June 2, 2011
Myles Helfand: Let's talk about people with HIV, specifically. Is there anything that either clinicians or their patients need to know about potential interactions with these new hep C protease inhibitors?
Barbara McGovern: Yeah, this is a biggie. Telaprevir is hopefully going to be a very important drug for our patients. Now, what's important to point out is that there are drug interactions with efavirenz (Sustiva, Stocrin). That calls for increased dosing of telaprevir. And in terms of some drug interaction studies that they did with protease inhibitors, it looked like atazanavir (Reyataz) was the least affected.
It's a little bit limiting, but to play it safe, I certainly wouldn't want to give telaprevir to someone where we might compromise either their HIV care or risk the hep C drug getting eaten up by the background [HIV] protease inhibitor.
We don't know enough about this yet. But it looks like the main interactions are that telaprevir makes the area under the curve [i.e., the lowest concentration of the drug in a person's blood] for the protease inhibitors go down significantly. But the effect on atazanavir is less than the other protease inhibitors. It's quite dramatic with darunavir and fosamprenavir; those are two drugs I would certainly not want to be giving in combination with telaprevir. As I mentioned, with the efavirenz, you must increase the dose of telaprevir.
Myles Helfand: That can get a little bit spooky for second line treatment, then. You're saying essentially it's OK for Atripla, as long as you adjust the telaprevir dose. But then when it comes to second-line therapies, when you start pulling in more protease inhibitors, like Kaletra (lopinavir/ritonavir) -- it sounds like you're saying it's maybe best to just go back to the peg plus ribavirin.
Barbara McGovern: Well, I think it's a discussion you have to have with the patient. If they're not on the background [HIV] drugs that were studied, then you have the conversation. You will need to change your background therapy to these drugs, either efavirenz or an atazanavir-based regimen if it's appropriate. Obviously, if you have a patient who has a history of drug resistance to either one of those HIV regiments, that's not going to be an option.
So you have to do it cognizant of the HIV resistance history. If there are issues where the patient is concerned about atazanavir, for example, because of cosmetic jaundice or things like that, at least you could have the conversation that says, "You know, you're only going to be on telaprevir for 12 weeks. So let's switch your regimen. I could give you the telaprevir; add it on to this new regimen. And then, once the telaprevir is over with, we can consider switching you back to the regimen that you like the best, if that's an issue."
I think those are the conversations you have to have. But keep in mind, telaprevir's only for 12 weeks. So I think as long as drug resistance isn't a major issue, I think you can get by.
Myles Helfand: Are there any other special indications that either of these drugs have when it comes to specific populations -- particularly African-Americans, who we know, as it is, are disproportionately impacted by hep C?
Barbara McGovern: I think that this is going to be such an important advance for that patient population. What we have known for a very, very long time is that African Americans do not respond to treatment the same way as Caucasians do. For a long time it was believed that the reason for that was because the proportion of patients who are African American who have genotype 1 is greater than 90 percent, whereas that's not the case in Caucasians.
But then when they did studies that took African-Americans and Caucasians with genotype 1 infection and compared them head-to-head, it was clear that the African Americans had almost half the treatment response rates of Caucasians. There are two very important studies that showed the same results. The response rates in African-Americans were like 22, 25 percent -- really discouraging.
But the data with the protease inhibitors seems to suggest response rates greater than 60 percent. So although it's not as high as Caucasians, it's still remarkably better. So it's a big advance for that patient population, as well.
I think when you're talking to a patient, when you say there's a 1 out of 4 chance of responding, that's pretty discouraging. But when you say 1 out of 2, that sounds a lot better.