Ethical and practical considerations for interventional HIV cure-related research at the end-of-life: A qualitative study with key stakeholders in the United States

Abstract

Background A unique window of opportunity currently exists to generate ethical and practical considerations presented by interventional HIV cure-related research at the end-of-life (EOL). Because participants would enroll in these studies for almost completely altruistic reasons, they are owed the highest ethical standards, safeguards, and protections. This qualitative empirical ethics study sought to identify ethical and practical considerations for interventional HIV cure-related research at the EOL. Methods and findings We conducted 20 in-depth interviews and three virtual focus groups (N = 36) with four key stakeholder groups in the United States: 1) bioethicists, 2) people with HIV, 3) HIV care providers, and 4) HIV cure researchers. This study produced six key themes to guide the ethical implementation of interventional HIV cure-related research at the EOL: 1) all stakeholder groups supported this research conditioned upon a clearly delineated respect for participant contribution and autonomy, participant understanding and comprehension of the risks associated with the specific intervention(s) to be tested, and broad community support for testing of the proposed intervention(s); 2) to ensure acceptable benefit-risk profiles, researchers should focus on limiting the risks of unintended effects and minimizing undue pain and suffering at the EOL; 3) only well-vetted interventions that are supported by solid pre-clinical data should be tested in the EOL translational research model; 4) the informed consent process must be robust and include process consent; 5) research protocols should be flexible and adopt a patient/participant centered approach to minimize burdens and ensure their overall comfort and safety; and 6) a participant’s next-of-kin/loved ones should be a major focus of EOL research but only if the participant consents to such involvement. Conclusions To our knowledge, this empirical ethics study generated the first ethical and practical considerations for interventional HIV cure-related research at the EOL. The ethical complexities of such research must be considered now. We must navigate this ethical conundrum so that we are good stewards of the participants’ extremely altruistic gifts by maximizing the impact and social value of this research. We hope that this study will serve as the foundation for future research and discussion on this topic.

People with HIV at the end-of-life and their next-of-kin/loved ones are willing to participate in interventional HIV cure-related research

“…PWH involved in research studies should be able to consider and/or raise issues related to treatment interruption, if desired. In an empirical ethics study investigating the acceptability of interventional EOL HIV cure research, most stakeholders (including community members) perceived the use of ATIs at the EOL favorably if needed to test an experimental intervention, but this would require robust informed consent and briefing about potential risks [33].…”

“…One such critical consideration would be to maintain a favorable benefit/ risk profile for any intervention tested at the EOL [25]. As such, we noted interventions that would be unfavorable for testing at the EOL, such as stem cell transplants in PWH who do not have a concomitant cancer [25,33].…”

“…Engaging this population enables researchers to compare HIV reservoirs before and after death across multiple body compartments while considering ART and other interventions [24,25,29]. PWH at the EOL may be willing to accept higher risks and some may elect to interrupt ART at the EOL [25,29]. Further, long-term risks are less relevant in this population.…”

“…The Last Gift serves as the research paradigm by which scientists may eventually start testing interventions in PWH at the EOL [33]. Our interdisciplinary team evaluated the willingness of PWH near the EOL and their NOK/loved ones to participate in different types of HIV cure research.…”

Lessons learned from the Last Gift study: ethical and practical challenges faced while conducting HIV cure-related research at the end of life

“…Ongoing consent checks may also be relevant for NOK/loved ones. We recommend NOK/loved ones be a focus of EOL research, but only if participants explicitely consents to such involvement 29. The research team should be respectful of these relationship dynamics.…”