April 29, 2022
PA-20-185- NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
PA-20-195- NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
PA-21-259- PHS 2019-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)
PA-21-262- PHS 2019-02 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)
National Institute of Allergy and Infectious Diseases (NIAID)
Background
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.
Research Objectives
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. Research topics of interest in the presence of HIV will include, but are not limited to:
Immunology
- Impact of HIV infection on HBV immune tolerance, immune activation/inflammation, and HBV viral persistence.
- Factors critical to induce immune control of HBV.
Virology
- Viral mechanisms and immune-related factors predictive of HBV reactivation.
- Mechanism for cccDNA biogenesis and decay.
- Role of integrated HBV DNA in HIV/HBV coinfection.
Therapeutics / Diagnostics
- Blood based biomarkers and non-invasive diagnostic tools as correlates to assess liver injury and indicators of treatment response/,
- In vitro, animal models of infection (includes nonhuman primates) for discovery and development of new agents.
- Assessing valid endpoints in various phases of HBV infection to be applied in treatment studies of new therapeutics.
Although clinical trials are not allowed, use of samples from clinical trials is allowed. Animal research is allowed, to include non-human primates.
The areas below will NOT be supported through this NOSI:
- Applications which propose clinical trials (all phases), the establishment of patient cohorts or adding patients to existing cohorts.
- Applications which focus solely on HIV or solely on HBV.
- Applications which focus on hepatitis viruses other than HBV.
Application and Submission Information
This notice applies to due dates on or after September 5, 2022, and subsequent receipt dates through May 7, 2025.
Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcements through the expiration date of this notice:
- PA-20-185- NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
- PA-20-195- NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
- PA-21-259- PHS 2019-02 Omnibus Solicitation of the NIH, CDC, and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)*
- PA-21-262- PHS 2019-02 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)*
* Note: PA-21-259 and PA-21-262 will be reissued in early July 2022.
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
- For funding consideration, applicants must include NOT-AI-22-043 in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.
Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.
Scientific/Research Contact(s)
Josh Radke, PhD
National Institute of Allergy and Infectious Disease (NIAID)
Telephone: 301-761-6525
Email: [email protected]
and Human Services (HHS)
