{
  "abstract": "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 ToxhighTCF-1-CD127- cells. Tpex enrichment extended to HBV-specific populations corresponding with more robust, polyfunctional HBV-specific responses in co-infection against surface and core antigens. HBV-specific CD8 T cells maintained enhanced proliferative capacity and checkpoint responsiveness to anti-PDL1 blockade compared with HBV mono-infection. While co-infection was characterised by lower HBsAg levels and longer treatment duration, these factors alone did not account for the distinct immunological profiles.Conclusions People with well-controlled HBV/HIV co-infection maintain robust CD8 + T cell responses with preserved stem-like properties supporting antiviral function. These results challenge assumptions about additive immune dysfunction in dual chronic infections and highlight the need for tailored immune-modulatory therapies.",
  "authors": [
    {
      "affiliations": [
        "Institute of Immunity and Transplantation, University College London, London, UK"
      ],
      "name": "Anucha Preechanukul"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK"
      ],
      "name": "Aljawharah Alrubayyi"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK"
      ],
      "name": "Bo Sun"
    },
    {
      "affiliations": [
        "Institute of Immunity and Transplantation, University College London, London, UK"
      ],
      "name": "Edward Arbe-Barnes"
    },
    {
      "affiliations": [
        "Institute of Immunity and Transplantation, University College London, London, UK"
      ],
      "name": "Jonida Kokici"
    },
    {
      "affiliations": [
        "Institute of Immunity and Transplantation, University College London, London, UK"
      ],
      "name": "Frances Gorou"
    },
    {
      "affiliations": [
        "Institute of Immunity and Transplantation, University College London, London, UK"
      ],
      "name": "Sarun Prasitdumrong"
    },
    {
      "affiliations": [
        "Institute of Immunity and Transplantation, University College London, London, UK"
      ],
      "name": "Kelly A S da Costa"
    },
    {
      "affiliations": [
        "Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK"
      ],
      "name": "Natasha Fisher-Pearson"
    },
    {
      "affiliations": [
        "Institute of Immunity and Transplantation, University College London, London, UK"
      ],
      "name": "Noshin Hussain"
    },
    {
      "affiliations": [
        "Institute of Immunity and Transplantation, University College London, London, UK"
      ],
      "name": "Stephanie Kucykowicz"
    },
    {
      "affiliations": [
        "Mortimer Market Clinic, Central Northwest London NHS Foundation Trust, London, UK"
      ],
      "name": "Indrajit Ghosh"
    },
    {
      "affiliations": [
        "Department of HIV Medicine, Royal Free London NHS Foundation Trust, London, UK",
        "Institute for Global Health, University College London, London, UK"
      ],
      "name": "Fiona Burns"
    },
    {
      "affiliations": [
        "Department of HIV Medicine, Royal Free London NHS Foundation Trust, London, UK"
      ],
      "name": "Sabine Kinloch"
    },
    {
      "affiliations": [
        "Department of HIV Medicine, Royal Free London NHS Foundation Trust, London, UK"
      ],
      "name": "Pedro Simoes"
    },
    {
      "affiliations": [
        "Department of HIV Medicine, Royal Free London NHS Foundation Trust, London, UK"
      ],
      "name": "Sanjay Bhagani"
    },
    {
      "affiliations": [
        "Barts Liver Centre, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London, UK"
      ],
      "name": "Patrick T F Kennedy"
    },
    {
      "affiliations": [
        "Institute of Immunity and Transplantation, University College London, London, UK"
      ],
      "name": "Mala K Maini"
    },
    {
      "affiliations": [
        "Department of Biochemistry, University of Oxford, Oxford, UK"
      ],
      "name": "Rachael Bashford-Rogers"
    },
    {
      "affiliations": [
        "Barts Liver Centre, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London, UK"
      ],
      "name": "Upkar S Gill"
    },
    {
      "affiliations": [
        "Institute of Immunity and Transplantation, University College London, London, UK",
        "Mortimer Market Clinic, Central Northwest London NHS Foundation Trust, London, UK",
        "Department of HIV Medicine, Royal Free London NHS Foundation Trust, London, UK"
      ],
      "name": "Dimitra Peppa"
    }
  ],
  "title": "Stem-like CD8+ T cells preserve HBV-specific responses in HBV/HIV co-infection",
  "uid": "518675ad-6e11-56a1-94f9-ad07e7cfd4c0"
}