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MK-0518
May 26, 2007

Dr Wohl,

I have a technical question that I hope isn't too much for this forum...

I recently started a Clinical Trial involving MK-0518. (MK-0518 vs Sustiva in treatment naive).

I consistently find this wording "Integrase is an enzyme that allows HIV to hide its DNA in the DNA of the host cell".

Pre-Viral DNA Integration: In a cell that has no HIV DNA integrated into the DNA of the host cell, this enzyme inhibitor prevents the viral DNA from being integrated into the host cell's DNA. This one is pretty clear.

Where I'm finding little or conflicting information is around POST DNA INTEGRATION.

If a cell's DNA already has been integrated with HIV Viral DNA is the Integrase Inhibitor "useless" in that cell, or is the "hiding" that they refer to something ongoing that "if exposed" allows some process in the cell to rid the viral DNA? If so, any hints or jargon to search on to find out more about this process?

THANKS!

Response from Dr. Wohl

The integrase inhibitors do just as you say, they block the DNA made by the virus from getting incorporated into the DNA of the infected cell. It will not do anything to rid the cell of viral DNA already integrated into the cell's DNA. So the major action of these drugs (there are two in late stage development: raltegravir (MK-0518) and elvitegravir) are to halt the life cycle of the virus in infected cells pre-viral integration.

DW



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