HIV/HCV Coinfection Update: From Testing to Treatment

A Discussion With Douglas Dieterich, M.D., and Daniel Fierer, M.D.

Executive Editor

HIV care providers tend to wear many hats: In addition to managing one of the most insidious infectious diseases in the history of humanity, an HIV care provider must also often manage a host of comorbid physical and mental conditions. In recent years, liver health -- particularly as it relates to hepatitis C (HCV) coinfection -- has increasingly become a prominent item on that comorbid condition list.

Meanwhile, within a stunningly brief span of time, our understanding of HIV/HCV coinfection has undergone a dramatic evolution. The landscape of coinfection risk, pathogenesis and treatment has utterly changed from just a few years ago.

To bring frontline HIV care providers up to date, I headed to the Mount Sinai School of Medicine in New York City and spoke with two of the foremost experts in HIV/HCV coinfection: Douglas Dieterich, M.D., a professor of medicine in Mount Sinai's division of liver diseases, and Daniel Fierer, M.D., an assistant professor of medicine in Mount Sinai's division of infectious diseases.

Table of Contents

The Nature of the Epidemic

Myles Helfand: Where are we at right now, in terms of our understanding of HIV/HCV coinfection -- the numbers, the risks? What has changed in the past few years?

Douglas Dieterich: I'll start with the chronic, and I'll let Daniel handle the acute, because that's his area of expertise. The numbers of chronically infected patients are actually not that different: It's still 30+ percent of the HIV patients in the U.S. that are coinfected with hepatitis C, though that number may be getting a little bit higher. It also varies from clinic to clinic, from practice setting to practice setting.

What has changed are the recommendations for testing everybody for hepatitis C -- at least yearly now, instead of just once forever. That's actually something that should be done. Many places do it more frequently than yearly -- some approaching every three months, like they do for RPR [rapid plasma reagin, for syphilis], for instance.

Daniel Fierer: Especially for very sexually active men who have sex with men. Active injection drug users, too.

Douglas Dieterich: Even active cocaine users. They don't have to inject.

I think what's also changed in the last five years, Daniel, is the men who have sex with men acute hepatitis C epidemic, which I'll let you discuss.

Daniel Fierer: Until we recognized that there is an emerging epidemic around the world -- and, certainly, in all the large cities in the U.S. -- of sexually transmitted hepatitis C in HIV-infected men who have sex with men, most of the hep C that we were seeing in HIV-infected people was hep C that they acquired quite a long time ago. There was a stable population -- about a quarter million coinfected people in the country -- that had long-term, chronic infection.

We noticed at Mt. Sinai in about 2006 -- and saw in the literature that the Europeans had noticed a few years earlier in Northern Europe -- that there were an increasing number of HIV-infected men who were getting hep C from sex. That recognition has resulted in a pretty clear guideline change in Europe and in the U.S. to recognize and test more frequently.

That's a very important thing to recognize: There is incident hep C now, where that was really pretty rare, unless you were taking care of active injection drug users or very heavy cocaine users.

Myles Helfand: There were initially a lot of assumptions made that, when we talked about sexual transmission in the context of HCV, we were talking about rougher sex, in which there's more likely to be blood contact. How true has that actually been proven to be?

Daniel Fierer: No one knows the exact answer to how hepatitis C is transmitted in sex that happens between men. There are many different kinds of things that happen during sex. The three case control studies that were done -- one we did here, one in London, and one in Germany -- all came up with somewhat different things as their highest risk factors associated with it.

To me, what that suggests is that there are a number of different ways that it can happen. Bleeding -- active, visible bleeding -- is not necessary. The Germans found that [rectal bleeding or pain was the largest risk factor], but that wasn't really found in London or here. I think, sure, if there's a lot of bleeding, that could do it. But we didn't have a lot of bleeding in our patients in New York -- and yet, they got hep C.

When (and How) to Test HIV-Infected Patients for HCV

Myles Helfand: You got a little bit into testing a moment ago. The recommendations changed pretty recently. This was as a direct result of these numbers?

Daniel Fierer: Yeah, exactly: recognition of a new risk group. The old suggestions were a little soft: "If you could be at risk for hep C, then you should test more often." But that didn't work all that well; even people who had injection drug use risks were not being tested frequently enough.

It comes down to: You have to be more conscious of it and do testing more. You have to consider what a risk might be and cast a broader net. We need more frequent testing and more awareness.

Myles Helfand: So, if you're an everyday HIV care provider, should you be testing all of your patients for HCV regularly?

Daniel Fierer: Yes, absolutely.

Myles Helfand: Or do you keep a look out for particular risk factors?

Douglas Dieterich: No, it takes too much time, and there's too much uncertainty -- and also a lack of admitting to risk factors, for the patients. Why even get into that? Just test them. It costs $8 for the antibody test.

Myles Helfand: And the frequency should be once a year? Or more, depending on --

Douglas Dieterich: Probably depending on their level of sexual activity. But officially, once a year.

Daniel Fierer: By comparison, there are no official guidelines for how often you test for syphilis. But if we're in the middle of a syphilis epidemic, and we have someone who is very sexually active, we test them quarterly -- whenever we see them. It's one of those things: You rely on your own clinical acumen, and the acumen of those around you.

I think that we have not done enough HCV tests. I've seen enough patients who have slipped through. You see them three years later and look back and say, "Oh, yeah. They had it three years ago; it just slipped through." There's a lot of that.

Douglas Dieterich: On the other hand, the antibody test is not completely adequate to diagnose somebody who has elevated liver enzymes and is very acutely infected. [It takes at least six weeks for the antibody to develop, sometimes a couple of months.]

People can be antibody-negative in the early stages of disease -- just like with HIV. When that's the case, then you need to bring them back in and either repeat the antibody or do the quantitative PCR for hepatitis C.

Daniel Fierer: The diagnosis of new hepatitis C infections that I've alluded to is tricky. There is no single test, so it is hard. Fortunately, HIV providers are fairly savvy on that. Experienced HIV providers are in a good position to get this, and to know that, if you suspect new infection, then you need to look at virus, for instance. You don't just say [to a sexually active MSM with a sore throat and fever], "Ah, it's strep throat. Go home." You get virus testing.

Douglas Dieterich: I think it's particularly important that HIV docs not ignore elevated liver enzymes. Particularly when they haven't really been elevated before.

Daniel Fierer: Yes.

Douglas Dieterich: That's something that, in large part, many HIV docs have been doing for many years: ignoring elevated liver enzymes without investigating fully what they might be. I think now is a time to start looking for hepatitis C.

You should assume, frankly, that anybody with new liver enzyme elevation and HIV who hasn't really switched their meds has got acute hepatitis C. That would be the number one diagnosis.

Daniel Fierer: I think that's a very good point. A very large proportion of people with a new ALT of, say, 400, may have hep C.

In fact, Doug, you made a couple of good pick-ups when patients have been started on new HIV antiretrovirals. Even in that setting, we've been almost fooled. Some savvy folks have picked up that, although starting efavirenz is known to cause an ALT elevation of 400, the elevations in their patients had, in fact, been the result of new hep C infection, and not due to the use of a new antiretroviral.

Myles Helfand: That speaks to the importance of regular HCV testing, especially when you're starting treatment.

Daniel Fierer: Yes. As Doug said, you can't stress too much that even a low-level ALT elevation can be the very beginning of something; we see this in new hep C infection. Bring them back for more testing -- not in the next three months, but in the next couple of weeks.

Douglas Dieterich: Acute hep C, in particular, doesn't have to have an ALT of 500, or 800, or 1,000; it could just be 100, which would often fall below many providers' radar screens, in terms of following it through and investigating the cause.

Treating Acute HCV Coinfection: A Crash Course for the HIV Care Provider

Myles Helfand: In the context of an HIV-positive patient newly diagnosed with HCV coinfection, what should the HIV care provider do next? Should he or she refer the patient to coinfection specialists such as you guys? To what extent should the HIV care provider be taking on responsibility for the management of that patient's HCV infection?

Douglas Dieterich: If the HIV providers are comfortable treating hepatitis C -- and I think many of them will be, and more so in the future -- they can certainly do this themselves.

We don't have U.S. guidelines; we have European guidelines that we use now for standard PEG-interferon and ribavirin. We'll soon have many more drugs available to us. Daniel's done a study on telaprevir (Incivek) in acute hepatitis C, and on shortening the course even further.

Daniel Fierer: Was your question about acute or chronic? Since we've been talking about acute, want to deal with the acute first?

Myles Helfand: It's probably good to differentiate between the two.

Daniel Fierer: Definitely. With acute hepatitis C, people who treat a lot of hep C are good at it. It's good if you know people in your community who are actively working on it; I think that this is something to try to better understand as an emerging epidemic.

There are not that many people across the country working on it. I'm advocating for more people to do it, to understand this, because sexually transmitted diseases don't just go away, so we need to have a better understanding of what's going on. Clinically, acutely infected people can be treated, and their response rate is much higher.

I think the real question, the big one that is an important one for HIV providers, is: Are there large numbers of chronically infected people? And how do you approach that?

Douglas Dieterich: Yeah. And that, in some ways, is more difficult. There are U.S. guidelines about what, when and where to treat. But with new drugs looming on the horizon, the same sort of paradigm is going on for the treaters of chronic coinfection as was happening for the treaters of chronic monoinfection. We expect two genotype 1 drugs to be approved by December of this year -- both with interferon, actually, and both of which have had early phase 2 studies in coinfected patients.

Of course, there are also telaprevir and boceprevir (Victrelis) coinfected studies, in which they have shown equal efficacy to studies in monoinfected patients. Those drugs are part of the guidelines for treating chronic hep C and HIV patients, though while obviously using very carefully measured drug-drug interaction data. In the past, we've had to change HIV antiretrovirals about 50 percent of the time to treat our coinfected patients.

Side effects from the present protease inhibitors are really tough. I think what we're all waiting for are interferon-free combinations, which will be available in mid-2014 -- from Gilead, a fixed-dose combination pill to be used with ribavirin, and from Abbott a four- or five-drug combination, although that combination has a boosted protease inhibitor in it, which will require some thought in terms of HIV drug-drug interactions.

There are also going to be other medications on the market that could be used with or without these drugs -- off-label combinations with phase 2 data supporting them. It's very unclear how that's going to shake out with the payers -- whether they'll pay for those all-oral combinations, even though they've only been shown to be highly successful in phase 2b trials.

Daniel Fierer: Fantastically successful. I mean, you'd have to say the small daclatasvir/sofosbuvir study curing failures of those who received the first-generation protease inhibitor --

Douglas Dieterich: It doesn't get better than 100 percent.

Daniel Fierer: A hundred percent of failures cured. People who not only failed PEG-interferon, but failed with telaprevir on top of that; and yet, they were all cured. Forty-ish patients, I think.

A slightly controversial subject we're talking about is waiting to treat. I think that's an important topic that's outside of the clinical trials. Patients who are not very sick -- they've made it 25 years now, and we've got two or three years before interferon-free drugs are here -- I've been looking at that situation and saying: If it were me, I would want to wait. It would be very hard to twist my arm into getting treated, almost no matter how sick I was.

Myles Helfand: What do you do as a health care provider in this case? How do you make that decision? What factors do you take into account when you're deciding if it's worth it?

Daniel Fierer: Firstly, let's deal very quickly with the acute infection, just to reiterate what I said before. I feel fairly strongly that the cure rate is very high. It's small numbers [so far in my study, but with] Telaprevir it is about 84 percent within just 12 weeks of therapy. With that being such a high cure rate, reasonably tolerable -- and with the fact that being cured can prevent further transmission -- I strongly advocate for keeping an eagle eye out, finding new infections and getting them treated.

I'm specifically saying: Don't sit on people and say, "Oh, it's a new infection. You'll be fine in three years when we have interferon-free drugs." That may or may not be the case.

Myles Helfand: Didn't you just have a study published about rapid progression in newly-diagnosed men who have sex with men?

Daniel Fierer: We did. There was a study that Doug and I published; there were four patients who progressed very rapidly to death -- and one had a liver transplant -- from two to seven years after their first infection. These, we acknowledge and believe, certainly are exceptions, rather than the rule. We just don't know how much of an exception they are.

So that is a cautionary note: The progression may be even faster when you have HIV first. And if you have AIDS at the time of hep C infection, that might be awful.

You also want to stop further transmissions as much as possible. We don't have evidence the way we have for HIV community viral load in cities such as San Francisco, but there's some evidence that treatment helps lower transmission rates. We don't have that direct evidence in hep C, but I believe that it's a reasonable extrapolation to consider.

So, right now, if you have acute infection, I would still treat, rather than sit on it.

**Douglas Dieterich:**I would agree, certainly, about that. And if they have a rapid virologic response, the six-month treatment course is perfectly rational now.

If they don't have a rapid response, I might be rethinking that paradigm -- you know, the European recommendations.

Daniel Fierer: Of treating longer?

Douglas Dieterich: Yeah, of going to 48 weeks [instead of 24]. Because we'll already be six months into new drugs at that point. It would be hard to justify continuing.

Daniel Fierer: You mean without telaprevir.

Douglas Dieterich: Yes.

Daniel Fierer: There are some other very experienced hep C treaters who are treating acute infections using telaprevir. They've told me, "Yeah, I've been doing this a little bit." In those cases, I think the responses would be very high. And they'll know quickly whether there's a response: They're going to check it by four weeks whether they're in good shape for a 12-week treatment course.

Myles Helfand: And if they're not, then do you strongly consider just saying, "You know what? Let's try again later."

Douglas Dieterich: Right. Wait until January, or next summer.

Daniel Fierer: Right. Rather than keeping someone on it a whole year -- at this point, it's hard to picture giving somebody a whole year of interferon.

Douglas Dieterich: Yeah, it's hard to justify.

Daniel Fierer: Without being able to tell them, "You're going to have an 85 percent or better chance of cure." And that's a segue into our thinking about chronic infection.

Douglas Dieterich: One of the very positive things that we've learned about treatment of chronic coinfection with the new drugs -- we have data now on telaprevir and boceprevir; simeprevir, faldaprevir, the two once-a-day protease inhibitors, which are coming this year or next year; and sofosbuvir -- is that all of them look like their SVR [sustained virologic response] rates will be almost exactly the same as in monoinfected patients.

HIV does not seem to decrease the SVR rate in hepatitis C coinfected patients at all. It doesn't seem to make any difference, like it did before there were direct-acting antivirals. So there's no reason not to treat based on perceived lower efficacy.

Daniel Fierer: I think that's a really important point to bring out to people who may not have been thinking about this since the early days of coinfection treatment -- the APRICOT study and the ACTG study, the really depressing SVR rates with genotype 1, in the 20s or below 20 percent. Now we're looking at something in the 50 to 60 percent range. In the real-life studies here at Mt. Sinai, as well. In fact, the HIV-infected patients appeared to perhaps even do a little better.

Douglas Dieterich: They did better than the monoinfected patients. Probably because they're better at taking their medication.

Daniel Fierer: This is a very different way to think about it. It's important that you shouldn't think: Oh, my HIV-infected patient is just not going to do as well. Well, that's gone. That is not the case anymore.

Treating Chronic HCV Coinfection: When to Start

Myles Helfand: In terms of the chronically infected patient, then, how does that translate to the recommendation to begin therapy? Do you approach it in the same exact way as you would for an acute patient: If you're on antiretroviral therapy and you're doing OK, might as well start the HCV therapy also? Or do you wait until liver enzymes get to a danger place, until you start to see evidence of fibrosis?

Daniel Fierer: In between.

Douglas Dieterich: Exactly. Liver enzymes really have nothing to do with it, in the broadest strokes.

Myles Helfand: HCV viral load doesn't necessarily, either.

Douglas Dieterich: No, it doesn't. It's really fibrosis. FibroScan has been approved in the U.S., so people are beginning to purchase those around the country. Non-invasive liver biopsy for fibrosis.

Daniel Fierer: This is an ultrasound-based, simple test.

Douglas Dieterich: There are also serum tests.

But honestly, I think the epidemiology of hep C and HIV is so clear-cut, in terms of reduction of new age-related infections, reduction of death by liver disease, liver cancer, liver transplant -- all of those things -- that it's really a no-brainer to treat hep C in HIV patients. It really should not require much thought. I think it's not a matter of if; it's just a matter of when, at this point -- whether you're going to wait until next year and use simeprevir or sofosbuvir, or you're going to wait a little longer and then use an interferon-free combination.

Myles Helfand: What would lead you to decide to wait at this point with a chronically infected patient?

Douglas Dieterich: If the patient has very low fibrosis and doesn't want interferon, it's perfectly OK to wait and watch. But the operative word is watch; not just wait. Not just say, "Come back in two years and we'll talk about it then."

Daniel Fierer: Right.

Douglas Dieterich: You have to stay on top of it; keep screening for HCC [hepatocellular carcinoma]. Keep making sure. Particularly if they have hepatitis B markers; you're screening for HCC with ultrasound every six months, and alpha-fetoprotein as often as you feel comfortable doing it. If they have cirrhosis, if it's early, they can probably wait six or 12 months. If it's not early, then you have to treat them now.

If they have lower platelets -- and I think this is an important thing that many HIV docs forget about -- if they have platelets of less than 110, they need endoscopic screening for varices, because variceal bleeding is a real problem. We've still got a 35 to 40 percent mortality rate from the first variceal bleed.

Low platelets in our world mean splenomegaly; it doesn't mean ITP [idiopathic thrombocytopenic purpura] anymore. We hardly ever see ITP in HIV. It's portal hypertension, and you've got to know if they have big varices or not, because we can fix them. We can band them prophylactically; prevent them from bleeding; give them nadolol.

I think that's a really important thing, particularly as HIV providers take over a lot of hepatitis C care. Whether it's coinfected patients or monoinfected patients, they've really got to understand two things. Those are the only two things about liver disease they need to really understand: Screen for HCC and and screen for varices if the platelets are less than 110,000.

Daniel Fierer: As an HIV doc, you need to learn about liver disease. That's not something we're taught, as far as ID training. When you have a [patient with a new hep C] diagnosis, first you want to "stage" the disease. You want to try to figure out how much fibrosis they have. The noninvasive tests are pretty good at telling you "unlikely to have very much," or "likely to have quite a bit." They're not so good in the middle. But if they have quite low fibrosis, then those people can probably wait a couple or three years for interferon-free treatment.

If, on the other hand, they have low platelets, even if their PT [prothrombin time] is not elevated, even if their albumen isn't low -- once those things happen, you've got very serious liver disease, so you've got to recognize that and not write it off to HIV infection. It could be subtle; a little bit below the normal range is not good. You really have to be savvy about that.

Things that we got used to [in the AIDS era] -- our patients, oh, they're so sick! They have so many abnormalities; they're pancytopenic; this, and this, and this. You have to reregister that when thinking in terms of liver disease: "Wait a minute, this might be bad liver disease. I need to look."

Douglas Dieterich: And your screening for HCC needs to go to MRI or CT scan, not just ultrasound, because it's not adequate. People have a much higher risk. People who have cirrhosis, they're the ones with the higher risks.

Daniel Fierer: The guidelines aren't going to tell you that [you need to perform a CT or MRI]. When we see some cellular carcinoma disease in our own patients, it's quite treatable in its early stages; if you get it small, you can get rid of it.

Myles Helfand: But if it's not in the guidelines, do we have reimbursement concerns here?

Douglas Dieterich: No. It's in the guidelines for the care of HCC. HIV doesn't disqualify you for guidelines for the treatment of hypertension or any other disease. I think it's perfectly rational.

Daniel Fierer: Right. The guidelines say screening with ultrasound. They don't say in it, "Oh, you need to use MRI." But I think that you can justify it to the payers. I've had some say, "You've got to do the ultrasound first," occasionally. But MRI is a better test, so you do what you can do. We try to get the best care for the person in front of us. I feel strongly about that.

Douglas Dieterich: The cost is actually relatively minimal, compared to the cost of a liver transplant, if that's even possible. It is possible in HIV patients, certainly, but it's very hard to get livers nowadays. At least a third of the people will die waiting on the liver transplant list. So that's not something you can count on.

Treating HCV Coinfection: What to Prescribe

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.

HCV Therapy: When Do You Stop?

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.

Everyday Patient-Management Tips for the Care of HIV/HCV-Coinfected Patients

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.

Framing the Message

Myles Helfand: I'll close with a general patient management question: What do you tell your newly diagnosed patients about their prognosis? About what they should be expecting to experience over the next few months?

Douglas Dieterich: In terms of the treatment of hepatitis C, what I tell my patients is that it's a really good time to have hepatitis C. There are about 30 new drugs on the way. We're almost certain to be able to cure your disease at some point in the very near future.

In terms of the acute hep C, Daniel, I'll let you take it for those recommendations.

Daniel Fierer: I think the idea is to try to get people treated really early. I can say the same thing to the patient: that the chance of cure, right up front, right now, is extremely high. It's close to 90 percent, I'd say, in our hands here. And the few people who aren't cured here, they will be in the same boat of having really great drugs in a couple of years. So this is a great time to have hep C. If you can have it now and not be super-sick from it already, then we're really going to be able to get people cured.

To reassure people: I think there are probably very few people who can't wait six months [to start HCV treatment]. We know about those people already, probably. They're clinically sick.

Douglas Dieterich: There may be other reasons that people want to be treated, and not just for the severity of their illness. Social reasons: They're getting married; they want to have a kid; they're leaving the country; they're changing insurance; they're getting Medicare and there are donut hole issues; while they have good insurance, they want to be treated now; etc. There are lots of social reasons to be treated now.

But there are probably not a lot of medical reasons. We're treating almost everybody now, compared to what we were doing two years ago.

Myles Helfand: It's an important point: That as clear as the clinical realities are, there might be social things that you need to get at as a provider in order to be able to really tease out whether the person is a good candidate for starting -- and whether, when they start, they will stick to that treatment until the course is complete.

Daniel Fierer: We believe most everybody now is a good candidate. The days of over-scrutinizing who might be a good candidate are over. As the amount of interferon decreases and the treatment effectiveness goes up, everyone becomes a good candidate.

Myles Helfand: Thank you both.

This transcript has been edited for clarity, grammar and length.

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Myles Helfand is the editorial director of and

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