Managing HIV/AIDS Therapy in Treatment-Experienced Patients What lessons have been learned about salvage regimens?
	Enlarged Version of Graphics Below	Dr. Wohlfeiler (OC): Salvage therapy is always the toughest challenge. It's pretty easy to treat patients who are just starting on treatment now. Salvage, that's tough. Dr. Wohlfeiler (VO): Really the rules I follow are first of all try to let resistance testing guide your decision as much as you can. Often you're showing pretty much across the board resistance to everything, which means your options are obviously very limited. And so what I do in that situation is, first of all, I always leave them on 3TC. I maintain whatever mutation I can that I know is going to undermine replication capacity of the virus. The most obvious one is M184V, though there can be other mutations. I'm then going to look for drug protocols or for expanded access medications that I think might be beneficial. Things like tipranavir, which now has been recently approved, but was available for a number of months through expanded access and through clinical trials. TMC114, which is another protease that's in clinical trials and hopefully, will in the near future have an expanded access program. And then also to go to the fusion inhibitors at that point and that's where I'm going to think about using enfuvirtide or Fuzeon.   See Slide Announcer (VO): TMC-114 boosted with ritonavir has shown potent activity in triple-class experienced patients. Interim 24-week analysis of combined data from two studies points to TMC-114 producing significant mean reductions in HIV viral load and increases in CD4 cell count. TMC-114 appears to be safe and well tolerated.   See Slide Dr. Wohlfeiler (OC): And you just hope that by including all those different factors, that you get enough benefit to get that virus at least enough benefit to get that virus at least enough suppressed. Your goal probably no longer is getting undetectable. But you hope to suppress enough to at least maintain immunologic stability or hopefully, even better immunologic improvement. Dr. Bellos (OC): I had mentioned earlier the issue-the TORO trial, which was the registration trial for T-20, and I think one of the lessons that we learned from that trial is the ability to add a new class of drug to the patient in salvage, and one of the lessons we learned from that trial was that you needed to have at least one or two active drugs, preferably two, in order to see a significant benefit in the salvage regimen, when adding a new class of drugs. I think that in my opinion, one can extrapolate that to the fact that if you have two active drugs, whether you're using a new class of drug or not, you can potentially have significant benefit in the salvage arena for patients that have failed multiple regimens in the past. So I think the take-home message is that the number of active drugs that you can include in a salvage regimen, the better off you are going to be in that salvage regimen. Dr. Bellos (VO): And I think we will also be seeing, in the near future-from some of the companies that do the genotypic and phenotypic testing, we will also be seeing how protease inhibitors' relative resistance is calculated. For example, you may not have 100% efficacy from a particular protease inhibitor, but you may have 50%, 60%, 70%, and we should be able to take that into consideration as we are designing a salvage regimen, to include the benefits from that drug that may not be 100% efficacious, but maybe 50%, 60% efficacious, and when one looks at that particular entity of resistance, then one can also play into the issue-the other issue that plays in is the issue of replicative capacity, and I think that's one of the things we've learned, is that as these protease inhibitors-and as we use them, they may be less efficacious, but they do affect the ability of the virus to replicate in their presence. And going back to what we spoke about earlier, that allows us to maintain this viral load/T-cell disconnect so that the patient remains immunologically confident, although they may have some degree of detectable viral load.   See Slide Dr. Kwakwa (OC): ...salvage therapies work best when the patient has not reached salvage yet, and so kind of trying to find when to initiate the salvage therapy, so that the patient has the best chance of durable efficacy, it's very important not to wait until the patient really only has one active regimen remaining in the armamentarium to put them on salvage therapy, and that is an important lesson. Another lesson, really, is as the goals change, really to determine how to best maintain the patient's immune system, whether it's by capitalizing on issues of hypersusceptibility, or whether it's by really driving down the replication capacity to the extent possible, and the extent that we are able to manipulate it for the patient on true salvage therapy.
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