Table 1 Benefit-Risk Assessment for HIV Cure-Related Research at the EOL
From: Ethical considerations for HIV cure-related research at the end of life
HIV Cure-Related Research Approaches | Possible Positive Outcomes | Potential Risks | Benefit-Risk Assessment for PLWHIV at the EOL | Other Considerations |
|---|---|---|---|---|
Latency-reversing agents | Stimulation of replication-competent provirus from latently-infected cells and perturbation of HIV reservoir (although this has no direct clinical benefit) | Side effects of latency-reversing compounds (various toxicity levels) | Favorable | Already being tested in ‘otherwise healthy volunteers’; long-term effects would not become manifest |
Immune-based strategies (e.g. broadly neutralizing antibodies) | Improved immune response to HIV | Risks of immune-based approaches, including potential for development of auto-immunity | Favorable | Already being tested in ‘otherwise healthy volunteers’; long-term effects would not become manifest |
Stem cell transplants | Modality aims at making cells resistant to HIV infection | Risks associated with irradiation and chemotherapy; hepatic effects, renal failure, graft-versus-host-disease (GVHD); too great to withstand for PLWHIV at the EOL | Unfavorable; cannot be justified in PLWHIV at the EOL | Not indicated in ‘otherwise healthy volunteers’; engraftment and chimerism may not have time to manifest at the EOL |
Gene editing or modification | Process of editing deoxyribonucleic acid (DNA) inside immune cells to make them less susceptible to HIV or better able to clear infected cells | Off-target modifications or activation of proto-oncogenes causing malignancies; other risks associated with gene editing | Contingent on the intervention | Long-term effects would not become manifest; EOL translational research model could still be useful to determine how gene editing techniques can be delivered safely to cells and tissues – including the brain |
Analytical treatment interruptions | N/A | Development of resistance to ART regimen; increased risks of developing opportunistic infections; other risks associated with analytical treatment interruptions | Favorable | Already being conducted in Last Gift study – in observational studies, PLWHIV should not be explicitly asked to interrupt ART, but should elect to do so on their own; some interventional studies (e.g. immune-based strategies) may include an analytical treatment interruption in the design |