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CXCR4 and CCR5 co-drug
Sep 27, 2007

I have a simple (yet maybe complex) question. Why, when developing the CCR5 inhibitors (and there seem to be many due), did they not, at the same time, try to develop one that also inhibits CXCR4? I just started on raltegravir, prezista and TMC125, I was given TMC125 because I found out that my virus uses CCR5 and 4. It's ok, in the first month, my t count went from 0 to 37 and viral load from millions down to 1500. But from what I have been reading, and we all know this virus and its ability to mutate, doesn't the idea of a CCR5 inhibitor seem NOT to make sense, since the virus will just switch over to CXCR4, and thus increasing the possibility of someone losing the effectiveness of several other new drugs.

This is a question I have had for some time, since they announced a CCR5 inhibitor. Final question, how far away might we be from a CXCR4 inhibitor? I feel (in my position) if I took them both at one time with several other new drugs, since they would still be a new class, this might be powerful, for a time anyway.

Response from Dr. Sherer

There are CXCR4 (which are termed 'X4' inhibitors) that are in development for the exact reason that you cite, i.e. to complement and even work alongside CCR5 (termed 'R5') inhibitors. Two candidates in phase I are INCB9471 and AMD11070. To date, they have established a proof of concept, in that they have antiviral activity in the range of 1-1.5 log viral load reductions, and there have been some issues with treatment toxicities.

Accordingly, it's not possible to put a time frame on their availability for use in the clinic, but probably it's in the range of 3-5 years.

I urge you to talk to your doctor about your question and these responses. Together you can follow the progress on this potentially important type of entry inhibitor. In addition, there are other types of entry inhibitors that may also be synergistic with R5 inhibitors, and these may be worth consideration as they become available in the next 3-5 years.


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