HIV and ID Observations

13 Responses to “XMRV and CFS: More Yay and Nay”

1. JH says:

   November 4, 2010 at 9:14 am

   Here is an interesting article from Ila Singh on the issue. ‘Detecting Retroviral Sequences in Chronic Fatigue Syndrome’ http://www.mdpi.com/1999-4915/2/11/2404/pdf

   Lets not forget that the same problems are cropping up with prostate cancer. At the XMRV workshop in September, a comment was made that they may have discovered why the negative studies have been unable to detect MLV-related viruses.

   “…we have learned, literally in the last two weeks, in the blood working group, that processing may be a key, and we may have found an opportunity to have a processing protocol where everyone would find at least viral RNA in plasma and blood products without culture.”

   As for antiretrovirals, it may appear to be foolhardy, but only if you unaware of the severity of the disease. Patients do die from ME, and perhaps it would be better to put money into research to actually test these treatments, instead of asking patients to wait whilst they are in pain. Is it any wonder they are choosing to take control of there own lives, when health authorities in the US have done nothing for 25 years, and in Europe for much, much longer.

   Thank you for covering this important story.

2. JH says:

   November 4, 2010 at 9:19 am

   It would also be helpful if those conducting studies used a known positive sample to calibrate there test to. How else will they know if their method works?

3. asleep says:

   November 4, 2010 at 12:07 pm

   This is a reasonably balanced article. It does miss a few aspects of the controversy that JH (and his link to Ila Singh) covers well.

   I would add that these (negative) studies should use not only a positive sample, but a positive clinical sample. Many of these studies have used positive samples spiked with a synthetic strain that may be too divergent from wild-type strains found in clinical specimens to serve as real validation of their ability to find the virus.

4. Jane Clout says:

   November 4, 2010 at 1:17 pm

   May I refer the author, and anyone of scientific curiousity, to the comments hosted at Retrovirology on the CDC Switzer negative XMRV study? You can find it here http://www.retrovirology.com/content/7/1/57/comments
   and this is an extract:

   Dr. Norbert Bannert, one of the co-authors of the Switzer et al. study, was also involved in a 2000 study entitled “Transspecies Transmission of the Endogenous Koala Retrovirus” (Fiebig et al., 2000). This paper was concerned with the detection of an endogenous gammaretrovirus in koalas that “induces leukemias and immune deficiencies associated with opportunistic infections, such as chlamydiosis.” Due to obvious similarities, its methodology should therefore have offered some relevant lessons for those attempting to detect XMRV in patient samples.

   For the Fiebig et al. study “a new KoRV isolate was obtained from mitogen-stimulated peripheral blood mononuclear cells (PBMCs)”. This was a technique used in the Lombardi et al. (2009) study but not by the CDC, despite Dr. Bannert’s previous experiences in successfully isolating a gammaretrovirus using this technique.

   Furthermore, “to study the host range of KoRV, human 293 kidney cells and the human T lymphocyte lines C8166 and CEM, as well as rat and mouse fibroblasts (rat1 and NIH 3T3, respectively), were used. Provirus integration was shown by PCR”. This was the same technique that was used for dramatically increasing proviral concentration in the Lombardi et al. study before PCR, and once again not used in this CDC study. One must ask why. “

5. Kati Debelic says:

   November 5, 2010 at 12:51 am

   Mr Sax, you quoted this (without source):

   In addition, they have strong words for those who are prescribing antiretrovirals for individuals with CFS:

   At this time, such an approach is premature and medically indefensible outside the secure oversight of a well‐controlled clinical trial. “Real world” coping with severe diseases like chronic fatigue syndrome and prostate cancer creates understandable desperation on the part of patients, caregivers, and health care professionals. Such pressures are not justification for testing of therapies in an uncontrolled manner. Indeed, because they are of no help whatsoever to other patients, physicians, pharmaceutical companies, or regulatory agencies, such uncontrolled therapy works directly against the goal of providing effective therapy to the million or more individuals experiencing these serious conditions.
   *******************************************

   While I may agree, may I please ask you WHEN will these clinical trials come for patients? When will any help come when on one side, a lot of health care professionals still do not know anything about Me/CFS, how to diagnose it, what tests to order and how to interpret them? Even the CDC is saying not to test for viral reactivations, cytokines and tilt table test for autonomic disorders such as NMH and POTS (and in fact all of the doctors I have dealt with do not know what POTS is).

   There is very little budget for Me/CFS research and the funds are not used properly (CDC studying cohorts handpicked via random telephone calls asking if anybody in the household is tired, and study about history of sexual abuse as a child as it relates to ME/CFS)

   In these conditions, after decades of being sick with despicable health care if any at all, I feel it’s reasonable for a patient to consider antiretroviral therapy under supervision of a knowledgeable doctor. This is called compassionate health care.

   Dr Jamie Deckoff-Jones discusses why she and her daughter have been on ART for 9 months now: http://treatingxmrv.blogspot.com/
   And journalist Mindy Kitei discusses an oncologist doing a 1 person clinical trial on ART to treat his ME/CFS AND his CLL:
   http://www.cfscentral.com/2010/11/month-five-of-michael-snydermans.html

   ME/CFS is this disease that no one want to talk about, no doctor want to treat, and no researcher wants to research, minus a handful of doctors that dedicated their lives on it: Dr Dan Peterson, Dr Nancy Klimas, Dr Paul Cheney.

   Thank you for starting the dialogue.

6. Andrea says:

   November 5, 2010 at 1:30 am

   People with CFS have been banned from giving blood in Canada, New Zealand, Australia, and Britain.
   When the Canadian Consensus Criteria were published in 2003 it carried a warning against anyone with CFS giving blood because of “unknown pathogens”.
   A blood ban should have been issued then. The United States needs to step up to the plate and ban people with CFS from giving blood.
   It’s not about cause or association, it’s about precaution.
   In the most litigious country in the world, people are going to discover that recommendations to ban CFS blood came early, and action came too late!!!

7. gerwyn says:

   November 5, 2010 at 6:45 am

   As he author of the above letter I felt I had to contribte. The studies that failed to find a hgrv all have one thing in common. They calibrated their PCR assays against a synthetic clone which has never been detected anywhere in blood. In other words the diagnostic sensitivities of their assays were not established. This is astonishing because Mulv viruses are known to display considerable genetic variability and undergo nmerous recomination events. Thus the failure to calibrate their assays against a known positive sample completely explains the negative results without even having to consider the numerous other variables between the studies.If one were to say to someone dealing with the HIV virus that an assay to detect HIV had been based on synthetic DNA they would almost certainly laugh.Yet these same people persist with this laughable approach, even though no one even tries to detect HIV like this!

   The Lombardi et al (2009) study merely followed the protocols established in the intitial discovery of HTLV1. The ones who could not detect XMRV(or any other HGRV) did not.Thus their failure to find a novel human retrovirus is hardly a mystery!

   The final point is that CFS is not a scientific diagnosis.By that I mean that there is no objective relationship between the label and the disease so labelled. Thus it is not that CFS has heterogenous causes but the same label is given to diseases of entirely different aetiologies and the features that would enable differential diagnoses to be made are excluded by many different diagnostic criteria.

   In most slection criteria (CDC,OXFORD,LONDON or Reeves) any one with neuruendocrine symptoms and immune abnormalities are excluded. Under the Canadian Consensus Criteria(CCC) however neuroimmune symptoms are mandatory for inclusion as is the phenomena of the post exertional worsening of global symptoms which is unique to this illness.

   Thus it does not require a great deal of intelligence to see that a cohort of patients produced by the Oxford or the Reeves criteria ,which have all tested negative, are completely different to the patient cohorts who fulfill both the CCC and FUKUDA criteria These cohorts invariably produce an extremely high level of HGRV positive people.

   The failure to detect even population levels in the negative studies also strongly suggests that the detection mehodology was hopelessly inadequate.

   The way they proved causation of AIDS by HIV by the way was via a number of trials with antiretroviral therapy. The person who called trials with antivirals undefensible has no knowledge of the level of profound disability caused by this illness.Research shows that the level of disability induced by this illness is greater than in Parkisons and Multiple Sclerosis.Perhaps this person would consider contacting physicians with experience of reating this illness before making such ill informed and prejudicial remarks.In such a person’s mind this illness is clearly trivual when in reality it is anything but!

8. gerwyn says:

   November 5, 2010 at 6:53 am

   where I says neuroimmune symptoms are mandatory for exclusion under CCC criteria it should read mandatory for inclusion.i would be greatfl if you could ammend please

9. gerwyn says:

   November 5, 2010 at 10:48 am

   When viwed as a whole a family of Human gammaretroviruses(HGRVs) have been discovered in the blood of people who suffer from ME/CFS which fulfill both the diagnostic requirements imposed by the CCC and Fukuda criteria. Much of the research work on AIDS has been conducted on animal models.These models are based on mice either infected with the LP-BM5 or the ts1 mutant of Moloney Murine Leukaemia virus. The behaviour of these viruses is considered to closely resemble the behaviour of HIV in humans. BOTH THESE VIRUSES ARE HGRV RELATED VIRUSES. IF they are considered to be such robust models of AIDS (LP-BM5 infection is termed murine Aids) why are well known lentivirologists dismissing HGRVs as harmless passenger viruses despite their potential to induce AIDS like pathology in humans.This view has such little scientific merit that one must suspect other polittical motives are involved

10. Larry Gilman says:

    November 5, 2010 at 11:54 am

    Kearney and Maldarelli’s righteous reprimand, which Dr. Sax quotes, is riddled with fallacies.

    (1) Off-label prescription of drugs (prescription for conditions not named in FDA approvals) is legal and common. One can slight such usage as “uncontrolled” — and it is, in the rarified sense that it is not overseen by an Institutional Review Board (as it would be in a research trial) — but it is not necessarily unreasonable, unethical, or ineffective.

    (2) It is also normal to prescribe therapies despite uncertainty about whether they will work for a given patient. Even approved treatments always carry some burden of uncertainty. It is clearly defensible to attempt any therapy for any patient if an informed judgment has been made jointly by patient and doctor that the likely benefits outweigh the risks. K&M, in condemning ad hoc treatment of retrovirus-positive ME/CFS with antiretrovirals found effective in vitro, imply that flawed risk-benefit judgments are being made. But in which cases? Flawed how? They haven’t said. Nor, so far as I know, has any other critic of these efforts.

    (3) Observations of statistically insignificant numbers of patients (e.g., clinical experience, pilot studies) often inform the design of large, rigorous studies. Far from preventing or impeding scientific studies, small-scale experience commonly stimulates them. Every rigorous study begins with an educated guess; clinical experience with small numbers is often part of the education. Researchers should welcome and observe the nonsystematic but clinically reasonable use of antiretrovirals with ME/CFS, not try to shame it out of existence.

    (4) It is not true that ad hoc treatment of a few patients with particularly dire, XMRV/MLV-positive ME/CFS outside of randomized, controlled clinical trials “works directly against the goal of providing effectual therapy” to other patients. The number of patients receiving ad hoc treatment — even if it grew to the tens of thousands, which it seems unlikely to do — is far too small to impede the conduct, now or later, of large, strictly designed trials, which have an ME/CFS population of at least a million (judging by CDC studies) to draw from in the US alone. K&M do not say _how_, they think, scattered ad hoc efforts will impede research — and I don’t think they can. The vanishingly tiny fraction of ME/CFS patients who receive antiretroviral treatment will simply be excluded from studies using such drugs, with no harm done.

    (5) Most seriously, K&M—like other critics of ad hoc treatment — seem to me to confound research ethics with clinical ethics. Researchers are obliged to gather the most objective, accurate scientific knowledge they can while doing, so far as is humanly possible, no harm: clinicians are obliged to do all the good they can for the people in their care, period. In the clinic, only the individual patient’s well-being, not the advancement of science, may be consulted. The patient has a right to demand, and the doctor a duty to provide, any treatment that in their joint judgement may improve the patient’s overall condition. Far from being obligatory, it is _forbidden_ for a doctor to consider the advancement of science in deciding whether to withhold any reasonable therapy from a patient who wants it.. The idea that patients must — or even _may_ — be denied treatment in order to advance science is nothing short of a Tuskegee mentality. Thus, even if it were true that ad hoc antiretroviral treatments are somehow impeding rigorous research (which they aren’t), it would still be unethical to urge the blanket denial of such treatments for the sake of the research.

    Strong words, yes — for radically wrongheaded condemnation of the treatments now being attempted.

    The ethical shoe is really on the other foot. Doctors prescribing antiretrovirals for retrovirus-positive ME/CFS are making a reasonable attempt to help very sick patients. Those who argue that doctors should never do any such thing because it might (how?) slow the gathering of scientific knowledge show a disturbing tendency to view patients as a source of scientific information, rather than as people deserving the best care possible—even in the midst of uncertainty.

    —————————————————

    I’ve posted a version of these remarks at my wife’s superb ME/CFS blog: http://www.heaveninmyfoot.com/

    My essay comparing the recent controversy over XMRV/MLV to an earlier controversy in bioscience, the maize transgene flap, is at http://www.heaveninmyfoot.com/2010/01/all-this-has-happened-before-xmrvcfs.html .

    I blog sporadically on science-related issues at http://www.nolongerbythinking.blogspot.com/. Professional site: http://www.larrygilman.net .

11. Maxine Smith says:

    November 5, 2010 at 7:21 pm

    In the storm of self-righteous indignation over “medically indefensible” off-label treatment of severely ill ME/CFS patients, WHERE, one might ask, was the moral compass of these disingenuous knights-for-our-wellbeing, as millions of patients have been systematically derided, ignored, and left in the wastebin of medicine – for decades? Where were the calls for physician colleagues to take our dire physical manifestations seriously? Where was the insistence that obvious epidemics be investigated as infectious? Where was the moral indignation at the medically indefensible mysoginistic dismissal of “hypochondriac” women? Where were the clarion warnings to the medical profession that patients were (and are) losing loved ones, careers, houses to this devastating disease, confined to their homes and beds for decades, and dying of lymphomas and viral cardiomyopathy?

    Today’s Heaven in My Foot blog (http://www.heaveninmyfoot.com/2010/11/tuskegee-mentality-condemning.html) shreds the seductive illusion of the moral superiority of this new breed of “physician advocate” who has been mute for decades on the scandal that is ME/CFS medical abuse and neglect. It sets the appropriate tone of disbelief that these physicians who are now miraculously “saving” us from the dangers of off-label treatment (a widespread and sanctioned practice in compassionate care for rare, rarely-diagnosed and poorly-understood diseases), are the same physicians who have for decades expressed moral indignation that ME/CFS patients are “wasting” healthcare resources by desperately shopping for a doctor who will actually listen to and address our complex, multisystem clinical history. And it illuminates the illogic of ME/CFS patients going from the “Undeserving Sick”, to the “Deserving of Further Neglect” category.

    Legions of ME/CFS patients would agree that it makes no sense to give every XMRV/MLV positive patient antiretrovirals. But to ignore the subset of severely ill patients who may and will die without swift and more aggressive intervention, is medically indefensible.

    The Heaven in my Foot blog nailed it: “Far from being obligatory, it is forbidden for a doctor to consider the advancement of science in deciding whether to withhold any reasonable therapy from a patient who wants(needs) it. The idea that patients must—or even may—be denied treatment in order to advance science is nothing short of a Tuskegee mentality.”

    What is medically indefensible is that these so-called physician advocates are not using their outside voices to DEMAND accelerated funding, clinical trials, and interim treatment strategies to redress the decades of neglect of ME/CFS patients – and to try to keep the severely ill ME/CFS patients alive while the majority wait for clinical trials.

12. gerwyn says:

    November 7, 2010 at 8:09 am

    you mentioned that Lo/Altler discovered a different virus to the one found by Lombardi and others. In fact mulv viruses comprise of xenotropic and polytropic strains.Given that the gammatretovirus isolated thus far are more closely related than different strains of HIV1 they are more likely to be variants og the same “parent” virus.This is in fact the situation found in murine hosts.Thus the findings of Lo/Atler are not odd at all but are to be expected by anyone experienced in dealing with these species of retroviruses

13. linda says:

    November 14, 2010 at 8:11 am

    so, even though i am bedbound, i’m supposed to refrain from trying antiretrovirals because it might not be good for “science”? ha. good luck with that one.