Most kidney transplants between people with HIV have long-term success

Recipients
living with HIV show no indication of secondary infection with donor HIV
strain.

New York, 02^nd October 2019. People living with HIV who received kidney transplants from deceased donors with HIV had high rates of overall survival and kidney graft survival after five years, according to an observational study published online in the New England Journal of Medicine. The study, which incorporated data from transplants beginning in 2008, was a collaboration of researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, and the University of Cape Town, South Africa, with joint support from NIH and the South African Medical Research Council (SAMRC). The investigators followed 51 study participants with HIV who received kidney transplants from deceased donors with HIV in South Africa.

“In South
Africa, the United States, and elsewhere, a growing number of people with HIV
have a need for kidney transplants. Unfortunately, these gifts of life are too
often in short supply,” said Anthony S. Fauci, M.D. “This observational study
provides additional evidence that organs from donors with HIV could be a new
donation source for people living with both HIV and end-stage renal disease. If
these findings are corroborated in ongoing clinical trials, we will have a
chance to improve the health of many people living with HIV and increase the
overall supply of transplantable organs.”

NIAID researchers worked closely with
University of Cape Town physicians and scientists to design and perform the
co-funded study. All kidney transplantations and primary laboratory analyses
occurred in South Africa, with additional laboratory support provided by
NIAID’s Laboratory of Immunoregulation in Baltimore.

“This
collaboration leverages expertise in both of our countries to address an urgent
common problem,” said SAMRC President and Chief Executive Officer Glenda Gray, MBBCH,
FCPaed (SA). “Our combined efforts have the power to make sure people with HIV
experiencing organ failure are not exempt from longer, healthier lives that
international HIV research has made possible.”

In the
study, researchers from the University of Cape Town found that people living
with HIV who received a kidney from a donor with HIV in South Africa had
outcomes similar to patients with HIV in a previous U.S. study who received a
kidney from a donor without HIV.

Five years
after undergoing kidney transplantation, 83.3% of people in the South African
cohort survived, and 78.7% still had a functioning transplanted kidney.

These findings are comparable to those from a
2010 NIAID-funded study in the United States that reported an 88.2% overall
survival rate and a 73.7% kidney graft survival rate after three years. In the
South African cohort, all participants were virally suppressed at the time of
transplantation, and the researchers did not observe any increases in viral
load — the amount of virus in the blood — among patients who maintained
consistent use of antiretroviral therapy (ART).

Deceased
donors in the study — many of whom were unaware of their status — had strains
of HIV genetically distinct from the transplant recipients. Recognizing this,
investigators sequenced the virus genomes of donor-recipient pairs and analyzed
blood samples collected from recipients at multiple follow-up visits to
determine if so-called HIV superinfection occurred.

HIV
superinfection refers to the acquisition and establishment of a second
genetically distinct strain of the virus in a person who already has HIV.
Research has shown that people with HIV superinfection usually respond well to
standard ART and generally do not experience worse clinical outcomes. However,
because some strains are resistant to certain anti-HIV medications, researchers
watched study participants closely for possible superinfections with strains of
HIV that might be resistant to a recipient’s ART regimen.

In this
study, investigators identified only one potential case of transient
superinfection, but extensive analyses determined that this was most likely
residual virus carried over from the donor during the transplant and not a true
sustained superinfection. Researchers will continue to monitor all the
participants for any signs of superinfection. While 10 participants changed
their ART regimens during the study, none did so because of drug resistance.

The study’s
lead researcher was Elmi Muller, M.D., Ph.D., of the Groote Schuur Hospital in
Cape Town. “This work builds on the groundbreaking research by Dr. Muller and
her team in South Africa beginning more than 10 years ago that opened the door
to the exciting field of organ transplantation between people with HIV around
the world,” said study author Andrew D. Redd, Ph.D., of the NIAID Laboratory of
Immunoregulation. “By using the most advanced laboratory techniques available,
our team showed that HIV superinfection is of limited risk in these patients.
Taken together with the positive long-term clinical outcomes we found in our
study, our data strongly support the expanded use of these life-saving
transplantations.

“This
project would not have been possible without the combined effort of our South
African and U.S. teams, which demonstrates the power of truly collaborative
international research,” he added.

People with
HIV have a higher risk of end-stage kidney diseases requiring organ
transplantation because of damage caused by the virus itself and by common
coinfections and associated comorbidities, such as hepatitis B and C viruses,
hypertension and diabetes mellitus.
Certain antiretroviral treatments also can cause toxicities that damage
these organs. Until recently, people with HIV were rarely eligible to receive
organ transplants from HIV-negative donors because health outcomes were
projected to be poor.

Such
transplants were illegal in the United States until the passage of the HIV
Organ Policy Equity (HOPE) Act of 2013. The law intended to spur an increase in
the availability of organs for transplantation for people with HIV, given the
high frequency of HIV-related comorbidities that can necessitate organ
transplantation. The HOPE Act of 2013 permits U.S. transplant teams with an
approved research protocol to transplant organs from donors with HIV into
qualified recipients with HIV and end-stage organ failure, a practice that may
shorten the time people wait to receive a transplant.

Previous
research supported by NIAID demonstrated that by carefully selecting people
with HIV and organ failure who are otherwise healthy to receive a kidney or
liver from an HIV-negative 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 initial HIV-positive to HIV-positive
kidney transplants in South Africa and the passage of the HOPE Act of 2013.

Two large
NIAID-funded clinical trials are ongoing to assess the safety and efficacy of
this practice at transplantation centers across the United States. The HOPE in
Action Multicenter Kidney Study (launched in 2018) and the HOPE in Action
Multicenter Liver Study (launched February 2019) will compare clinical outcomes
among people living with HIV who receive organs from deceased donors with HIV
to those who receive HIV-negative organs.

The current
work was supported by the NIH and SAMRC’s United States–South Africa Program
for Collaborative Biomedical Research under grant 1U01AI116061-01. The
Poliomyelitis Research Foundation and the Centre for the AIDS Programme of
Research in South Africa (CAPRISA) Center of Excellence, as well as NIAID’s
Division of Intramural Research, provided additional support.

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses.

Most kidney transplants between people with HIV have long-term success was first published 0n NIAID.

Recipients living with HIV show no indication of secondary infection with donor HIV strain.

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Recipients
living with HIV show no indication of secondary infection with donor HIV
strain.