Hepatitis B and HIV Cure Consortium (BICC)

About This Grant

The Hepatitis B HIV Cure Consortium (BICC) aims to establish a multinational cohort of people with HIV and chronic hepatitis B (PWHHB) in which to apply novel technologies to advance a hepatitis B virus (HBV) functional cure. An HBV cure is needed for the >300 million people with chronic hepatitis B (CHB) and the 10% of people with HIV who also have CHB leaving them at increased risk for liver death and limiting novel HIV treatment options. Functional cure requires sustained loss of hepatitis B surface antigen (HBsAg) off treatment, but HBV control represents a continuum; thus, we investigate factors associated with both HBsAg loss and decline. The science is based on samples from 675 participants (450 PWHHB and 225 people with hepatitis B alone) followed semi-annually from Uganda, Brazil, India, Senegal, and the United States that includes most of the major HBV genotypes. We plan to recruit 40% females. Liver biopsies and large-volume blood draws will be obtained from 90 individuals at study entry and 30 will have repeat procedures performed at year 4. The Virology Core will use state-of-the-art virological assays to characterize blood markers of HBV replication and transcription that will be used by all three projects (Clinical, Immunology, and Translational). The first aim is to build the cohort and a clinical and specimen HBV repository through the Shared Resources Core. This repository will provide all projects with human specimens (blood, liver tissue, peripheral blood mononuclear cells). The second aim is to build research capacity at each of the collaborating sites and to train early-stage investigators providing a pipeline of HBV cure investigators. The third aim characterizes mechanisms of intrahepatic persistence during treatment using novel techniques to study HBV transcription from the HBV replication template, covalently closed circular DNA (cccDNA), and from HBV integrated into the host genome (iDNA) (Translational Project). This project synergizes with the Multiomics Core to study factors associated with cccDNA transcriptional silencing and synergizes with the Immunology Project to find HBV-specific clonotypes in blood that are enriched in the liver. The fourth aim characterizes virological and immunologic dynamics associated with HBsAg loss or decline including virological markers tested in the Virology Core, T-cell and B-cell phenotypes characterized by multiparameter flow, neutralizing antibody responses, and B cell and T cell clonotypes (determined by Immunology and Multiomics Core) with HBsAg loss or decline during HBV treatment. These data are then integrated data to develop a multiscale mechanistic model of HBV control that can provide crucial information needed to develop a functional cure and informs how HIV affects functional cure. All the data generated will be stored in a HIPAA-compliant database and analyzed in the Statistical and Data Management Center. The Administrative Core manages all aspects the different Cores and Projects such as regulatory, financial, specimen allocation, training, travel, so that scientific efforts are maintained towards the goal of HBV Cure.