According to findings from a multicenter study led by Johns Hopkins Medicine and released today in The New England Journal of Medicine (NEJM), transplanting kidneys from deceased donors who had the human immunodeficiency virus (HIV) to recipients with HIV is safe. Perhaps more importantly, the study authors also found that HIV-to-HIV kidney transplants are comparable in effectiveness to those using organs from donors without HIV.
"Based on the evidence generated at the 26 U.S. transplant centers collaborating on this study, we support expanding HIV-to-HIV kidney transplants from their current 'research-only' authorization — as enabled by Congress passing the HIV Organ Policy Equity [HOPE] Act in 2013 — to routine clinical practice," says study co-lead author Christine Durand, M.D., associate professor of medicine and oncology at the Johns Hopkins University School of Medicine, and medical director of the Johns Hopkins Transplant Research Center.
"Expansion of HIV-to-HIV kidney transplantation outside of research would be a win-win situation, because it will first benefit people with HIV [PWH] who need kidneys by increasing the numbers of organs available from donors with HIV, and then, in turn, there will be more kidneys from donors without HIV for recipients without HIV," says Durand.
When the HOPE Act was enacted, it enabled kidneys and livers from people with HIV to be legally donated to PWH in need of transplants, as "part of approved clinical research studies." The first deceased donor kidney and liver transplants under the HOPE Act were conducted by Johns Hopkins Medicine in 2016. Three years later, Johns Hopkins also performed the first living donor HIV-to-HIV kidney transplant in the United States.
In July 2023, Johns Hopkins Medicine and three collaborating medical institutions reported on a case series that included the four-year outcome for the donor in that historic 2019 operation — Nina Martinez — along with the outcomes for the second and third kidney donors with HIV in the nation to undergo the procedure. Based on their findings, the researchers concluded people with HIV can safely donate kidneys without an increased risk of developing end-stage kidney disease or other kidney problems later in life.
In the new study, investigators with the HOPE in Action multicenter consortium (co-led by Johns Hopkins Medicine) compared the safety and effectiveness of the HIV-to-HIV procedure for PWH needing a kidney transplant with that of the established transplant surgery using kidneys from donors without HIV.
The researchers evaluated 198 kidney transplant recipients with HIV — 99 who received their organ from a deceased donor with HIV and 99 who received theirs from a donor without HIV. The researchers evaluated both patient groups for primary negative outcomes known as "safety events," such as death from any cause, graft loss (failure of the transplanted organ), serious adverse complications, a breakthrough HIV infection, persistent failure of HIV treatment, or an opportunistic infection. Secondary outcomes studied included overall patient survival, survival without graft loss, organ rejection, infection, cancer and an HIV superinfection (when a PWH is infected with a second strain of HIV).
The relationships between the two patient groups were defined using a statistical model that produces a hazard ratio — a measure comparing how often specific events (in this case, whether a donated kidney led to a primary or secondary negative outcome) happen in a study group compared to their frequency in a control group. In the NEJM study, a hazard ratio of 1 suggested no difference between the groups. A ratio greater than 1 indicated an increased likelihood of having a negative outcome, and a ratio less than 1 showed a decreased chance.
"The adjusted hazard ratio for each of the primary outcomes was approximately 1, which shows 'noninferiority' of the HIV-to-HIV kidney transplant procedure," says Durand. "This means statistically, it is just as safe and effective as transplants using a kidney from a donor without HIV."
Durand says hazard ratios for the secondary outcomes assessed were free of meaningful differences, with one exception.
"We did see a number of breakthrough HIV infections that resulted in an adjusted hazard ratio of just above 3, but that was likely the result of patients interrupting their HIV medication rather than the use of organs from donors who had HIV," she explains. "Fortunately, all these breakthroughs were controlled when HIV medications were resumed."
Currently, the U.S. Department of Health and Human Services is reviewing public comments on a proposed rule, the Organ Procurement and Transplantation: Implementation of the HIV Organ Policy Equity (HOPE) Act. If finalized, this rule would move HIV-to-HIV kidney transplantation from research use only to an authorized clinical procedure.
"This proposed rule is based on rigorous analysis of published, peer-reviewed data, such as our NEJM study," says Durand. "This body of solid evidence shows that HIV-to-HIV transplantation, both from deceased and living donors with HIV, is safe, successful and ready to be broadly used to save lives and help tackle the worldwide shortage of organs available for transplants."
Along with Durand, the other members of the research team from Johns Hopkins Medicine are Serena Bagnasco, M.D.; Diane Brown; Niraj Desai, M.D. (now with the Northwell Health Transplant Institute at North Shore University Hospital); Yolanda Eby, M.S.; Tao Liang, M.S.P.H.; Fizza Naqvi, M.B.B.S.; Darin Ostrander, Ph.D.; Andrew Redd, Ph.D. — jointly with the National Institute of Allergy and Infectious Diseases (NIAID) — and Aaron Tobian. Ph.D.
Team members from other medical institutions are study co-lead author Allan Massie, Ph.D., and study senior author Dorry Segev, M.D., Ph.D., from the New York University (NYU) Grossman School of Medicine and the NYU Langone Transplant Institute; Erica Brittain, Ph.D., Jonah Odim, M.D., Ph.D., and Natasha Watson, M.S., from NIAID; Marcus Pereira, M.D., M.P.H., from the Columbia University Irving Medical Center; Joanna Schaenman, M.D., from the David Geffen School of Medicine at the University of California, Los Angeles; Alexander Gilbert, M.D., from Georgetown University; Rachel Friedman-Moraco, M.D., from Emory University; Meenakshi Rana, M.D., from the Ichan School of Medicine at Mount Sinai; Oluwafisayo Adebiyi, M.D., from Indiana University Health; Nahel Elias, M.D., from Massachusetts General Hospital; Jose Castillo-Lugo, M.D., from the Methodist Health System Clinical Research Institute; Sander Florman, M.D., from the Mount Sinai Hospital; Valentina Stosor, M.D., from the Northwestern University Feinberg School of Medicine; Sapna Mehta, M.D., from the NYU Langone Transplant Institute; Jonathan Hand, M.D., from Ochsner Health; Emily Blumberg, M.D., from the Perelman School of Medicine at the University of Pennsylvania; Carlos Santos, M.D., M.P.H.S., from the Rush University Medical Center; Shikha Mehta, M.D., from the University of Alabama at Birmingham; Emmanouli Giorgakis, M.D., from the University of Arkansas for Medical Sciences; Peter Stock, M.D., from the University of California, San Francisco; Salma Aslam, M.D., M.S., from the University of California, San Diego; Senu Apewokin, M.D., from the University of Cincinnati College of Medicine; John Baddley, M.D., from the University of Maryland School of Medicine; Michele Morris, M.D., from the University of Miami Miller School of Medicine; Ghady Haidar, M.D., from UPMC at the University of Pittsburgh; Karthik Ranganna, M.D., and David Wojciechowski, D.O., from the University of Texas Southwestern Medical Center; Catherine Small, M.D., from Weill Cornell Medicine; and Maricai Malinis, M.D., from the Yale School of Medicine.
The work was supported in part by NIAID and by National Institutes of Health grants R01AI120938, R01DK131926, U01AI134591, U01AI138897, U01AI177211 and R01DK101677.
Because of the study's large number of co-authors, their names, financial disclosures and conflict-of-interest statements are not listed here. That information may be found in the published paper.
On the Web
Study Shows Positive Outcomes for First Three U.S. Living HIV-to-HIV Kidney Transplant Donors
First Living Donor HIV-to-HIV Kidney Transplant in the U.S.
