Table 1 IRB-approved interview guide: ethical and practical considerations for ethical and practical considerations for designing and implementing combination HIV cure trials

Introduction

• First, thank you so much for your time

Considerations for combining interventions towards HIV cure

• What ethical considerations should be in place for combining different HIV cure research approaches?

• What considerations should be in place when designing combination protocols?

• How do we ensure combination regimens remain within acceptable benefit/risk parameters?

• What regulatory considerations should be in place for combining different HIV cure research approaches?

• Is it important to know the effect of each intervention when designing a combination strategy? Why/why not? Is it important to know whether combination strategies have additive/synergistic/antagonistic effects? Why/why not?

• How do we prioritize which combination should be tested? What type of information is needed to make these decisions?

• How many different strategies do you think we should use in combination? Can you please explain your answer?

• Which one is better: administer regimens together or to administer regimens in sequence? Can you please explain your answer?

• What considerations should be in place when sequencing interventions? How do we decide when to ‘time’ interventions?

Considerations for specific combination HIV cure regimens

• Do you think the following regimens should be used in combination? Why/why not?

        • Combination broadly neutralizing antibodies [follow-up question: what safeguards should be in place for these protocols (e.g., resistance development for one antibody?)]

        • Combination cell and gene modification approaches (follow-up question: what safeguards should be in place for these protocols?)

        • Combination latency-reversing agents with immune-modifying agents (follow-up question: what safeguards should be in place for these protocols?)

Additional considerations

• How do we ensure combination regimens represent improvements above antiretroviral therapy (ART) for people living with HIV?

• What are some of the challenges of designing combination regimens? How can we best overcome these challenges?

• How can we best engage people living with HIV and communities around HIV cure research involving combinations?