Multidisciplinary Research to Accelerate Hepatitis B Cure in Persons Living with HIV and HBV (U19 Clinical Trial Not Allowed) | RFA AI 23 057

Opportunity Information: Apply for RFA AI 23 057

The National Institutes of Health (NIH) is soliciting applications for a cooperative agreement under Funding Opportunity Number RFA-AI-23-057, titled "Multidisciplinary Research to Accelerate Hepatitis B Cure in Persons Living with HIV and HBV (U19 Clinical Trial Not Allowed)." This is a discretionary health research funding opportunity (CFDA 93.855) designed to bring together multidisciplinary teams to tackle key scientific barriers to curing hepatitis B virus (HBV) infection specifically in people living with HIV (PLWH) who also have HBV. The central idea is that HIV/HBV coinfection is not a one-size-fits-all condition; differences in the host (human biology, immune function, comorbidities, treatment histories) and in the virus (HBV genotypes, variants, replication dynamics) can change how disease progresses, how long the virus persists, and how the immune system contributes to both control and damage. The NOFO prioritizes research that clarifies these sources of heterogeneity and uses that knowledge to guide realistic, evidence-based HBV cure strategies tailored to PLWH.

A defining feature of this opportunity is the requirement to build an observational cohort rather than run interventional clinical trials. The NOFO explicitly states "Clinical Trial Not Allowed," which means applicants should not propose studies where participants are prospectively assigned to receive a specific intervention to test an outcome. Instead, the cohort is meant to accelerate discovery through careful, structured observation of participants over time, coupled with deep clinical characterization and integrated laboratory science. In practical terms, NIH is looking for programs that can collect and harmonize clinical data, biospecimens, and immunologic/virologic measurements in a way that enables robust translational research. The goal is to connect what is seen at the bedside (clinical phenotypes and outcomes) with what is measured in the lab (viral markers, immune signatures, mechanisms of persistence and immunopathology), so the field can identify which cure approaches are most promising for which subgroups of coinfected individuals.

Because this is a U19 cooperative agreement, the expectation is not a single-project, single-lab effort, but a coordinated program made up of multiple, linked research components. Multidisciplinary teams are expected to span clinical expertise (such as infectious diseases, hepatology, HIV medicine, cohort management, and clinical phenotyping) and basic/translational science (such as virology, immunology, systems biology, biomarker discovery, and pathogenesis research). The cooperative agreement mechanism also signals substantial NIH involvement beyond standard grant administration, typically through collaborative oversight, milestone-driven progress, and program-level coordination to maximize shared value and comparability across studies. The emphasis on accelerating discovery and increasing clinical impact suggests that the cohort and associated research infrastructure should be designed for broad utility, enabling the team to generate insights that can directly inform future cure-directed trials or interventions even if such trials are not part of this award.

The scientific scope centers on understanding how host and viral heterogeneity shape three interrelated areas: (1) pathogenesis of disease, meaning how liver disease develops and progresses in the setting of HIV/HBV coinfection; (2) viral persistence, meaning the mechanisms that allow HBV to remain in the body despite immune pressure and antiviral therapy, including reservoirs and molecular forms of viral nucleic acids that are difficult to eradicate; and (3) immunopathology, meaning how immune responses may contribute both to control of HBV and to liver inflammation or injury. By mapping these factors in PLWH, the funded research is intended to reveal mechanistic targets and practical biomarkers that can guide cure strategies, including identifying who may benefit from particular approaches and how to measure meaningful movement toward cure.

Eligibility for this funding opportunity is broad and includes a wide range of domestic organizations and governmental entities: state, county, city/township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; Native American tribal organizations other than federally recognized tribal governments; public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (outside of higher education institutions); for-profit organizations (other than small businesses) as well as small businesses; and other eligible entities. NIH also explicitly highlights additional eligible applicant categories aimed at broadening participation and representation, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, non-U.S. (foreign) entities, regional organizations, Indian/Native American tribal governments that are not federally recognized, and U.S. territories or possessions. This breadth aligns with the cohort-based nature of the work, where partnerships with community, public health, and diverse clinical settings can be essential to enrolling and retaining participants and ensuring findings generalize across populations.

Key administrative details include the sponsoring agency (National Institutes of Health), the funding instrument (cooperative agreement), and the original closing date of March 13, 2024. While the source data lists an award ceiling and expected awards fields without values, the structure and complexity implied by a U19 cooperative agreement typically point to larger, programmatic awards that support multiple integrated projects and shared cores or resources. Overall, the opportunity is best understood as an NIH effort to build coordinated, high-impact research programs that can generate a clearer, more actionable picture of HBV persistence and disease mechanisms in PLWH, using a well-designed observational cohort as the engine for discovery and for translating mechanistic findings into credible cure-focused strategies.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Multidisciplinary Research to Accelerate Hepatitis B Cure in Persons Living with HIV and HBV (U19 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.855.
• This funding opportunity was created on 2023-10-10.
• Applicants must submit their applications by 2024-03-13. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

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