still. Triage. Impact the process where you can. Take care of the people circling the drain first. I am very far down the road so I am in that category. 

I am trying to decide whether to continue the third drug or not. I would not stop the other two right now for anything. Just having the malaise controlled is worth it for me. I am not particularly frightened that anything is going to happen that won’t reverse with stopping one or more drugs. Calculated risk. I know what happens if I don’t treat it.

The lessons of HIV and HAART

All antiretroviral drugs work by stopping replication of new virus that can spread and infect uninfected cells. Currently, we have entry inhibitors (block HIV from binding or entering the CD4 cell), reverse transcriptase inhibitors (two classes of drugs: nucleoside and non-nucleoside), integrase inhibitors (block integration of viral DNA into the DNA of the cell) and protease inhibitors. HIV enters a CD4 cell, uses reverse transcriptase to convert single stranded viral RNA into double stranded DNA, uses integrase to integrate viral DNA into the cell genome, thus that cell now has integrated proviral DNA. When cell replication is turned on and viral polypeptides are manufactured from the integrated viral DNA, the viral protease cleaves the large peptide into smaller pieces of protein which are then assembled into a new virus that will then bud off the cell. Thus, new virus is produced and will seek out another cell to infect. Blockade at any of these enzymatic steps stops the process and that cell likely undergoes apoptosis.

We know from treating AIDS for 20 years, that inhibiting virus at several steps in its life cycle, using multiple drugs, is the way to go. HIV replicates quickly and has a high copy error rate resulting in mutations most of which do not convey an advantage. But when a mutation is superior, for example conveying drug resistance, the other drugs in the protocol, by keeping the copy rate low, prevent replication of that mutation. Experience has taught that combination therapy is definitely the way to go for HIV.

At this point, we have three studies (see links to Sakuma, Paprotka , Singh papers in Essential Reading). All three show that AZT inhibits XMRV in vitro. Two studies also show that raltegravir and tenofovir are inhibitory. In addition, the Singh study showed that all three 2 drug combinations of the three effective drugs are synergistic in vitro. HIV drug combinations can produce positive or negative synergies, so knowledge of likely combination synergies is very important. Unfortunately, the three available drugs that should work have not been tested together in vitro to see if further synergy occurs. Current starting HAART protocol is usually a triple cocktail, most commonly 2 NRTIs + a PI/NNRTI. We only have 3 drugs available, so we don’t have to think about the subtleties of which combinations are effective for HIV.

There is evidence that the virus is stable compared to HIV. It is possible that drug resistance will not be as much of a problem as it is with HIV. Because of the high prevalence of drug sensitivity in this patient population, I have heard of people thinking of taking doses of drugs that are not therapeutic for HIV. The Singh study showed that the drug concentrations to inhibit XMRV in vitro are somewhat higher than for HIV. Therefore, my personal decision is not to experiment with the doses. Also, the relatively slow progression of the disease should not lull us into complacency in my opinion. It’s a bad bug and should not be underestimated. We don’t know if the viral load may not be high in some tissues.

We don’t have a measure of viral load available to us, but nobody is thinking of treating anyone for XMRV who isn’t very sick. Current guidelines for HIV are to treat all symptomatic individuals. Asymptomatic individuals with a high viral load are left to physician discretion. The early credo of hit it early, hit it hard has given way to a more moderate approach to HIV infection, waiting for a certain viral load to be reached before treating, though I don’t know how much of this trend is financial.

I would like to add as a caution, that rapid suppression of HIV can produce an inflammatory immune reconstitution syndrome (IRIS). We have no way of knowing what will happen with treatment of XMRV. There has been some reasonable criticism of my letter on the CFS boards. I would like to state publicly that I am not advocating that anyone who is XMRV positive try HAART. That is a decision for an individual to reach with a prescribing doctor. I am only reporting my decision and the science and medicine that are informing my decisions.

There is also a rumor circulating that raltegravir will cause autoimmune problems to increase. The only evidence for this is that it causes autoimmunity in genetically susceptible MLV infected mice (see Beck-Engeser paper). If there were other drug choices that might have given me pause, but under the circumstances, raltegravir is the most potent inhibitor of XMRV that we have.

I started tenofovir this morning.

Open letter to the ME/CFS/Lyme communities.

I am a 56 year old physician with ME/CFS/atypical MS. I have a daughter with ME/CFS/Lyme Disease. I was an emergency physician. After I got sick, I recovered enough to have a private practice. I treated brain injury with neurofeedback and HBOT. In that context, I treated  patients with Lyme/CFS/ASD/PTSD/mood disorders. I am also well versed in complementary, alternative, integrative, functional medicines and bioidentical hormone replacement.

When I read the paper in Science about XMRV being highly associated with CFS, it was apparent to me as a physician and a patient that this was it. When I realized that the virus is sensitive in vitro to existing safe HIV drugs, I thought and still think that it is a miracle. In fact, I am stunned by the sudden overabundance of caution in the treating physicians. It would seem that nobody wants to try it. Despite being given the key. Never mind that we are a patient population that has been experimented on for decades.

Frankly, I didn’t see what I had to lose. We are culture positive at VIP Dx. We have tried everything to no avail. So with the assistance of a wise, compassionate friend who is an ID doc, and a smart family practitioner, I started AZT 300mg on March 4 and Isentress 400mg on March 11, both twice a day. It was my intention to wait for some sort of confirmatory data before reporting anything publicly. But watching all that isn’t happening with respect to figuring out how to help the patients, I don’t think that anything should depend on how a few patients do, especially a patient like me who may have been infected for as many as 40 years. I don’t think it is wise to wait while scientists argue about the validity of lab tests. There are too many who need help emergently. HAART is a safe existing protocol for AIDS which includes three drugs which inhibit XMRV in vitro. We even know that the three possible combinations of those drugs are each synergistic in vitro. But, the sickest will die while the scientists try to figure it out, so it seems to me that it is up to the doctors to treat with the information available. As always.

I believe that there is a rationale for treating the sickest patients now. Physicians are allowed to prescribe drugs off-label. I think they should be testing their patients, at VIP Dx, the only commercial lab right now that seems to be able to find XMRV in peripheral blood, using the methods validated in the Science paper. I would be happy to share with any physician willing to consider treating.

I certainly don’t expect that it will be as easy as taking a few pills. There is lots of downstream damage that will need to be treated. But treating all of the problems that have been identified over the years in this patient population will likely be more effective for many more patients than it has been in the past. We will finally be able to identify the commonalities and differences in the various neuroimmune cohorts. Always treat the causative agent if you can. Then modify the host environment to the best of your ability so that whatever is left functions at its highest possible level.

In my opinion, too many of our physicians have gotten caught up in their own ideas and lost track of the goal, which is to get the patients well. As a group, doctors and patients alike, we must support a willingness for the truth to come out, whatever that is. New discoveries have to be incorporated into our thinking as they occur.

I thought that it would be OK to sit back and let the dust settle. Whenever momentous discovery happens in medicine, there is a flurry of resistance from those who have been made wrong. But this is uglier than that. Now the WPI is in need of funding. Connect the dots. And the band is playing on while we go down…

I am no activist. I am politically naive. But I know the power of the internet. I know how marginalized we have been as patients. The people at the WPI are our friends. They are fighting for us, when no one has. As a community, we are often too sick to fight. So we have to let other’s slay the dragons for us. We have to support them in any way we can. Read: SEND AS MUCH MONEY TO THE WPI AS YOU CAN AFFORD. Please tell everyone you know. Pull out all the stops.

Sincerely,
Jamie Deckoff-Jones MD
Santa Fe, NM