Background: We assessed perceptions of what is “too much risk” in HIV cure clinical research in the United States. Data inform possible risk thresholds and risky features that would make participants reluctant to join studies or regulators to approve them.
Methods: We implemented a cross-sectional survey among 400 HIV-positive adults in the United States in 2015. The sample was ethnically diverse and 38 U.S. states were represented. We also conducted key informant interviews with 36 people living with HIV, researchers, bioethicists, members of IRBs and regulatory agencies.
Results: Preliminary results revealed a high degree of variability in perceptions of what constitutes “too much risk” in HIV cure research. Activation of genes that would cause cancer (49% [95% CI: 44, 54%]; n = 358) and development of resistance to ARVs (37% [95% CI: 32, 42%]; n= 358) were the clinical factors most likely to discourage participation among HIV-positive volunteers. Perceptions of “too much risk” among this group ranged from first-in-human studies without underlying proof of concept, painful procedures, significant increases in viral load and decreases in CD4, interventions that would cause viral rebound, irreversible long-term side effects, damages to vital organs, immune system shut down, anything that would cause HIV to become unmanageable, progression to AIDS, hospitalization, debilitation or risk of death. Unacceptable social risks included drastic changes in quality of life, transmission of HIV to others, and inability to work or care for family. Financial risks included loss of disability income or insurance coverage. A minority did not place an upper limit on acceptable risk. For regulators, any intervention that would result in clinical hold or high likelihood of serious adverse events would be “too much risk.” Clinicians-researchers provided examples of risky modalities such as stem cell transplants in cancer-free patients, studies using PD-1 blockers or latency-reversing agents without demonstrated substantial reductions in reservoir size with treatment interruptions.
Conclusions: Despite challenges of making risk determinations at this juncture, knowing what risks are unacceptable is important to inform study design and accrual as well as informed consent. We should strive to maintain public confidence in the HIV cure research enterprise.

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