NIH Study Will Examine Outcomes in Transplantation from HIV+ Donors to HIV+ Recipients

In the late spring, the National Institutes of Health (NIH) announced the start of the first large-scale clinical trial of kidney transplantations between people with HIV. The trial is being conducted at clinical centers across the United States. The study follows the passage of the HOPE (HIV Organ Policy Equity) Act of 2013, that allowed organ donation from individuals with HIV. The trial, the HOPE in Action Multicenter Kidney Study (NCT03500315), is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH.

Since 2008, successful organ transplants between donors and recipients with HIV have been completed in South Africa; however, such procedures were illegal in the United States prior to the passage of the HOPE Act. The act allows transplant teams in the United States with an approved research protocol to transplant organs from donors with HIV into qualified recipients with end-stage organ failure who also have HIV. It is hoped the practice will shorten the time patients with HIV are waitlisted for transplant. It is still illegal in the United States to transplant organs from donors infected with HIV to patients not infected with HIV.

Due to the damage caused by HIV and its associated comorbidities, including hepatitis B and C viruses, hypertension, and diabetes mellitus, individuals living with HIV have a higher risk of end-stage liver and kidney diseases. Further, toxicity from some antiretroviral drugs used to treat HIV infection may also lead to increased risk of end-stage organ disease.

At the beginning decades of the HIV/AIDS pandemic, individuals infected with HIV were rarely eligible to receive organs from donors not infected with HIV. Results of studies sponsored by NIAID on organ transplant provided consistent results that by carefully selecting individuals living with HIV to receive a kidney or liver from a donor not infected with HIV, patients and graft survival rates were similar to those among recipients without HIV; those findings provided the scientific basis for passage of the HOPE Act of 2013.

NIAID director, Anthony S. Fauci, MD, said, “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. 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 received approval of the Institutional Review Board by following research criteria and guidance mandated by the HOPE Act of 2013. The study is designed to track the clinical outcomes of 160 kidney transplant recipients. Eligibility criteria include living with HIV. Of the 160 participants, 80 will receive a kidney from a deceased donor who had HIV, and 80 will receive a kidney from a deceased donor who did not have HIV (control group). Study participants and healthcare teams will know the HIV status of the organ donor.

Christine Durand, MD, assistant professor of medicine at Johns Hopkins University and lead researcher, said, “If proven safe and effective in our study, kidney transplantation 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.”

Study participants will be monitored for signs of organ rejection, organ failure, failure of previously effective HIV medications, and HIV-related complications. Outcomes of participants who received a kidney from an HIV-infected donor will be compared with outcomes of those whose donor was not infected with HIV. Also tracked will be participants’ psychological and social responses, changes in reservoirs of latent HIV, and the potential development of HIV superinfection, a condition of infection with more than one strain of HIV.

Patients who undergo successful kidney transplantation experience improved quality of life, fewer complications, and extended lifespans compared with individuals who remain on maintenance dialysis. Daniel Rotrosen, MD, director of NIAID’s Division of Allergy, Immunology, and Transplantation, said, “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.”

HOPE in Action Multicenter Kidney Study participants are also eligible to co-enroll in a separate study supported by NIAID, Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients, a phase 2 clinical study enrolling at 10 of the 19 sites in the HOPE in Action study. The concurrent study will evaluate the safety and immune responses to the anti-HIV drug maraviroc in kidney recipients and determine whether the drug reduces rates of kidney rejection seen in the HIV-positive transplant population.

More information on the HOPE in Action Multicenter Kidney Study is available at clinicaltrials.gov under study identifier NCT03500315; for information on the Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients, use study identifier NCT02741323.

 

Takeaway Points

  1. The NIH is conducting the HOPE in Action Multicenter Kidney Study to assess the safety and efficacy of kidney transplantation from donors infected with HIV to recipients infected with HIV.
  2. The trial (NCT03500315) will be conducted at 19 transplantation centers throughout the United States. The study cohort will include 80 HIV+ patients who receive a kidney from an HIV+ donor and 80 HIV+ patients who receive a kidney from a non-HIV infected donor.
  3. Study participants will be monitored for signs of organ rejection, organ failure, failure of previously effective HIV medications, and HIV-related complications.