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Kidney Transplants Between People With HIV Offer Long-term Success

Creator: Ishwarya Thyagarajan
Keywords: HIV, HIV Donors, HIV recipients, kidney transplants, HIV and end-stage renal disease, kidney transplantations, antiretroviral therapy, transplantation, hepatitis B, HIV-negative donor, deceased donors with HIV

by Ishwarya Thyagarajan on October 14, 2019 at 5:27 PM

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Highlights:

Overall survival and kidney graft survival rates of HIV-infected patients who received kidney transplants from deceased donors with HIV have been high even after five years
The findings of this study may help in improving the health of many with HIV having kidney diseases
It would also expand the pool of organs available for transplant

Most kidney transplants between people with HIV were found to have long-term success. Overall survival and kidney graft survival rates of HIV-infected patients who received kidney transplants from deceased donors with HIV have been high even after five years, reveals an observational study published in the New England Journal of Medicine.

The Study

The study was a collaborative effort involving scientists from the National Institute of Allergy and Infectious Diseases (NIAID), U.S. National Institutes of Health and the University of Cape Town, South Africa. It was also jointly supported by NIH and the South African Medical Research Council (SAMRC).

Around 51 people with HIV who received kidney transplants from deceased donors in South Africa were the study participants, the research team followed, and data from transplants beginning in 2008 were used for the study.

‘Overall survival and kidney graft survival rates of HIV-infected patients who received kidney transplants from deceased donors with HIV have been high even after five years. The findings of this study may help in improving the health of many with HIV having kidney diseases.’

"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.

"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," he added.

The co-funded study was designed and performed by a research team from NIAID and a group of physicians and scientists from the University of Cape Town who worked closely. While all the kidney transplantations and primary laboratory analyses took place in South Africa, NIAID's Laboratory of Immunoregulation in Baltimore provided the supplementary laboratory support.

Glenda Gray, the SAMRC President and Chief Executive Officer said, "This collaboration leverages expertise in both of our countries to address an urgent common problem. 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."

Findings of the Study

The findings made by a research team from the University of Cape Town in this study were similar to an earlier study from the U.S. While the South African study looked at people living with HIV who received kidneys for transplant from donors with HIV, in the U.S. study the donors were without HIV.

From the South African group, 83.3 percent survived and 78.7 percent continued to have a functioning transplanted kidney. The findings from the 2010 NIAID-funded study in the U.S. reported an overall survival rate of 88.2 percent and kidney graft survival rate of 73.7 percent after three years.

At the time of transplantation, all the participants from the South African group were virally suppressed and the research team did not notice any increase in the amount of virus (viral load) in those patients who had consistently used antiretroviral therapy (ART).

HIV Superinfection

Many of the deceased donors who were part of the study were unaware of their status, had HIV strains that were genetically different from the transplant recipients. Knowing this, the virus genomes of donor-recipient pairs were sequenced and blood samples collected from the recipients were analyzed by the scientists to note any occurrence of HIV superinfection, during multiple follow-up visits.

When a second genetically distinct strain of the virus gets acquired and established in a person already living with HIV, the condition is referred to as HIV superinfection.

People with HIV superinfection typically respond well to the standard ART and mostly do not experience poor clinical outcomes as research shows. Nonetheless, the study participants were closely observed for likely superinfections with strains of HIV that might remain unaffected by a recipient's ART regimen as there are certain strains that are resistant to some anti-HIV medications.

Only one probable case of transient superinfection was identified by the scientists, which was established to be a residual virus carried over from thee donor following the transplant and not a genuine sustained superinfection. All participants would be monitored continuously by the research team for signs of superinfection. Though the ART regimen of 10 participants changed during the study, none was due to drug resistance.

Significance of the Study

Dr. Elmi Muller of the Groote Schuur Hospital in Cape Town is the study's lead scientist. Andrew D. Redd, of the NIAID Laboratory of Immunoregulation who is the study author commented: "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. 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, we feel our data strongly support the expanded use of these life-saving transplantations."

He further said, "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."

HIV Organ Policy Equity (HOPE) Act

People living with HIV are at a higher risk of developing end-stage kidney diseases and because of the impairment caused by the virus, common coinfections and related comorbidities like hepatitis B and C viruses, hypertension and diabetes, requiring organ transplantation.

Organ damage can also result because of the toxicities caused by certain antiretroviral treatments. As the health outcomes were expected to be worse, people with HIV were hardly considered fit to receive organ transplants from HIV-negative donors, until recently.

Until the passing of the HIV Organ Policy Equity (HOPE) Act of 2013, such transplants were considered illegal. Considering the high incidence of HIV-related comorbidities that would make organ transplantation necessary, the law intended to increase organ availability for people with HIV.

The HOPE Act allows U.S. transplant teams to retrieve organs from HIV donors and transplant them to eligible people with HIV, having end-stage organ failure, with an approved research protocol. This practice may help reduce the wait time for those requiring a transplant.

The earlier research supported by NIAID exhibited that the patient and organ graft survival rates of those without HIV who receive transplants and people living with HIV and organ failure (but otherwise healthy) receiving kidney or liver from HIV-negative donor, could be the same if the candidate is chosen carefully.

The findings of this study offered the scientific basis for the early HIV-positive to HIV-positive kidney transplants performed in South Africa and passing of the HOPE Act of 2013.

Two large trials, funded by the NIAID, are underway to assess the safety and effectiveness of this practice at various transplantation centers in the U.S. The HOPE in Action Multicenter Kidney Study (started in 2018) and the HOPE in Action Multicenter Liver Study (launched February 2019) will equate clinical outcomes between people living with HIV who receive organs from deceased donors with HIV and those who receive HIV-negative organs.

Reference:

Most Kidney Transplants Between People with HIV Have Long-Term Success - (https:www.niaid.nih.gov/news-events/most-kidney-transplants-between-people-hiv-have-long-term-success)

Source: Medindia

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