Michael Saag: I will now introduce Dr. Cal Cohen. Dr. Cohen is a clinical instructor of medicine at Harvard Medical School in Boston and is the Research Director of the Harvard-Vanguard Medical Associates and Community Research Initiative in New England in Boston. Cal is going to present an overview of data supporting the use of FDC tenofovir/emtricitabine.

Cal Cohen: Thanks, Mike.

What I'm going to do, as Mike mentioned, is review some of the highlights and data that support the use of FDC tenofovir/emtricitabine when initiating treatment, and also in treatment-experienced patients in a variety of settings.

These are the recent recommendations for initial antiretroviral therapy from the International AIDS Society-USA. And like the DHHS [US Department of Health and Human Services] guidelines that were most recently updated in March, they've divided their recommendations in a simple manner to those combinations they think are most recommended and those that are considered alternatives for a variety of reasons. Those reasons might include good data initially, but perhaps less of it, or less durability, or other concerns that the authors had about these nucleoside options and other drugs listed.

Interestingly, as with the DHHS guidelines, the combinations based on tenofovir and lamivudine are considered highly recommended choices. These guidelines, because they're so recent, allow us also to see that this guideline committee listed abacavir/lamivudine as an alternative backbone. What I'm going to focus on is what is it that the committee looked at that allowed them to say that the combination of tenofovir and either lamivudine, or in the case of tonight's discussion, tenofovir plus emtricitabine, why that was considered a recommended component for initiating treatment.

Everyone is probably familiar with study 903, which compared tenofovir/lamivudine/efavirenz vs stavudine/lamivudine/efavirenz. This 3-year trial in treatment-naive patients is a really large dataset that we use to justify the efficacy of tenofovir in initial therapy.

At the end of 3 years, what we can see is that 70% of patients have a viral load < 50 copies/mL. Importantly, as you can see also on this slide, there was no difference between the success of this regimen in patients who entered the study with low viral loads or high viral loads, with a 5-log stratification. We saw similar response rates above and below this threshold, indicating the more than ample potency associated with this very simple regimen.

We've also seen some recent data that was just announced to the public in press-release form in the past few weeks about the potential differences between tenofovir/emtricitabine vs Combivir or zidovudine/lamivudine. And in this case, unlike study 903, which was a tie, here we've got a difference in favor of tenofovir/emtricitabine. Indeed, 88% of patients receiving tenofovir/emtricitabine had viral loads < 400 at the end of 24 weeks, compared to only 80% of patients receiving zidovudine/lamivudine. And these differences are statistically significant. You can see the P value here of .019.

We have only a few additional data from the press release, but the other additional point that was made is that there was a striking difference in adverse events. Overall, there was a 3% rate of adverse events leading to discontinuation in the tenofovir/emtricitabine arm vs 9% in the zidovudine/lamivudine arm; again, with a significant P value of .013. And this difference certainly underscores the tolerability of tenofovir and emtricitabine, as we see a very high acceptance rate with only a 3% dropout rate for patients receiving this combination.

Now, tenofovir/FTC [emtricitabine] has excellent efficacy, and as we'll discuss tonight, it has also some interesting data in terms of resistance. Let's look at the next slide.