HBV is a major global health problem. Two billion people are infected and more than 257 million are chronic carriers. More than 887,000 deaths occur annually from HBV-related complications, namely cirrhosis and hepatocellular carcinoma (HCC).
Higher prevalence of HBV is observed in people living with HIV (PLWH). The global prevalence of HBV infection in PLWH is 7.4% but rises to 15 to 28% in high endemic areas. HIV accelerates the natural course of HBV infection resulting in more rapid progression to cirrhosis and HCC.
Antiviral drugs suppress viral replication and retard disease progression, but treatment is not curative. The response to HBV vaccination may be reduced in PLWH.
Access to treatment may be limited in low and middle-income countries due to lack of diagnostics, medication costs, and shortage of trained health-care providers.
The challenges towards a cure for HBV are many. HBV cccDNA persists in infected hepatocytes. Direct-acting antivirals (DAAs) only suppress viral replication and may retard disease progression but do not eliminate or silence cccDNA. Current treatment endpoints do not consistently correlate with the presence of virus and degree of liver injury. Current use of biomarkers and noninvasive diagnostic tools to assess liver injury, treatment response, and the presence of cccDNA are imprecise. The nature of the immune response in PLWH and how co-infection affects the natural history of HBV are not completely understood.
Research Objectives and Scope
This FOA will support hypothesis-driven, innovative basic, translational, and clinical research to identify and address the unique challenges to achieving HBV cure. Research on HBV relating to the following areas are encouraged: (1) immunology; (2) virology; and (3) therapeutics.
Research topics of interest in the presence or absence of HIV include, but are not limited to, those listed below:
- Investigate how to stimulate HBV-specific innate immune response.
- Investigate how to restore HBV-specific adaptive immune response.
- Study the impact of HIV/HBV-coinfection on the immunological response to HBV.
- Explore basic mechanisms of HBV replication or HBV protein expression.
- Elucidate the mechanisms responsible for cccDNA biogenesis, homeostasis, and decay.
- Study epigenetic regulation of cccDNA transcription.
- Explore the influence of the host on the HBV life cycle.
- Identify new viral targets and strategies, including drugs to prevent resistance.
- Develop reproducible cell-free test systems for high-throughput antiviral screening.
- Develop animal models that resemble HBV infection in humans.
- Discover diagnostics that accurately measure cccDNA.
- Identify biomarker(s) for various stages of liver injury and viral replication with the ultimate goal of utilization in clinical care.
The following types of applications will NOT be supported through this FOA;
- Applications which propose clinical trials (all phases), the establishment of patient cohorts or adding patients to existing cohorts. However, the use of existing samples and data are encouraged.
- Applications which focus solely on HIV without HBV components.
- Applications which focus on hepatitis viruses other than HBV.
Deadlines: standard dates and standard AIDS dates apply
Filed Under: Funding Opportunities