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In 2013, the passage of the HOPE act allowed HIV-positive recipients to receive organs from HIV-positive donors under the auspices of research studies. This historic act, meant to increase the availability of donor organs to people living with HIV (PLWH), was a significant acknowledgement that, due to combination antiretroviral therapy (ART), HIV is no longer a life-limiting disease. Rather, PLWH are living near normal lifespans and developing other diseases of ageing such as coronary artery disease or heart failure (HF). Furthermore, PLWH develop cardiovascular disease more frequently and at younger ages due to a complex interplay of socioeconomic and disease-specific risk factors. The increased prevalence of end-stage heart disease within this vulnerable group makes equitable access to advanced heart therapies a matter of clinical urgency. This paper will focus on the role of cardiac transplantation for PLWH, with special emphasis on the global context.
The historical context for solid organ transplantation in PLWH
Most data on solid organ transplantation in PLWH come from the kidney and liver transplantation literature. With effective ART, kidney and liver transplant has now become the standard of care among PLWH with end-stage disease in high-income countries. Initial fears of increased rates of infection leading to higher morbidity and mortality among PLWH were proven to be unfounded.1 For example, 1-year survival is similar for PLWH who receive a kidney transplant, regardless of whether the donor is HIV positive or HIV negative (HIV D+/R+ vs HIV D+/R−).1 Similarly, for liver transplantation among PLWH, outcomes continue to improve, even in those with coinfection with other viruses. PLWH alone have comparable liver transplantation outcomes as HIV-negative individuals, and patients with both HIV and hepatitis C virus (HCV) have significantly improved outcomes with direct antiviral agents.1
Despite these successes, solid organ transplantation for PLWH faces unique challenges. There are limited data around the ideal maintenance immunosuppression regimen for PLWH undergoing transplantation. Protease inhibitors, used in some antiretroviral regimens, have notable interactions with immunosuppressive medications such as calcineurin inhibitors. Additionally, studies have shown that there are higher rates of acute rejection among PLWH transplant recipients, though the mechanism for this is still not well understood.2 Even monitoring for allograft dysfunction in PLWH presents unique challenges. For example, cell-free DNA-based assays used to monitor for allograft dysfunction have not been well studied in PLWH.2 Finally, systemic barriers decrease the likelihood of successful referral and listing for kidney transplants in PLWH. For many PLWH, the initial transplantation referral process is prolonged given the rigorous HIV management and assessment that occurs prior to referral to transplant medicine, often delaying referral.3 Additionally, racial disparities affect equitable access to transplantation medicine. PLWH with end-stage kidney disease are more likely to be black, though over half of all kidney transplants in HIV-positive recipients are white, and black patients with HIV are significantly less likely to have completed an evaluation for kidney transplantation than their white counterparts.3
Heart transplantation among PLWH
Heart transplantation remains the gold standard treatment for advanced HF, with a median length of survival following transplantation of 10.7 years. PLWH are at increased risk of developing HF compared with the general population, even when controlling for traditional risk factors.1 Fortunately, improvements in ART have significantly reduced the incidence of HIV-related cardiomyopathy, with ischaemic heart disease now being one of the primary causes of advanced HF in PLWH.
While there are significantly fewer heart transplants among PLWH, small case studies have shown that, as with the kidney/liver populations, the 5-year survival between PLWH and HIV-negative patients undergoing heart transplantation was similar.4 Yet, as with kidney and liver transplantation, cardiac transplantation in PLWH lags significantly behind heart transplantation in HIV-negative patients. In addition to similar challenges around ideal immunosuppressive regimens, increased risk of rejection and challenges in equitable transplantation workup, PLWH heart recipients also struggle with a scarcity of available transplantation centres equipped for cardiac transplantation for this vulnerable patient population. Between January 2012 and February 2013, Uriel et al surveyed 89 heart transplantation centres within the USA and Canada and found that 57% viewed HIV as a contraindication for advanced heart therapies including transplant.5 Of the 25 centres interviewed that performed solid organ transplantation in PLWH, 23 of these centres had never performed a heart transplantation in PLWH.5 In fact, nine of these centres viewed HIV as a contraindication for cardiac transplantation even though they performed other solid organ transplants in PLWH.5 When transplant centre directors were interviewed, they noted limited long-term data on heart transplantation among PLWH as a continued concern.5
The global burden of advanced heart disease and HIV
Unfortunately, the global burden of advanced heart disease and HIV infection is greatest in countries with the least capacity to perform heart transplantation. According to the WHO, as of 2020, roughly 37.7 million individuals are living with HIV.6 The brunt of the burden of HIV is within the African continent, where nearly 1 in every 25 adults has HIV. Similarly, heart disease remains a significant cause of mortality worldwide, with ischaemic heart disease as the number one cause of mortality worldwide. HF is estimated to affect 26 million people worldwide, and its prevalence is expected to continue to increase given increasing life expectancy. This has a particularly profound effect on low-income and middle-income countries, which often lack the robust preventive medicine infrastructure to combat worsening heart disease.
Worldwide, most heart transplantations take place in the global west. Within Africa, only South Africa—which performed the first heart transplantation in the world in 1967—has a robust heart transplant programme. An overview of the significantly more prevalent renal transplantation programmes highlights the challenges transplant medicine faces on the continent.7 Algeria, Cote d’Ivoire, Ethiopia, Kenya, Namibia, Nigeria and South Africa all have advanced kidney transplantation centres, yet only South Africa offers deceased donor transplantation. Barriers to deceased organ donation include absence of infrastructure such as organ procurement programmes, tissue typing and cross-matching facilities and financial constraints.7 These barriers present challenges in creating and maintaining robust cardiac transplantation centres. However, building advanced cardiovascular care capacity in low-income countries is possible, as has been demonstrated over the past decade for cardiac catheterisation and paediatric heart surgery in Uganda.8 Yet, even those African nations who already have the available infrastructure and expertise, such as Uganda, are often limited from a governmental perspective which has not enacted clear laws and regulations on organ donation.
Given the increasing burden of advanced heart disease among PLWH, now is the time to improve access to cardiac transplantation for eligible PLWH worldwide, from high-income countries where disparities persist to low-income countries where solid organ transplantation programmes are few or only nascent. As the field of advanced heart therapies advance with innovations such as xenotransplantation, it is increasingly important to invest in equitable development of cardiac transplantation programmes globally, to avoid further widening current inequalities. Increased experience with heart transplantation in PLWH in Africa could provide important insights that would benefit PLWH elsewhere in the world. Attitudes and practices are changing, but more work is needed. We advocate for a two-pronged approach. First, transplant capacity at regional centres of excellence in Africa could be achieved by addressing key organisational, financial and legal barriers. As was the case in building a cardiac catheterisation programme in Uganda, public–private partnerships and both North–South and South–South training collaborations will be required to build solid organ transplant capacity in Africa. Legislatures will need to provide clear frameworks for transplant centres to ensure regulatory and ethical standards. Second, advocacy and education efforts aimed at established transplantation programmes and governments are needed to address persistent disparities for PLWH in higher-income countries. Although the task appears daunting and the competing priorities are many, we are inspired by the words of Nelson Mandela—‘It always seems impossible until it’s done.’
Patient consent for publication
This study does not involve human participants.
Contributors All authors contributed to the drafting of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Commissioned; internally peer reviewed.