Notice of Special Interest (NOSI): Towards Developing a Cure for HBV in HIV/HBV Co-Infection

Funding Agency:
National Institutes of Health

Hepatitis B virus (HBV) is a major global public health challenge, with estimates of more than 296 million HBV carriers worldwide, of whom approximately 820,000-887,000 die annually due to cirrhosis and hepatocellular carcinoma (HCC). Roughly 8.4% of the 820,000-887,000 are thought to be coinfected with HIV. HBV co-infection is associated with an increased risk of cirrhosis, HCC, and overall death in People Living With HIV (PLWH). The HBV specific immune response is impaired with declined CD4+ T cell response in HBV–HIV co-infected individuals. Despite the widespread use of antiviral agents active against both HBV and HIV, liver-related mortality remains the second leading cause of death among PLWH.

A major challenge in the management of both HIV and HBV is that antiviral treatment must be continued lifelong as both viruses have long lived forms that persist on antiviral therapy, thus the inability to attain a functional cure. The covalently closed circular DNA (cccDNA) remains permanently in infected hepatocytes. The main barriers to cure HBV include the persistence of cccDNA and HBsAg. The use of currently available nucleoside reverse transcriptase inhibitors (NRTI) can suppress replication of HBV DNA and reduce but not eliminate HBsAg production but have little impact on cccDNA; HBV DNA rebounds following cessation of NRTI. Although suppression of plasma HBV DNA leads to decreased levels of fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), levels of HBsAg still remain elevated which may be related to the persistence of cccDNA. There are no FDA-approved drugs to eliminate the cccDNA and no standardized assays to measure cccDNA. The development of new therapies is targeted at developing treatment regimens of finite duration with low risk of virologic relapse, low toxicity, and minimal risk of liver disease progression after the treatment is stopped. In addition, clinically relevant biomarkers and diagnostics are needed including reliable markers to assess HBV cure and extent of liver injury.

The Notice of Special Interest (NOSI) seeks to fill scientific gaps needed to (a) inform HBV cure strategies by furthering our understanding of unique challenges impacting HBV and HIV co-infected hosts; and (b) advance the discovery and development of novel HBV interventions that are safe and achieve a cure in HIV and HBV co-infected individuals.

The purpose of this NOSI is to encourage applications for support of innovative basic, translational, and clinical research to identify and address the unique challenges to achieving HBV cure in the presence of HIV. Research on HIV/HBV co-infection relating to the following areas will be encouraged: (1) immunology; (2) virology; and (3) therapeutics.

This notice applies to due dates on or after September 5, 2022, and subsequent receipt dates through May 7, 2025.

NOT-AI-22-043

Eligibility

Faculty

Category

Medical
Medical - Basic Science
Medical - Clinical Science
Medical - Translational

External Deadline

January 5, 2022