Policies and practice of solid organ donation amongst people living with HIV in Canada: time for education and re-evaluation

Abstract

The numbers of organ donors in Canada and the USA fall short of increasing demand, resulting in increased morbidity, poor health outcomes, higher medical costs and death of many individuals waitlisted for transplantation. In the US, since 2013 when the US HIV Organ Policy Equity (HOPE) Act lifted the ban on organ donation between people living with HIV, the option of using organs from People with HIV became a reality. In Canada, HIV diagnosis was an exclusion criterion to organ donation until 2017, when permission was granted if requirements for ‘exceptional distribution’ could be met. Still, donation of organs from people with HIV poses challenges. Herein, we overview policies involving donors with HIV in Canada in order to inform healthcare providers, researchers and the community. We also advocate for the need to reassess these policies, highlight educational needs and engage interest in advancing research to inform policy reforms.

Keywords:

• Organ donation
• HIV
• HOPE act
• exceptional distribution

Keypoints: People with HIV may serve as either organ donors or recipients. While increasing organs available in the donor pool, important challenges merit consideration and ongoing education and research are needed.

The Canadian HIV Trial Network (CTN) is a Canada-wide partnership of researchers, People with HIV, their caregivers, and health advocates committed to generating knowledge and maximizing the impact of research on health care. One of the ways of achieving this is through knowledge transfer and the organization of educational events. In April 2023, the CTN’s Vaccines and Immunotherapy Core organized a webinar tackling current trends in organ donation in People with HIV. Entitled ‘Organ donation in people living with HIV: Experiences and perspectives from Canada and the United States,’ the webinar gathered transplant specialists from the US and Canada (see Table 1). The event was advertised through various CTN partner organizations, the CTN website and by ‘word of mouth.’ Speakers were chosen based on their research interests and involvement in HIV and/or organ transplant medical care. During the meeting, Dr. Wolfe, the panellists and the audience discussed their experience in selecting organ donors, possibilities of People with HIV as living donors, challenges faced, community engagement/reluctance and key research priorities for the future.

Table 1. Organ donation in PWH: Experiences and perspectives from Canada and the United States – speaker and panelists.

Speakers	Affiliation
Dr. Cameron Wolfe, MBBS, Transplant Infectious Diseases Specialist – guest speaker	Duke Transplant Clinic, Duke University, Medical Center, North Carolina, USA
Dr. Deepali Kumar, Director of Transplant Infectious Diseases	Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada
Dr. Ruth Sapir-Pichhadze, Transplant nephrologist	Division of Nephrology, Department of Medicine, McGill University and Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada
Dr. Jean Tchervenkov, Transplant surgeon	Multiorgan Transplant Program, Departments of Medicine and Surgery, Department of Medicine, McGill University and Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada

The webinar was recorded and posted to CTN YouTube channel. It can be viewed and shared here: https://youtu.be/z2l8UVEIjXM.

At the end of the webinar, numerous questions from the audience revealed the lack and the need for knowledge surrounding this subject. People with HIV in the audience inquired about the benefits of organ donation, possibilities for People with HIV to donate their organs in the US or Canada (if not for transplant, then for research and education) and the existence of lists of people (living with HIV or not) who are willing to receive organs from People with HIV. Prompted by these questions and discussion, this review article aims to shed light on current problems and barriers to organ donation within the HIV community, with a special focus on the Canadian context.

The changed landscape of HIV infection

Since the discovery of HIV as the virus causing Acquired Immune Deficiency Syndrome (AIDS) in the 1980s, the introduction of combined antiretroviral therapy (cART) has been a game-changer for People with HIV. By taking a single tablet daily, or receiving an intramuscular injection every couple of months, People with HIV can now maintain suppressed viral load (VL) and have near-normal life expectancies that are only a few years lower than those in the general population [1]. Increasing longevity has been accompanied by parallel increases in the burden of chronic diseases, with non-AIDS-defining illnesses surpassing AIDS-related cancers and opportunistic infections [2–4]. Today, End-stage Kidney Disease (ESKD) and End-stage Liver Disease (ESLD) are prevalent illnesses in People with HIV [5, 6], both of which may become indications for organ transplantation. While diabetes and hypertension are major drivers of renal disease [7], hepatitis B or hepatitis C co-infection, non-alcoholic steatohepatitis (NASH) and NASH-related liver fibrosis drive increased risk of ESLD [6, 8]. Furthermore, the accelerated incidence of heart disease in People with HIV also raises the potential requirement for heart transplants [9, 10].

The pool of donors (living or deceased) in Canada and the United States falls far short of the increasing demand for organs, resulting in the deaths of many patients waitlisted for transplants. As of December 31, 2022, a total of 3,777 Canadians were on wait lists to receive a transplant [11]. As organ shortages persist, the option of transplanting living or deceased donor organs from people with chronic viral infections such as HIV has become a therapeutic reality. While some countries already accept organ donations from People with HIV to other People with HIV in need of an organ, this practice is yet not widespread.

People with HIV donating organs to recipients with HIV: medical considerations

Superinfections

Various factors must be considered in the context of organ transplantation involving People with HIV, the most obvious being the risk of HIV superinfection. The risk of clinically significant superinfection, with the introduction of another strain of HIV with donated organ, can be minimized with careful review and, if need be, modification of cART at the time of transplant. Although transient infection with donor virus has been documented in recipients, loss of viral control due to superinfection has not been demonstrated [12, 13]. Furthermore, the chances of transmitting a highly mutated virus that could not be controlled with cART are probably smaller than the risk of death waiting for an organ [14]. A multicentre, prospective, cohort study involving patients with HIV donor/recipient kidney and liver transplant [15] showed that out of 14 HIV-positive to HIV-positive kidney, and eight liver transplants, none had multiclass drug-resistant mutations detected or evidence of HIV superinfection. This potential issue is completely manageable in cases of living donors as commercially available assays can determine whether a donor with HIV has cART resistance and match appropriate donors to recipients [16].

Another major clinical challenge is recognizing potential cART drug interactions with immunosuppressive drugs, particularly calcineurin or mTOR inhibitors (e.g. tacrolimus, cyclosporin, sirolimus). Furthermore, cART regimens must be tailored to be active not only against the recipient HIV strain but also the donor’s. With contemporary integrase inhibitor-based regimens, drug interactions have become less problematic.

Concerns about organ quality have led to greater caution in the US, at least, when it comes to donor selection. According to federal guidelines set forth in the HOPE Act [17], recipient centers need to be reasonably assured that a donor does not have an active opportunistic infection or malignancy at the time of their terminal illness. Generally, standard measures of donor organ quality have been used. Donation is permissive of active donor viremia, prior AIDS-defining illness that has resolved, and viral hepatitis coinfection [17].

Higher rate of organ rejections

Overall outcomes following organ transplants involving People with HIV are improving. In a study describing patient survival rates from 2000 to 2019, the 15-year recipient survival post-kidney transplant in People with HIV was 53.6%, compared to 79.6% for HIV-negative individuals, while recipients’ post-liver transplant survival was 70% in People with HIV compared to 75.7% for HIV-negative individuals [18]. Of note, in both cohorts’ organs came from donors without HIV infection. In this retrospective study, authors concluded that long-term AIDS–related comorbidities led to reduced survival after the kidney transplant, while the successful treatment of HCV coinfection helped bridge this gap when it came to liver transplant. Higher rejection rates have been seen in People with HIV, in both those who receive organs from donors without or with HIV infection. Better strategies for immunosuppression are still needed, and although optimal immunosuppression is not defined, most centers believe that it should be at least as aggressive in People with HIV as it is in HIV-negative recipients [19], if not slightly more.

Promising future for people with HIV living donor

Living donation from People with HIV is also permitted, although more caution is required when assessing the donor, to ensure their long-term organ health, and requirement to be suppressed on adequate cART. A case series looking at three living donor kidney transplants by donors with HIV under the HOPE Act (this time to recipients with HIV) showed promising outcomes at two to four years, providing proof-of-concept to support living donation [20].

Organ donors with HIV to recipients without HIV

The first intentional liver transplant from a living donor with HIV, involving a mother to her HIV-negative child, was performed in Johannesburg in 2017 [21]. Documented inadvertent transplants involving organs transplanted from donor with HIV to individuals without HIV [22] showed that the five organ recipients who were followed for four years all had undetectable viral loads within two weeks following transplantation while maintained on cART. Furthermore, individual and graft survival with continuous cART were both 100%.

The scenario of organ transplantation from a donor with HIV to individuals without HIV still poses a dilemma involving public health and personal considerations. This practice would knowingly increase the number of People with HIV – a concern for public health. Individual risks extend to the spouses and partners of organ recipients, who would require notification of the risks by the transplant. Yet, with more options becoming available for the protection of the uninfected partner this is not a ‘deal-breaking’ concern if a potential resolution of the recipient’s medical situation is considered. Similar risks (infection with the virus) are present when using hepatitis C or B virus-positive donors, yet both the US and Canadian systems have been using these donors for many years. While hepatitis C can ultimately be cured, Delman et al. also describe the transplantation from Hepatitis-B Virus positive (HBV) donor of a kidney and liver allografts into HBV seronegative recipients without consequent HBV viremia in recipient or decreased 1-year patient and graft survival [23]. This study recorded 16% kidney and 27.3% liver post-transplant viremic episodes that were resolved after a median of 80 days of entecavir (HBV antiviral) therapy [23]. When the alternative is prolonged dialysis or imminent death, the decision to use an organ from an HIV-positive donor becomes proportionally desirable.

The US HIV Organ Policy Equity (HOPE) Act

In US in 2013 HIV Organ Policy Equity (HOPE) Act, which mandates that the Secretary of the Department of Health and Human Services develop and publish criteria and conduct clinical research for organ transplantation from HIV donors [24]. These changes to the legal and regulatory environment, including carefully designed clinical research protocols and infrastructure for safety reporting, resulted in 24 US hospitals performing a total of 223 transplants (170 kidney and 53 liver transplants) by 2020 (https://unos.org/news/in-focus/hope-act-impact-continues-at-five-year-milestone/). The HOPE Act enlarged the pool of donors: before its implementation, organs from deceased donors with suspected false-positive HIV screening tests were generally discarded due to the chance that the test was truly positive. A retrospective study that examined outcomes of 177 organ transplantations in the period of March 2016 and March 2020 (131 kidneys and 46 livers) from 92 donors (98% of HOPE donors) found 34 false positives that were, thanks to the HOPE Act, not discarded but used for life-saving organ donation [25]. In the US, by 2014 eighteen heart transplants were performed in patients with HIV, with 1-, 2- and 5-year survival of 100%, 100% and 63%, respectively. Yet, most heart transplant centers still explicitly consider HIV + status as a contraindication [26].

Organ donation involving people with HIV in the Canadian landscape

In Canada, the Canadian Standards Association (CSA) Technical Committee on Cells, Tissues, and Organs as well as the Subcommittee on Organs sets the safety standards for organ transplants. These standards are then adopted into regulation by Health Canada. According to these regulations, HIV infection is still an exclusion criterion to become a donor even to another People with HIV. However, organs can be transplanted using the ‘exceptional distribution’ clause with agreement from the transplant team and consent from the transplant candidate. Legislation from 2017 was prompted by the estimated number of potential donors with HIV in Canada [27], noting that among 335,793 hospital deaths between 2005 and 2009 in Canadian provinces excluding Quebec, 39 potential HIV-infected donors were identified.

As of December 31, 2022, a total of 3,777 Canadians were on waiting lists to receive a transplant, and of these 7% had died while waiting (information from Canadian Institute for Health Information: Summary statistics on organ transplants, wait-lists and donors). Given these numbers and in light of data supporting the better outcomes of transplants performed at an earlier stage of diseases using the ‘exceptional distribution’ clause for transplantation is easily justifiable. Additionally, organ donations by deceased donors at high risk for HIV acquisition (sex workers, persons having sex with HIV-positive partners, persons who use intravenous drugs), who have indeterminate screening tests but are otherwise ideal donors, need to be reassessed. Their inclusion can prove to be a lifesaving opportunity for recipients with HIV while simultaneously liberating another organ for individuals without HIV awaiting an organ. For men having sex with men, the CSA standards say that having sex with men in the last 12 months is exclusion for donation, and this regulation has also been adopted into Health Canada regulations. The tissue (blood) banks generally follow this guideline, while solid organs are used all the time, but under exceptional distribution (i.e. with consent from the recipient) – mostly because organ demand is greater than supply.

Today, the actual number of potential deceased donors with HIV with suppressed viremia is estimated to be approximately 3 to 5 per year [27]. Most Canadian provinces and territories have implemented online registries to indicate willingness to donate organs after their death. New Brunswick and Newfoundland and Labrador require registration using forms that can be submitted to the provincial health insurer. Recently, Nova Scotia introduced a ‘presumed consent’ approach – virtually all residents are considered possible organ donors, except for individuals who express their opposition. Still, even with this approach, the application of ‘exceptional distribution’ shrinks the pool of donors (especially considering HIV status).

Opportunities for research

Several opportunities exist to advance knowledge through research around organ transplants. For example, the study of the transplantation of organs from People with HIV to individuals without HIV provides the opportunity to study different HIV strains and mutation development under different immunological pressures [13]. Since viral sequences provide a clear fingerprint, an analysis of longitudinal samples obtained from the recipient can provide important insights into the viral dynamics, the potential of the kidney or liver to serve as a viral reservoir and the effect of renal or liver HIV infection on long-term allograft function. In addition to better understanding the various factors which impact transplant outcomes, such studies also have implications for HIV cure research: learning more about hidden HIV compartments and HIV recombination.

The perspectives of people with HIV and a need for education of health care providers and community

Many barriers to general organ donation have been previously identified, including religious and cultural beliefs, family influences, concerns about body integrity, medical mistrust, questions about the validity of brain death, fear of premature organ recovery, and lack of knowledge or reservations about the donation process [28], many of these shared by People with HIV [29]. In a survey from 2018 by Nguyen et al. 62% of People with HIV respondents were willing to be living donors, but still had concerns about complications of the surgery, post-donation health, or the need for changes in HIV treatment [29]. A following qualitative survey done by the same team found that respondents with HIV willing to be living donors felt they were not informed enough to know the additional risks of living with HIV and being an organ donor [30].

As a person living with HIV since 1985, DL’s had a devasting blow to realize that society looked upon him as an “evil being who somehow was deserving the virus (fueled by media and the medical community) and further aggravated by the sitting government’s enacted laws to prevent People with HIV from donating blood or organs and/or criminalized them for transmission in any form. In all of this, the very thought of donating organs for transplant or research became a moot point. He was no longer a part of society who could make the greatest sacrifice of all after death, ‘I could give so others could live.’ He hoped that with the new laws allowing for organ donation by People with HIV, society would come to understand a new tool has been added to the donor toolbox and those on the list of needing an organ will get to make another choice within their healthcare journey. As a Person with HIV, he will get to choose if he wants to make the sacrifice of becoming an organ donor with the same rights and privileges as someone who is not living with HIV. DL believes that more education and conversations, based on good science, are needed to move the dial.

Other questions and opinions heard at this webinar prompted us to propose an action plan on how to tackle organ donation in the context of living with HIV in Canada. The plan we developed throughout and after the meeting has intertwined goals (Figure 1):

Figure 1. Improvements needed in order to expand organ donation practices involving People with HIV.

1. Asses the knowledge within People with HIV and health care providers about the subject.

2. Provide education and knowledge transfer: advocating for the integration of Donor Registration Cards in Outpatient HIV Clinics, educating of health care providers (for People with HIV and organ transplantation alike) and organizing more webinars and educational programs.

3. Embark on research protocols that will examine efficiency and safety of transplantation of organs from donors with HIV.

This webinar was a first step in a discussion of ongoing challenges, perspectives, and research related to organ donation in People with HIV. It exposed the main barriers to wider spread practice of organ transplant in, and for, People with HIV – lack of awareness and stigma. Participants in the webinar left with a commitment to advance the understanding of the risks and benefits of organ donation by People with HIV, and to push for change in policies and improve associated health care – adding more donor possibilities to a much-needed organ pool. Some steps have already been taken. Authors from the Research Institute of the McGill University Health Centre and the Ottawa Hospital Research Institute who were part of the webinar are currently executing a survey among People with HIV on their knowledge and their opinion on organ transplantation from donors and recipient perspective. Using the information gathered through this survey, more knowledge translation events will be organized, followed by creation of educational material for medical care providers. The final goal we are aiming to achieve is re-evaluating current policies regarding HIV infection and organ transplantation that will then benefit everyone.

Disclosure statement

D.K. has received clinical trials grants from GSK and consulting fees from Roche, GSK, Merck. RSP has received educational grant to support a post-graduate trainee from Paladin. Peer-reviewed funding from Genome Canada, CIHR, FRQS, Kidney Foundation of Canada, RI-MUHC, MUHC Foundation, MI4. CTC has received speaker honorariums from Gilead, consulting honorariums from Viiv and Moderna, travel support to attend conferences from Gilead and Viiv and grant support from Gilead, Merck and Tilray Inc. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Additional information

Funding

This webinar and manuscript was supported by the CIHR Canadian HIV Trials Network (CTN) and the Canadian HIV Cure Enterprise (CanCURE) 2.0.