June 19, 2013
Myles Helfand: We touched on it a little bit earlier, but let's talk more about what to start with. Is the standard of care currently still interferon and ribavirin? Or has that really shifted now that we have the two new drugs out?
Douglas Dieterich: For chronic disease, the guidelines suggest judicious use of the protease inhibitors and analysis of drug-drug interactions with the antiretrovirals. The studies support that. The SVR rates are quite good.
Daniel Fierer: It's genotype 1, still [for protease inhibitors].
Douglas Dieterich: For genotype 1, right. They only work for genotype 1. For genotype 2/3 the standard is still PEG and ribavirin. And for acute, I'll let Daniel talk about that; the guidelines are different than some people's use.
Daniel Fierer: We have no U.S. guidelines for acute hep C, and the European guidelines are pieced together -- very small studies, and they're all observational. So the evidence-based guidelines for acute hep C are thin.
But those of us who do it know that if you get treatment started early, the success rate of interferon and ribavirin is quite good, though it varies a lot between the published studies -- from 50 percent up to 80-ish percent. There are all sorts of unmeasured variables in these studies that are making them impossible to actually compare.
Overall, it's still at least twice as good as treating them for chronic infection. Most people get half the treatment course: instead of a year, half a year. This is with interferon and ribavirin, comparing the chronic and acute infection.
Doug mentioned before, with the availability of telaprevir: I decided that it was a very good possibility, since it was proved in chronic infection in HIV-infected patients, that it would likely have some benefit in acute infection. Our pilot studies suggest that the treatment course can be cut in half again, to 12 weeks; and the SVR is very high, 84 percent, as high as anybody's published at a 24-week PEG/ribavirin SVR rate.
If you feel comfortable and you're good at treating chronic hep C infection, then you should be able to treat acute infection.
Myles Helfand: And otherwise, consult and refer?
Daniel Fierer: I think it's a good idea to pick up the phone. I'm always available by email or phone. I talk to people all over the country. They ask, "What do you think about this scenario?" Acute infection can be tricky because the presentation is not clear, because of the no single test -- and so they say, "we're not quite sure someone's had it, or the viral load seems to fluctuate to undetectable, or the liver tests are higher or lower." It's a chimerical presentation. But it's imminently treatable. I think it's so valuable to find it when it's new, because it's so much more treatable, and the treatment course should be shorter.
Myles Helfand: How has our understanding shifted in terms of determining at what point to decide whether to continue with therapy -- whether to extend therapy or whether to stop entirely?
Daniel Fierer: Response-guided therapy, perhaps, is what you're referring to -- how fast the treatment response is and then using that to determine how to move forward.
From what we know and what we've done here in acute infection, if people have what we had been calling an undetectable hep C viral load at week 4 of treatment, then that predicts strongly that they'll have a cure at 24 weeks of treatment, if you're using interferon and ribavirin. For me, with telaprevir, it's a 12-week treatment course.
Rolling into the chronic infection, though, and the new agents, that's less clear.
Douglas Dieterich: Yeah. Looks like response-guided therapy in coinfection, just like SVR, is going to be the same as in monoinfection. So it's perfectly OK to do that.
Daniel Fierer: Completely undetectable by week 4, maintaining that through week 12, you could stop at 24 weeks?
Douglas Dieterich: Right, but with certain caveats, just like there are caveats with the monoinfected. Those are guidelines; they're not commandments. I think you have to adjust. Lots of times we'll treat a 65-year-old stage 3 patient; we're not going to stop at 24 weeks, whether he has HIV or not.
Daniel Fierer: Or cirrhotics.
Douglas Dieterich: Or cirrhotics, for sure: All cirrhotics get treated for 48 weeks.
Even though the stage 3 would fit in the recommendations to stop early, when I've seen people do that, they've often relapsed. So I think you have to still look at the patient across the desk from you and individualize based on their characteristics. The older they are, the more fibrosis they have, the less likely they are to respond, or the more likely they are to relapse.
Daniel Fierer: An important point here: What you just heard here was the voice of incredible experience giving you that little extra. People who only treat some cases here and there may miss these things.
We're not advocating though, by any means, simply referring to the most experienced provider. In fact, Doug is quite active in saying we need to have many more people learn how to treat hep C. We have a quarter million coinfected people. We're going to need a lot of providers to treat hep C.
Nonetheless, it doesn't mean you can't pick up the phone, or send an email.
Myles Helfand: What other quirks of coinfection care have you guys noticed in your practice that you'd want to share?
Douglas Dieterich: Coinfected patients take their medicine better than the monoinfected patients. They have half the side effects, and the medicine works just as well. So I don't think there are any particular quirks. It's all the same rules.
The only issue is drug-drug interactions with HIV medication. You've got to make sure you've got those right before you start. Because if you don't, then you'll run into trouble with both HIV and hep C.
One thing that's slightly different -- and this is not generally understood by most HIV docs -- is if you have to switch HIV meds to a less-than-perfect combination that you think is not going to last very long. If you're using interferon, you have a 1-log anti-HIV activity from the interferon to cover you. But the thing is -- and we've made this mistake, too -- you forget once the patient is cured. Then their HIV viral load will start to rebound. Once they're off the interferon, you have to switch them back to the more potent HIV regimen.
It's OK if, for instance, you don't think the raltegravir [Isentress] is going to last as a potent HIV medication; when they're on the interferon, it's perfectly OK. Just, when they stop the interferon, you've got to switch them back to what they were on.
Daniel Fierer: Or at least for the 12 weeks they're on the telaprevir. The 44 weeks on boceprevir makes me bite my nails a little bit more. But if you can make quick switches in and out, then your half-log, or whatever, effect of interferon does help you. But you have to be very thoughtful about that.
We are, as HIV providers, sometimes concerned with "if it ain't broke, don't fix it." If somebody's been on a regimen for five or six years, especially if they had clinical AIDS before and had a lot of drug resistance, you're concerned about switching. Those are the people for whom you may want to consider waiting for the hep C drugs with fewer drug interaction to come out, such as sofosbuvir. If you get someone who is highly HIV drug-experienced and on a salvage regimen, that might be a very good reason to wait, at least, for sofosbuvir. There are many things to consider.
This is something we also run into with people who have had liver transplants, and people who are also on very drug-interactive medications for immunosuppression. We don't know how you can use these new [hep C PI] drugs. They're stuck in a very tight place of having a horrible liver disease, yet there are contraindications to using the new drugs. You can, with good intentions, hurt somebody.
We are quite cautious. Physicians agree to do no harm. I think, if you as a provider have any questions, then those are the patients you probably should be asking someone else about, as you get to learning more and more about how to use these drugs.
Myles Helfand: Outside of the context of therapy, would daily management just be advising the patient not to drink alcohol, etc.?
Daniel Fierer: Very important. Avoid the known liver toxins, certainly alcohol and Tylenol together.
Douglas Dieterich: Also, controlling metabolic syndrome helps slow down fibrosis progression. That's obviously a big issue in a lot of our older HIV patients; they are the ones that are suffering from metabolic syndrome from the HIV meds themselves. Controlling that well will definitely help, because fatty liver increases the fibrosis progression rate of hepatitis C.