Shared Resources Core

Johns Hopkins University, Baltimore MD

Investigators

Abstract

Globally, there are over 300 million people living with chronic hepatitis B virus (PWHB) infection and an estimated 39 million people living with HIV (PWH) – about 90% of PWHB and PLHIV live in low and middle- income (LMIC) settings. Given shared routes of transmission, prevalence of HBV among people living with HIV is ~10%. Mortality, particularly liver-related mortality, among people living with HIV and HBV (PWHHB) is several-fold higher than PWH. Therefore, it is imperative to identify ways to cure HBV. Given the diversity of HBV and HIV, a global cohort comprising participants of varying strains of HIV and HBV infection is essential; to our knowledge, no such cohorts with detailed characterization of HBV and HIV markers currently exist. Accordingly, we propose to: Aim 1: Establish a global longitudinal cohort of PWHHB and PWHB to foster HBV cure research; Aim 2: Establish a well-characterized data and specimen repository that can be utilized to carry out proposed clinical, translational, and immunological projects related to HBV cure; Aim 3: Develop a platform for data/specimen sharing to promote globally/locally relevant research associated with HBV cure. To achieve these objectives, we have brought together a team from academia, industry, and in-country organizations who have been involved in the establishment of cohorts related to HIV and HBV for over two decades. The Hepatis B HIV Cure Consortium (BICC) cohort will capitalize upon existing cohorts and supplement with new participants to achieve a diverse global sample. In each of Brazil, India, Senegal and Uganda, we will recruit 150 participants (100 PWHHB and 50 PWHB) ensuring at least 30% of the PWHHB cohorts include participants who are on ART for ≤1 year. In a subset (n=90; ~60 PWHHB and 30 PWHB), we will perform liver biopsies and leukapheresis at entry and a subset of these will undergo a second (paired) liver biopsy/leukapheresis. We will monitor recruitment to ensure that about 40%-50% of the sample are HBeAg positive. In the US, we will recruit a subset of 75 participants from the MACS WIHS Combined Cohort Study (MWCCS). The cohort will be established between Month 7-18 and will be followed semi-annually (median anticipated follow-up: 4 years). At each visit, participants will complete an electronic survey, undergo a clinical exam, provide a blood sample. All samples will be tested for HIV and HBV markers that are being donated by Abbott Laboratories. This includes FDA approved as well as research use only (RUO) assays that have been developed by the Abbott team on this proposal. All sites already have established repositories that contribute to NIH and/or Abbott funded protocols. In collaboration with the Statistical and Data Management Core (SDMC), we will host on the BICC website a codebook of data available and a virtual repository that investigators across the world can utilize to submit concepts. Given our teams' long-standing history in establishing cohorts, developing diagnostic tests, data management, and history of collaboration, we are confident we will achieve the proposed aims.