An ongoing dialogue on HIV/AIDS, infectious diseases,
November 4th, 2010
XMRV and CFS: More Yay and Nay
Does XMRV cause Chronic Fatigue Syndrome? Or more accurately, is it even associated with CFS?
I’ve been putting off writing about this for a while, as I knew colleagues of mine had a paper in press on the topic, and I wanted the dust to settle a bit more on the controversy.
But of course the controversy, and the scientific inquiry, are just getting started. There was a recent HHS meeting on the topic; anecdotal reports of patients with CFS receiving antiretroviral agents for treatment; patients with the condition have been discouraged by one group from donating blood.
Now, my colleagues’ paper has been published in The Journal of Infectious Diseases — and it shows no detection of XMRV in patients with CFS, and furthermore no XMRV in comparison groups of patients with HIV, rheumatoid arthritis, transplantation, or a group just presenting for general medical care.
The score is getting hard to tally, especially because negative studies get way less press. On the plus side, there was the original Science paper that got the field started, and the more recent PNAS one; the latter, oddly, found a slightly different retrovirus (MLV).
I am sure there are many others in various stages of gestation.
How could highly-qualified scientists come to such disparate conclusions? Here are some admittedly unoriginal thoughts:
- CFS has many causes. (See here for my view.)
- Related: Some CFS is of the “epidemic” variety; sporadic cases are different, less likely to be caused by infection.
- Geographic variability in XMRV incidence/prevalence.
- Different assays and/or different primers used in different labs.
- Contamination of assays. (It is PCR, after all. Isn’t that an inherent risk for any highly-sensitive amplification procedure?)
- Replication of XMRV is variable, or low level, a la HTLV-1 or HIV in “elite controllers.”
- XMRV detection is an epiphenomenon, and “true-true, and unrelated” — hence detection of the virus may be a random event, or merely an association.
- Some other issue no one has thought of.
Regardless, I highly recommend the editorial by Mary Kearney and Frank Maldarelli that appears in the same issue. They call for the following:
- Standardization of detection assays.
- Prospective epidemiologic surveys.
- Sharing reagents and samples. [Amazing this hasn’t been done yet!]
- Comprehensive and rigorous phylogenetic sequence analysis.
- Development of tractable animal models.
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.
Wise words indeed.