Clinical Education Initiative HEPATITIS C AND HIV CO- INFECTION. Speaker: Kelly Ramsey MD

Transcription

1 Clinical Education Initiative HEPATITIS C AND HIV CO- INFECTION Speaker: Kelly Ramsey MD 5/2/2018

2 Hepatitis C and HIV Co-infection [video transcript] [00:00:05] So, it's, this is a very quick presentation today. If anyone knows me, I usually have a lot of slides. So, I'm going to, I was able to limit myself and we're just going to run through these. As you can see my title slide, I'm the medical director of substance use disorders at Hudson River Health Care. I treat HIV, hepatitis C, and opioid use disorder with medication assisted treatment. I don't have any disclosures. So, the learning objectives for this talk are describe the epidemiology and prevention of hepatitis C, discuss the screening and diagnostic workup of hepatitis C, and describe the clinical management for hepatitis C and HIV co-infected persons. First we're going to talk about the epidemiology and prevention. So, here's a very simple chart showing a comparison between HIV and Hepatitis C. So, what the viruses are, how they're most commonly transmitted. Both of them are rapidly producing viruses, so both have high levels of viremia. Where they target the cells, so, for HIV in the CD4 cells and in hepatitis C in the liver cells or hepatocyte. They both have frequent mutations. The clinical illness, time to clinical illness for HIV, it is years and for Hep C it's it's decades. So, often, unfortunately, people with hepatitis C are completely asymptomatic and unless they're tested have no idea they have hepatitis C. There is a nuclear reservoir for HIV there is not for hepatitis C, that has helped us to find a cure for hepatitis C. And as we know regarding the curability we can manage HIV we cannot reasonably cure HIV. [00:01:49] Obviously there's one cure after a bone marrow transplant but that's not a feasible solution for persons with HIV. And, as we know, with all our direct acting antivirals for hepatitis C our cure rates are all now well above 95 percent. This is going backwards. Anyway, so transmission of hepatitis C. So, the most efficient route of transmission is parentral routes. So, any kind of injection drug use and that includes all the paraphernalia used for injection drug use, so cotton, cup of water, needle and syringe. I can also be transmitted via sniffing and skin popping and and remember with these it's important that it does not take visible blood. It could just be microscopic blood exposure. There's perinatal transmission, so vertical transmission from a pregnant woman to her fetus is about 5 percent, and that's usually during the birth process. And then we also know about sexual transmission primarily through anal intercourse and it's been documented most consistently in the MSM population. So, transmission risk after a needle stick. So, with hepatitis B, there's a 30 percent chance of transmission for hepatitis C, it's 3 percent. Little bit of variability, 1 to 3 percent. And with HIV, 0.3 percent. We know that both of these diseases have a high burden worldwide. So, you can see for hepatitis C the burden is a lot higher than actually for HIV and there is an overlap between the two patient populations, about 20 to 30 percent of people will have both HIV and hepatitis C. So, what is the significance of having a co-infection? [00:03:32] So, it is important to identify persons with HIV who also have hepatitis C because they have an increased susceptibility to mucosal transmission and decreased rates of spontaneous clearance of hepatitis C. They also have a more rapid course of progression of liver fibrosis and higher rates of cirrhosis relatively speaking compared to hep C mono infected persons, and they have higher rates of l iver decompensation and higher rates of mortality due to liver disease. It's a very complicated process of 1

3 the interaction between HIV and Hep C and I'm not going to go into the details of this graphic. Certainly, you can look at it on your on your own. But, we can see that there's a complicated interplay between a variety of cytokines et cetera. So, the prevalence of hep C in the United States reported is approximately up to 4 million. But, as as we can see this is an underreporting of the true prevalence which is more likely in the range of 5 to 7 million and growing, as we know, due to injection drug use associated with the opioid epidemic. So, why is there a gap between what we have as reported values for prevalence and what we know to be the true prevalence. And that's because we have a failure to count a variety of patient populations including the homeless, those who are incarcerated, those who are undocumented, nursing home residents, hospitalized patients, military personnel, and people who are injecting drugs, and or people who are using drugs. So, there's a relative under diagnosis of hepatitis C. You can see that with HIV we've done a pretty good job of identifying those with HIV, with Hepatitis B we haven't done such a good job and that's because I think there is low knowledge level of chronic Hepatitis B in this country comparatively to other places in the world where it has a higher prevalence rate. [00:05:36] And then you can say with hepatitis C we've done a very bad job of actually diagnosing persons with it. So, this is a treatment cascade for chronic hepatitis C in the U.S. This slide is a little dated I haven't seen a more updated one recently. But my my expectation is that for the percentage of those who are actually treated and cured that we're going to see those cure rates go up, quite a bit, with the DAA's. What We do see is that part of the problem is we know that there's a large pool of chronically infected people with hepatitis C and as I mentioned a lot of those folks are not getting diagnosed but even those folks that do get diagnosed often are not linked successfully to care. You can see that only about half of people actually receive a confirmatory hep C viral load to determine whether they have spontaneous clearance of their hep C or have chronic hepatitis C. The liver biopsy in this cascade is moot at this point, we really, rarely need, if ever, need to do a liver biopsy; I have not refer a patient for liver biopsy in years. And then this is a graphic that's looking at the hep C treatment cascade in dual diagnosed folks, so, folks in both HIV and hepatitis C at one particular clinic at UCSD. And you can see again the cure rates pretty poor. Now again, this this is an old slide meaning we don't have updated data showing charades in populations looking at duly infected folks. My expectation, again, is that folks would have a higher uptick to accept treatment and higher cure rates with more therapies. [00:07:18] So, what can we do to prevent hepatitis C in people who inject drugs? So, we have lots of points where we can intervene and hopefully prevent acquisition of hepatitis C. So, before exposure, obviously that's making sure that people are counseled on harm reduction strategies to prevent hepatitis C acquisition and that people are tested appropriately and counseled appropriately if they are infected on how to avoid passing it on to others. If people are open to and want substance use disorder treatment, then obviously that's an effective means of addressing as well. Harm reduction again, so reducing transmission from other positive people to them if they're sharing works with people, and then vaccinating certainly with hepatitis A and B, unfortunately we don't have a vaccine for hepatitis C yet but maybe in the pipeline. So, at the point of transmission, really important to do harm reduction education with folks make sure that they change the way that they're injecting, sniffing, smoking, et cetera; So, not 2

4 sharing any drug paraphernalia. Again, most folks have gotten the message about not sharing a needle and syringe, but sometimes the other aspects of drug sharing behaviors are lost on a lot of people who are either sharing impliments for sniffing, or for smoking, or they're not sharing needle and syringe, but they're sharing cotton cooker and water. Making Sure that folks have access to clean drug paraphernalia, so whether that's at syringe exchange programs, or at pharmacies, or writing prescriptions for people for needle and syringes. And then safe injecting sites, which certainly are commonplace in other parts of the world including Canada, most of Europe, and Australia, but not yet in the US. Hopefully, we will be seeing some safe injection sites piloted in the U.S. in the near future. [00:09:15] And then after exposure really important again we don't test people enough and then often we test them as far as the antibody, but we don't do a confirmatory viral load. So, making sure that people are tested and referred appropriately and then that we are treating everybody with hepatitis C with the DAA's. So, as I mentioned briefly we are seeing a huge increase in incidence of hepatitis C infections because of the opioid epidemic. So, this is a graphic from about three years ago that looked at increases in hepatitis C virus related specifically to injection drug use among persons less than 30 year olds. And again, I think historically, we thought of the urban population but, as you can see from this slide, in this population it was primarily in the non-urban population. So, now we certainly have patients injecting in urban, non-urban, and rural populations. This is another graphic again similar to the last one showing the trend in non-urban young persons who inject drugs. So, I think everyone's pretty familiar with the huge surge in overdose deaths primarily due to opioids. And this graphic goes through 2016 which is where we have the latest data and you can see the sharp spike related to dust, due to synthetic opioids, primarily illicit fentanyl and due to heroin. So, this is just sort of to show you the complex mileu that you see with hep C co-infection and HIV positive MSM via sexual transmission. [00:10:54] So, it's a combination of the patient's HIV characteristics related to viral load and CD4, use of aids during sexual experiences, so that could be with crystal meth, sildenafil, which is Viagra, or with amyl nitrate or poppers, which increase suceptability to, let's say riskier sex practices. And then in the third bucket, it shows that patients are often engaged with multiple partners using a variety of sexual practices, and then if they have another STI, that can certainly make them more susceptible to getting either HIV or hepatitis C. So I'm going to quickly go through the screening and diagnostic work up for hepatitis C. So, I think everybody is familiar that the CDC guidelines changed, so, instead of doing a risk based screening now we recommend that everyone born in the birth cohort, born between 1945 and 1965, is tested because there is high prevalence in that birth cohort group. And then all other folks will be test based on their risks, so, that would be any history of any drug use. There are specific other groups related to haemodialysis or receipt a variety of blood products, which I'm not me go into in detail you can look at the guidelines specifically for that. I would say anybody who has HIV, any children of an HIV infected mother, or if someone has elevated liver functions that just don't have a good explanation. Folks that have been incarcerated, I know I here where I practice everybody who is in enters into the jail is tested for hepatitis C, again just an antibody not with a viral load. 3

5 [00:12:40] So, it's really important that folks coming out from incarcerated settings would also be tested for hepatitis C. And then yes if someone's receiving tattoos or piercings in any kind of an unregulated setting, and includes while they're incarcerated, we would want to test them. So, this echoes what I mentioned at the beginning of the presentation, that for every 100 people diagnosed with hepatitis C at least 40 percent of them are not referred for appropriate follow ups and never receive that confirmatory Hep C viral load or are linked to persons who are going to actually treat them for their hepatitis C. So, this is a graphic showing Hep C testing algorithm. It basically takes you through the process that you would need to do to confirm if somebody has chronic hepatitis C. So, first testing with the antibody and then depending on what that results shows, if it's non-reactive and there's no suspicion that this person could have acute hepatitis C when, the anybody might not yet be positive, then you will be done. And if they have no ongoing risk factors then that would be the one time test that they would get. If it is reactive then you need to confirm that with a hep C viral load. So, if it's not detected, I always repeat it again, in six months, so I have two separate viral loads that are six months separated in time both showing a non detectable viral load, and then I would confirm that that person had had an infection in the past that they had cleared spontaneously. If the RNA is detected, that may have a current active hep C infection and we would link them to care if you are not going to treat them yourself So, the initial workup for chronic hepatitis C is comprehensive and it has several aspects. [00:14:29] There's assessing both the patient and the virus, so, things that you would do with any patient, you going to do a physical exam, you're going to do appropriate labs, which are listed here and I'm not going to go into detail. You do labs that are specific for the virus, you want to determine their hep a and b status, vaccinate as appropriate. Their HIV status if this were not known in HIV infected patient, and then they may get their Hep C genotype subtype viral load. You need to do fibrosis staging on any patient that's diagnosed with hepatitis C. Different clinic sites may have access to different modalities to do that. There are several validated tests through most of the commercial labs. You may have FibroSure, FibroTest, HepaScore, FibroSpect, any of those are all are appropriate. You can do, just take lab data and then use an APRI, FIB-4 or an AST/ALT ratio, again and to give you an estimate of cirrhosis versus not. And then if you do get back scores that would lead you to believe that this person has advanced liver fibrosi, such as of F3 or F4, then you would want to refer, if you have access to it, to FibroScan, which is using either ultrasound or MR elastography. Again to assess the degree of fibrosis. If someone comes back with F3 or F4, regardless of whether you treat them or not, regardless of whether they share their hep C or not, you're going to be monitoring them and screening for liver cell carcinoma every six months for the rest of their life with an ultrasound, a CT, or an MRI depending on the patient. You're going to do education in harm reduction with your patients and that includes educating them on how to prevent transmission. [00:16:10] So, again, not sharing drug paraphernalia as we previously discussed, but also not sharing any kind of personal hygiene items such as razors, toothbrushes, nail clippers. You're going to educate on safer sex practices. You need talk to all people about reinfection, reinfection is not common, but it does happen and if you're certainly treating an active drug use in population you don't expect reinfections. 4

6 And the only way that we're going to limit how much our incidence rate is for hep C in this country, is if we do treat people who are actively using drugs. And if you're not getting any more infections then you're not reaching people who are actively using drugs. So, we do talk about avoiding reinfection. We need to always reassert harm reduction education. Again, if people have opioid use disorder, you want to offer treatment if they're ready and asking for treatment. If people have an elevated BMI, and I suspect fatty liver or I get an ultrasound that shows fatty liver, I'm going to talk to people about diet and weight loss. And then, again, if someone is an active substance user, to me, I treat anybody; if they can show up at an appointment with me and get labs, then I treat them. The cure rates are exactly the same in people who are actively using on treatment, actively using not on treatment, and regardless of what drug they're using. So, we know that that people want hepatitis C treatment and they are capable of taking hepatitis C treatment, regardless of whether they're using or not. Though I certainly would offer treatment for their substance use disorder if they were interested in that. It's really important to immunize, so we already talked about hep A and B. [00:17:49] But, I also give people influenza vaccine yearly and I make sure they're up to date on their Prevnar, Pneumovax, and Tdap, particularly if they have more advanced liver fibrosis I'm going to push that pneumovax and Prevnar harder. And then, psychosocial, certainly this has gotten much easier in the era of the DAA's. Therapies are shortened duration and they are well tolerated, but we talk adherence with everybody, I talk about the cost of medications with everybody, and we offer social support during treatment from our care managers. So, I'm going to move into the clinical management of HIV and hep C, and I'm going to go really quickly through these slides because the important thing for you to notice is regardless of what regimen you use the cure rates are the same for co-infected persons as they are with mono-infected persons. So, I'm not going to dwell, we're just going to quickly look at these and see that all our rates, pretty consistently, are 95-ish or above. Regardless of which regimen you're using. So, these are in the slide decks you can look at them in more detail, but I just wanted everyone to get a sense that the meds are effective and they work for co-infected persons. The one thing I think is important to be aware of is there are some drug drug interactions between the DEA, the DAA's and ART. And so, it's really important to use one to have a variety of tools that you can access easily online. You pop in your medications and just make sure that they're on drug drug interactions. And generally, there's going to be a regimen that you use for your patient, regardless of what their genotype and subtype are. Sometimes you do have to change their regimen that they're on but often you're changing into a better regimen. [00:19:38] So, I think that that hasn't really been an issue, at this point all my co-infected patients were treated at least three years ago. And I changed a few people to get through their course of treatment and then we usually ended up staying on the on the new ART regimen. And then, you know, why is this important? Why do we want to cure hepatitis C in all of our patients? So, obviously when I was talking about people who actively use drugs, we're talking about a public health benefit. So, we want to have a lower transmission rate out in the community and we want to have just a lower pool of hep C out there. But, there's also the individual health benefit. So, they, clinically, they improve. You have decreased 5

7 rates of cirrhosis, you have decreased rates of decompensation with cirrhosis, you have decreased rates of hepetocelluar carcinoma. But, again, not eliminated. And all folks, whatever they staged had before Hep C treatment, even if you think their fibrosis improved with treatment. If they are a three or four, you need to continue that hepetocelluar carcinoma screening for their lifetime. You have decreased rates of transplantation, decrease all cause mortality, decrease risk for diabetes mellitus type 2, and decreased other other hep C related complications, such as cryoglobulinemia, and have an increased quality of life for patients. Often patients will tell me that they didn't think they had any symptoms from their hepatitis C but after they, we cure that they actually noticed less fatigue, less brain fog, and they just feel better when they didn't even realize they didn't feel bad. So, that's certainly a plus. [00:21:21] So, couple summary slides and then we'll turn it over to the case. So, first of all the treatment summary slide. So, as I mentioned HIV co-infection no longer adversely affects Hep C treatment outcomes. So, I think this is really important because this is very different from the era of interferon. And so, on SVR rates, so sustained virologic response rates, I=in co-infected patients are equivalent to those in hep C mono-infected patients. Of note, is that an eight week regimen with Sofosbuvir/Ledipasvir which is brandname Harvoni, is too short for HIV hep C co-infected persons. So, there were lower SVR rates in the eight week regimen for those persons. You can do an eight week regimen in hep C the mono-infected persons who have a viral load less than 6 million, but that is not the case with co-infected persons. And what we think so far from the data is that an eight week regimen Glecaprevir/Pibrentasvir is likely adequate for co-infected persons. So, that's the brand name Mavyret which is a lot easier to say. And then, you know, early in the studies they were saying that people should be on ART and virially suppressed, and stable for eight weeks before starting hep C treatment. But, we really don't think that that's necessary. And I have patients who, I have a minority of patients, but I have a couple patients for example who are long term non progressors. And just don't want to be on ART, not willing to take ART, but they were willing to take hep C treatment and so they cured just like my other duly infected patients. The last slide. [00:23:08] So, in conclusion, we know the hep C continues to be underdiagnosed and undertreated. We know that there are new epidemics of HIV hep C co-infection occurring both among IDU and HIV positive MSM. So, it's really important that we do adequate harm reduction education with our patients. We know that hep C treatment with the DAA's is well tolerated and efficacious. And as I mentioned, equivalent SVR rates between co-infected and mono-infected patients. All HIV positive persons should be tested for hep C minimally, annually. Elevated LFT's or reported risk factors should prompt testing or action more often than that. Fiberosis staging must occur and all hep C positive persons and ongoing hepatocellular carcinoma screening for F3's and F4's must continue status post SVR. And then drug drug interactions between the DAA's and ART are potentially significant. So, consult one of the online tools know, the person's ART history, and know their HIV resistance testing before starting them on hep C treatment. And then I have a side of resources as well need if you need it. [end] 6