Managing HIV/AIDS Therapy in Treatment-Experienced Patients Are double-boosted PI regimens valid options for salvage?
	Enlarged Version of Graphics Below	Dr. Kwakwa (OC): Double boosted protease inhibitors, I think, will continue to be an option for patients on later lines of therapy or in salvage. The difficulty comes in determining which protease inhibitors to use together, and this is a recent difficulty, trying to figure out what doses of fosamprenavir and Kaletra to use, for example, and will remain an issue with the use of Aptivus, or tipranavir, and potentially other protease inhibitors. Dr. Bellos (OC): In my opinion, I think they are of significant benefit. We have not had a lot of hard data to look at dual boosted PIs, but in patients who are in salvage therapy where I wanted to use an entry inhibitor, I have been able to use a dual boosted PI in those patients with something, for example, like T-20, or with some of the newer CCR5 inhibitors that are currently in trials. We have designed and optimized a background consisting of a dual boosted PI, added a T-20 plus the CCR5 inhibitor, and are actually having good response in those patients. The other thing about dual boosted PIs is the issue of simplification. In patients who have relatively resistant virus to the nucleosides and the non-nukes, because that has essentially been their regimen from the get-go, a dual boosted PI regimen would work well in those patients, and especially with the dosing regimens we discussed earlier with fosamprenavir and the convenience of dosing fosamprenavir with ritonavir, one could add, for example, Invirase or-saquinavir -but if we add saquinavir to that regimen, and use a dual boosted PI regimen, and have significant efficacy. Dr. Wohlfeiler (OC): I certainly do use double boosted PIs. It's I think becoming more complicated to use double boosted PIs because we're finding that the pharmacokinetics can be much more complicated than we realized. Things like the use of fosamprenavir and lopinavir, which seemed like a great combination, but we've come to realize we've got some very complicated pharmacokinetics and may not really be well combined. The problem with most double boosted PIs, if you look at the old fashioned combinations of relatively high dose ritonavir and saquinavir, that's a well studied double boosted PI combination. But for the most part, the double boosted PIs have not been well studied. And so we really don't have a lot of data on them. Dr. Wohlfeiler (VO): There's certainly interest in things like atazanavir and saquinavir. There's some information that would indicate that maybe these are synergistic. But the one study that was done looking at combining the two of them, which was combining them without boosting with ritonavir, showed a very inadequate response. Now maybe if you add ritonavir boosting in there, you're going to get a great response.   See Slide Dr. Wohlfeiler (OC): But we're still pretty much in the dark when it comes to a lot of these double PI combinations.
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