Over one million people in the U.S. grapple with HIV. Although life expectancy has increased, end-stage organ diseases have a relatively high mortality rate for these patients. Learn about HIV-to-HIV kidney transplants from Shikha Mehta, M.D., director of the UAB HIV and Hepatitis C Transplant Program. She explains how her interdisciplinary team has made successful kidney transplants for over decade despite numerous challenges and comorbidities of those with HIV.
Shikha Mehta, MD is an Associate Professor of Medicine Medical Director, Kidney and Pancreas Transplant Program Director, HIV and Hepatitis C Transplant Program.
Intro: Welcome to UAB MedCast, a continuing education podcast for medical professionals, providing knowledge that is moving medicine forward. Here's Melanie Cole.
Melanie Cole, MS (Host): Welcome to UAB MedCast. I'm Melanie Cole. And joining me today to highlight kidney transplantation in patients with HIV is Dr. Shikha Mehta. She's an Associate Professor of Medicine, the Medical Director of the Kidney and Pancreas Transplant Program, and the Director of the HIV and Hepatitis C Transplant Program at UAB Medicine.
Dr. Mehta, it's a pleasure to have you join us. I'm so glad that you could talk about this topic. And research shows the opportunity to achieve transplant is especially vital for HIV-positive patients. Can you tell us a little bit, as we're updating this podcast, what's changed since the discovery of HIV and AIDS back in the '80s? Give us the latest information on HIV-positive patients and transplantation opportunities.
Shikha Mehta, MD: Melanie, thank you for this opportunity to share my insights on HIV and transplantation with you and everybody today. Going to your question, in our global community, nearly 37 million individuals grapple with HIV. And among them, about 1.1 million reside in the United States itself.
The fortunate advent of effective antiretroviral therapy led to a dramatic improvement in life expectancy for the patients infected with HIV. However, this remarkable progress has brought forth a new challenge, which is end-stage organ diseases. They have emerged as significant contributors to both morbidity and mortality, even as AIDS-related deaths have witnessed a decline.
The incidence of end-stage kidney disease has shown a decline over the last few decades. However, its prevalence continues to rise, which means more HIV-infected individuals are in need of dialysis or transplant today. Unfortunately, recent data has shown about two to four-fold increase in risk of end stage kidney disease amongst those who are living with HIV. This concerning trend is further compounded by the fact that mortality rates on dialysis are notably higher for individual infected with HIV when compared to their uninfected counterparts. Factors such as extended durations on dialysis and inadequate access to transplantation contribute to this disparity. One of the studies actually demonstrated that up to 8.7% of HIV-positive end-stage kidney disease patients die annually, nearly doubling the mortality rates seen in HIV-uninfected patients.
But what about transplant for an individual living with HIV? Historically, it was a very challenging endeavor. If I go back to 1980s, transplantation among HIV-infected individuals was principally unintentional and marked with poor outcomes. Concurrently, in '88, US Legal Code was amended to prohibit transplantation of tissues from HIV-infected donors. From '87 to around 1997, only 32 HIV-infected kidney transplants were reported in the US, and these came with poor patient and graft survival rates. Despite effective antiretroviral therapy, our healthcare professionals refrained from recommending kidney transplants for individuals with HIV, expressing worries about infection, mortality and improper allocation of a limited resource as their primary reasons.
Between 2003 and 2009, there was a groundbreaking study conducted by NIH at 19 US centers, which enrolled about 150 kidney transplant recipients, and demonstrated the safety and feasibility of transplanting organs from HIV-uninfected donors to HIV-infected recipients. The analysis confirmed excellent one and three-year graft survival rates of 90% and 74% respectively, which are on par with survival rates in older HIV-negative adults in the national registry.
Another study actually done by our own center using National Transplant Registry data demonstrated a significant reduction and mortality rates of HIV-infected end-stage kidney disease patients by nearly 80% as compared to the HIV-infected individuals who stayed on dialysis. Some of these landmark studies not only shattered long standing barriers, but also offered hope to countless individuals who are living with HIV who had been excluded from the process of transplantation.
Melanie Cole, MS: Wow. That was such a comprehensive answer. Dr. Mehta, thank you so much. And this is really such an interesting topic and so many advancements. I'd like you to speak about patient selection because I think that that's going to really reach other providers and that they're going to see that this is something that now is routinely done. So, speak about patient selection, the importance of this and the safeguards that you use at UAB so that other providers know what's going on.
Shikha Mehta, MD: So, for patients who are potentially kidney recipients who are also HIV-positive and 18 years or older with chronic kidney disease, eligibility is determined based on our institutional guidelines for deceased donor kidney transplantation or living donor kidney transplantation.
I would just reflect to where HOPE Act was passed just because it's so pertinent to this conversation. Like I mentioned before, numerous studies had showcased remarkable outcomes in this patient population. And following the pioneering NIH trial, the annual number of transplants had gone up significantly. And these patients continued to face substantial mortality while waiting transplantation. So, an innovative solution to address this disparity emerged in form of HIV-to-HIV transplantation, which involved using organs from HIV-infected donors to save the lives of those with end-stage kidney disease. This groundbreaking approach was initially pioneered actually in South Africa in 2010. In the United States, utilization of HIV-positive donors was previously prohibited under the amendment to the NOTA Act of 1984. However, in 2013, the HOPE Act, which is also called the HIV Organ Policy Equity Act, was enacted by Congress, and signed into law by President Obama, which ushered a pivotal change.
The legislation eliminated the restrictions on using organs from HIV-positive donors and, in its place, introduced a new regulation which allowed HIV-positive donor organs to be transplanted into HIV-infected individuals, but under carefully controlled research protocols, which were aligned again with federal safeguards and criteria.
To that effect, when you talk about recipient selection criteria, patients have to meet the standard eligibility for receiving a kidney transplantation, and also have to meet HHS HOPE Act research criteria to receive HIV-positive organs. This included having a CD4 count of greater than 200 cells per microliter within the last 16 weeks, and receiving antiretroviral therapy with HIV RNA levels which are undetectable or below 50 copies per mL. Some of the exclusion criteria for recipient selection involved having an ongoing opportunistic infection or a history of certain condition like CNS lymphoma or progressive multifocal leukoencephalopathy.
So, the next question was about safeguards around transplantation process. And rigorous safeguards are standard practice for every donor organ, ensuring the safe transplantation of these organs. These measures include meticulous donor evaluation, clear labeling of organs, electronic health record systems to track HIV status, double-checking protocols using universal contact precautions, effective team communication, and ongoing training and education for healthcare professionals.
And lastly, but not the least, informed consent procedures for our recipients. These safeguards collectively ensure that HIV-positive organs are only transplanted into HIV-positive recipients, reducing the risk of transmission and allowing individuals with HIV to access transplantation when needed.
Melanie Cole, MS: Dr. Mehta, then as they're going through this process, I'd like you to speak about your multidisciplinary approach and your team and the management of the comorbidities that go with the HIV itself.
Shikha Mehta, MD: So, the process of transplantation itself is very intricate. It requires a multifaceted approach as well as collaborative teamwork reminiscent of a village working together to ensure its success. Our HIV transplant team extends beyond the standard pre-transplant team with a APP, an experienced transplant nephrologist and surgeon, a dedicated research coordinator and an actively-engaged social work team, along with specialized transplant infectious disease providers. These experts not only deliver the standard of care for transplantation, but also oversee medication management, collaborate with the external infectious disease providers and dialysis units, facilitate patient access to organs from HOPE donors, and diligently assess for any signs of coercion. This multidisciplinary approach optimizes transplant outcomes and also supports patient education, fosters research and innovation in the field of HIV transplantation, and ultimately ensures that these patients receive the highest standard of care and improved quality of life. When you talk about comorbidities and management of HIV in the era of antiretroviral therapy, individuals living with HIV often have multiple, multiple medical comorbidities. Our transplant team actually works in close collaboration with our infectious disease colleagues at UAB, specifically within the 1917 Clinic, our infectious disease partners throughout our state, as well as neighboring states, enabling us to provide that kind of comprehensive care for the diverse health needs of individuals, managing both HIV as well as all the other medical conditions.
Melanie Cole, MS: Dr. Mehta, before we wrap up, I'd like you to speak to other providers now about the awesome work that you're doing at UAB Medicine when it comes to transplantation for HIV-positive patients. I'd like you to tell them what you would like them to know and when you want them to refer to the specialists at UAB Medicine.
Shikha Mehta, MD: So at UAB, we offer transplantation in HIV-infected individuals. We have been doing this for more than a decade. We were also one of the centers who was the first center in Southeast United States to offer an HIV-infected kidney to an HIV-infected recipient under the HOPE safeguards under a research umbrella, and we performed our first transplant in 2016.
Having said that, every HIV patient with CKD or chronic kidney disease who's eligible for transplant should be referred to UAB Transplant Clinic so that these patients have an opportunity to receive a kidney transplant from either a living donor or a deceased donor who's infected with HIV or not infected with HIV.
As for any chronic kidney disease patient, an early referral for patients with HIV with CKD is better. We like to see these individuals as soon as their GFR is around 20 or below. The one thing that we look for in these individuals, since they have heightened risk of rejection, is that they are switched from a protease inhibitor-based regimen to an integrase inhibitor-based regimen at least 16 weeks before transplant. This switch actually helped mitigate potential drug interactions between transplant rejection medicines and protease inhibitors. The other thing that we hope to see in these individuals is that their HIV is well controlled and they do not have any opportunistic infections.
Lastly, I would like to say the data from all the studies that have been done at UAB and by our colleagues in United States has always shown that the outcomes have been excellent and undeniably promising in HIV-infected kidney transplant recipients using both HIV-infected kidneys or HIV-uninfected kidneys.
And one of the biggest benefits that has emerged from using or utilizing HOPE donor organs is reduction of wait times for our recipients with HIV. To me, one of the biggest things and biggest medical impact that HOPE donation has allowed is it has signified a profound paradigm shift where HIV transitioned from being a life-threatening condition to one that actually offers the gift of life to patients who have HIV infection.
Melanie Cole, MS: Beautifully said. Thank you so much, Dr. Mehta, for joining us today, and giving us an update on what's going on with HIV-positive patients and transplantation. Thank you again. And for more information, please visit our website at uabmedicine.org/physician. That concludes this episode of UAB MedCast. For updates on the latest medical advancements, breakthroughs and research, please follow us on your social channels. I'm Melanie Cole. Thanks so much for joining us today.