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Integrase Inhibitors
Jun 7, 2006

Hi Dr. Young, thanks for everything...really mean it. I have a question about the integrase inhibitors. I am very hopeful that this class of drugs will come through sometime in the near future or at least sometime in the future, but I am curious as to why they are considered so important. I know that they target a new enzyme in HIV and, thus, present a new target for attacking replication of the virus and, of course, this is really important. But aside from this, do you think inhibiting the integrase enzyme offers significant benefit over inhibiting the nucleoside reverse transcriptase enzyme or the protease enzyme? I'm just wondering because I read something by Dr. Ho...something along the lines of integrase inhibition being a more imporant (or attractive) target for stopping viral replication than inhibition of the protease and NRT enzymes bc of the specific step in viral processing that it targets. I'm not sure if I read his words correctly, but I think he did say this. If you can block all three of these enzymes simultaneously, does this mean HIV would have a significantly harder time garnering resistance? Just wondering if you think integrase inhibitors have the potential to be a new "backbone" of hiv therapy (sort of like the nucs) or if they will more likely be used as "add-on" drugs to supplement failing regimens (I've heard that the entry inhibitors, at least at this point, are headed in this direction). Your thoughts, as always, are warmly appreciated.

Response from Dr. Young

Thanks for your post and thoughts.

I think that all of Dr. Ho's comments are accurate on this point. Integrase inhibitors (INIs) are attractive because they inhibit a new target, thus, patients with drug resistance should benefit from INIs.

Because of INIs prevent the establishment of chronic infection of the CD4, the drug class offers some particularly attractive theoretical advantage in decreasing the amount of latently infected cells.

Early studies have shown very impressive results, with very large viral load decreases, even in highly drug-resistant patients.

As to how INIs will be optimally used, this remains an area of research and probably for novel clinical trials design. I'd expect to see novel drug combos in the future that explore the way that we combine treatments.

Thanks for your interest, BY



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