When I first heard that a retrovirus had been identified as a possible cause of chronic fatigue syndrome, I withheld judgment and awaited further developments. When I heard that two subsequent studies had failed to replicate the findings of the first, I assumed that the first had been a false alarm and would be disregarded. Not so.
It’s a classic case of wishful thinking outweighing good judgment. One unconfirmed report of an association between the XMRV virus and chronic fatigue syndrome (CFS) resulted in a rush to test for the virus, speculation about possible implications, and even suggestions for treatment. And the subsequent negative studies did little or nothing to reverse the trend.
XMRV is Xenotropic murine leukemia virus-related virus. In the past, there were reports that this retrovirus was associated with prostate cancer, but then other reports found no link. In 2009 a study was published in Science, “Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome” by Lombardi et al., reporting an association with CFS:
we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus–related virus (XMRV), in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthy controls.
Later, the researchers reported that up to 95% of CFS patients test positive with antibody testing. The study did not prove a causal relationship. The authors suggest that the retrovirus may reactivate other viruses, such as herpes viruses (the opposite is also possible). There could be many different viruses behind CFS/ME. And it could be that XMRV is an incidental finding secondary to the immune dysfunction in CFS/ME. Two subsequent studies in the UK, here and here, also looked for the virus in CFS patients but both failed to find it.
CFS is still a controversial diagnosis. Some observers have implicated psychological factors and somatization. Sufferers are on the defensive, wanting to validate CFS as a real physical entity. The finding of a virus was just what they were hoping for. They want to believe in it, and their emotions have clouded their judgment.
A battle has erupted between retrovirus believers and non-believers, each side attacking the other’s research and accusing them of bias. Some of the criticisms are based on virological laboratory procedural details that I am not competent to judge. Some of the other criticisms are about things I can understand.
The Science study came out of the The Whittemore-Peterson Institute. This institute was founded by a couple (the Whittemores) whose daughter had CFS and who was treated by Dr. Peterson with an experimental antiviral drug. They are clearly biased towards finding a viral etiology. The researchers in the UK were similarly accused of bias towards finding a psychological etiology. Accusations of bias may be credible but don’t necessarily mean that the bias contaminated the results. Another criticism is less credible: the UK studies used a different set of criteria for diagnosing CFS. Even if you think that some of the UK subjects didn’t qualify as having CFS, if even a few of them had CFS and the virus was really associated with it, the virus should have shown up in at least a few subjects. Critics have tried to rationalize away the negative findings in the UK by suggesting that the virus occurs regionally and is absent in the UK; but then if the virus were the cause of CFS, there wouldn’t be any CFS in the UK.
So far we have one study for and two against the association of XMRV with CFS. More studies are underway that should settle the debate. If the virus is there, it will be found by other labs and a consensus will eventually develop as to whether there is an association. If an association is confirmed, there will still need to be further research to determine what the association means and whether there is a causal relationship. The logical response is to stay tuned, not to leap prematurely into testing and treatment.
Tests are already commercially available. One is offered by VIP Diagnostics, a company owned by the Whittemore family. It costs $450 and uses the same methods as were reported in the Science article. The website discloses that the tests have not been approved by FDA for diagnostic purposes and that medical expertise is required for test interpretation. The lab pays a royalty to the Whittemore-Peterson Institute for each test it performs.
In his Nov. 3, 2009 Lyndonville Times newsletter, Dr. David Bell offered this cogent advice:
I am reluctant to suggest to anyone that they spend big bucks for a commercial test now. We do not know if a particular test is accurate, and even if it is accurate we do not know what it means, and even if we did know what it meant we would not know what to do with it.
That pretty much says it all. Nevertheless, patients are flocking to be tested. If they test positive, they can feel vindicated. If they test negative, they can rationalize that they may actually be positive but have a viral load too small to be picked up on the test at the moment; they might even rationalize that they are better off than if the test had shown a larger viral load. Win/win.
Antiretroviral treatments are already being proposed by some doctors. Most proposals are based on the drugs used for HIV/AIDS, on the assumption that antiretroviral AIDS drugs would be equally effective for the XMRV retrovirus. But that might well be a false assumption, and these are powerful drugs with worrisome side effects, not the sort of thing that you would want to try “just in case.”
Other concerns have been raised by the CFS community. Is XMRV sexually transmitted like HIV/AIDS? If you have chronic fatigue syndrome or another XMRV-related condition, should you take special precautions with your sexual partners, even if you’re in a committed relationship? Should you opt for not breastfeeding your children? Should you not even have children?
I can understand the desperation of these patients. I can understand their need to believe anything that would validate their suffering. I can understand their motivation to try anything that might bring them relief. But I don’t want to see people wasting money on useless tests, I don’t want to see mothers unnecessarily worrying about whether it is safe to breastfeed their children, and I don’t want to see people suffering side effects from drugs they don’t need. A cautious wait-and-see approach is dictated by common sense and by an understanding of how often initial scientific research findings turn out not to be true. Like remarriage after divorce, the overblown enthusiasm for the XMRV/CFS connection is a triumph of hope over experience.
*This blog post was originally published at Science-Based Medicine*