CROI 2010 Wrap-Up: The HIV Drug Development Pipeline

Summing Up: The Outlook for Treatment-Experienced Patients -- and Their Clinicians

Myles Helfand: As a whole, then, this is not a terribly rich drug pipeline, when you consider what we were looking at when we went to CROI five, six, seven years ago. Then it was a very rich, rich field of candidates. This is not quite that wealth of options.

Admittedly, that may just be part of the nature of having about 30 drugs that are currently approved for use. But given what you have said about vicriviroc, the nature of studying treatment-experienced patients and the nature of trying to develop a drug that will help these people, what kind of situation is playing out for the future of HIV treatment? You'd said only one out of your 350 patients have untreatable virus, meaning extreme treatment experience, significant drug resistance across the board. But presumably, over the next few years, as our newer candidates spend more time out on the market, people are going to increasingly develop that level of resistance.

Given that it's becoming more difficult to study drugs for treatment-experienced patients, and that the pipeline does not appear to be rich, what kind of situation are we facing a few years down the road? What do we say to patients who develop extreme drug resistance?

Joel Gallant: I worry about that. Because if you put yourself in the shoes of some pharmaceutical company's CEO -- very expensive shoes, I'm sure -- and you look out and say, "Should I develop a new HIV drug?" Well, you'd be crazy to do that, because it costs billions of dollars to do it. And everybody's doing just fine.

Now, as you say, that may not last. We may be in a little honeymoon period where, four or five years from now, we're going to be facing integrase resistance and extensive resistance to non-nukes and PIs. And we're going to be in trouble, without a lot of stuff to bail us out. I don't know. When I put people on so-called salvage regimens, I really explain that. I say, "You know, this could be it for five or more years. So you've really got to make this work."

On the other hand, you could look at it in a more positive way and say, you know, given the situation right now, it's amazing that we have any drugs at all being developed. And I would also point out that not every drug that's in the pipeline gets presented at every meeting. For example, we didn't hear about the Progenics [Pharmaceuticals, Inc.] CCR5 antagonist at this one, or some of the other second-generation NNRTIs. We didn't hear about rilpivirine, which is in development. There are drugs out there that don't get presented every time. So the pipeline is a little bigger than it would appear, just looking at CROI. But I do worry about this.

I'm very glad that there is, for example, a second-generation integrase inhibitor in development. Because I'm sure that we're going to see Isentress resistance starting to pop up. And that's going to be a hard one, unless we have a drug that will rescue us from that.

Myles Helfand: It sounds like that just gets more to the point that you raised just a little bit ago, about how maybe this raises the importance of counseling patients on the importance of adherence, and making sure that they don't face obstacles to adherence -- whether it's social, psychological, financial, emotional -- that may prevent them from taking their drugs as often as they need to for them to retain their effectiveness.

Joel Gallant: Oh, it's absolutely the case. When you look at patients who are on complicated, multidrug salvage regimens these days, they can kind of be divided into two groups. There's the group that developed all that resistance because they've been on drugs since the late '80s or early '90s and, through no fault of their own, they took what we gave them. And because it wasn't fully suppressive, they developed lots of resistance. That's a very common scenario. Now they are having to take these difficult regimens.

But there's also a big group who have started therapy in the HAART [highly active antiretroviral therapy] era, after 1996, and who have failed because they weren't taking their medications the way they should. And they are now on these regimens. The problem is, of course, if they thought the first regimens were hard, imagine what it's like taking these.

So we really have to make sure that people understand that a first regimen these days is as easy as it's going to get. And if they want to continue on something like that, they need to really make sure that they take it right, and don't get to the point where they are having to take salvage therapy.

This transcript has been lightly edited for clarity.

Read part two of this two-part interview; part two focuses on already-approved antiretrovirals, the question of when to initiate antiretroviral therapy and the evolution of the CROI meeting itself.

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