Table 3.

Summary of recommendations suggested by LTS on interventional Hiv cure research at the EOL

Key Considerations	Refined Actionable Strategies
Ethical and Informed Consent Protocols	• Develop informed consent frameworks ensuring comprehension of risks, expected outcomes, and participant rights. • Engage bioethicists, regulators, advocates, community advisors, and next-of-kin/loved ones to co-design accessible informed consent and decision-making support materials. • Implement reassessment mechanisms for ongoing informed decision-making as participants’ health evolves. • Provide educational resources tailored for older adults about EOL research.
Guidelines for Analytical ART Interruption in EOL Research	• Address psychological and clinical concerns through tailored participant counseling before analytical ART interruption. • Evaluate immune responses and viral rebound dynamics in aging populations to guide EOL-specific ART policies. • Develop structured protocols for medical oversight, symptom management, and voluntary ART reinitiation. • Conduct sub-studies on physiological impacts of viral rebound in aging populations.
Adapting Study Designs for Feasibility	• Ensure flexibility in research participation, offering home-based, hospice-supported, and telehealth-integrated options. • Reduce participant burden through streamlined procedures with minimal disruption to palliative care. • Establish contingency plans for participant deterioration, ensuring dignity and data integrity.
Managing Risks of Latency-Reversing Agents (LRAs)	• Limit LRAs to low-toxicity candidates with manageable side effects in older populations. • Conduct preliminary safety testing in younger populations before extending trials to older participants. • Implement real-time safety monitoring and immediate ART reinitiation pathways if adverse effects arise. • Conduct post-mortem assessments to evaluate LRAs’ effects on latent reservoirs.
Enhancing Safety of Immune-Based Approaches	• Prioritize immune-based therapies with lower risk of overactivation, tailored to aging immune systems. • Evaluate the feasibility of bNAbs and therapeutic vaccines specifically in LTS and EOL cohorts. • Investigate immune-based strategies’ potential synergy with latency-reversing agents in EOL settings.
Ethical Oversight in Gene Therapy Interventions	• Ensure rigorous safety validation of gene-editing interventions before EOL implementation, with clear communication about risks and unknowns. • Address participant concerns about potential unintended consequences by providing transparent data on prior safety trials and ethical oversight. • Limit gene therapy trials at EOL to interventions with established safety profiles to minimize uncertainty and potential harm.
Feasibility and Implementation of Block-and-Lock Strategies	• Validate long-term effectiveness and safety of block-and-lock approaches in preclinical models. • Determine feasibility for individuals with short life expectancy by assessing stability of viral suppression. • Communicate realistic expectations, addressing whether ART may still be required long-term.
Designing Effective Combination Cure Strategies	• Identify optimal intervention pairings to balance efficacy and participant burden. • Ensure robust safety and feasibility trials before introducing multi-modal interventions at EOL. • Establish systematic data collection frameworks to maximize the scientific impact of EOL combination studies.
Expanding Awareness and Accessibility of EOL Cure Research	• Leverage HIV advocacy networks, hospice organizations, and patient-led initiatives for outreach. • Deploy peer navigators and tailored educational resources. • Address misconceptions through ongoing community dialogues and research transparency efforts.
Policy, Structural, and Regulatory Support	• Advocate for policy adjustments supporting ethical EOL interventional research. • Secure long-term funding for EOL cure trials to ensure sustainability and scientific rigor. • Promote regulatory adjustments to accommodate accelerated approvals for promising interventions.