Impact of antiviral therapy on infection and replication derived hepatitis b virus DNA integration

Active Project Grant Awarded

Award ID
R03AI201866
Recipient
Awarding agency
Obligated
$78,300

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date 16% complete
Place of performance
Doylestown, PA 18901, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Hepatitis b virus (HBV) chronically infects 254 million people worldwide and accounts for 1.1 million deaths per year due to cirrhosis and liver cancer. Currently, there are two types of antiviral drugs approved to treat chronic hepatitis b (CHB) including nucleos(t)IDE analogues and pegylated interferon-alpha, but cure remains rare. Due to the fact that chronicity of HBV infection and intracellular viral replication is only incompletely suppressed by antivirals, the rather infrequent viral integration can eventually accumulate to high level over decades-long presence of the virus. High integration burden not only worsens viral pathogenesis by being extra resources for HBV surface antigen production, but also directly contributes to tumorigenesis by disrupting chromosome genetic stability. Therefore, IT is not surprising that HBV integration is associated with more than 90% of HBV-associated HCC. However, significant knowledge GAP remains in the field with respect to the efficacy of different clinical and experimental drugs in block HBV integration. One of the reasons is that the virological and clinical significance of HBV integration has long been underestimated but only recently brought into the spotlight. Another reason is the lack of efficient and robust assay to measure HBV integration. We recently modified the traditional HBV integration assay by combining IT with a cost-effective PCR amplicon based next generation sequencing technique (amplicon-SEQ), which reduces method bias and enhances quantitative power. The purpose of this R03 grant application entitled "impact of antiviral therapy on infection and replication derived hepatitis b virus DNA integration" is to address this important knowledge GAP by using our improved HBV integration assay to characterize how antiviral drugs targeting distinct HBV replication steps impact the frequency and pattern of integration. Knowledge gained through this study will shed light on improving treatment strategies to reduce HBV integration burden and mitigate the risk of HCC.

Quick answers

Who received award R03AI201866?

R03AI201866 was awarded to Baruch S. Blumberg Institute by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on July 1, 2026.

How much is award R03AI201866 worth?

$78,300 has been obligated on R03AI201866.

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