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Melanie Cole (Host):  Historically, patients with HIV were excluded from liver transplant programs. But with the introduction of highly effective antiretroviral regimens, HIV may no longer be a contraindication. Welcome to UAB Med Cast. I’m Melanie Cole and today, we’re discussing HIV positive liver transplant. Joining me is Dr. Robby Cannon. He’s the Director of Liver Transplant Surgery at UAB Medicine. Dr. Cannon, it’s a pleasure to have you with us today. Before we get into this, tell us a little bit about the state of HIV today and what was historically, the situation for organ transplant issues?

Robert Cannon, MD (Guest):  Yeah, well thank you for having me. Well you know, in the early days, when it first came out and was discovered, we really didn’t have a good understanding of HIV and treatment options were limited. So, that really made it a contraindication to transplant because we just weren’t sure how the patients were going to survive in the first place. Then, once we started to develop more effective antiretroviral therapy for HIV, there was still fear that after transplant, we’d have to intentionally weaken the immune system with antirejection medicine to prevent rejection. And there was concern that that would cause the HIV to get worse. So, the introduction of treatment still didn’t sort of allow for access to transplant for people living with HIV.

As time as gone on, we’ve developed better antiretrovirals for HIV that don’t have interactions with our immunosuppression regimen, so the dosing doesn’t have to change. And we’ve seen that the antirejection medication regimen after transplant does not cause any issues with the HIV infection as long as patients are on a stable dose and stable regimen of their antiretrovirals and have their disease well controlled. We found we can actually have very good outcomes in patients with HIV that are actually equivalent to those seen in patients without HIV. So, now we’ve sort of come full circle to where once it was an absolute contraindication to transplant, then we started transplanting patients living with HIV and we had worse outcomes and now we’re at a place where the outcomes are actually equivalent and now we’re moving forward in trials actually looking at using donors who are infected with HIV as a way to expand the donor pool and give increased access to transplantation for our patients who are living with HIV.

Host:  Wow, that is fascinating. So, is it already possible Dr. Cannon to define the group of patients who will do as well as other non-HIV infected recipients for liver transplant and will simple changes to the selection of candidates improve outcomes further?

Dr. Cannon:  It is. And many patients now on HIV, the antiretrovirals have become so good that many patients can achieve an undetectable viral load. And that’s what we need for transplants. Furthermore, we also – there’s a regimen known as an integrase inhibitor, that’s a class of drugs for HIV and those are ones specifically that don’t affect our immunosuppression dosing. So, here at UAB, and actually in many centers, we would look for patients who have stable with undetectable viral loads on an integrase inhibitor based regimen. Those patients should do as well as patients who don’t have HIV particularly, one other concern was we saw higher rates of coinfection with hepatitis C in the past. There were worse outcomes with those patients who were coinfected with HIV and hep C. We don’t have as good of data on that now, but I suspect that now that we’re actually able to cure hepatitis C as well, I suspect even that will no longer become a sticking point in terms of worse outcomes.

Host:  So, where does poor adherence to treatment, drug resistance in potential organ donors pose a threat to organ recipient outcomes? Are you transplanting HIV to HIV or clear livers to HIV? Explain a little bit about the donor process.

Dr. Cannon:  Sure. So, donors right now, essentially a donor with HIV historically has been a contraindication to donation. With the enactment of the HOPE act recently, HIV to HIV transplant has become possible and allowed by law. But of course, these donors will only be available to patients who already have HIV because it’s not curable as it is for hepatitis C. And this is being done in the context of NIH sponsored clinical trial known as HOPE in Action. So, it’s not routine practice for HIV to HIV transplantation but as we settle out these issues, in this ongoing clinical trial, the hope is that one day, that as well will become a routine practice.

Now in terms of transplanting the recipients who have HIV with a donor who does not have HIV, that is routine clinical practice now and it’s done outside of clinical trials.

Host:  Tell us a little bit more about the HOPE Act and how that changed the landscape of the work that you do for organ issues in HIV patients.

Dr. Cannon:  Yeah so, the HOPE Act essentially, I mean it was in many ways a game changer in the terms of transplantation for patients with HIV because it was again, it was actually illegal to use donors who had HIV prior to the passage of the HOPE Act. So, but now that we know again, a much better therapy for HIV, it is now legal, and we can use those donors who have HIV and it’s just a way to increase the donor pool and give increased access to a patient population with HIV whose historically been disadvantaged.

It's early enough in our experience with HIV to HIV transplant. We don’t know how many additional donors a year will become available because of this and estimations run probably about 500 to 600 a year additional donors available to patients with HIV for transplant as a result of the HOPE act.

Host:  That’s so interesting. So, tell us a little bit about your outcomes, what you’ve seen, where do you think that this is going Dr. Cannon and how exciting is it for you physicians on the frontlines of this kind of exciting acceleration to help people with HIV that need a liver transplant?

Dr. Cannon:  No, it’s very exciting to us and I think as I allude to earlier, I think the outcomes are no different anymore than patients who don’t have HIV. So, what this really becomes now and we’ve seen this with several diseases, we’ve seen it with hepatitis B, we’ve now more recently seen it with hepatitis C and now we’ll see it with HIV, that things that were once considered contraindications to transplant or associated with much worse outcomes; as the therapies and medical management of these diseases get better, they all of the sudden just become routine and we’re able to routinely offer transplant for patients who were previously disadvantaged and it just allows us to help more people and offer the lifesaving benefits of transplant to more people who need it.

Host:  And what would you like to see Dr. Cannon as far as the liver transplant community and their response to this challenge and the use of the currently available evidence which seems to be really updated and changing all the time to help in the selection criteria, and with outcomes and rejection and adherence after the fact? What would you like to see changed or what do you think the liver transplant community can do to help accelerate these changes?

Dr. Cannon:  You know I think the liver transplant community has really caught on. I think the key is just in driving referral. I think still in the community there’s still this perception again, because of our past practices, that you may have a patient who has HIV and end-stage liver disease, but you may not refer the patient because you don’t think they are a candidate. So, I think that’s what’s on us as liver transplant physicians is to really sort of spread the message that heh, we are willing and able to transplant patients with HIV. Please refer them to us. And it is not a contraindication and we can proceed with them as we would for any other patient for transplant and they shouldn’t be disadvantaged anymore.

Host:  What a fascinating field of work that you’re in Dr. Cannon and thank you so much. Before we wrap up, do you have any final thoughts for other providers? You’ve mentioned referral. Is there anything else that you’d like to add or what you see happening on the horizon?

Dr. Cannon:  No, I mean that’s the main thing again, and I said, anyone who has end-stage liver disease please send them to us. We’d be happy to see them. It does not – the burden of kind of deciding whether someone can be transplanted or not really doesn’t need to be on the physicians in the community. They don’t need to have to make that decision. We’re happy to see anybody and give our best shot at transplanting anybody who can qualify and again, HIV is no longer a contraindication and really should not adversely affect someone’s chance of transplant as long as they are well controlled.

Host:  Thank you so much Dr. Cannon for joining us today. This has been UAB Med Cast. A community physician can refer a patient to UAB Medicine by calling the MIST line at 1-800-UAB-MIST. For more information on resources available at UAB Medicine, please visit our website at www.uabmedicine.org/physician. Please also remember to subscribe, rate and review this podcast and all the other UAB podcasts. I’m Melanie Cole.