Managing HIV/AIDS Therapy in Special Populations What are the treatment considerations for HIV patients coinfected with hepatitis C?
	Enlarged Version of Graphics Below	Dr. Kwakwa (OC): We are not finding an increase, but we have a fairly large percentage of our population with hepatitis C to begin with; I would say about 70%. Dr. Bellos (OC): Approximately 85% of those patients will need therapy to clear their hepatitis C, whereas 15% will ultimately clear it on their own. Dr. Wohlfeiler (OC): HCV is generally a more dangerous infection, a more serious infection. It's definitely a much tougher infection to treat. We don't have the benefit of well-tolerated oral medications that are going to suppress hepatitis C. Treatment of hepatitis C involves interferon in combination with ribavirin, which are both medications that have a lot of potential side effects associated with them. Dr. Kwakwa (OC): The hepatitis C treatment outcomes are better with higher CD4 counts, so with those who are diagnosed earlier, they may have higher CD4 counts to begin with, and the decision is often made to treat the hepatitis C then. For the majority of our patients who come in with fairly low CD4 counts, the initial strategy is to reconstitute the immune system with antiretroviral therapy, and then treat the hepatitis C when that is done adequately. Announcer (VO): In patients with HCV and HIV coinfection, there is a greater potential for drug-drug interactions and additional toxicities developing. The DHHS guidelines recommend avoiding using ddI and AZT with ribavirin. Patients must be monitored closely for hepatotoxicity from their HAART regimen, as well as for neutropenia and anemia from their HCV therapy.   See Slide Dr. Wohlfeiler (OC): You obviously want to use antiretrovirals that are going to have less liver toxicity. The ones that have more liver toxicity, we associate more liver toxicity with medications like nevirapine and a number of the protease inhibitors like lopinavir, certainly some of the older protease inhibitors that we tend not to use as much. Dr. Wohlfeiler (VO): Probably with regard to the PIs, the most liver friendly are going to be nelfinavir, atazanavir, and fosamprenavir. And so you would probably tend to want to try to design a regimen utilizing those proteases.   See Slide Dr. Bellos (OC): With respect to hepatitis C, in addition to the nucleoside analogue toxicities that one can see, one also has to worry about potential hematologic toxicities that can occur with the pegylated interferons, such as anemia, thrombocytopenia, and neutropenia. So those would affect what drugs one would initially start therapy with, if this was a naïve patient. Dr. Bellos (VO): With respect to hepatitis C, my goal is generally initiate therapy for a patient's HIV infection, and then initiate therapy for their hepatitis C. I figure I have a little bit more time with respect to their hepatitis C, since the likelihood is that they may have had it as long as or longer than their HIV infection, and for that reason, I would like to get their HIV infection under control, so that I can attain maximal immunologic benefit, because what will happen with interferon is that I will drop their T-cell count, simply because it is a side effect of the interferon, and so, I would like to have their T-cell count as high as I can prior to the initiation of the interferon therapy.   See Slide Dr. Wohlfeiler (OC): The other thing is that I always tell patients that even though these medications can be difficult to tolerate, if I knew that there was a 90% likelihood or greater of eradicating hepatitis C infection, of curing, then it would almost always be worth trying to get through the treatment. The reality is that the success rate isn't anywhere near 90%. And so you really have to again do this balancing act of is it worth it to put the patient through treatment that's going to be often a year's duration if you're not likely to get a good outcome. Dr. Bellos (OC): One of the common things I see in patients that are referred to me for their hepatitis C is that their dosages of pegylated interferon or ribavirin have been reduced because of toxicities. As you reduce those doses, the efficacy of therapy is going to be significantly less, and so, when I have treated those patients, we've actually had a better response, because I have not reduced the dose, and have used the growth factors in combination with pegylated interferons, and patients seem to tolerate that relatively well. Dr. Kwakwa (OC): With the hepatitis C coinfected patients, we use all of the antiretroviral agents. The intensity, the frequency of follow-up may be a little bit different. Dr. Kwakwa (VO): We may see the patient more frequently. We may check their liver function tests more frequently. We may call them at home more frequently, to see how they are on the medication.   See Slide Dr. Kwakwa (OC): All of the medications are potentially hepatotoxic, and so there isn't a single medication that I would say I do not use in the person with hepatitis C coinfection. Now, in the person who is on treatment for hepatitis C coinfection, it's a different story. There are medications such as ddI that I would not use, or AZT that I would use with caution. Dr. Bellos (OC): The other thing that I think people have to be careful with is that you can get acute exacerbations of both hepatitis B and C when one initiates antiretroviral therapy, and I think what has to be very careful about that, because you can have profound liver disease, even to the point of fulminate liver failure in those patients. Dr. Wohlfeiler (OC): I think that the main thing that you use in terms of criteria is really looking at a liver biopsy. I think that people really have to have liver biopsies because you can look at markers, you can look at transaminases and hepatitis C viral loads, but they aren't really very good prognostic indicators. What you really need to do is you need to see tissue and you need to see how much inflammation, whether they've started to develop fibrosis and so forth. And I've got plenty of patients who have hepatitis C, but on their biopsies they're minimal disease. They're grade 1, stage 0 and so forth. Those patients I'm not worried about sitting and monitoring them. Patients who have more aggressive hepatitis C that is really pushing them to fibrosis and cirrhosis, those patients I think that you really have an obligation to try to get them on to treatment. And even if it's not going to be curative, hopefully it will give them benefit and delay progression. Dr. Bellos (VO): We will obtain a baseline viral load, hepatitis C viral load, and we will also obtain a genotype for their hepatitis C. If the patient happens to be genotype 1a or b, then we will proceed with liver biopsy on those patients, so that we will have baseline histology prior to the initiation of therapy. In coinfected patients, I think one has to remember that the likelihood of response to a genotype 1a or b is about 30% in those patients, if the patient's hepatitis C is the genotype 2 or 3, we generally just initiate therapy on those patients, because their likelihood of response is relatively good and the important caveat that-I think our "pearl," if one would consider that an appropriate term-is that one does not want to dose reduce either the interferon or the ribavirin, because as you dose reduce either one of those, the efficacy for your therapy for hepatitis C is going to decrease.   See Slide Dr. Bellos (OC): So the goal in terms of managing those patients is to use growth factors to maintain hematologic stability of those patients, using either G-CSF or recombinant erythropoietin to maintain their hemoglobin, hematocrit, and white cell count. Dr. Wohlfeiler (OC): In patients who are on treatment with interferon you need to be able to monitor frequently. I would say initially you probably want to monitor them every couple of weeks, and then certainly at least every four weeks after that. Dr. Kwakwa (OC): ...We would typically check with lab work about two weeks after they initiate therapy. If they have been started on a nevirapine-containing regimen, which I tend not to use as much in people with hepatitis C, then we would follow them up within a week of initiating therapy, rather than two weeks. Dr. Wohlfeiler (OC): Maybe the only other issue is that I think that there needs to be better hepatitis C education out there, especially in the gay community. It's always been stated that hepatitis C has got almost no sexual transmission component to it. But I know that in my gay population where I have a lot of patients coinfected with hepatitis C, I know that the vast majority of them have never used IV drugs, did not receive blood transfusions, those kind of traditional ways of getting hepatitis C.
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