Advancing Innovative Therapies for HBV Cure in People with HIV/HBV and HBV in the United States

About This Grant

7. PROJECT SUMMARY/ABSTRACT Globally, approximately 300 million live with chronic HBV (CHB) and 40 million people live with HIV. Due to shared transmission routes, approximately 10% of people with HIV (PWH) also live with HBV (PHBV). Importantly, HIV/HBV coinfection is associated with increased mortality. Like HIV, while effective HBV treatments are available, there is no cure for HBV. Hepatitis B surface antigen (HBsAg) loss, the definition of HBV functional cure, decreases incidence of hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD), yet is not easily attained with current therapy. As such, the development of novel HBV therapies, aiming for HBV functional cure, is rapidly advancing. HBV functional cure research has become a scientific priority of the NIH, industry, academia, and the community with over 50 clinical trials and compounds in development. Interestingly, HBV functional cure occurs more often in PWH/PHBV, making this an ideal cohort in which to study HBV curative therapies. Despite the pace and volume of HBV cure research, there is little knowledge about patient and provider perspectives on key HBV clinical trial approaches – unlike in HIV cure research, where over a decade of experience has informed priorities. One of the key clinical trial–related questions is whether and how to implement HBV treatment discontinuations, which will be necessary to study the efficacy of curative and finite HBV novel therapies. This will pose specific challenges in PWH/PHBV, such as the heightened likelihood of rebound hepatitis and the ongoing need for HIV antiretroviral treatment (ART). There is a notable lack of data regarding both patient and provider knowledge and priorities concerning this pivotal research phase, including questions of whether HBV treatment discontinuations are desired, the duration of discontinuation, or how to manage it. Similarly, there are limited data on trial design elements such as type of novel therapies, timing of therapy initiation, and willingness to participate in HBV cure trials. These knowledge gaps remain key hurdles to advancing effective, safe, and acceptable HBV cure strategies. Data from this application will be crucial for the development of HBV clinical trials attractive to PWH/PHBV and PHBV. Our proposed work will inform outreach, recruitment, consent, and retention of participants in future HBV clinical trials. To this end, our Specific Aims are as follows: Aim 1 will explore priorities of PWH/PHBV, PHBV and providers around key aspects of HBV clinical trials including HBV treatment discontinuations, choice of novel HBV agents, and trial participation using in-depth interviews. Aim 2 will quantify priorities of PWH/PHBV and PHBV around these same trial elements through a national U.S. survey. Aim 3 will develop ethical considerations and obtain feedback on provider- and patient- facing materials in collaboration with key stakeholders. Together, our three aims will clarify therapeutic advancement priorities and guide the ethical design of future innovative HBV clinical research with significant implications for population health. This work is directly relevant to the health of all Americans, as it addresses chronic disease management, co-morbidities, and the reduction of long-term burdens on the healthcare system.