Craig Sterritt: Now I'd like to introduce our expert moderator, Dr. Michael Saag. Dr. Saag is Professor of Medicine and Director of the AIDS Outpatient Clinic at the University of Alabama at Birmingham. Good evening, Dr. Saag.

Michael Saag: Good evening. Thanks, Craig, and welcome, everyone.

I'm going to briefly go over the issues in choice of initial antiretroviral regimens and sort of set the stage for the value and the role of fixed-dose combinations, predominantly in primary or initial therapy, but also these agents could be used in a fixed-dose combination form later in the course of disease, as well. We're already used to fixed-dose combinations in the sense that we already know about Kaletra, which is lopinavir/ritonavir. We also know about Combivir, AZT/3TC [zidovudine/lamivudine]. And so now there are 2 new ones that we're going to really focus on for the most part this evening.

The issues to consider when initiating a new regimen are listed on this next slide, where we talk about potency, tolerability, convenience, coburden, long-term toxicities, and then future potential therapeutic options. And I think we all are very comfortable balancing out these different issues.

I would add to that, these are the issues that I think play a large role in how patients accept new therapies, especially for the tolerability and convenience and pill burden. And the physicians are thinking about potency, long-term toxicities, and options.

The other thing that I think is new on the horizon that a lot of us are facing in practice is the issue of copayments for patients; when you have fixed-dose combinations, sometimes it's easier for patients who have third-party payers in terms of just having 1 copay for 2 drugs, as opposed to separate copays. And then finally, some of the issue of convenience in terms of how much time does it take for the provider to go over the instructions, which is becoming more and more of an issue as we're faced with pressures from our administrators to see as many patients and in the most efficient way possible.

Getting back to the issue of potency, my opinion is that a lot of the success of first regimens is really about not so much potency, but really the tolerability.

In this survey of 24 weeks of response rates to initial antiretroviral regimens, you can see that there is an improvement over time. This listing starts with a meta-analysis that John Bartlett and Ralph DeMasi did back in the late '90s, early 2000 range, where only about 54% of patients achieved viral loads < 50 copies/mL. Then we have a smattering of additional studies that have come on the heels of that, such that by intent-to-treat analysis, we can see response rates as high as 82% to 83% or so with some of the newer regimens.

My position would be that this trend doesn't reflect, for example, that an efavirenz-based regimen is inherently more potent than, say, a lopinavir/ritonavir-based regimen, but rather that the tolerability, and to some degree the convenience, of drug regimens is playing a role here. In my opinion it's really mostly an issue of tolerability. Thus it's important when selecting a regimen to concentrate not only on what's convenient, but what the patients will be able to tolerate over the short-to-intermediate term.

Here, I simply point out some of the advantages and disadvantages of fixed-dose combinations. I think the advantages are pretty straightforward; I'm not going to read through them, but just point out that in the case of these 2 new fixed-dose combination formulations, they are thymidine-sparing.

The disadvantages are that if they miss a dose as a 48-hour gap, then we have to think about the forgiveness of a missed dose. I would like to add, however, that every dose of medicine -- whether we give it q12 or q24 -- is really based on an exposure that would allow that type of dosing. So I'm not sure that missing a dose of a q24 drug is inherently worse than a missing a dose of a q12-hour drug, but it is a potential issue. Also, with respect to disadvantages, we have with FDC [fixed-dose combination] agents a lack of flexibility in dosing. You can't necessarily just cut the pill in half and use it that way.

Finally, because these are relatively new agents, there may be some unanticipated interactions or long-term toxicity that we haven't really noted as yet, but could emerge over time. Obviously, we've been surprised throughout the years at how certain drug combinations, that we could have sworn we [understood] and didn't anticipate problems with, turned out later to have longer-term problems. This is just a caution.