# HBV-specific T cell immunity in HBV/HIV coinfection

> **NIH NIH R37** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $725,950

## Abstract

Project Summary/Abstract
Among people living with HIV (PLWH), hepatitis B virus (HBV) is a common coinfection that contributes to high
rates of liver-related mortality. Even with early initiation of antiretroviral therapies that include HBV-active
nucleoside analogs (NA), mortality in people with HBV/HIV coinfection remains unacceptably high. There is a
strong rationale for additional HBV therapies for people with HBV/HIV infection. The HBV cure research agenda
is to (1) understand HBV biology, particularly the mechanisms that lead to HBV functional cure (FC), which is
defined as seroclearance of the hepatitis B surface antigen in blood, and (2) to evaluate novel antiviral and/or
immunotherapies that can increase HBV FC from its current rate of ~1% per year. However, at the present,
PLWH are poorly represented in HBV cure research, and HIV infection is an exclusion criterion in virtually all
clinical trials of novel HBV therapeutics. To accelerate the use of novel therapies in patients with HBV/HIV
coinfection, a better understanding is needed of host control of HBV in the setting of HIV. This project focuses
on cellular immune mechanisms of HBV control, particularly HBV-specific T cells. Our central hypothesis is that
in HBV/HIV coinfection, CD4 T cells represent a critical component of the immune response mediating HBV
control, including FC. This hypothesis will be tested through 3 specific aims. In Aim 1, we will investigate the
impact of HIV coinfection-associated immune dysregulation, especially CD4 depletion, on the quantity and
quality of HBV-specific T cell responses. In Aim 2, we will investigate the T-cell responses mediating HBV FC in
patients with HBV/HIV coinfection who are treated during inactive HBV infection (i.e., low HBV DNA, normal ALT,
no-minimal liver disease). In this group, we previously reported relatively high rates of HBV FC. In Aim 3, we will
characterize the evolution of HBV-specific T cell responses and the intrahepatic immune landscape during adult
acute HBV infection that typically results in HBV FC, with and without HIV coinfection. The above scientific
investigation will occur within a unique HBV clinical cohort in Zambia (Southern Africa), which includes adult
patients with chronic and acute HBV infection, with and without HIV coinfection, and features longitudinal large
volume blood and liver sampling before and during NA therapy. To date HBV FC has been ascertained >40
times in the cohort, mainly in participants with HBV/HIV coinfection. Successful completion of this project will
change the field by identifying immune mediators associated with HBV FC in HBV/HIV coinfection and by defining
specific immunological barriers to HBV FC in PLWH. It also will help to identify patient groups with coinfection
who may be more or less amenable to cure with emerging drugs based on their current or nadir CD4 and current
level of HBV control. In-depth analysis of specific CD4 T cells and the intrahepatic immune milieu will al...

## Key facts

- **NIH application ID:** 10900779
- **Project number:** 5R37AI179640-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** GEORG Michael LAUER
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $725,950
- **Award type:** 5
- **Project period:** 2023-08-07 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900779

## Citation

> US National Institutes of Health, RePORTER application 10900779, HBV-specific T cell immunity in HBV/HIV coinfection (5R37AI179640-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10900779. Licensed CC0.

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