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CCR5 and CXCR4
Sep 8, 2007

Dr Sherer, if a good CXCR4 drug could be found and combined with a CCR5 inhibitor, would this mean a two drug combo would be all that is needed to beat HIV forever. I thought that HIV latches on to the CD4 receptor then needs a co-receptor to drag itself into the cell. If both of these co-receptors are blocked by CCR5 and CXCR4 inhibitors, would HIV find another way in?

Yours, Steve.

Response from Dr. Sherer

This is a good question. There are reasons to think that a combination of a CCR5 (R5) entry inhibitor and a CXCR4 (X4) inhibitor would be synergistic, i.e. would work better together than either would work alone. These data come from in-vitro test tube studies of the behavior of these drugs in laboratory HIV virus. Whether this possibility is true in people with HIV in clinical practice remains to be demonstrated.

However, you have described the picture of HIV cell entry in terms that are too simplistic. While most cell entry appears to be mediated by CCR5 (80% in a recently infected person) and CXCR4 (20% in a recently infected person), additional entry paths have recently been identified in which no entry protein has been clearly established. So a combined approach with R5 and X4 inhibitors would not be expected to 'beat HIV forever'.

An additional positive possibility is that other varieties of entry inhibitors such as the fusion inhibitors and other new drugs that act on other parts of the HIV entry could also be used with the R5 and X4 inhibitors for additional synergistic effect.

I urge you to talk to your doctor about your question and these responses.


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