Hope for kidney transplantation in candidates with human immunodeficiency virus

Abstract

Kidney transplantation continues to be the kidney replacement therapy of choice for patients with end stage kidney disease (ESKD) associated with a survival benefit over remaining on dialysis. Patients living with both ESKD and human immunodeficiency virus (HIV) have traditionally faced barriers accessing the kidney transplant (KT) waiting list given need for special considerations in addition to general listing requirements for KT candidates. The HIV Organ Policy Equity (HOPE) Act in 2013 and HOPE Act Variance in 2015 restricted HIV positive donor (+D) to HIV positive recipient (+R) transplants to research protocols or Institutional Review Board approved programs. Federal regulatory changes in 2024-2025 removed the above restrictions making HIV +D to HIV +R KTs standard of care practice for approved centers. Removal of the research criteria requirements in alignment with federal regulatory changes will likely expand access so that more individuals living with HIV can obtain a KT. Herein we will provide a narrative review of the available literature in the PubMed database on studies completed under the HOPE act as well as the special considerations in evaluating HIV positive renal transplant candidates and their subsequent post-transplant care to help ensure clinician and patient comfort in this era.

Key Words: Human immunodeficiency virus; Kidney transplantation; Public health policy; Immunosuppressants; Antiretroviral therapy

Core Tip: Patients living with both end-stage kidney disease (ESKD) and human immunodeficiency virus (HIV) have faced barriers accessing the kidney transplant waiting list. The HIV Organ Policy Equity (HOPE) act in 2013 and the HOPE act variance in 2015 restricted HIV positive donor (+D) to HIV positive recipient (+R) transplants to research protocols. Federal regulatory changes in 2024-2025 removed the above research restrictions for transplant centers. The evidence supports kidney transplantation as the standard of care for patients living with both ESKD and HIV, and that HIV +D to HIV +R transplantation is non-inferior to the use of donors without HIV for candidates living with HIV.

INTRODUCTION

There has traditionally been an observed disparity in patients who are human immunodeficiency virus (HIV) positive living with end stage kidney disease (ESKD) who pursue kidney transplant (KT) evaluation compared against patients who are HIV negative living with ESKD[1]. This is despite findings in the seminal National Institute of Health (NIH) study that transplantation of organ transplant candidates living with HIV who have no evidence of acquired immunodeficiency syndrome (AIDS) can prolong meaningful life for people living with HIV (PLWH) who need a KT[2-5]. This concerning disparity is further compounded by the prevalence of the black race being significantly higher among KT candidates living with HIV compared to the HIV-negative transplant referral population, especially given KT candidates of the black race have also been noted to have significant disparities in access to transplantation[1,6,7]. Given that PLWH are at increased risk for kidney disease and subsequent ESKD due to a litany of factors ranging from direct kidney injury by HIV (with HIV associated nephropathy as a leading cause in the early days of the epidemic) and renal toxicity of their antiretroviral therapy (ART), mitigating the burden of ESKD for PLWH is an ethical priority[8-12]. Additionally, it has been noted that KT candidates living with HIV experience higher waitlist mortality compared to their HIV negative cohort[13,14]. To help address the disparity for KT candidates living with HIV and help attenuate the organ shortage and waitlist mortality, the potential donor pool was sought to be expanded to include HIV-infected deceased donors (HIVDD)[15]. The 1988 amendment to the National Organ Transplant Act banned the utilization of organs procured from donors “infected with the etiologic agent for AIDS”, making this endeavor challenging[15]. Since then, several studies emerged looking at the potential safety and efficacy of adding HIV positive kidney donors to the potential donor pool for these HIV positive candidates to challenge the law in the United States banning the transplantation of HIV-infected donor organs[5,15,16]. With the passage of the HIV Organ Policy Equity Act and its recent removal of the research requirement, this expands the potential kidney donor pool for patients living with HIV to include donors with HIV and will likely bring about more KT patients living with HIV[17]. We aim to provide a narrative review of selected studies detailing kidney transplantation in PLWH indexed in the PubMed database that helped bring about this new era in transplantation, with particular emphasis on key studies completed under the HOPE act. Additionally, in an effort to ensure clinician and patient comfort in this era, we will provide an overview of specific considerations in the evaluation and care of KT patients living with HIV based on current practices from selected recent studies indexed in the PubMed database.

A HISTORY OF THE HOPE ACT

As advances in ART significantly improved the life expectancy of persons living with HIV, it challenged the notion of HIV being considered a contraindication for organ transplantation[2,4,18-20]. With the growing body of evidence from efforts conducted in resource limited South Africa with positive results of transplanting kidneys from HIVDD into patients living with HIV, the United States Congress was called into action[16,18,21,22]. Additional retrospective studies reviewing the associations of transplant era and transplant center experience measures, such as participation in NIH consortium, on outcomes for KTs for PLWH found improving outcomes in subsequent transplant eras but no significant difference in outcomes based on center level experience further supporting expansion centers offering KTs for PLWH[23]. On November 21, 2013, the HIV Organ Policy Equity (HOPE) act was signed into law, permitting the legal transplantation of kidneys from HIV positive donors into HIV positive recipients as part of a research protocol[24-26]. The estimated impact at the time for the United States donor pool was a potential increase of 500-600 HIVVD[15]. As another significant part of the HOPE Act, the United States Organ Procurement and Transplant Network (OPTN) was required to revise the standards of quality and policies for HIV positive donor organs, creating what came to be known as the “open variance”[10]. This mandated any transplant center that sought to enact HIV positive donor (+D) to HIV positive recipient (+R) transplants must first apply to join the open variance, provide sufficient documentation of local institutional review board (IRB) approval, then be subject to regular data monitoring safety reports, while abiding by the Final Human HOPE Act Safeguards and Research Criteria published by the Department of Health and Human Services (HHS) in 2015 to do so safely[10,26].

With this framework for clinical research into HIV +D to HIV +R transplantation established, the first pilot clinical trial was approved by the OPTN under these criteria on January 8, 2016 with the first HIV +D to HIV +R kidney and liver transplants in the United States performed in March 2016 at John Hopkins Hospital[10,27]. By November 2017, there were 22 transplant centers approved to perform HIV +D to HIV +R transplants in 10 United Network for Organ Sharing regions[28]. Based on findings of the IRB-approved studies completed under the HOPE act variances in 2024 the United States Department of HHS abolished the research mandate to permit transplant centers in the United States to transplant organs from HIV +D to HIV +R as part of clinical practice[29,30].

FINDINGS OF HOPE

We begin our discussion of the findings of studies completed as a result of the HOPE Act with an unexpected benefit, the increased utilization of deceased donor organs with suspected false-positive screening HIV tests, as the practice before the HOPE act was that these organs were generally discarded due to the chance the test was truly positive[31]. Based on a small prospective cohort study of 10 HIV + deceased donors with false positive HIV testing and established false positive rates of the approved assays used to screen deceased donors, it has been estimated that there would be an increase of 50-100 donors with false positive HIV results that could be utilized per year for transplantation[31]. The impact on wait time and higher kidney transplantation rate was apparent based on registry data of 324 transplant candidates living with HIV willing to accept organs from donors with HIV and 46025 transplant candidates who were not listed for kidneys from HIV+ donors were noted to have shorter wait times (10.3 months vs 60.8 months)[32]. A notable limitation of this study is that OPTN only captures HIV status for transplanted candidates and so the ideal comparison group KT who were PLWH who were not willing to accept organs from donors with HIV was not able to be utilized[32].

Turning to one of the potential concerns of HIV +D to HIV +R transplantation was the potential for recipients to acquire a new strain of HIV from the donor that is resistant to their ART (e.g., a HIV superinfection), a concern that, among others, mandated HIV +D to HIV +R transplantation occur solely under research protocols[33]. On longitudinal analysis of viral dynamics of HOPE act KT recipients, Travieso et al[34] was able to demonstrate that donor HIV can be detected in blood and urine specimens collected from organ transplant recipients and were largely dependent on donor plasma viral load and that this was transient, with no recipient having donor HIV detected a later time points beyond 16 days indicating lack of sustained HIV superinfection. Similarly, in other long-term follow-up analyses of HIV +D to HIV +R transplant in South Africa, although drug-resistant mutations were found in samples, none of them were donor-derived[35]. It is likely that for recipients of HIV +D organ, being on ART at the time of exposure to donor HIV (i.e., time of transplant) and maintained thereafter, is protective[33]. This conclusion is based on the findings that although transient donor-derived HIV strains have been detected, there has been a lack of sustained donor-derived superinfections that were found in the studies completed in recipients who were ART suppressed the lack of clinically HIV breakthrough infections as well in the same[35-38].

There is some data available on living kidney donors with HIV transplanting to candidates with HIV as part of studies completed under the HOPE act variance, and though it was limited to very small case reports/series, it serves as a proof of concept, given positive results concerning safety[39,40]. Kidney donation by PLWH is controversial, given that there are estimates that up to 30% PLWH will experience kidney dysfunction due to traditional and HIV related risk factors, including those borne from being on ART therapy[41-43]. There was found to be a strong willingness to donate reported in a study involving semi-structured in-depth interviews of the patients living with HIV[44]. There is cautious optimism found in a study involving semi-structured in-depth interviews amongst infectious disease healthcare providers regarding patients with HIV being living donors, should thorough evaluations to prioritize donor safety be conducted, as well as formal educational materials be available to permit obtaining an informed consent[45].

Finally, we turn to the findings of the landmark multi-center observational study of kidney transplantation in people with HIV by Durand et al[46] in 2024, in which transplantation from donors with HIV appeared noninferior concerning the primary outcome of a safety event to that of donors without HIV. This study spanned 26 United States centers and 198 deceased donor KT recipients (99 from a donor with HIV and 99 from a donor without) and reviewed the composite of death from any cause, graft loss, HIV breakthrough infection, persistent failure of HIV treatment, and opportunistic infection (OI), which was not significantly different between the two groups[46]. Additionally, overall survival at 1 year and 3 years, survival without graft loss at 1 year and 3 years, and serious infection were non-inferior. While there was a threefold increase noted in the risk for HIV breakthrough infections in the group with donors with HIV, this was predominantly in the context of nonadherence with ART. Study limitations included that true randomization of organs from donors with and without HIV was not possible due to OPTN allocation constraints and HIV and transplant immunosuppression and prophylaxis regimens were heterogenous[46]. A fortuitous strength of this study however is that the control group of recipients whose donors did not have HIV included 27 donors who had false positive HIV tests and were treated as having HIV during allocation representing an ideal counterfactual control[46].

These findings led to the United States Department of HHS to remove the IRB-approved research requirement for approved transplant centers to permit transplantation of donor kidneys from donors with HIV into recipients with HIV as routine clinical care[29,30] (Figure 1).

Figure 1 Kidney transplantation and human immunodeficiency virus timeline. This figure depicts the advances in kidney transplantation in people living with human immunodeficiency virus through the years, with emphasis on landmark events and studies impacting its practice (created in BioRender). HIV: Human immunodeficiency virus; ART: Antiretroviral therapy; KT: Kidney transplant; +D: Positive donor; +R: Positive recipient; HHS: Health and Human Services; HOPE: Human immunodeficiency virus Organ Policy Equity; PLWH: People living with human immunodeficiency virus; ESKD: End stage kidney disease.

CONSIDERATIONS FOR EVALUATING RENAL TRANSPLANT CANDIDATES LIVING WITH HIV

This expansion of potential donor kidneys is particularly exciting as patients with HIV continue to experience disparities in access to transplantation, as they are less likely to be listed for renal transplantation than patients without HIV, often due to uncontrolled HIV infection, substance use, or incomplete evaluation[47,48]. Lower completion rates were observed among Black patients and patients with a history of illicit drug use[1,49].

In general, PLWH who are KT candidates should have a CD4 count greater than 200 cells/mm³, an undetectable HIV viral load (less than 50 copies/mL), and be on a stable ART regimen with good medication adherence for 3-6 months before transplantation[50,51]. Opportunistic infections without effective therapy, such as progressive multifocal leukoencephalopathy or chronic gastrointestinal cryptosporidiosis, are typically contraindicated as they are likely to significantly worsen after immunosuppression[50].

Many HIV+ patients also have hepatitis C virus co-infection, which is associated with worse graft and patient survival compared with HIV infection alone[52]. In transplant recipients, HCV can progress more rapidly due to immunosuppression and is linked to higher risks of infections, liver disease, proteinuria, chronic allograft nephropathy, graft loss, and death[53]. Because of this, many studies recommend treating hepatitis C before transplantation when possible.

Overall, the literature shows that renal transplantation can be safe and effective in carefully selected HIV+ patients. Good outcomes depend on controlling HIV infection before transplant, carefully managing drug interactions between ART and immunosuppressants, and coordinating care through a multidisciplinary transplant team that includes HIV specialists[49,54].

ART MANAGEMENT AND DRUG INTERACTIONS

A key consideration before transplantation is drug interactions between ART and post-transplant immunosuppressive medications. Managing ART in KT recipients living with HIV after transplant is complex because of pharmacokinetic interactions between antiretrovirals and immunosuppressants[55,56]. Common immunosuppressants, including calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus, are metabolized through the cytochrome P450 3A4 (CYP3A4) enzyme pathway, and some HIV medications can impact this pathway[57].

Protease inhibitors (PIs) that inhibit the last step in HIV maturation also inhibit CYP3A4, can significantly increase CNI drug levels and require substantial dose reductions[58-60]. This interaction can cause increased and unpredictable levels of CNIs, raising the risk of nephrotoxicity or, if not managed carefully, under-immunosuppression and resulting rejection[55,58]. The clinical effects of these interactions are explained by Muller et al[55] and Botha et al[56], who highlight the importance of intensive therapeutic drug monitoring. Early multicenter experiences revealed major difficulties in stabilizing CNI doses among recipients on PI-based ART, often requiring major adjustments and close pharmacologic monitoring[58,61]. Similarly, the key trial by Stock et al[5] reported large variability in tacrolimus levels in patients on PI regimens, emphasizing the narrow therapeutic window in this setting. Frassetto et al[58] also showed that tacrolimus doses might need to be reduced by more than 90% when used with PIs.

On the other hand, non-nucleoside reverse transcriptase inhibitors (NNRTI) such as efavirenz and nevirapine induce CYP3A4, which can lower immunosuppressant drug levels and thus increase the risk of rejection[58]. These NNRTIs inhibit deoxyribonucleic acid (DNA) synthesis by allosteric binding on the viral reverse transcriptase inducing a conformational change impeding its regular functioning[62].

In addition, certain ART medications such as the nucleoside(tide) reverse-transcriptase inhibitor (NRTI) tenofovir disoproxil fumarate can cause renal toxicity and proximal tubulopathies thus require close monitoring in transplant recipients[63]. NRTIs act to impede HIV DNA synthesis by mimicking naturally occurring nucleosides for viral reverse transcriptase leading to premature termination[64].

ART pharmacokinetic boosters such as ritonavir and cobicistat enhance the action of their corresponding drugs by potent inhibition of the CYP3A enzyme responsible for their metabolism and as such also have significant interactions with CNIs[60,65].

Because of these interactions, many transplant programs in consultation with transplant infectious disease specialists may favor un-boosted integrase strand transfer inhibitor (INSTI) based ART regimens, such as raltegravir, bictegravir or dolutegravir, which have minimal CYP3A4 interactions and allow for more stable immunosuppressive management post-KT[63,66]. Grupper et al[40] provide evidence that INSTI-based ART can be effective over the long term; they described a case where a patient maintained viral suppression and stable tacrolimus levels for seven years following HIV-positive to HIV-positive kidney transplantation. These INSTIs prevent HIV DNA integration into the genome of the host by binding to the responsible enzymes[67]. An important consideration with INSTIs that transplant professionals should be aware of is their inhibition of the renal transporters organic cation transporter (OCT) 2 and multidrug and toxin extrusion (MATE) 1, which can lead to decreased creatinine excretion, increased serum creatinine, decreased estimated glomerular filtration but does not negatively impact measured glomerular filtration rate[67]. This INSTI interaction with OCT2/MATE1 was experienced by HOPE in Action researchers firsthand on follow up of 2 of their 3 study living kidney donors with HIV on INSTIs who were found with significantly lower estimated vs measured glomerular filtration rates post donation[39].

ART regimens often require adjustments after transplants, not because of HIV failure but due to pharmacological conflicts with immunosuppressants[55,56]. These cases highlight the importance of collaboration between transplant and HIV specialists to develop regimens that minimize adverse interactions while ensuring viral suppression[55,56]. Overall, available evidence supports using INSTI-based ART in transplant patients whenever possible, to simplify management and reduce the risk of drug interactions[55,56]. Early and regular monitoring of drug levels after transplant is essential to prevent rejection and toxicity[55,58]. A summary of the different classes of ART utilized for HIV and considerations for renal transplantation based on current evidence and clinical guidelines is presented in Table 1.

Table 1 Summary of different classes of medications used in human immunodeficiency virus antiretroviral therapy and considerations in renal transplantation.

Drug class	Examples	Mechanism of action	Renal transplant considerations	Ref.
Protease inhibitors	Atazanavir; darunavir; fosamprenavir; nelfinavir; tipranavir	Inhibition of the last step in HIV virus maturation that renders assembled immature viral particles noninfectious	Potent inhibitors of CYP 3A4 with major interaction with CNIs. Should be avoided, if possible, in transplantation	[60,65]
Nucleoside(tide) reverse transcriptase inhibitors	Abacavir; emtricitabine; lamivudine; tenofovir (tenofovir alafenamide or tenofovir disoproxil fumarate); zidovudine	Inhibition of HIV viral replication process by mimicry of nucleoside(tides) thus blocking viral reverse transcriptase and ending the DNA elongation step in HIV-1 and HIV-2 infection life cycle	Tenofovir disoproxil fumarate can cause renal toxicity and proximal tubulopathies requiring close monitoring	[63-65]
Nonnucleoside reverse transcriptase inhibitors	Efavirenz; etravirine; nevirapine	Blocking of DNA prolongation through binding the HIV-1 viral reverse transcriptase at a separate allosteric site	Inducers of CYP 3A4 with major interaction with CNIs. Should be avoided, if possible, in transplantation	[62,65]
Integrase strand inhibitors	Raltegravir; dolutegravir; bictegravir	Inhibition of the integration of transcribed viral DNA into the host genome	Potential for decreasing creatinine excretion, increasing serum creatinine and decreasing estimated glomerular filtration without impacting measured glomerular filtration. Regimens generally preferred in transplantation	[65,67]
Boosters	Ritonavir (e.g., in ritonavir-boosted lopinavir). Cobsistat (e.g., in elvitegravir boosted with cobicistat)	Pharmacokinetic enhancer by potent and selective inhibition of cytochrome P450 3A enzymes	Potent inhibitors of CYP 3A4 with major interaction with CNIs. Should be avoided, if possible, in transplantation	[60,65]

CNIs: Calcineurin inhibitors; HIV: Human immunodeficiency virus; CYP 3A4: Cytochrome P450 3A4; DNA: Deoxyribonucleic acid.

IMMUNOSUPPRESSION AND REJECTION RISK POST-TRANSPLANT

HIV-positive KT recipients experience higher rates of acute rejection than typically reported in general KT cohorts, with a multicenter prospective study finding that approximately 31% of recipients developed biopsy-confirmed acute rejection within the first-year post-transplantation[5]. Early multicenter data also indicated increased rejection rates, though patient and graft survival remained acceptable at 1 year and 3 years[61]. Potential reasons include ongoing immune activation despite viral suppression and complex pharmacokinetic interactions between ART and CNIs, as more than 50% of the patients with HIV in the NIH were on regimens with ritonavir-boosted PIs[21,49,56,68].

Despite these risks, the long-term outlook remains encouraging. Research indicates that transplantation offers a survival advantage over continued dialysis for individuals living with HIV[69]. A 16-year study from a single center demonstrated durable graft survival when structured monitoring protocols were used[63], and a recent systematic review and meta-analysis validated favorable five-year graft results in HIV-positive KT patients[53]. Additionally, outcomes tend to improve with later transplant era with no significant difference reported in outcomes between centers early in experience vs advanced in experience[23].

An analysis based on the scientific registry of transplant recipients indicated that neither induction therapy with antithymocyte globulin (ATG) nor interleukin-2 receptor antagonist (anti-IL2R) significantly increased infection risk in HIV-positive KT patients compared against those recipients that received no induction[70]. Additionally, ATG induction was associated with lower acute rejection rates compared with anti-IL2R or no induction therapy[70]. More recent multicenter studies also show reduced rejection rates and differences in graft survival in patients who received lymphocyte-depleting induction agents, such as rabbit ATG with ART regimens that were PI sparing, compared with non-lymphocyte-depleting strategies and other ART combinations[57].

INFECTION PROPHYLAXIS AND OPPORTUNISTIC INFECTIONS

HIV-positive KT recipients are at increased risk of infections post-transplant due to immune dysregulation and immunosuppressive therapy[5,68,71]. This necessitates tailored prophylactic strategies to prevent OIs while considering toxicity and antimicrobial resistance[55]. A United States national survey by Batiuk et al[72] revealed significant variability in prophylaxis protocols for cytomegalovirus (CMV), pneumocystis carinii pneumonia (PCP), tuberculosis, and fungal infections. Most centers used trimethoprim–sulfamethoxazole for PCP and valganciclovir or ganciclovir for high-risk CMV patients, though protocols varied[72]. Data from Stock et al[5], gathered across multiple centers, showed post-transplant viral and bacterial infections in HIV-infected recipients, including CMV viremia and BK virus replication, with low rates of classic OIs like PCP and cryptococcosis, likely due to effective ART and structured prophylaxis. Similarly, Ailioaie et al[71] reported infectious complications in HIV-infected KT patients, highlighting that viral reactivation, especially CMV and BK virus, are common as in transplant recipients without HIV, while traditional AIDS-defining OIs are now rare in the ART era.

In HIV/HCV-coinfected patients, outcomes have significantly improved since the advent of direct-acting antivirals (DAAs)[52]. Camargo et al[52] observed fewer liver-related complications and better post-transplant outcomes in the DAA era than in the pre-DAA period, highlighting the critical role of viral eradication in reducing infection-related morbidity. Moreover, effective multidisciplinary collaboration, particularly involving transplant infectious disease specialists, is essential in current practice to improve outcomes and prevent infections[46,56]. Overall, with standardized prophylaxis, vigilant virologic monitoring, and interdisciplinary coordination, OIs in HIV-positive KT recipients have decreased in the ART era, although bacterial infections and viral reactivations still require careful monitoring[5,71].

POST-TRANSPLANT MALIGNANCY RISK

Malignancy remains a major long-term complication for post-transplant patients, with individuals with HIV being at increased risk of virus-related cancers such as Kaposi sarcoma, non-Hodgkin lymphoma, and anogenital cancers, while organ transplant recipients are more prone to lymphoma and other cancers[73,74]. Consequently, HIV-positive transplant patients may share overlapping risk factors, highlighting the importance of vigilant screening[73,74]. Large registry data indicate that transplant recipients face significantly higher malignancy rates than the general population, especially lymphomas and virus-associated cancers[74]. HIV-positive KT recipients have several independent risk factors for developing cancer; therefore, ongoing surveillance, including routine cancer screening and dermatologic exams, is essential, especially for high-risk groups[73,74]. As transplant success and survival improve for HIV-positive individuals, monitoring for and prevention of malignancies will become increasingly vital components of long-term care[74].

LONG-TERM OUTCOMES AND VIROLOGIC MONITORING

Over the last twenty years, long-term outcomes for KT patients living with HIV have greatly improved, mainly thanks to advances in ART, structured post-transplant care, and optimized transplant protocols[61,63]. Initial concerns about graft survival and patient mortality have been alleviated by growing evidence of sustained results in selected patients[5,61,69]. A 16-year study from a single center showed consistent graft survival and acceptable long-term patient outcomes in HIV-positive recipients[63]. Likewise, multicenter prospective data from Stock et al[5] indicated that, despite higher early rejection rates, most recipients maintained long-term graft function. Survival comparisons demonstrated that transplantation provides a clear survival benefit over remaining on dialysis for HIV-positive candidates[69]. A recent systematic review and meta-analysis confirmed that five-year graft survival rates in PLWH are promising and similar to those in higher-risk HIV-negative groups[53].

Consistent data indicate that patients maintain virologic suppression after transplantation[61,63]. Both earlier and more recent studies report high rates of sustained undetectable HIV RNA levels when ART is properly administered[5,46]. In individuals coinfected with HIV and HCV, outcomes have significantly improved since the advent of DAAs, resulting in fewer HCV-related complications in the DAA era[52]. Overall, current evidence shows that with integrated transplant and HIV care, careful ART management, and structured monitoring, HIV-positive patients can achieve long-term graft survival and viral suppression similar to that of carefully selected HIV-negative transplant recipients[5,53,69].

PSYCHOSOCIAL, ETHICAL, AND EQUITY CONSIDERATIONS

While the clinical care for KT patients living with HIV has significantly advanced, important psychosocial and ethical challenges continue to persist[17]. These include inequalities in access to transplantation, HIV-related stigma, difficulties in obtaining informed consent, and emerging ethical concerns regarding the use of HIV-positive donors under the HOPE act[17,39]. Historically, PLWH were often denied access to transplantation due to fears of poor outcomes and HIV progression with over 88% of 148 responding transplant centers surveyed in the United States stating as such in the 1990s[19]. Nonetheless, recent evidence indicates that with careful recipient selection, acceptable patient and graft survival rates are achievable. This underscores the need for expanded eligibility and the ethical imperative of equitable access[5,61,69].

Moreover, experience with living HIV-positive kidney donors broadens the ethical discussion to include donor protections, long-term follow-up, and the infrastructure needed for safe implementation[39]. Especially considering that consistent political and resource commitment is essential, and inconsistent access to ART for PLWH due to major disruptions in funding can impair key quality outcomes in care for PLWH[65]. Despite some advancements, disparities in access remain. Recent studies underscore ongoing barriers at multiple levels, such as stigma, limited participation at centers, logistical problems, and other structural issues that restrict transplant access for PLWH, even when outcomes are similar[17,28,75,76].

Practical considerations to address these challenges include emphasizing patient education and consistent long-term follow-up with providers and medication adherence. Informed consent for HIV-positive recipients, particularly in HIV D+/R+ transplantation, should clearly outline potential risks like HIV breakthrough infection in the absence of consistent ART adherence and an increased rejection risk particularly with certain combinations of CNIs with PI and/or NNRTI containing ART regimens and use of non-lymphocyte-depleting immunosuppressant induction therapies[46,77]. Recent reviews and guidelines underscore these concerns and stress the importance of thorough counseling and ongoing monitoring to ensure viral suppression[55,56]. Additionally, long-term follow-up data from living HIV-positive donors showing results over a 7-year period post-transplant support the feasibility and the ethical responsibility to provide continuous access to ART, long-term follow-up, and detailed informed consent for both donors and recipients[40]. Overall, the literature suggests that as transplantation options for patients living with HIV expand, policies and programs promoting equity, patient education, and inclusive research are essential to addressing ongoing psychosocial and ethical issues[17,39,78].

CONCLUSION

In the current era of available and effective ART, there is substantial evidence to support kidney transplantation as the standard of care for patients living with both ESKD and HIV, and an ever-increasing body of evidence to support that HIV +D to HIV +R transplantation is safe and non-inferior to the use of donors without HIV for KT candidates living with HIV. While there is limited evidence of long-term risks for potential living donors living with HIV available, there is a strong willingness to donate reported in the PLWH community and an overall cautiously optimistic view held by healthcare providers. This viewpoint of healthcare providers is contingent on thorough donor evaluations that prioritize donor safety, as well as formal educational materials be available to permit obtaining true informed consent. Unfortunately, the transplant team cannot currently guarantee continued lifelong access to ART for living donors living with HIV post donation, which may compromise post donation kidney function, and this needs to be disclosed. After all, health care providers, to the best of their ability, have a responsibility to help ensure that PLWH (be they donors or recipients) have a life expectancy as close to that of the general population.