Monday, June 28, 2010

DETERMINING XMRV'S MUTATION RATE

One concern during antiretroviral treatment is drug resistance. That’s why HIV patients are usually on a three-drug cocktail, known as HAART, which stands for Highly Active Antiretroviral Therapy.  HIV is a lively, rapidly replicating retrovirus, leading to a high mutation rate:  As in most arenas, mistakes occur more commonly in haste.  The more mutations, the greater the risk of a favorable mutation popping up that confers drug resistance.

But XMRV replicates slowly and doesn’t appear to mutate much.  If XMRV proves to be the cause of ME/CFS and patients begin antiretroviral therapy, will patients still require a triple cocktail?

At present, only three FDA-approved HIV drugs have been shown to have efficacy against XMRV in vitro (in the test tube): AZT, tenofovir and raltegravir.  One possible way to determine whether CFS patients need all three would be for researchers to conduct retrospective longitudinal studies.  Examining the banked blood of HIV patients who’ve been followed for years, they would locate the positive XMRV samples.

Even if HIV patients aren’t infected with XMRV in large numbers, there may be a background rate of 3 to 7 percent, as per the findings of the soon-to-be-published FDA and NIH study, or the more conservative 3.7 percent background rate found in a study by Dr. Judy Mikovits, published in Science in October.

While the HIV patients have been on any one of the three antiretrovirals that appear to be effective for XMRV, has XMRV mutated?  If XMRV hasn’t mutated over several years, a single drug might be sufficient.  If it has mutated, researchers could examine the mutation rates of patients on two of the drugs that appear to be active against XMRV, and so on.

It would also be helpful to examine the banked blood of ME/CFS patients who’ve been followed over many years to determine the natural XMRV mutation rate over time. Researchers may also discover that some strains of XMRV are less likely to mutate than others.

It would be risky for patients to go on monotherapy until more is known about drug resistance and XMRV.  Because once you developed resistance, the drug is essentially useless.

3 comments:

  1. As someone who writes about medicine for a living and who has written the gold standard book of CFS/ME treatments, I'm really not convinced antiretrovirals are a good idea in CFS/ME, even if XMRV is found to be the culprit. They aren't even such a good idea in HIV/AIDS, because there are much safer treatments available, like low dose naltrexone.

    (And, it has been shown that antiherpesvirals can treat, or even cure, CFS/ME in many cases, and most of them are far less toxic than antiretrovirals.)

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  2. I saw a news article on Xmrv in Aids a while before your article came out. I think this is the abstract ...
    http://www.ncbi.nlm.nih.gov/pubmed/20597166
    They measured zero Xmrv. I figure they never LNCaP cultured before PCR. I hope they find out about culture and re-do their studies.

    Maybe then they'll find info about mutation.

    Apparently, retroviruses are known to recombine with other retroviruses, hence, their urgency to test. They seem well funded and organized.

    Maybe someone is tracking mutation in lab samples of XMRV fast-replicating in culture and our favorite anti-retrovirals.

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  3. zac,

    I actually did the coculture experiment. Zero evidence of viral replication, and 0.3% mutation rate, if you want to call it that. Breathe easier, my friend.

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