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Double protease inhibitor regime?
Oct 22, 2001

If resistent to all transcriptase inhibitors but to none of protease inhibitors, what would you think of a double protease inhibitor and new Tenofovir regime? Would it be potent enough?, as it is usually the other way around; 1 p.i. and 2 t.i.. Thank you

Response from Dr. Cohen

Studies over the past 5 years have shows pretty clearly that a double PI combo - especially one that has the "booster" impact of ritonavir included - can do well. The primary data of this comes from the combo of just ritonavir and saquinavir. For those who viral loads were, when off meds, less than 100,000 - this combo alone - just two PIs - was ample to achieve viral suppression for now 5 years. For those with higher viral loads, the addition of other agents was needed - so in this case tenofovir would be an example of what would be added. You don't mention the NonNucleosides - but these too can be added for increased potency. Similar studies using two PIs without ritonavir as one of them were less impressive and awkward given the pill burden.

That dual PI combo - rit/saq - is the most studied but certainly can be also seen as an example of what else could be useful. Since low dose ritonavir boosts the levels of virtually all of the other PIs - other dual PI combos could be used altho we have fewer data. And since Kaletra, the newest PI, contains a low dose of ritonavir in the capsule, it could be one of the two PIs chosen for added simplicity. What the "best" two PI combo is, however, is unclear as there as always are pros and cons to each. But studies of using Kaletra with a second PI - such as saquinavir - are underway to answer this precise question. One added note is that since one common side effect on PIs is diarrhea - this is one place where the old invirase formulation of saquinavir may be useful as it has less diarrhea and "boosts well" when ritonavir is around.

Hope that helps. Cal Cohen


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