The Body Covers: The 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention
IAS 2007 Highlights: An Interview With Trevor Hawkins, M.D.
July 24, 2007
Well, I'm glad you said, "in terms of clinical practice," because I think we sometimes forget just what very important things have been talked about at this conference in terms of the global epidemic. Of course, as practitioners, we love to pass data on new clinical studies, but I think it's important to see where it is in perspective.
However, having said that, probably the most interesting clinical study we saw today was the TITAN study,1 which was a look at boosted darunavir [brand name: Prezista; also known as TMC114] versus boosted lopinavir [brand name: Kaletra; also known as LPV/r] in early-experienced patients.
Why did you think it was so important?
Darunavir, up to now, has been almost exclusively used to treat drug-resistant virus, and it's been very, very exciting to use it in that context, particularly when we have been able to put it with other effective drugs, some of them new, as well. So that's been very exciting.
But this [clinical trial looked at] actually moving it out of that [use in the multi-drug resistant] and moving it up the food chain, as it were, and looking at [the use of] it in first failure. Of course, the stakes are high, and they went head to head [-- a regimen with darunavir compared] with [a regimen with] lopinavir, which is a very, very well-established, well-researched protease inhibitor [PI], with studies of seven-year data and so on. So it was, I think, important because actually what it did do is show that darunavir is worthy of consideration in that particular field, in that particular patient.
What about the side effect profile? How did that compare?
Pretty well. In terms of actual side effects, there was a difference in diarrhea. There was more diarrhea in the lopinavir group, about twice as much. There was a little bit more rash in the darunavir arm. Actual discontinuations for adverse events were pretty similar in the two arms, and there actually wasn't a lot of discontinuation. It was relatively low, about 7%. But a little bit more rash in the darunavir arm, significantly more diarrhea in the lopinavir arm.
In terms of lab abnormalities, not a huge difference between the two.
I spoke to Dr. Bernard Hirschel today, who wrote the editorial in The Lancet about this. He noted that he wasn't impressed with the diarrhea data, because he said that it was the old formulation of lopinavir. What was your feeling about that?
Hard to say about that. About 18% of patients in this study actually switched during the study from the capsule to the tablet, but that's a pretty small number. Certainly, there is some data to suggest that the tablet has less diarrhea. I think it's a little hard to say. We're basing it on an industry-sponsored switch study, where people were already pretty stable. So it's a little hard to say whether that would have made a big difference or not. It might have done.
So, you're going to change your perspective on sequencing darunavir now, based on this study?
I think so. By the way, they did include about a total of 58 patients in this 600-patient study who were, in fact, somewhat resistant to lopinavir. [Those patients] had a greater than 10-fold resistance, so they were only partially sensitive at baseline. [The investigators] present an analysis where those patients were excluded. And I think that's the right thing to do. If you're looking at a phenotype and you see greater than 10-fold lopinavir, fully sensitive to darunavir, I don't think there's any doubt that you're going to choose darunavir these days.
However, even when those patients were excluded, everything trended in favor of darunavir. Certainly, it met non-inferiority at every stage. And in every subanalysis, however you slice the data, it clearly met non-inferiority. In some subsections, it demonstrated superiority. So that's in terms of patients going to less than 50 copies and less than 400 copies.
The other significant thing, in terms of virologic failure: There were less virologic failures. Again, even if you exclude the patients with only partial sensitivity to lopinavir, still there were more failures and more primary PI mutations and more nucleoside mutations in the lopinavir arm. Now, these weren't huge differences, so I think we need to look at it in perspective. This doesn't mean that there was a huge difference between them. Everything did trend in darunavir's way. I think, given the experience with this drug, it's looking like it's certainly worthy of consideration in patients for their first failure.
Well, thank you very much.
You're very welcome.
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