Ethical frameworks and community engagement in HIV cure-related research at the end of life: looking back, moving forward

Abstract

Purpose of review

HIV cure-related research at the end-of-life has created a rare opportunity to study viral persistence in tissues that cannot be safely or repeatedly sampled during life. This review examines ethical frameworks and community engagement approaches in this field from 2016 to 2026, with attention to potential new scientific directions and implementation across diverse settings.

Recent findings

The literature has developed important recommendations on informed consent, autonomy, dignity, altruism, patient-participant-centeredness, next-of-kin/loved one involvement, staff coordination, rapid research autopsy, and tissue stewardship. Much of this work has emerged from the Last Gift program and related studies in the United States, with growing documented evidence from Canada and emerging biospecimen infrastructure work in Brazil. As the field expands toward novel approaches, such as organoids, organ-on-chip systems, ex vivo models, and possible in vivo testing of HIV cure-related research strategies, ethical questions increasingly extend to tissue transformation, future use, commercialization, acceptable risk, oversight, and long-term governance.

Summary

HIV cure-related research at the end-of-life has been ethically deliberate from the outset. The next task is to define the practices, safeguards, and engagement processes needed to conduct this work responsibly across more diverse cultural, legal, clinical, and community settings as scientific innovations evolve.

INTRODUCTION

HIV cure-related research at the end-of-life (EOL) offers a rare opportunity to study viral persistence in tissues that cannot be sampled safely or repeatedly during life [1,2]. Blood-based measures provide only a partial view of HIV persistence, while rapid research autopsy and tissue donation allow investigators to examine reservoirs across deep tissue layers, lymphoid sites, the central nervous system (CNS), and other anatomical compartments relevant to HIV cure-related science [1,3–5]. The ethical stakes are equally high as EOL research takes place during the course of serious illness or near death, involving relationships with next-of-kin/loved ones, cultural considerations, tissue donations, rapid research autopsy, and future use of donated tissues [6–10]. Recent ethics guidance for clinical research involving persons with terminal illness further underscores that such studies should be evaluated through core research ethics requirements, including social value, favorable risk-benefit balance, fair participant selection, informed consent, and respect for participants and affected third parties [11▪▪]. Foundational work, especially through the Last Gift program at the University of California, San Diego, has shown that such research can be conducted with careful attention to informed consent, autonomy, voluntariness, dignity, altruism, patient-participant-centeredness, next-of-kin/loved one involvement, staff coordination, and community engagement [6–10,12–14].

The field is now beginning to move beyond observational tissue collection alone. Samples donated at the EOL may increasingly inform tissue-derived platforms, organoids, organ-on-chip systems, ex vivo models, longer-term tissue and data resources, and possible future in vivo testing of novel cure-related approaches [2,11▪▪,15–19]. These directions raise questions about tissue transformation, future use, commercialization, data sharing, acceptable risk, therapeutic or curative misconception, and long-term governance. This review examines ethical frameworks and community engagement approaches in HIV cure-related research at the EOL from 2016 to 2026. We synthesize the current evidence base, consider emerging scientific and ethical frontiers, and propose a forward-looking, cross-setting conceptual framework to guide responsible research as the field expands across technologies, institutions, and global contexts.

CURRENT ETHICAL AND COMMUNITY ENGAGEMENT EVIDENCE BASE

Although the literature on HIV cure-related research at the EOL remains limited, it has developed a substantive ethical foundation [10]. Much of this work has come from the Last Gift program and related studies in the United States, where ethical reflection and community engagement were built into the research at its inception [6,9,10]. Early work made the scientific and ethical case for this research model: people with HIV (PWH) near the EOL are willing and able to contribute tissues and biological information that cannot be obtained during life, but this possibility relies on scrupulous attention to informed consent, autonomy, voluntariness, vulnerability safeguards, dignity, and respect for the person [1,3,6]. A 2018 normative ethics paper framed EOL HIV cure-related research as ethically appropriate only when scientific value, informed consent, voluntariness, dignity, vulnerability safeguards, and altruism are considered from the outset rather than added after study design [6]. Importantly, early ethics papers did not treat EOL research as simply a technical pathway to tissue access. They framed it as a form of research that must remain attentive to participants’ terminal illness, which is often distinct from HIV itself and may include advanced cardiovascular disease, neurodegenerative disease, or solid tumors, as well as community trust, participant values, and the significance of tissue donation near death [6,9,13]. Table 1 summarizes the main types of inquiry that have shaped ethical and community engagement considerations in this area, including normative and empirical ethics, participant and next-of-kin/loved one perspectives, staff experience, implementation of lessons learned, community-driven tissue governance, hypothetical interventional research, cross-setting evidence, and emerging tissue platform ethics.

Table 1.

Ethical and community engagement considerations in HIV cure-related research at the end-of-life, 2016 to 2026

Evidence areas	Representative papers	Key contributions	Ethical and community engagement considerations	Gaps and future implications
Foundational rationale and rapid autopsy model	Gianella et al., 2017; Rawlings et al., 2020; Chaillon et al., 2020; Riggs et al., 2022	Early work made the case that end-of-life HIV cure-research can address questions that cannot be answered through blood based or routine clinical sampling alone. Rapid research autopsy created a pathway to study HIV persistence across anatomical compartments with minimal disruption to clinical care when carefully planned.	Scientific and social value; body donation; rapid research autopsy; tissue access; feasibility; participant contribution to cure-related and persistence science.	Future studies should continue to justify why end-of-life participation is necessary and how the scientific value of tissue access is balanced with participant dignity, next-of-kin/loved ones needs, and cultural expectations around death and tissue donation.
Normative ethics foundations	Dubé et al., 2018	This work established the early ethical architecture for HIV cure-related research at the end-of-life. It argued that such research can be ethically appropriate when informed consent, voluntariness, patient-participant-centeredness, altruism, and dignity are considered from the outset rather than added later.	Informed consent; autonomy; voluntariness; patient-participant-centeredness without automatic exclusion; altruism; dignity; respect for persons; ethical safeguards.	These foundational considerations remain relevant, but newer models require attention to long-term tissue use, governance, and risk boundaries in possible future interventional studies.
Participant experiences and motivations	Perry et al., 2020; Dubé et al., 2023; Ahmed et al., 2025	Participant-facing studies show that some people with HIV understand end-of-life research as a meaningful act of contribution, legacy, and reciprocity. These studies help move the discussion beyond abstract ethical principles by showing how participants themselves describe the value of participation.	Altruism; legacy; meaning making; agency; dignity; perceived risks and benefits; desire to help future communities.	Broader participant perspectives are needed, including women, people outside North America, long-term survivors, and people in settings where death, autopsy, or tissue donation may carry different cultural meanings.
Next-of-kin and loved one perspectives	Dubé et al., 2020; Javadi et al., 2021; Ndukwe et al., 2024	These studies show that end-of-life HIV cure research is relational. Even when participants are the primary decision makers, next-of-kin/loved ones may be involved in understanding the decision, supporting rapid research autopsy logistics, and living with the emotional meaning of donation after death.	Relational ethics; next-of-kin/loved ones communication and understanding; bereavement sensitivity; acceptability of rapid research autopsy; respect for participant wishes.	Future work should examine next-of-kin/oved ones experiences across cultural and religious contexts, including authority, burial timing, grief practices, disclosure concerns, and possible tensions between participant wishes and next-of-kin/loved ones expectations.
Staff experience and implementation ethics	Perry et al., 2020; Kanazawa et al., 2023	Staff experience studies show that ethical implementation depends on people, relationships, and workflows. Coordinators, clinical teams, and rapid research autopsy teams carry logistical and emotional responsibilities that are central to whether the research is conducted respectfully.	Team coordination; role clarity; emotional labor; communication workflows; rapid research autopsy logistics; staff preparedness; implementation burden.	Future programs should report how staff are trained, supported, and debriefed, especially as rapid research autopsy models are adapted to new institutions or settings with different resources and infrastructure.
Lessons learned from Last Gift and related implementation experience	Kanazawa et al., 2022; Kanazawa et al., 2023	Lessons learned papers translate ethical commitments into practical procedures. They show how informed consent, tissue donation, death notification, rapid research autopsy timing, next-of-kin/loved ones communication, and disposition of the body become concrete implementation issues.	Participant-centered communication; operational flexibility; tissue donation; body disposition; timing of procedures; coordination with clinical and mortuary systems.	The field would benefit from shared reporting expectations so that future studies describe informed consent processes, community input, next-of-kin/loved ones communication, rapid research autopsy workflows, and practical safeguards more consistently
Community driven tissue governance	Dubé et al., 2023	The community-driven tissue prioritization framework shows that community engagement can guide decisions about the use of scarce and precious donated biological materials. This moves engagement from consultation toward governance	Tissue prioritization; community accountability; transparency; future use; stewardship; return of value; respect for donor intent	Governance models should address long-term storage, secondary use, data sharing, commercialization, tissue transformation, and possible use of donated samples in future tissue-derived platforms, including organoids, organ-on-chip systems, and ex vivo models
Interventional HIV-cure research at the end-of-life	Kanazawa et al., 2021; Kanazawa et al., 2022; Ndukwe et al., 2024; Ahmed et al., 2025	This body of work begins to examine whether, and under what conditions, interventional HIV cure-research could be ethically considered near the end of life. Constituent and participant facing studies highlight willingness to consider such research, but also emphasize the need for strong safeguards, realistic expectations, careful risk communication, and community input	Acceptable risk; risk comprehension; therapeutic and curative misconception; autonomy; voluntariness; scientific justification; oversight; participant-centered protocols; next-of-kin/loved one involvement; community review of risk boundaries	The field needs clearer criteria for when in vivo testing near the end of life is ethically appropriate. Future guidance should address independent oversight, limits on risk, participant understanding, next-of-kin/loved communication, no expectation of direct clinical benefit, and the role of communities in defining acceptable boundaries
Non-US and cross-setting evidence	Lessard et al., 2022; Lessard et al., 2023; Scholte et al., 2025	Canadian studies provide the clearest non-US empirical and case-based evidence, including willingness to participate in end-of-life HIV cure research, biobanking, research autopsy, and body donation in the context of medical assistance in dying (MAiD). Emerging Brazil and Latin America work points to growing infrastructure for biospecimen research	Cross-setting ethics; MAiD; legal context; rapid research autopsy acceptability; biobanking; community education; cultural adaptation; regional biospecimen infrastructure	Peer-reviewed documentation from Europe, South Africa, and other settings remains limited. This should be framed as a documentation gap rather than an absence of activity. Future work should examine how local law, religion, family authority, burial practices, privacy concerns, and research trust shape ethical implementation
Organoids, organ-on-chip systems, and ex vivo platforms	Yin et al., 2024; Ingber, 2022; Truskey, 2018	Tissue-based HIV cure-related science is moving toward platforms that may extend the value of end-of-life samples beyond immediate reservoir measurement. Organoids, organ-on-chip systems, tissue explants, and microphysiological models may help model HIV reservoirs, immune responses, comorbidities, and intervention effects in more physiologically-relevant systems	Tissue transformation; model creation; future use; donor and family understanding; data sharing; translational research; long-term platform development	Informed consent and engagement processes should explain, in accessible language, how donated tissues may be transformed into durable experimental platforms and used in future studies not yet fully defined at the time of donation
Organoid, tissue, and biobanking ethics	Boers et al., 2016; Boers and Bredenoord, 2018; Mollaki, 2021; Lewis and Holm, 2022	Organoid and biobanking ethics literature is useful because it shows the limits of relying only on one-time consent when donated tissues may be stored, modified, shared, commercialized, or used in future technologies	Informed consent limitations; donor expectations; governance; commercialization; intellectual property; privacy; patentability; long-term storage; fair access; oversight	These debates should be integrated into HIV cure-related end of life research before tissue derived platforms become routine. Governance should include transparency, accountability, community input, and clarity around future use and benefit sharing
Broader HIV cure research ethics and community engagement literature	Dubé et al., 2021; Dubé et al., 2025	Broader HIV cure ethics and socio-behavioral literature situates end-of-life research within wider debates about uncertainty, risk, community engagement, fair implementation, implementation readiness, and translation	Community priorities; community engagement; trust; fair implementation; translational ethics; implementation readiness; accountability.	Future end-of-life HIV cure-related research should remain connected to broader cure research ethics debates, especially around access, benefit sharing, return of value, and accountability to participating communities

MAiD, Medical Aid in Dying.

Empirical research with PWH near or at the EOL, their next-of-kin/loved ones and research staff have given this literature much of its depth. Findings from the Last Gift program suggest that most PWH understand participation as a final contribution to science, a way to give back, and an opportunity to leave a legacy for future communities [12,13,20▪▪]. These accounts challenged the narrow perception that people near the EOL are inherently vulnerable and simultaneously reminded researchers that altruism requires careful consideration [9,12,13,21]. Legacy and contribution can be meaningful expressions of agency, but they should not lessen scrutiny of illness burden, voluntariness, or the absence of expected direct clinical benefit at the EOL [9,12,13,20▪▪]. Interview studies with next-of-kin/loved ones added another layer: even when participants remain the primary decision makers, close contacts may help interpret the participant’s wishes, communicate with study teams, and navigate the practical and emotional realities of rapid research autopsy following death [7,8,15]. Their involvement can support transparency and planning, but it can also raise concerns about disclosure, pressure, and bereavement-sensitive communication [7,9,14,22].

The evidence also suggests that ethical conduct depends not only on principles, but also on the people, relationships, and systems responsible for implementing EOL research. Papers on staff experience and lessons learned describe the meticulous coordination required among clinical teams, clinical research staff, rapid research autopsy teams, mortuary services, participants, and next-of-kin/loved ones, often under time-sensitive and emotionally difficult circumstances [3,5,9,10,14]. These studies show that staff members, in carrying out procedures, are heavily implicated in translating ethical commitments into daily practice through communication, planning, responsiveness, and care for participants and next-of-kin/loved ones [5,10]. A recent research coordinator reflection extends this point by showing that the “logistics” in rapid research autopsy studies are not merely administrative; they are how teams sustain trust, coordinate decisions, support participants and next-of-kin/loved ones, and make time-sensitive discovery possible [23]. Operational coordination is therefore part of the ethical work needed to support the scientific enterprise [23]. Communication failures, unclear roles, or poorly planned autopsy logistics can affect participant dignity, next-of-kin/loved one trust, and staff burden; flexible protocols, role clarity, and practical support can facilitate research team alignment with participants’ values and clinical realities [9,10,14,23]. Recent work on compassion training among EOL HIV research professionals further suggests that staff well being is not peripheral to ethical implementation; emotional preparedness, self-compassion, and supportive work environments may help teams sustain the relational and practical demands of this intensive work [22].

The strongest published evidence, however, remains concentrated in a small number of programs and settings. Studies conducted in Canada within the Canadian HIV Cure Enterprise program have begun to broaden the evidence base by examining willingness among Canadians with HIV to participate in HIV cure research at the EOL, biobanking, and research autopsy, and by describing tissue donation in the context of participants requesting medical assistance in dying [24▪,25,26]. Emerging work from Brazil points to growing interest in regional biospecimen infrastructure [27▪]. Concurrently, related postmortem and tissue-based HIV research is being reported beyond the U. S.-based Last Gift context, including European postmortem reservoir studies using brain and other tissues and minimally invasive autopsy research among adults with HIV in South Africa [28–30]. However, peer-reviewed documentation of the ethical and community engagement practices supporting such work remains limited. This gap should be understood as a need for better context-specific ethics reporting, not as evidence that ethical reflection or community engagement is absent. This matters because local law, culture, religion, family authority, burial practices, HIV stigma, health system capacity, and community trust will shape how this research is explained, conducted, and governed [20▪▪,25,27▪].

COMMUNITY ENGAGEMENT AS ETHICAL INFRASTRUCTURE

Community engagement has played a central role in HIV cure-related research at the EOL, but its value exists across more than protocol review, recruitment or consultation [31▪,32,33]. In the Last Gift program, community members have served as co-investigators since inception, helping shape the program’s ethical orientation, study materials, informed consent processes, recruitment approaches, and communication practices [6,7,9,10]. Their involvement has supported research teams in understanding how sensitive information should be explained, how participants and next-of-kin/loved ones may interpret tissue donation and rapid research autopsy, and what mediums of communication are likely to build or weaken trust [6,7,9,10]. This is especially important when participation is connected to altruism, legacy, or a desire to contribute to current and future cure science; these motivations should be respected without overselling contributions [12,13,20▪▪].

Community engagement also helps guide decisions after tissue donation [33]. Donated tissues from EOL research are rare, scientifically valuable, and personally meaningful [3,16]. A community-driven framework led by Thomas Villa has shown that PWH and community partners can contribute to decisions about how donated materials should be used, prioritized, shared, and stewarded [33]. This places engagement not only at study entry, but also in later decisions about tissue access, transparency, future use, and return of value [18,19,33]. Return of scientific value may include aggregate findings, community updates, or other posthumous communication that honors participants’ contributions, supports legacy, and strengthens accountability to contributing communities [12,13,20▪▪,31▪,32,33]. Such communication should be developed with community input, protect confidentiality, and avoid overstating scientific findings. It also helps research teams identify language and workflows that are sensitive to grief, disclosure concerns, communication with next-of-kin/loved ones, and cultural expectations around death and donation [7,8,24▪]. As HIV cure-related research at the EOL expands across diverse and global settings, community engagement practices will need to be described more consistently, evaluated for how they shape decisions, and adapted to local regulations, religious beliefs, family authorities, burial practices, and research histories [24▪,25,27▪,31▪,32].

EMERGING SCIENTIFIC AND ETHICAL FRONTIERS

HIV cure-related research at the EOL is now expanding beyond the immediate mapping of viral persistence. Rapid research autopsy has revealed the scientific value of accessing deep tissues and CNS compartments that are rarely available during life and are important for understanding HIV persistence across the body [3–5,34]. Newer tissue-based platforms extend these questions beyond tissue access alone. Donated tissues may support organoids, organ-on-chip systems, ex vivo models, and other microphysiological systems that can model HIV reservoirs, immune responses, comorbidities, and responses to candidate cure-related research interventions under more physiologically relevant conditions [16,35]. These developments broaden the ethical scope of EOL HIV research because donated tissues may become durable research resources used across studies, institutions, and time [36].

The organoid and biobanking ethics literature clarifies why standard consent language may be insufficient for this next phase [37–39]. Donor-derived materials may be stored, modified, shared, linked with data, used in commercially relevant platforms, or incorporated into studies that were not envisioned when initial consent was obtained [18,19,39]. In HIV cure-related research at the EOL, this is especially sensitive because tissue donation is often connected to legacy, altruism, trust, and the hope that one’s contribution will benefit future communities [12,13,20▪▪]. Participants, next-of-kin/loved ones, and care partners, may support broad scientific use, but they should not be expected to infer that donated tissues could later contribute to living models, intellectual property, commercially relevant technologies, or studies conducted years after death [12,13,18,19,33,37]. For this reason, protocols should describe potential future uses in accessible language and specify how tissue access, prioritization, data sharing, commercialization, and return of value will be governed [18,19,33].

A second frontier involves evaluating experimental HIV cure-related research interventions in people near or at the EOL. As cure science advances, EOL research may raise questions about whether selected interventions, including latency-reversing or permanent silencing agents, immune-based strategies, or cell and gene-based approaches, and combination modalities, could ever be evaluated in carefully designed studies involving PWH near or at the EOL [2,6,9,20▪▪,40,41]. These interventions would be envisioned as cure-directed strategies intended to expose, reduce, silence, modify, or eliminate persistent HIV reservoirs, rather than as interventions expected to provide direct clinical benefit to participants near the EOL. Such possibilities should be considered cautiously. While they may offer important scientific opportunities, they also raise concerns regarding safety, reversibility, transmissibility, durability, clinical burden, oversight, and the potential for misunderstanding or exploitation. Accordingly, carefully considered safeguards should be in place [2,15,20▪▪].

Constituent and participant-facing studies suggest that some PWH at the EOL, including long-term survivors, may be willing to consider interventional cure-related research when the purpose, risks, and limited prospect of direct clinical benefit are clearly explained [2,9,15,42]. Willingness, however, should not be treated as ethical permission. The more important issue is what conditions would make such research responsible. At a minimum, interventional HIV cure-related research at the EOL would require a strong scientific rationale, risks proportionate to the knowledge expected, independent oversight, careful assessment of understanding, safeguards against therapeutic or curative misconception, participant-centered procedures, alignment with palliative goals of care, minimization of participant and caregiver burden, clear stopping or modification criteria and community involvement in defining acceptable boundaries [2,11▪▪,15,42,43]. Ongoing community, regulatory, and ethics consultation will be needed before interventional HIV cure research at the EOL becomes a reality and such models can be responsibly embedded in practice.

TOWARD A CROSS-SETTING FRAMEWORK AND FUTURE RESEARCH AGENDA

HIV cure-related research at the EOL requires practical recommendations that can support study teams while recognizing that no single model will be suitable for every jurisdiction, culture, or health system. Existing studies provide an essential foundation, but the evidence base remains concentrated in a small number of settings, limiting what can be assumed about generalizability or transferability [6,9,10,13,14,31▪]. The field needs to clarify which ethical, operational, and community-engagement practices are broadly transferable, which require local adaptation, and which need to be developed with affected communities in specific settings [31▪,32]. Figure 1 summarizes the evolution of HIV cure-related research at the end-of-life from 2016 to 2026 and outlines possible future directions for the next decade.

FIGURE 1.

Timeline of key developments, Ethical milestones, and future directions in HIV cure-related research at the end-of-life, 2016 and beyond. This timeline summarizes major developments in HIV cure-related research at the end-of-life during the 2016–2026 review period and outlines anticipated directions for the decade or so. The retrospective portion highlights the emergence of rapid research autopsy and tissue donation as a model for studying HIV persistence beyond blood-based sampling, the articulation of ethical foundations, growing attention to community, participant, next-of-kin/loved ones, and staff perspectives, early discussion of interventional end-of-life cure-related research, implementation lessons, tissue governance, and newer tissue-derived platforms. The future-oriented portion identifies priorities for reporting standards, cross-setting guidance, governance of tissue-derived platforms, and clearer boundaries for possible future interventional studies. Recurring priorities include informed consent, acceptable risk, dignity, community engagement, tissue governance, equity, and return of scientific value.

Rather than prescribing a universal model, a cross-setting framework can help organize the decisions that study teams, community partners, and ethics committees should make explicit. Decisions include why HIV research participation at the EOL is scientifically necessary, how participant burden can be minimized, how informed consent can remain responsive to illness progression evolving participant goals, decisional capacity, next-of-kin/loved ones dynamics, and future tissue uses, how postmortem samples and data should be governed, and how acceptable boundaries for possible interventional studies could be defined and implemented with community input [2,6,15,18,19,20▪▪,37,42]. Because EOL research unfolds over changing illness trajectories, consent should be approached as an ongoing process rather than a single authorization. Research teams should create opportunities to revisit consent and reaffirm participant preferences when clinical status changes, when the desired involvement of next-of-kin/loved ones shifts, or when rapid research autopsy planning and future tissue-use decisions become more immediate [2,6,9,10,15]. These processes should also be aligned with palliative care principles, including goal-concordant care, symptom management, comfort, dignity, next-of-kin/loved ones or caregiver support, and quality of life [43]. Communication between clinical, palliative care, and research teams can help ensure that study activities remain responsive to changing symptoms and care priorities, and that research procedures do not supersede clinical care or the participant’s EOL priorities [10,23,43]. The goal is not to standardize every practice, but to make core ethical and operational decisions visible, reviewable, and adaptable across settings.

EOL HIV research should be designed with equity considerations from the outset. HIV has disproportionately affected specific communities, including people from racially, ethnically, and gender-diverse groups, people who use drugs, older adults with HIV, and long-term survivors, many of whom may also experience intersecting and compounding forms of stigma, economic insecurity, racism, transphobia, ageism, and HIV-related discrimination [42,44,45▪]. These experiences can shape how people understand research opportunities at EOL, how they weigh risks and benefits, whom they want involved in decision-making, and what protections they consider meaningful [9,42]. Future protocols should therefore include early and sustained engagement with communities most affected by HIV, as well as people with lived experience of serious illness, caregiving, bereavement, and research participation [31▪,32]. Such engagement is most meaningful when it extends beyond consultation to include opportunities for community members to serve as co-investigators, review consent language, discuss acceptable levels of risk, contribute to culturally grounded communication strategies, participate in research design, and support the transparent dissemination of findings [31▪,32]. Figure 2 outlines a proposed cross-setting conceptual framework that links established ethical foundations, emerging scientific directions, and practical considerations for implementation.

FIGURE 2.

Proposed cross-setting framework for ethical and community-engaged HIV cure-related research at the end-of-life. The figure presents a proposed conceptual framework for ethical HIV cure-related research at the end of life. The framework encompasses eight interconnected ethical and operational domains: scientific and social value; informed consent and decisional support; participant dignity and burden reduction; tissue, data, and future-use governance; communication with next-of-kin/loved ones; equity and intersectionality considerations; community engagement and accountability; and oversight of future interventional research. While broadly applicable, these domains will require careful adaptation and implementation across diverse legal, cultural, religious, community, and healthcare contexts, with appropriate documentation of local practices and considerations.

A critical next step will be to examine how these proposed ethical frameworks operate across diverse settings and contexts. Additional empirical research is needed with PWH, next-of-kin/loved ones, care partners, research teams, community representatives, clinicians, rapid research autopsy teams, ethics committees, and community advisory boards across settings. Such work will be particularly important in regions outside the United States, where cultural, social, regulatory, and healthcare contexts may differ [31▪,32]. Future studies should also describe more clearly key ethical and community engagement practices, including consent and ongoing consent processes, community engagement activities, next-of-kin/loved one involvement, rapid research autopsy workflows, tissue and data governance, participant and caregiver support procedures, and approaches for communicating aggregate findings or study updates. Greater attention is also needed to document ethical and community engagement practices across contexts, especially where postmortem, tissue-based, or autopsy-related HIV research is already occurring, but the accompanying consent processes, community input, next-of-kin/loved ones communication pathways, and governance practices are not yet well described in the peer-reviewed literature.

CONCLUSION

HIV cure-related research at the end of life demonstrates that rigorous basic science and careful ethical practice can advance in unison. The work to date offers important lessons about informed consent, dignity, participant agency, next-of-kin/loved one involvement, staff coordination, community engagement, and the stewardship of donated tissues. As the field moves toward more innovative approaches, such as tissue-derived platforms, possible testing of HIV cure-related approaches in vivo, and broader implementation across different cultural and legal settings, these lessons need to be carried forward, adapted, and made more explicit. Future work should move beyond broad claims that this research can be ethically acceptable and focus instead on the concrete practices that make this research responsible in specific settings and scientific contexts. This includes clearer expectations for governance, risk boundaries, community input, and return of scientific value. When a single model is unlikely to fit all contexts, the field needs shared ethical commitments that can guide responsible HIV cure-related research while honoring the altruistic individuals, next-of-kin/loved ones, and communities whose contributions make this important and humbling work possible.

KEY POINTS.

• HIV cure-related research at the end-of-life enables study of viral persistence in tissues and anatomical compartments that are difficult or impossible to access during life.

• Existing literature provides recommendations on informed consent, autonomy, dignity, altruism, patient-participant-centeredness, next-of-kin/loved one involvement, staff coordination, rapid research autopsy logistics, and tissue governance.

• Community engagement should guide not only recruitment and informed consent, but also tissue prioritization, future use, dissemination, and return of scientific value.

• Organoids, organ-on-chip systems, ex vivo models, and possible in vivo testing of HIV cure-related strategies raise newer questions about acceptable risk, tissue transformation, commercialization, oversight, and longterm governance.

• A proposed cross-setting framework should remain adaptable across cultural, legal, clinical, and resource settings, and future studies should better document how ethical and community engagement practices are implemented across contexts.