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IDCM CME Issue 1-10: Solid-organ Transplants and HIV: A 30 Year Journey
Author: Chris Lippincott, MD, MPH
In the early years of the HIV epidemic, before the widespread use of effective antiretroviral therapy (ART), HIV-infection was considered by many to be an absolute contraindication to solid-organ transplantation. In the U.S., prior to routine screening for HIV in 1985, patients were at risk of acquiring HIV-infection through solid organ transplantation, and numerous such cases were documented.1 Due to the inability to treat HIV infection at that time, outcomes were predictably poor compared with current standards.
As a response to such cases, the National Organ Transplant Amendments (NOTA) Act, passed in the U.S. in 1988, legally prevented patients from receiving organs from HIV-infected individuals.2 This legislation had the unfortunate impact of stifling solid organ transplant research for HIV-infected patients for decades. The global landscape of HIV treatment and management has dramatically changed since the NOTA Act was passed. Over the ensuing 3 decades, global achievements in HIV research, patient advocacy, and legislation— particularly in South Africa and the U.S. in the last 10 years—have paved the way for record numbers of solid organ transplants to HIV-infected recipients and from HIV-infected donors.
HIV Donor-negative/Recipient-positive (D-/R+)
In 1996, ART became widely available in the U.S., although the dramatic impact on morbidity and mortality was not fully known for several years. Before 2000, HIV-infected transplant recipients were scarce, with poor morbidity and mortality outcomes likely attributable to the lack of ART availability. Once the ART era ushered in improved treatment outcomes, interest in solid organ transplants for HIV-infected patients was renewed. Announced in 2001 and beginning enrollment in 2003, a multicenter, pilot study prospective trial was conducted to study HIV D-/R+ kidney transplants in the U.S. With 150 patients across 19 institutions, it was the largest cohort of HIV D-/R+ kidney transplants to date. In 2010, the results demonstrated high patient- and graft-survival rates at 1 and 3 years.3 There was no observed increase in complications attributable to HIV infection although rejection rates were higher than anticipated at nearly 3 times the rate of HIV-uninfected recipients (31% and 41% at years 1 and 3, respectively).3 Since 2010, HIV D-/R+ kidney transplants have nearly tripled in the U.S. with 221 performed in 2018 alone.4
HIV Donor-positive/Recipient-positive (D+/R+)
Robust improvements in the efficacy and safety of ART over the last 30 years have led to HIV-infected patients living longer, healthier lives, and have effectively eliminated transmission of HIV when suppressed with ART. Despite these advances, the global landscape of solid-organ transplantation in HIV infection was slow to change. The U.S. has been routinely transplanting HIV D-/R+, since the early 2000s,3 however high-burden HIV settings equipped with solid organ transplant programs, such as South Africa, were slower to offer solid organ transplantation to HIV-infected patients.5,6 For the majority of South Africans, access to dialysis relies upon limited state sector resources and is reserved for the healthiest and most compliant patients who must be eligible for transplantation. Due in part to the high demand for organs as well as the stigmatization of HIV, South African HIV-infected patients were not eligible for organs from HIV-uninfected patients, and thus were not eligible for long-term dialysis through the state sector.6 Following the state sector roll out of ART in the mid-2000s, researchers in Cape Town began exploring options for transplants for HIV-infected recipients. Organs from eligible deceased HIV-infected donor organs were not being utilized and were essentially discarded; they, therefore, became an obvious life-saving resource to address the unmet treatment needs for HIV-infected patients with end-stage renal disease. Beginning in 2008, and despite significant controversy within the South African medical community, South Africa became the first country in the world to perform a deceased donor HIV D+/R+ kidney transplant.5,6 Since that time the program has been a tremendous success. As of 2018, 43 kidneys from 25 deceased donors have been successfully transplanted into HIV-infected patients.6
Despite the promising HIV D+/R+ data coming out of South Africa by 2010,7 the U.S. was still bound by the NOTA Act of 1988 and unable to utilize donor organs from HIV-infected individuals. An advocacy campaign leveraged the compelling HIV D-/R+ data from the U.S.3 and HIV D+/R+ data from South Africa4 as well as estimates of at least 500-600 HIV-infected donors/year being otherwise unutilized8 to increase awareness of the need for new legislation. Advocates subsequently identified congressional sponsors and in 2013, at perhaps the height of legislative gridlock during the Obama administration, the U.S. Congress unanimously passed the HIV Organ Policy Equity (HOPE) Act.2 The HOPE Act allows for research into transplanting organs from HIV-infected donors into HIV-infected recipients (HIV D+/R+). Two years later, in 2015, the U.S. Department of Health and Human Services formally adopted the HOPE Act as federal policy and thus opened the doors for U.S.-based transplant programs to embark on such efforts. In early 2016, Johns Hopkins became the first U.S. institution to be approved for HIV-infected donor organ transplants and that year performed the first deceased donor HIV D+/R+ kidney transplant.9 From 2016–2018, at least 102 deceased donor HIV D+/R+ transplants have been performed in the U.S., including 71 kidney transplants and 31 liver transplants.4,10 Most recently, in March 2019, physicians at Johns Hopkins successfully performed the first HIV D+/R+ living donor kidney transplant.11
HIV Donor-positive/Recipient-negative (D+/R-)
While HIV D-/R+ and D+/R+ kidney and liver transplants have demonstrated tremendous success over the last 2 decades, intentional transplantation of an organ from an HIV-infected donor to an HIV-uninfected recipient (HIV D+/R-) had previously not been attempted due, among other issues to ethical concerns for the risk of HIV transmission. In 2018, the first such case was reported out of South Africa.12 The patient was a 7-month old child with biliary atresia complicated by end-stage liver disease who was ultimately wait-listed for a deceased-donor liver transplant. The mother requested an evaluation to be a living donor but was denied due to being HIV-infected, despite being an otherwise suitable donor. Two other family members were evaluated but were not suitable. After another 6 months on the waiting list, the then 13-month old child was admitted to the ICU for life-threatening complications of end-stage liver disease. With risk of death imminent and no other medical options to save the child’s life, the medical team was approved for a pilot study to proceed with the HIV-infected mother as a liver donor. She met HIV donor criteria, including a CD4 count >200 with a suppressed viral load for 6 months and no concomitant opportunistic infection (including tuberculosis) or malignancy. The recipient, who was HIV-negative, was placed on ART prior to transplantation and the HIV D+/R- transplant was successfully performed. The recipient seroconverted their HIV antibody within 43 days of transplant, followed by steadily declining antibody titers to the point of becoming undetectable just over 1 year after the transplant. However, HIV-1 RNA has never been detected in the recipient’s blood, who remains on ART.12 Thus, it remains uncertain whether the recipient is truly HIV-infected.12,13 In this particular case, the initial detection of HIV antibodies in the recipient may not be a reliable marker for HIV-infection, and the undetectable viral load while on ART could be indicative of either a treatment response or lack of true infection.12,13 This case highlights the need for further research on the risks, benefits, and outcomes of HIV D+/R- solid-organ transplants.
Bottom line: Propelled by rigorous science, strong advocacy, and landmark legislation, HIV D-/R+ and HIV D+/R+ kidney and liver transplants have demonstrated robust outcomes and are becoming more common worldwide. The recently successful HIV D+/R- liver transplant in South Africa further highlights the potential for HIV-infected and -uninfected donors and recipients to mutually benefit from solid-organ transplantation.
The author would like to acknowledge and thank Dr. Jeremy Nel, infectious diseases consultant, Helen Joseph Hospital (Johannesburg, South Africa), for his thoughts and review of this work.
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Johns Hopkins performs first HIV-positive to HIV-positive organ transplants in U.S. Johns Hopkins HUB. March 31, 2016. https://hub.jhu.edu/2016/03/31/first-kidney-liver-transplant-hiv-positive/
100 people transplanted thanks to HOPE Act. United Network for Organ Sharing. December 20, 2018. https://unos.org/news/100-people-transplanted-thanks-to-hope-act/
Johns Hopkins is the first center in the U.S. to be approved for living donor HIV-positive to HIV-positive kidney transplants. Johhns Hopkins HUB. January 11, 2018. https://hub.jhu.edu/2018/01/11/living-organ-donation-hiv-positive/
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Nel JS, Gay CL, Lachiewicz AM. Further complexities in interpreting the serologic responses in HIV-negative recipients of HIV-positive organs. AIDS. 2019 Mar 1;33(3):595-596. https://pubmed.ncbi.nlm.nih.gov/30702525/