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protecting the nnrti's
May 6, 2003

If the nnrti's are so important and cross resistance a big problem, can't we use a second nnrti to protect the first. Would using two nrti's and two nnrti's together be any good. Also if the four drug regimen were too toxic could the second nnrti be dosed at just theraputic level so as to minimise side-affects. I just feel that if resistance can occur when using say sustiva thus screwing up the entire class, why not just use two nnrti's to begin with. Steve

Response from Dr. Young

This is a great and well formulated question.

Turns out that the mechanism of action of the NNRTIs makes it unlikely that two will work better than one, since the two drugs would compete for the same binding site in the viral reverse transcriptase.

Several studies have looked at using both efavirenz and nevirapine-- most recently, the so-called "2NN" study presented at this years CROI meeting (see TheBody's Conference coverage for details). Long and short of it, is that there was no additional benefit to patients in taking 2 NNRTIs simultaneously.

So it would seem that the best way to prevent resistance to the NNRTI class is to combine the medication with a potent couple of other medications-- and to make sure that adherence is really good. The good news, is that in recent studies (at least the efavirenz-based ones), virological failure and drug resistance was a very rare event (among treatment naive persons). -BY



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