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HIV Management In Depth

HIV/HCV Coinfection Update: From Testing to Treatment

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

June 19, 2013

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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.

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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.

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Reader Comments:

Comment by: patricia (Concord, nc) Thu., Oct. 10, 2013 at 2:19 pm EDT
Doug you have been hiv pos. since 1981, what is your regime.
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Comment by: Terry (SF) Mon., Aug. 19, 2013 at 12:29 pm EDT
Perhaps the answer is not really more testing, but a return to the normal standards of mom and dad with God's rule in the heart. Why get sick? Why die?
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Comment by: Doug H (rural MN) Mon., Jul. 8, 2013 at 2:20 pm EDT
My doctor told me I had Hep. non A - non B in 1986. We tried several injections of gamma globulin and interferon through 1991. The liver enzymes were controlled. In about 1998 after returning to MN, physical symptoms appeared. A biopsy was done and I was diagnosed w/stage III Hep. C. After 15 months of Ribavirin and Alpha Interferon (hell!,) I've since been Hep. C free.For a variety of reasons I wasn't tested for HIV until 1987. I started HAART W/Trizivir, in 2000. HIV loads have been undect. w/cd4s mostly and still 1000-1200+. We estimate initial HIV infection to be c.1981.
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Replies to this comment:
Comment by: r.morales (walla walla) Tue., Sep. 17, 2013 at 5:17 pm EDT
wau 1000 to 1200 is fantastic congrats.


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