Background Chronic hepatitis B virus (HBV) infection disproportionately affects people living with HIV, who are often excluded from functional cure studies. Objective This study investigates CD8 + T cell profiles in HBV mono-infection versus HBV/HIV co-infection, examining the impact of long-term therapy on virus-specific responses to inform therapeutic strategies for immune restoration.
Design We analysed CD8 + T cell responses in 61 participants (HBV n=20, HBV/HIV n=20, HIV n=21), on suppressive antiviral therapy, assessing transcriptomic and proteomic profiles, focusing on exhaustion markers alongside virus-specific functional capabilities. Results Transcriptomic analysis revealed distinct signatures in co-infection, with upregulation of TCR signalling genes, inhibitory pathways and progenitor-exhausted markers ( XCL2, TCF7, PDCD1, IL7R ).
This profile scored highly for a precursor exhausted (Tpex) CD8 + T cell signature, reflecting stemness that maintains plasticity despite chronic antigen exposure. Proteomic analysis confirmed higher frequencies of Tpex (TCF-1 + CD127 + PD-1 + ) CD8 + T cells in co-infection, while HBV mono-infection showed predominance of terminally exhausted Tox high TCF-1 - CD127 - cells.
Gut (BMJ) published a clinical update in Research Highlights on 09 Jun 2026.
The item focuses on Stem-like CD8+ T cells preserve HBV-specific responses in HBV/HIV co-infection.
Review the original article for the full source wording and details.