Advancing Acceptability and Ethical Readiness for Innovative HIV Cell and Gene Therapies in the United States

About This Grant

7. PROJECT SUMMARY/ABSTRACT The biomedical landscape is undergoing a rapid transformation driven by advances in cell and gene therapy (CGT), a field revolutionizing treatment and clinical research for conditions once deemed untreatable. Within this evolving context, HIV cure research has reached a pivotal phase where CGT approaches have moved beyond theory and into clinical trials. These novel interventions hold the potential to achieve durable, antiretroviral therapy (ART)-free viral suppression. Such a breakthrough would have profound implications for public health in the United States (U.S.) and globally. With over 1.2 million Americans living with HIV (PWH) and the healthcare system bearing the substantial costs of lifelong ART, a scalable and durable ART-free regimen could reduce clinical burden, improve quality of life, and transform HIV care. CGT strategies, designed to make cells HIV- resistant or enhance immune responses, are among the most promising candidates for a globally scalable HIV cure. Current approaches under investigation include chimeric antigen receptor (CAR) T cells, CRISPR-Cas9 gene editing, and genetically modified hematopoietic stem cells. Despite scientific and regulatory progress, several critical barriers remain to their ethical and effective implementation. First, there is limited understanding of how PWH perceive the risks, benefits, and overall acceptability of CGT-based interventions. Although early- phase HIV CGT trials are underway, real-world data on community perspectives are scarce, complicating efforts to design person-centered trials. Second, little is known about how PWH and research staff navigate the complexities of CGT trial implementation. These trials are time- and resource-intensive; yet the experiences and support needs of staff, who play a critical role in trial success, are seldom studied. Third, innovative models such as end-of-life (EOL) translational research offer unprecedented opportunities to study HIV cure-related strategies. The University of California San Diego's Last Gift program engages terminally ill PWH who voluntarily donate tissues at the EOL to study HIV persistence; some interventional experiments are already underway ex vivo. The next frontier will involve in vivo testing of experimental CGT strategies in this translational research model. While promising, this raises novel ethical, regulatory, and logistical challenges requiring careful evaluation. Our Specific Aims are: Aim 1 will determine the anticipated acceptability of HIV CGT approaches among PWH in the U.S. Aim 2 will characterize the experiences of PWH participating in, and research staff implementing, CGT-based HIV cure trials. Aim 3 will establish the ethical, regulatory, and procedural feasibility of introducing in vivo CGT interventions into the EOL translational research model at UCSD. This R21 will generate critical insights into the social, operational, and ethical dimensions of HIV CGT implementation in the U.S. Findings will inform trial design, stakeholder engagement, and policy development to ensure ethical, feasible, and acceptable CGT strategies. Ultimately, this research will support innovation in HIV cure science, reduce the long-term burden of HIV care, and promote innovation that is relevant to the health of all Americans.