The first large-scale clinical trial to study kidney transplantations between people with HIV has begun at clinical centers across the United States. The HOPE in Action Multicenter Kidney Study will determine the safety of this practice by evaluating kidney recipients for potential transplant-related and HIV-related complications following surgery. The study is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
While organ transplants between donors and recipients with HIV have been successfully completed in South Africa since 2008, such transplants were illegal in the United States until the passage of the HIV Organ Policy Equity (HOPE) Act in 2013. The HOPE Act permits U.S. transplant teams with an approved research protocol to transplant organs from donors with HIV into qualified recipients with end-stage organ failure who are also living with HIV, a practice that may shorten the time people living with HIV wait to receive a transplant. The transplantation of organs from donors who have HIV to individuals uninfected with HIV remains illegal in the United States.
Individuals living with HIV have a higher risk of end-stage liver and kidney diseases because of damage caused by HIV and its coinfections and associated comorbidities, such as hepatitis B and C viruses, hypertension and diabetes mellitus, as well as toxicity from certain antiretroviral drugs used to treat HIV infection. In the early decades of the HIV/AIDS pandemic, individuals living with HIV were rarely eligible to receive organs from HIV-uninfected donors, which are consistently in short supply and high demand. However, NIAID-sponsored organ transplant studies demonstrated that by carefully selecting individuals living with HIV to receive a kidney or liver from an HIV-uninfected donor, patient and organ graft survival rates could be similar to those of transplant recipients without HIV. These findings provided the scientific basis for the eventual passage of the HOPE Act of 2013.
"Highly effective antiretroviral therapy and new antiviral drugs to treat hepatitis C have dramatically improved the health of people living with HIV, such that a young person newly diagnosed with HIV today can expect to live a nearly normal lifespan," said NIAID Director Anthony S. Fauci, M.D. "The HOPE Act of 2013 opened the door for researchers to explore a potential new source of donor organs for those living with HIV--a population with a significant and growing need for transplants. This study offers a chance to improve the health of those living with HIV, and increase the overall supply of transplantable organs."
The HOPE in Action Multicenter Kidney Study is the first study of its type in the United States to receive Institutional Review Board (IRB) approval by following the research criteria and guidance mandated by the HOPE Act of 2013. The study will track the clinical outcomes of 160 kidney transplants. All transplant recipients in the study will be living with HIV; 80 of them will receive kidneys from deceased donors who had HIV, and 80 will receive kidneys from HIV-uninfected deceased donors serving as the control group. Health care teams and study participants will be made aware of the HIV status of the organ donor.
"A kidney transplant can mean a second chance at a normal life for a person with end-stage renal disease who may otherwise need hours-long dialysis sessions, multiple times per week," said Christine Durand, M.D., assistant professor of medicine at Johns Hopkins University and principal investigator of the HOPE in Action Multicenter Kidney Study. "If proven safe and effective in our study, kidney transplants between people with HIV may result in people living with HIV receiving donated organs sooner and the overall organ transplant waiting list shrinking--to the benefit of everyone who needs a kidney transplant, regardless of HIV status."
Throughout the clinical trial, researchers will monitor kidney transplant recipients closely for signs of organ rejection, organ failure, failure of previously effective HIV medications and HIV-related complications. The HOPE in Action team will compare the results of those recipients who received kidneys from donors with HIV to those who received kidneys from HIV-uninfected donors. Researchers will also track participants' psychological and social responses, changes in their reservoirs of latent HIV, and the potential development of HIV superinfection, a condition of infection with more than one strain of HIV.
"Not only is the quality of life improved for patients who undergo kidney transplantation, they also have fewer complications and longer lifespans compared to those who remain on dialysis," said Daniel Rotrosen, M.D., director of NIAID's Division of Allergy, Immunology, and Transplantation, which will oversee the study. "An important question is whether those living with HIV will also receive these same clinical benefits. The HOPE in Action trial depends on the expertise and collaboration of the Organ Procurement and Transplantation Network, that of participating organ procurement organizations, and 19 major transplant centers throughout the country."
The study will comply with all current federal laws surrounding organ procurement and transplantation and meet the HOPE Act Safeguards and Research Criteria as set forth by the U.S. Department of Health and Human Services in a 2015 Federal Register notice. These safeguards, developed for HHS with NIAID's leadership, include kidney recipients discussing the study with an independent advocate prior to transplantation. Additionally, participating kidney recipients must be in good immune health and on effective antiretroviral therapy. Recipients must also be willing to adhere to HIV- and transplant-related medications.
Participants in the HOPE in Action Multicenter Kidney Study are also eligible to co-enroll in a separate NIAID-supported study, Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients. This Phase II clinical study, which is enrolling at 10 of the 19 clinical sites conducting the HOPE in Action study, will evaluate the safety and immune responses to the anti-HIV drug maraviroc in kidney recipients with HIV and assess whether the drug reduces rates of kidney rejection observed in the HIV-positive transplant population. Should this intervention prove successful, scientists may further evaluate this drug for similar efficacy in HIV-negative transplant recipients.
Another related study called the HOPE in Action Multicenter Liver Study, will test the safety and efficacy of transplanting livers from deceased donors who had HIV and deceased HIV-uninfected donors into recipients living with HIV. The development of this study, which is projected to begin at the end of 2018 pending scientific and IRB review, is supported by NIAID grant R34 AI123023-01.
The HOPE in Action Multicenter Kidney study is supported by the NIAID grant U01AI134591. The Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients study is supported by the NIAID grant U01AI118594.
For more information about the HOPE in Action Multicenter Kidney Study, please visit ClinicalTrials.gov under study identifier NCT03500315. For more information about the Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients study, please visit ClinicalTrials.gov under study identifier NCT02741323.
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