This is Gerald Pierone from the AIDS Research and Treatment Center of the Treasure Coast. I'm here in Mexico City at the International AIDS Conference with Dr. Ben Young, and we're at a poster presentation. The title of the poster is "Switching to Fosamprenavir Led to Similar Efficacy and Safety in HIV-Infected Subjects on Their First PI Regimen: A Prospective, Open-Label, Multicenter, Randomized Trial."1
Ben, can you tell me a little bit about this study and what you found?
Be happy to, Gerry. It's great to see you here in Mexico.
This was a GSK [GlaxoSmithKline]-sponsored study to look at the safety and efficacy of taking patients who are receiving stable protease inhibitor regimens, and then switching those patients to fosamprenavir [FPV, Lexiva, Telzir]. The study design was such that patients were randomized initially either to switch to fosamprenavir, dosed either once or twice daily, with 200 mg total ritonavir, or to continue their baseline protease inhibitor. After 24 weeks, which was the primary endpoint of the study, patients were allowed to either continue on their control initial protease inhibitor, or elect to switch to fosamprenavir.
About 250 patients were enrolled in the study in multiple sites across the United States. And these are the results of a planned 24-week interim analysis. Overall, the patients were well matched in both groups, and what we found after 24 weeks, in brief, was that the virologic efficacy was maintained in both groups. There was no virologic penalty, if you will, for switching. The side effect profile was actually quite similar in both groups. There were very few new incident adverse events. There was slightly more diarrhea, but similar effects on triglycerides, similar effects on cholesterol, and so on.
I'm curious. What typical regimens were patients switched from?
There was a mixture. There was no particular preset limitation as to what the patients could come in on. Thirty-three percent of the patients came in from atazanavir [ATV, Reyataz], 6% from indinavir [IDV, Crixivan]. The majority of the patients were coming in from [ritonavir (Norvir)-]boosted lopinavir regimens. Patients could be in the study receiving either boosted or unboosted fosamprenavir. Overall, 60% of the patients received boosted fosamprenavir.
An early look: You said that, at week 24, patients had the option to switch to fosamprenavir. Do you know, did many of them do that?
Yes. Actually, a significant number of them did. Approximately 54 of the 150 patients switched to fosamprenavir at the 24-week time point. What was quite interesting about this is that the patients who switched later actually maintained the virologic suppression better than the overall cohort. Overall, at 48 weeks, approximately three quarters of patients sustained undetectable viral loads; 91% of the switched patients sustained that. So the patients who switched seemed to be selected for patients who were motivated, who already had done well, virologically speaking.
I see. You mentioned an overall improvement of side effects, or about the same?
Actually about the same, overall. My take on this is actually sanguine, what with several other studies suggesting that among the current boosted protease inhibitors, and even the unboosted protease inhibitors, the side effect profiles are actually more similar than one might expect, at first blush. This study is consistent with that. If you switch from one boosted protease inhibitor to another, or one unboosted to a boosted, you actually don't see dramatic changes in side effect profile.
Yes. And again, these patients received 200 mg of ritonavir. Although it's not related to your poster, are you using much 100-mg ritonavir to boost fosamprenavir?
Yes. The majority of my patients now receiving first-line PI therapy with fosamprenavir are receiving 100 mg of ritonavir.
The reason you're doing that is primarily for side effect management?
Actually, our patients tolerated the 200-mg dose quite well. Our principal reason for doing this wasn't to improve side effects, as much as it was to reduce the total number of pills and reduce the total cost of the drug regimen.
Would it be fair to say that the take-home message from this poster is that if patients are on a boosted protease inhibitor regimen and are clinically stable, switching them for whatever reason to fosamprenavir, boosted with ritonavir, would be an effective strategy?
Absolutely. In fact, I think it goes one step further, which is to say that what we do in clinical management is to look at individual characteristics of patients. These data, taken in total, and some of the other data we discussed, suggest that among the protease inhibitor class, there are actually more similarities than dissimilarities. What we do in studies is to look at the overall population effect. Here, what we're really suggesting is that patients who select to switch for specific reasons can do so safely. So what we can do, as patients or as physicians, is to tailor therapies to the individual characteristics, not of a population of people, but of an individual person.
I think that's an excellent point. Thank you very much.
This transcript has been lightly edited for clarity.
- Young B, Dejesus E, Lamarca A, et al. Switching to fosamprenavir (FPV) led to similar efficacy and safety in HIV-1-infected subjects on their first PI regimen: a prospective, open-label, multicenter, randomized trial (ESS100290). In: Program and abstracts of the XVII International AIDS Conference; August 3-8, 2008; Mexico City, Mexico. Abstract TUPE0067.
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