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

Abstract

The Last Gift is an observational HIV cure-related research study conducted with people with HIV at the end of life (EOL) at the University of California San Diego. Participants agree to voluntarily donate blood and other biospecimens while living and their bodies for a rapid research autopsy postmortem to better understand HIV reservoir dynamics throughout the entire body. The Last Gift study was initiated in 2017. Since then, 30 volunteers were enrolled who are either (1) terminally ill with a concomitant condition and have a prognosis of 6 months or less or (2) chronically ill with multiple comorbidities and nearing the EOL.Multiple ethical and logistical challenges have been revealed during this time; here, we share our lessons learnt and ethical analysis. Issues relevant to healthcare research include surrogate informed consent, personal and professional boundaries, challenges posed conducting research in a pandemic, and clinician burnout and emotional support. Issues more specific to EOL and postmortem research include dual roles of clinical care and research teams, communication between research personnel and clinical teams, legally required versus rapid research autopsy, identification of next of kin/loved ones and issues of inclusion. Issues specific to the Last Gift include logistics of body donation and rapid research autopsy, and disposition of the body as a study benefit.We recommend EOL research teams to have clear provisions around surrogate informed consent, rotate personnel to maintain boundaries, limit direct contact with staff associated with clinical care and have a clear plan for legally required versus research autopsies, among other recommendations.

A Community-Driven Framework to Prioritize the Use of Donated Human Biological Materials in the Context of HIV Cure-Related Research at the End of Life

“…These ethical considerations include 1) protecting autonomy through informed consent, 2) avoiding exploitation and fostering altruism, 3) maintaining favorable benefit/risk criteria, 4) safeguarding against vulnerability by focusing on patients/participants, and 5) ensuring acceptance of next-of-kin/loved ones and community members [ 19 ]. The Last Gift team also prospectively documents ethical and practical lessons learned [ 20 ]. For example, we learned that PWH at the EOL wanted to exercise their right to die with dignity and compassion [ 20 , 21 ].…”

“…The Last Gift team also prospectively documents ethical and practical lessons learned [ 20 ]. For example, we learned that PWH at the EOL wanted to exercise their right to die with dignity and compassion [ 20 , 21 ].…”

“…This implies disclosure of information, comprehension, and voluntariness [ 19 , 23 ]. In addition, we follow process (or continuous) informed consent to ensure participants continue to agree to research procedures and tissue donations as they approach the EOL [ 19 , 20 , 24 ]. For any donation of human biological materials outside the scope of HIV cure research, the Last Gift team reviews the need for separate informed consent on a case-by-case basis.…”

“…Before each rapid research autopsy, the Last Gift observes a minute of silence to honor the life of each participant and express gratitude for their gift to science and society [ 19 ]. We also strive to minimize the degree of invasiveness of study procedures necessary to generate the scientific benefits and avoid disfigurement during rapid research autopsies [ 11 , 20 ].…”

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

“…The Last Gift also values the involvement of NOK/loved ones [30,31]. The research team uses a broad definition of NOK/loved ones, recognizing that familial arrangements may vary among PWH [32].…”