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ICAAC 2007 Study Summaries: An Interview With Joseph Eron, M.D.

September 20, 2007

Joseph J. Eron, M.D.
Listen (2.5MB MP3, 6.5 min.)

This is part one of a two-part interview with Dr. Eron. To hear his take on ICAAC 2007 highlights, click here.

I'm Joseph Eron, professor of medicine at the University of North Carolina, and also an investigator on this Merck phase 2 trial that was presented yesterday at the ICAAC meeting1. Basically, this was a phase 2 trial in highly treatment-experienced patients of raltegravir, in combination with optimized background therapy. In the phase 2 trial, they tend to be smaller trials, as you know, with only about 40 patients per treatment arm. Usually what the phase 2 is trying to do is find the dose. So there were three different doses of raltegravir that were given in a trial. What we saw at the slide session yesterday was the 48-week results from this comparative trial.

In the trial, after 24 weeks, all of the patients who received raltegravir actually moved to the 400-mg twice-a-day dose. What we saw is that basically, after 48 weeks, there still was this sustained suppression, below detectable. The proportions less than 50, depending on the treatment arm, were between 46 and 64 percent, which was obviously substantially better than placebo.

This trial was a little different than the BENCHMRK trials2, 3, because in this particular trial, there was no darunavir [Prezista] in the optimized background; there was no tipranavir [Aptivus] in the optimized background. So really, this was probably some of the most highly treatment-experienced patients, with sort of minimal background therapy. So this kind of prolonged effect, I think, was encouraging ... though the numbers were small. It's a small trial.

Was there use of T-20 [enfuvirtide, Fuzeon]?

There was use of T-20. And I think the percentage was approximately 20 percent. I'd have to check that, or we can check it from the presentation. Naïve use of T-20 was about 20%. That was probably the most active agent in background for most of the patients.

Was there a breakdown to see if those patients did better?

I don't think they have actually shown us those data from that trial. They have certainly shown it from the BENCHMRK trials at the CROI meeting2, 3. But I don't think they have shown us that data from Merck 05, this phase 2 trial. It would be interesting to see those data broken out.

What is the meaning of this kind of trial in 2007? Now that we have drugs available like raltegravir the selection of optimized background is forever changed. What is an optimized background in 2007, then?

I think that, first of all, you know -- the optimized background now -- we need to figure out how to combine these new drugs. We have maraviroc. We will have raltegravir. Hopefully, we'll have etravirine. So we really have to figure out how to combine these drugs. There's no trial yet that tells us how to do it. So I think the important thing from this particular trial is that with raltegravir, even with kind of relatively modest support, you saw a pretty substantial number of patients suppressed, in that it was sustained. So that gives you an idea of the potency of raltegravir.

But it's clear that to get the best result, to get the highest proportion of patients below detectable, we really need to do better with optimized background. I think the challenge to clinicians is to figure out how to combine these new drugs so can really get the true optimized background. So, you're right on the money.

I think this smaller trial helps us know what to dose, tells us about kind of the longer term durability of raltegravir-based regimens, and also tells us a little bit about safety. It looked like there was pretty comparable safety between raltegravir, and the placebo arm. So this is just a little bit longer-term safety data, too. So that's useful.

What were some of the adverse events?

The adverse events were really virtually -- well I don't want to say identical -- but really very similar between the placebo-treated patients and the raltegravir-treated patients. There really wasn't a kind of a sentinel toxicity. There really wasn't one particular toxicity that kind of stood out in the patients that received raltegravir. I think we're still kind of waiting to see whether there is a particular toxicity for raltegravir. So far, we haven't seen anything substantial in the clinical trials.

I can tell you, in my own patients' experience, the drug tends to be pretty well tolerated. In other words, those low level toxicities that don’t usually show up in clinical trials -- well, we don't seem to see a lot of that either. But that's a smaller number of patients that I have just treated personally.

Thank you very much, Dr. Eron.

You're welcome.

This is part one of a two-part interview with Dr. Eron. To hear his take on ICAAC 2007 highlights, click here.

 

Footnotes

  1. Grinsztejn B, Nguyen B, Katlama C, et al, and The Protocol 005 Team. 48 week efficacy and safety of MK-0518, a novel HIV-1 integrase inhibitor, in patients with triple-class resistant virus. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-713.
  2. Cooper D, Gatell J, Rockstroh J, et al, for the BENCHMRK-1 Study Group. Results of BENCHMRK-1, a phase III study evaluating the efficacy and safety of MK-0518, a novel HIV-1 integrase inhibitor, in patients with triple-class resistant virus. In: Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, Calif. Oral 105aLB.
  3. Steigbigel R, Kumar P, Eron J, et al, for the BENCHMRK-2 Study Group. Results of BENCHMRK-2, a phase III study evaluating the efficacy and safety of MK-0518, a novel HIV-1 integrase inhibitor, in patients with triple-class resistant virus. In: Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, Calif. Oral 105bLB.


This article was provided by TheBodyPRO.com.
 



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