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This is part two of a two-part interview with Dr. Eron. To hear his thoughts on the phase 2 raltegravir trial in highly treatment-experienced patients, click here.

Could you comment about some of the highlights of this conference.

I think a couple of big HIV highlights were: one, we saw 48-week data on maraviroc [MVC,Selzentry] from the MOTIVATE 1 trial¹. I think that was also really encouraging, because the CCR5 inhibitors ... I think everybody has a little bit of concern. [I.e.,] Do patients all have those X4 viruses at some low level? What we saw is, really, the proportion below 50 copies really was absolutely sustained from 24 to 48 weeks. So I thought that was a really important presentation.

We also saw a comparison between darunavir [Prezista]/ritonavir [Norvir] and lopinavir/ritonavir [Kaletra]in treatment-naive patients, the so-called ARTEMIS trial², in which kind of the top line result is that darunavir/ritonavir -- both of them were combined with tenofovir/FTC [Truvada]-- was non-inferior, or almost the same. But in fact, the proportion less than 50 copies at 48 weeks was actually higher in the patients that were treated with darunavir/ritonavir didn't quite reach statistical significance. But if you looked at the patients with the highest viral loads above 100,000, you actually saw a significantly better effect of darunavir/ritonavir, compared to lopinavir/ritonavir, in combination with tenofovir and FTC.

So I'm not quite sure how that's going to change things. Lopinavir/ritonavir comes in one pill. It's pretty convenient. We like darunavir because it's active against highly resistant variants. So I'm not sure how this is going to affect clinicians yet. But it certainly proved that darunavir/ritonavir was quite effective in treatment-na?ve patients.

And TITAN³,⁴ also showed the same thing.

TITAN was a head-to-head comparison in kind of modestly treatment-experienced patients. And again, showing a very similar thing. Actually, in that study, darunavir/ritonavir was actually superior to lopinavir/ritonavir in the overall analysis. That study ... You know, there were people who were entered in the study that had lopinavir resistance. So I think any clinician, if we had a patient that on phenotype had lopinavir resistance, we wouldn't be putting them on lopinavir. So I think we have to look at that trial carefully. But you're right. Again, head-to-head with kind of one of our standards, lopinavir/ritonavir, and darunavir/ritonavir looked at least as good, if not better, in both TITAN and ARTEMIS.

Any other highlights that struck you? Did you like the study looking at IL-2⁵?

I thought the IL-2 was very interesting. This was a trial where patients who had not yet been treated, or had minimal previous treatment, were given IL-2 to kind of forestall starting antiretroviral therapy. It wasn't a giant trial, but it was a pretty big trial. And it seemed to delay the need for antiretroviral therapy in the majority of the patients -- significantly delayed. You might say, well, IL-2: it's expensive; it's toxic. But, really, it was given in a couple of series. Then it really only had to be given once a year, I think, in some of the patients. So it's a possible strategy. It was intriguing. I think we need to see a little bit more, maybe a little bit larger data set. But that was intriguing.

I think that we're seeing more data today on some of these non-AIDS-defining illnesses, like non-AIDS-defining malignancies, and non-AIDS-defining serious medical illnesses. And perhaps there's a relationship to CD4 cell count. I think the flavor that we have got from IAS [Conference on HIV Pathogenesis, Treatment and Prevention that took place in July 2007] and a little bit here at ICAAC is, perhaps we should be treating patients a little bit earlier. No hard data, no comparative trial. But I think that's the flavor, I think, I'm getting from these meetings.

What's the new CD4 count that treatment initiation should be started at, do you think?

This is just a personal opinion. I certainly think that patients who reach 350 CD4 cells should definitely start therapy. There are always issues, and every patient is an individual, obviously. But in my practice, when patients start getting below 500, I start talking to them about, you know, maybe it's getting time to think about starting therapy. So somewhere, I think, between 350 and 500 is where my practice is. But I wouldn't be surprised, over the next five years, that that moves up even higher. We'll see.

Do you think the guidelines that will soon be released, I hope, will reflect that?

I'm not part of the guidelines panel. I have friends that are on the guidelines panel, and I know it's a very active discussion. That's the best I can tell. I don't know what they are going to decide. I really don't know. Because there is no... We don't have any hard data yet. So I think it will be a matter of opinion. But I think the guidelines will probably come out a little more strongly with starting earlier. But I doubt it will be a firm recommendation. But that's just my guess.

One more question about all these new antiretrovirals. What are the metabolic ramifications? Do they look a lot better? Is there hope that there will be less fat accumulation and fat wasting?

Yes, I think so. We have seen lipid data with maraviroc. We have seen lipid data with raltegravir (MK-0518, Isentress). And that looks very promising. Thinking back, we really didn't see the problems with the protease inhibitors or d4T [stavudine, Zerit] until people were kind of on therapy for more than just 24 weeks. We started recognizing it after a year. So I'm cautiously optimistic. But I think at least the early signs are that these drugs are unlikely to have substantial metabolic effects. But we have to wait and see to be sure.

Thank you very much, Dr. Eron.

Yes, thank you very much.

This is part two of a two-part interview with Dr. Eron. To hear his thoughts on the phase 2 raltegravir trial in highly treatment-experienced patients, click here.

Footnotes

1. Lalezari J, Mayer H, for The Motivate 1 Study Team. Efficacy and safety of maraviroc (MVC) in antiretroviral treatment-experienced patients infected with CCR5-tropic HIV-1: 48-week results of MOTIVATE 1. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-718a.
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2. DeJesus E, Ortiz R, Khanlou H, et al. Efficacy and safety of darunavir/ritonavir versus lopinavir/ritonavir in ARV treatment-naive HIV-1-infected patients at week 48: ARTEMIS. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-718b.
   View slides: Download PowerPoint
3. De Meyer S, De Paepe E, Vangeneugden T, et al. Development of resistance in patients with virologic failure on darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r): results of a randomized, controlled, phase III trial in treatment-experienced patients (TITAN). In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-1020.
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4. Madruga JV, Berger D, McMurchie M, et al, on behalf of the TITAN study group. Efficacy and safety of darunavir-ritonavir compared with that of lopinavir-ritonavir at 48 weeks in treatment-experienced, HIV-infected patients in TITAN: a randomised controlled phase III trial. Lancet. July 7, 2007;370(9581):49-58.
5. Molina J, Levy Y, Hamonic S, et al. Intermittent interleukin-2 therapy to defer antiretroviral therapy in patients with human immunodeficiency virus infection. In: Program and abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 17-20, 2007; Chicago, Ill. Abstract H-718.