Table 4 Summary of ethical and practical considerations for HIV cure-related research at the EOL

Whether HIV cure-related research at the EOL should be done

 Because of the potential scientific knowledge to be gained, HIV cure-related research at the EOL may be ethically permissible, but adequate safeguards must be in place [3]

 PWH near the EOL should not be treated as an inherently vulnerable class and should not be automatically barred from participating in HIV cure-related research

Concerns about HIV cure-related research at the EOL

 Investigators should be cognizant that PWH at the EOL may feel an obligation to participate in the study and be careful of exerting any undue influence

 Regulators should avoid being overly paternalistic with PWH as they may desire to exercise their autonomy and agency at the EOL

Conducting HIV cure-related research at the EOL

Effective Implementation of HIV cure-related research at the EOL

 Research teams should engage relevant stakeholders, including community representatives, in the design of protocols, during the studies, and in the dissemination of findings

 Research teams should ensure diverse populations are aware of, and have access to, HIV cure-related research at the EOL to ensure justice and equity

 Research teams should be multidisciplinary and should engage PWH before the EOL process

Ethical Implementation of HIV cure-related research at the EOL

 Robust ethics steering committees, IRBs, and DSBMs should oversee proposed studies and ensure studies remain within acceptable risk–benefit parameters

Ensuring HIV cure-related research at the EOL is attuned to the needs of study participants

 Research teams should place great import on empathy and communication with the participants, their next-of-kin/loved ones/intimate partners [20], and their communities

 Research teams need to consider the diverse and evolving needs of patients/participants at the EOL in the protocol trial design and actively engage PWH in designing these protocols

 There should be adequate acknowledgement of the extreme generosity and altruism of PWH who participate in this research [24, 34]

Ensuring social acceptability of HIV cure-related research at the EOL

 Research teams should be very intentional and transparent in their communications with the general public on issues surrounding HIV, science, medicine, and death

Navigating potential conflicts between research aims and clinical care

 To preserve autonomy, research teams should err on the side of what patients/participants would want at the EOL

 Research teams should deal with potential conflicts between research aims and clinical care needs on a case-by-case basis and with the help of bioethicists

Role of advance directives in HIV cure-related research at the EOL

 Research teams should ask PWH who desire to participate in HIV cure-related research at the EOL whether they have a recent advance directive in place in a discussion that is separate from the informed consent process

Role of palliative care in HIV cure-related research at the EOL

 Research teams and palliative care teams should remain in communication with each other to ensure that participants remain comfortable at the EOL

Additional considerations for HIV cure-related research at the EOL

Role of HIV care providers in EOL translational research

 HIV care providers should be involved in the EOL translational research process; however, it should be recognized that researchers and providers have two distinct roles that must be made clear to participants to avoid therapeutic misconception

Relevance of EOL translational research to other fields

 The EOL translational research model may prove highly relevant to other medical fields, such as COVID-19, hepatitis, rare diseases, cardiac disease, and diabetes, among others. Lessons learned from the field of HIV cure-related research may also be translatable to other fields of research

Cultural considerations

 Cultural differences should be considered when implementing HIV cure-related research at the EOL; research teams should engage and inform communities early and throughout research efforts

COVID-19 and rapid research autopsy

 Protecting the rapid research autopsy team, ensuring timely collection of tissue samples, and surmounting the widespread disbelief in science should be considered when conducting HIV cure-related research in the COVID-19 era

Medical-assistance-in-dying (MAiD)

 Additional ethical considerations and safeguards are warranted should a patient choose MAiD within HIV cure-related studies at the EOL; the MAiD decision should be completely divorced from the research process to prevent any perception of undue influence [11]