Table 1 Open Research Ethics Questions for HIV Cure Research
Social Value Ongoing and Emerging Biomedical Research • What are ethical considerations for specific HIV cure research approaches (e.g., cell and gene therapy, immune-based approaches, latency-reversing agents, stem cell transplants, etc.)? • What are ethical considerations for combining HIV cure research regimens? • What are the ethical considerations of conducting HIV cure research with PLWH at the end-of-life—including interventions? • How do we adapt ethical guidelines for such rapidly evolving scientific field? Scalability Considerations • What additional ethical considerations are relevant when implementing HIV cure trials in resource-limited settings? |  |
Scientific Validity Study Design Considerations: Analytical Treatment Interruptions • When are extended ATIs that may trigger extended periods of viremia ethically appropriate? • What are robust yet practical ethical considerations for mitigating risks to sexual partners of ATI trial participants in diverse circumstances (e.g., anonymous partners, domestic violence potential, access to PrEP/condoms, local criminalization laws)? Use of Placebos • When are placebo arms ethically acceptable in HIV cure research? |  |
Fair Selection of Participants Equity and Justice Considerations • How can HIV cure research be implemented utilizing ethical principles of equity, social justice, and solidarity? |  |
Favorable Benefit/Risk Balance Early-Phase Research Considerations • What are the criteria for judging the ethical permissibility of early-phase HIV cure trials? • How can we ensure trial participants are protected from excessive risks? • How should we navigate the issue of therapeutic ambiguity as HIV cure trials start showing signals of potential efficacy? Additional Benefit/Risk Considerations Acceptable Benefit-Risk Balance • What are practical and innovative methods to evaluate acceptability of risk thresholds for emerging HIV cure interventions? • How do we continue to engage relevant stakeholders around the notion of unacceptable risks? • What is the best way to establish additional safeguards for emergent situations that may alter the risk balance (e.g., SARS-CoV-2 pandemic)? Risk Perceptions • What risk thresholds are ethically permissible in different populations of PLWH? • What are ethical considerations and acceptable risks related to extended ATIs requiring PLWH forego ART for extended periods of time? Psychosocial Benefits and Harms • What are the psychosocial benefits of HIV cure research participation, and how should these shape benefit/risk evaluations? • What are some of the non-clinical harms (e.g., psychological, social, legal, and financial) of HIV cure research participation, and how should these shape benefit/risk evaluations? Pediatric HIV Cure Research • How should we evaluate interventional pediatric HIV cure research to ensure acceptable benefit-risk? |  |
Informed Consent Language Considerations • What are innovative ways to engage participants, especially diverse communities, around the ethical use of language to describe HIV cure research? Decision-Making • What would be the best ways to facilitate participant decision-making in early-phase HIV cure trials? • How should research teams measure therapeutic (or curative) misconception and misestimation in HIV cure trials? Informed Consent Processes • What would be the best ways to enhance the quality of informed consent in early-phase HIV cure trials? • Should a separate category of scientific uncertainty disclosure be mandated as part of regulations (i.e., Common Rule)? Scientific Uncertainty • What are ethical considerations for communicating scientific uncertainty? |  |
Respect for Enrolled Participants and Communities Perspectives of PLWH and Affected Communities • How can the perspectives of PLWH and HIV care providers help prioritize interventions under development to augment their acceptability? Community Representation • What are ethical considerations necessary for meaningfully engaging all stakeholders, including patients, providers, government, and the overall community in early-phase HIV cure research? |  |