The Body Covers: The 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention
IAS 2007 Highlights: An Interview With Cal Cohen, M.D.
July 25, 2007
I think for many clinicians the focus of this conference was on the new drugs, and the role of these new agents. And so probably amongst the most important research would be the contribution of data from the DUET studies,1 the TITAN study2 -- which was darunavir [brand name: Prezista; also known as TMC114] versus lopinavir/ritonavir [brand name: Kaletra; also known as LPV/r] -- and, of course, the maraviroc [brand name: Selzentry; also known as MVC]-naive trial,3 and clearly, the raltegravir [also known as MK-0518]-naive trial,4 as well.
Why were these the most important? What's the big take-home that came out of these studies for you?
What makes these studies important for us is that the question in many of these studies is: Are we able to change practice in a way that improves the likelihood of getting this virus under control, and doing it with a safe, well-tolerated regimen? So, for example, with the case of the raltegravir-naive study, what we see is raltegravir versus efavirenz [brand name: Sustiva, Stocrin; also known as EFV]. At week 48, what we see is that raltegravir and efavirenz both have the vast majority -- 85 to nearly 90% -- of patients with a viral load that's suppressed. Raltegravir has a different safety profile. It doesn't share some of the common toxicities of a drug like efavirenz. That doesn't mean we should switch to it, but it means we have another option in case we don't want to use efavirenz, for some reason.
Now, with maraviroc we have a somewhat more complicated question. Because that trial showed diminished activity by using a very stringent approach to judging activity. Yet, we also saw a better-tolerated drug. What made that result also particularly interesting is that a lot of the reason why it was not quite as successful came from results in patients who were in the Southern Hemisphere. Patients of the Northern Hemisphere appeared to have an identical response on efavirenz and maraviroc, and that raises the question whether, if that's verified in terms of additional analyses that are done, if that's real. Certainly, there may be reasons why that's real -- different clades of viruses and different geographies. Then these data may also contribute to giving us another treatment option for starting therapy.
How is this going to change your clinical practice? You know now that you have more options. Anything else?
Well, the treatment-experienced patient studies are really the places that are going to change practice, because we already have great regimens for starting therapy. So with the DUET trial, we now know for sure that the addition of etravirine (TMC125) clearly has a major impact in improving the likelihood of response, particularly in people who need a new regimen, a new option.
What we saw in this study here is, even if the background is compromised, patients in whom we don't expect a non-nucleoside [NNRTI] to have durable activity, we saw dramatic evidence -- with nearly nine-fold improvement in the durability of maximal viral suppression up to week 24, with the addition of this new novel NNRTI [etravirine]. That's important stuff for us because we don't think of an NNRTI in that way. And here, this drug has proved itself in two identically designed studies.
I think in terms of the PI [protease inhibitor] discussions, we once again have a very interesting discussion about the ability of darunavir and lopinavir to be used in treatment-experienced patients. We know from POWER5,6 that if lopinavir is minimally active, darunavir should be used instead. That we have already established years ago.
The question that was asked in this trial is: Where does that difference start? If both drugs are fully active, we'd expect both drugs to be similarly successful. But if there's a little bit of resistance, does darunavir do better? And how much resistance do we need before lopinavir is less successful than darunavir?
The TITAN study starts to get at that. And while it wasn't a precise answer, it certainly begins to suggest that at some point, perhaps earlier than the POWER studies would suggest, clearly darunavir needs to be considered an important option for some of our patients.
What are you hoping to see in future studies of darunavir?
Well, I think that we all are aware that, in this coming year, there's a [treatment] naive study that will complete, and results have been submitted to some major conferences. So, as this study here moved darunavir, or at least it moved the data of darunavir, earlier on, in terms of [giving it to patients with] less resistance, we now will see a head-to-head trial in treatment-naive patients to really understand: What does darunavir contribute as both a well-tolerated and simple drug, as well as an efficacious drug?
So, looking forward to that. Is there anything else about the conference? Anything surprising? Anything that caught you a little off guard that was presented?
Well, I'm not sure that there was anything too surprising as I think of it, but I do think that one of the focuses of this meeting was a very important focus on the issue of when do we start treatment. The theme of CROI [Conference on Retroviruses and Opportunistic Infections], I think, perhaps last year and this year was that the implications of stopping therapy are severe and important and worth avoiding. But at this conference, the question was: What are the ramifications of that? Since, if stopping leads to viremia, which causes damage, at this conference what we saw is that that may also be true for people who have never started therapy. This conference spent a lot of attention on [the fact that] maybe our drugs are good enough so that even people with high CD4s can benefit from starting therapy. That doesn't mean people should, or that we have enough data to say that people would do better if they did. But we certainly are beginning to get data that suggest that that question is worth talking about. And Tony Fauci himself [Anthony Fauci, M.D., Director of the U.S. National Institute of Allergy and Infectious Diseases] seemed to suggest that he's willing to fund, at least the pilot for such a study this year.
What are you doing with your patients? Are you starting people with high CD4 counts on treatment right away?
I'll confess that I'm part of a network that wants to study this, because I think the data are convincing that it is possible. We can do more good than harm by starting therapy in people whose CD4s are greater than 500. That's why many of us have been collaborating on getting a definitive answer to the question, because the treatment of HIV shouldn't be based on my opinion, or somebody else's opinion. It should be based on, what happens when we do it. That's why we want to answer the question with a definitive study. We think we've got the right tools, and we think we've got the right question. And now we just want to see: Are we right?
Dr. Cohen, thank you so much. Always a pleasure.
Thanks very much.
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