Table 3 Ethical Considerations for HIV Cure-Related Research at the End of Life

EOL clinical research, rapid research autopsy and gifting relationship

The research team should:

 • Anticipate issue of prognostic uncertainty, including ensuring that timing of research initiation is right and be prepared in case participants live longer than 6 months.

 • Maximize generalizability of EOL scientific data to HIV cure-related research field.

 • Allow co-enrollment in another research protocol to help advance science for disease participants are dying of, provided there is no inclusion/exclusion criteria conflict.

 • Follow established guidelines related to rapid research autopsy, including: having staff available at all times, treating the body of the deceased in a dignified manner, minimizing and justifying degree of invasiveness in relation to the expected scientific benefits, and respecting pre-mortem wishes of Last Gift study participants.

Protecting autonomy through informed consent

 • The informed consent process must clearly state that EOL HIV cure-related research will not be curative, and must convey the research objectives, methods, procedures, decision will not affect medical care, and right to refuse enrollment or withdraw from research at anytime.

 • Last Gift study participants should consent for themselves and participants should be assessed for cognitive functioning.

 • Last Gift study team should view the informed consent process as continuous and carefully consider Last Gift participants’ wishes until the EOL (e.g., process consent) or advance directives.

 • The informed consent process must remain free from coercion, or undue influence or persuasion. Possible ways to reduce coercion include: 1) physician taking care of patient should not provide consent to enroll in Last Gift study, 2) decisions should be made over multiple visits; 3) research team should emphasize voluntary nature of research; 4) financial incentives should not be primary motivator to participate.

 • Shared decision making should be used as a way to enhance the recruitment experience, promote trust and view participants as true partners in research.

 • The risk of therapeutic misconception should be minimized.

 • For additional considerations, see [12].

Avoiding exploitation and fostering altruism

 • Protection from exploitation relates to the principle of distributive justice, in that there should be fair distribution of the benefits and burdens from the transaction.

 • The Last Gift study team should ensure that participants have genuinely altruistic motives for participation and understand that they are entering a gifting relationship.

 • Further empirical research is needed to examine the role of altruism and psychological characteristics of Last Gift study participants to understand their decisions to participate in EOL HIV cure-related research.

 • IRBs and regulatory bodies should place limits on ethically permissible risks of clinical research to protect the HIV cure-related research enterprise.

Maintaining a favorable benefits to risks balance

 • EOL HIV cure research should minimize risks, enhance potential benefits, and ensure that risks and burdens are justified in relation to prospective benefits.

 • A favorable risk-knowledge balance should be obtained, since EOL HIV cure research will not alter disease course or prolong survival.

 • The research team should pay attention to evolving participant goals, including relief from symptoms, dignity and meaning, social relationships, and other possible psychosocial risks and benefits.

 • More empirical research is needed to determine how terminally ill PLWHIV view acceptable benefits and risks.

 • PLWHIV as well as terminally ill individuals and families/loved ones of recently deceased patients should be included in protocol design and during ethics reviews.

 • Benefit-risk assessments should take into considerations the risks of HIV cure research interventions and other clinical factors. In general, latency-reversing agents and immune-based strategies have a favorable benefit-risk balance, while stem cell transplantation do not. The EOL translational model could be helpful in evaluating components of gene modification and editing (e.g. safe delivery to cells and tissues – including the brain).

 • Analytical treatment interruptions can be ethically permissible at the EOL; however, participants should elect to interrupt beneficial ART on their own for observational studies. Some interventional study designs may warrant analytical treatment interruptions.

Safeguarding against vulnerability through patient-participant centeredness

 • Vulnerability implies the need for specific protection or safeguards.

 • Last Gift participants should not be categorized as vulnerable simply because they are terminally ill. Rather, attention should be paid to what participants may be vulnerable to, and adequate protections should be put in place to alleviate possible sources of vulnerabilities.

 • Research with terminally ill PLWHIV requires careful design and execution, and incorporate sensitivity to participants’ needs, including physical, psychological, mental, spiritual and social needs (see Table 2). For example, researchers should pay attention to issues related to depression, social isolation, insomnia, and body image that may be of import to PLWHIV.

 • Appropriate boundaries should be maintained between the Last Gift team and the study participants. Special attentions such as special foods should not be presented as study benefits, but as tokens of appreciation, reverence, gratitude and respect.

 • The research team should be careful to not be intrusive while attempting to honor the participants’ wishes until the very EOL.

Ensuring acceptance of loved ones and community

 • The research team should ensure acceptability of the research from next-of-kin/loved ones, and clarify the role of next-of-kin/loved ones in study participation. Next-of-kin/loved ones should also be briefed on the study to be willing to let go of the Last Gift participants’ body at the time of death. The research team should actively support and (if needed) protect next-of-kin/loved ones, and account for the fact that next-of-kin/loved ones arrangements may be untraditional for PLWHIV.

 • The research team should be sensitive to socio-cultural issues. Extensive and ongoing community consultation should take place before, during and after the study.

 • More empirical research is needed to better understand the perceptions of next-of-kin/loved ones and community stakeholders around HIV cure-related research at the EOL.