Thursday, November 19, 2009

Raltegravir is likely effective against XMRV

Raltegravir (Trade name Isentress), is a drug that inhibits retroviral integrases.  In the article Beck et. al "Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir", the author states in Proceedings of The National Academy of Science that "the activity profile of raltegravir on the replication or murine leukemia virus is similar to that for HIV, and that the drug specifically affects autoimmune disease in mice, in which endogenous retroelements are suspected to play a role."  Both parts of this statement are highly significant.

The inhibition of Murine Leukemia Virus Integrase, which is almost identical to XMRV integrase, is not that surprising after all.  The catalytic sites of retroviral sequences have a series of conserved residues which are essential for activity, meaning that this enzyme is probably the best therapeutic target for XMRV.  Integrase inhibitors alone could work very well as monotherapy, and Dr. Mikovits stated that HAART is probably not necessary.  Because XMRV is a slow replicating virus, the chances of the virus becoming refractory to inhibitors of retroviral integrase are slim, as compared to HIV.  The drug raltegravir has a much, much better safety profile than NNRT's, which inhibit reverse transcriptase - which have side effects such as lipodystrophy, and the possibility of liver damage.  The downside is: Isentress is very expensive, costing about $1100 a month, something insurers definitely will frown upon - which may lead to some of them requiring a trial course of an NNRT before covering an integrase inhibitor.

The second part, where raltegravir induced lupus in genetically succeptible mice also could have a very profound effect in treating autoimmune diseases in the future.   What is significant is that Lupus favors one arm of the immune system, while Rheumatoid Arthritis, Psoriasis, Ankylosing Spondylitis, Crohn's disease favor the opposite arm.  This is significant, in that XMRV could induce the translation of endogenous retroelements - of which there are over 7,000 on the human genome -which human cells do not have the machinery to transform them into proteins (no human promoter can activate them), leading to the expression of foreign proteins on the surface of human cells, which makes the immune system recognize these cells as foreign.  It also lends credibility to the fact that Fibromyalgia is often co-morbid with disorders such as Rheumatoid Arthritis.  It also lends credence that Lupus is the polar opposite of RA, AS, Psoriasis - leading me to theorize that an antiretroviral could bring about a clinical remission in AS, RA, PsA patients - the same groups that currently benefit from anti-TNF therapy, but could exacerbate lupus.  So Lupus might be a true autoimmune disease, while on the opposite side a viral mediated quasi-autoimmune state exists.

**It is also noted that Echinacea extracts have been reported to produce lupus flares.

G.B. Beck-Engeser, D. Eilat, T. Harrer, H.-M. Jack, M. Wabl (2009). Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir Proceedings of the National Academy of Sciences : 10.1073/pnas.0908074106


  1. I am interested in what you have to say. I'm a fibro sufferer with osteoarthritis. One doctor wrote that I have a malar rash. I also have a persistent rash on my chest that my allergist suspects is due to lupus.

    So, what can you tell me about this "other arm" and are there any drugs that you know of that might end up being better-suited to treat the "other arm"?

    Also very interested in how XMRV relates to fibromyalgia. The only study I've heard of is that 12 out of 20 fibro patients tested positive. I want to hear there is a larger study being done. I asked the NFA about it and got a response that they ran a short news item on XMRV in their Sept. newsletter but that the "scientific work focused on CFIDS, which is clinically different from fibromyalgia."

    I am confused by the apparent lack of interest from the leaders in the fibro industry.

    Thanks for your blog. I am eager to learn more.

  2. I wonder which arm Sjogren's is in. I would bet the opposite of Lupus since I have CFS, psoriasis, and Sjogren's. I also had a bout of Ulcerative Colitis when I was young that subsequently went into remission. That would be a miracle for me if this one drug would knock out all of it. It figures that the drug is very expense.

  3. I have cfs, graves disease, celiac sprue, and irritable bowel among other things. I participated in Ampligen phase III drug trials, so I am sure I have cfs/me . How would raltegravir affect me? From fit and 45 to fat and 62, 16 yr. 6mo. of tired of being tired.

  4. A recent paper on pubmed, published a few weeks after this posted, indicates AZT is highly effective at inhibiting XMRV replication.

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