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Edurant (Rilpivirine): The HIV Treatment Dating Game Just Got More Interesting

An Interview With Cal Cohen, M.D.

May 26, 2011

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Side Effects and Drug Interactions

Are there any side concerns that come into play when considering starting treatment with Edurant?

The main concerns I think are the following, and the FDA label certainly points these out: One thing is that this drug needs to be taken with food to be absorbed. Therefore, somebody has to time this around meals. It's fair to say almost everybody eats at least once a day, so I don't think that's a particular burden. Nevertheless, it's something that people need to be mindful of. If somebody takes it in between meals, this drug won't be as well absorbed, and we want this drug to be absorbed so that it can do its work.

"I think we can say with confidence that this is an excellent choice for people whose viral load is less than 100,000, and there's ongoing research to understand if or when this is the right drug for people whose viral load is over 100,000."

The other concern that the FDA label points out is that in people who had a high viral load, over 100,000, there was more virologic failure observed on Edurant than there was on efavirenz. We certainly have seen that in other drugs that we use, and it's also showed up here. Which means that there's at least a question, or a caution, for clinicians in terms of when this is the right drug [to take]. I think we can say with confidence that this is an excellent choice for people whose viral load is less than 100,000, and there's ongoing research to understand if or when this is the right drug for people whose viral load is over 100,000.

What we want to do is understand how best to use Edurant -- when are we confident that it is the right choice -- with the highest degree of confidence that we can have. The FDA certainly highlights that baseline viral load is one way to ensure that kind of confidence. There's an ongoing study that the manufacturers are doing to further understand why this drug had some question marks at higher viral loads.

It gets into, I guess, a larger question about the growing number of first-line options, too, which we can get into in a couple of minutes. First, how about drug interactions? Anything in particular that people should be on the lookout for?

"This drug is not the right choice for somebody who must take potent drugs that lower stomach acid -- specifically drugs we call proton-pump inhibitors, like omeprazole [Losec, Omesec, Prilosec]."

Probably the single most important thing is that, as I mentioned, this drug needs food in order to be absorbed. It also needs stomach acid, so this drug is not the right choice for somebody who must take potent drugs that lower stomach acid -- specifically drugs we call proton-pump inhibitors, like omeprazole [Losec, Omesec, Prilosec]. Edurant needs acid, so somebody who requires medicine to reduce stomach acid will find that this is not the ideal choice. Note that we already have seen this with atazanavir [Reyataz], for which there is a similar issue, and the field has learned to work with this issue.

Some people are on a proton-pump inhibitor every day. These days, in fact, the field of medicine is revisiting whether somebody who's on those drugs should stay on them the rest of their lives, or if maybe there is an opportunity to come off those drugs, because of some long-term toxicity issues with the proton pumps. Nonetheless, there are people who can't come off them, and for them Edurant is not the best choice.


Concerns for Specific Populations (Women, African Americans)

Looking over the volunteers who were involved in the clinical trials for this drug, how diverse was that study population? Were there any differences, let's say, in terms of how the drug acted in women, African Americans or Hispanic Americans?

To answer your first question, the drug was studied worldwide, so there were participants from all over the globe, on several continents. And in terms of diversity, if we take a look at the pooled data sets, it certainly had amongst the most diverse populations for any kind of initial trial population. So I think on that level, we can be confident of these results.

"Efavirenz and Edurant perform similarly regardless of the population: similarly in women, similarly in men, similarly by race, and so on."

At the Glasgow meeting, and also at the IDSA meeting, we presented data with regards to specific subsets, including what you're asking about. Probably the simplest way to summarize that is that efavirenz and Edurant perform similarly regardless of the population: similarly in women, similarly in men, similarly by race, and so on. There weren't kind of striking differences of, "This is the right drug for this population, but not for that population." That did not show up.

That doesn't mean every population does the same. We certainly see different patterns of adherence in different countries and different races. But nevertheless, there was certainly no evidence that rilpivirine and efavirenz are better in one population versus another. It was similar response rates for both the drugs within each of the populations.

Is it safe to take if you're pregnant?

The FDA gave this drug a pregnancy category B. What that translates to is that there's always a need to be cautious, because we don't have as much data -- if any -- in any woman who becomes pregnant while taking this drug. Nevertheless, the FDA reviewed the animal data and did not find anything to raise a caution.

B is the most permissive criteria that the FDA gives in the absence of a lot of human experience to show that the drug is in fact safe when pregnant women take it during pregnancy. As I understand it, this category rating is the most reassuring categorization that a new drug will get.


Drug Resistance Issues

Let's switch to resistance for just a minute. There were some findings in the clinical trials about how Edurant appears to be a little bit more susceptible to cross-resistance if a person fails treatment on it. Can you talk a little bit more about that?

"Resistance is not a consequence of treatment, it's a consequence of treatment that was not successful."

The first point I think we should start with is that we should make sure people understand the basics: Resistance only happens in people who did not achieve virologic suppression, in whom the viral load doesn't go down and stay down. In most patients who started both drugs (Edurant and Sustiva), the viral load went down and stayed down. So resistance is not a consequence of treatment, it's a consequence of treatment that was not successful.

For the subset, for example, of people whose viral load was less than 100,000 who took rilpivirine and two nukes, nine out of 10 had virologic response, they got their viral load down. So when we talk about resistance, we understand we're talking about that other 10 percent, the people in whom the viral load didn't go down or didn't stay down. Sometimes that's a consequence of inadequate adherence -- not taking it with meals, for example -- though sometimes that may be a consequence of the baseline viral load, despite excellent adherence. Why failure happens is an important piece that we are still learning about. Clearly we don't want failure, and thus far adherence is one important contribution to ensuring success. Nonetheless, there were patients who had, for any number of reasons, some degree of inadequate response, and therefore resistance can occur.

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The pattern of resistance for Edurant is different than for efavirenz. The main difference comes down to another non-nucleoside called etravirine. A couple of years ago, Intelence was approved by the FDA based on studies in people who had already been on, and had resistance to, NNRTI drugs including efavirenz. We needed a drug that would work against efavirenz-resistant viruses, because we had, unfortunately, a lot of people who had efavirenz-resistant viruses -- because whether it was efavirenz or nevirapine, we sometimes used them in unsuccessful combinations. So we had thousands of patients who really needed a drug like Intelence. And it worked.

Now we're talking about treatment-naive patients. It is fair to say that people who start therapy are, first of all, unlikely to have any resistance at all, so Edurant will work for them, and most people will respond. But it is true that if someone takes Edurant and doesn't respond, if there is resistance, then there will be cross-resistance to Intelence. These two drugs are related in terms of resistance patterns. So the use of Edurant will, when successful, maintain all options, and when unsuccessful, unlike efavirenz, etravirine may not be the best choice to follow it.

Fortunately, it is entirely possible that one might never need to use etravirine. If someone takes Edurant and two nucleosides as his or her first combination, and it stops working, that person can still take all the protease inhibitors, the integrase inhibitors, and probably the CCR5 inhibitors, as well as some of the nucleosides, like tenofovir [Viread]. [Editor's note: Two nucleoside reverse transcriptase inhibitors (NRTIs), Emtriva (emtricitabine, FTC) and Epivir (lamivudine, 3TC), which are a part of many antiretroviral combo pills, do appear to often lose their effectiveness as well if a person develops resistance to Edurant. Research is continuing in this area.]

So, if resistance should occur with someone on rilpivirine, it is entirely likely that we would have an excellent combination that should work quite well to reestablish virologic control. While they may have lost etravirine, they are still quite likely to be successful in terms of reestablishing suppression with another regimen.

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This article was provided by TheBody.com.
 
See Also
FDA Approves Complera (Edurant + Truvada), the Second "All-in-One" Pill for First-Line HIV Treatment
Next Single-Pill HIV Treatment Approved, and It's Not Called "B-Tripla"
Approval of Complera: Emtricitabine/Rilpivirine/Tenofovir DF Fixed-Dose Combination (Official FDA Announcement)
More on Edurant (Rilpivirine, TMC278)

 

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