Impact of HIV-Induced Immune Activation on Hepatitis B Virus Pathogenesis and Treatment Response in Co-Infected Nigerian Patients

HIV-HBV co-infection is associated with accelerated HBV-related liver fibrosis and differential responses to tenofovir-based antiretroviral therapy compared to HBV monoinfection, but the immunological mechanisms driving these clinical differences are incompletely understood in sub-Saharan African co-infection settings. This study characterises the impact of HIV-induced immune activation on HBV pathogenesis and tenofovir treatment response in a prospective co-infected Nigerian cohort. HIV-HBV co-infected patients (n=120), HBV-monoinfected patients (n=120), and HIV-monoinfected patients (n=120) will be recruited from hepatology and HIV clinics at three teaching hospitals in Lagos, Abuja, and Kano. At baseline and at 6, 12, and 24 months, HBV DNA quantification, HBsAg quantitative titre, HBV surface antigen mutations, liver stiffness by transient elastography, and liver function tests will be assessed. Peripheral blood immunophenotyping by mass cytometry will characterise HBV-specific CD8 T cell function and exhaustion status, NK cell cytotoxicity, and systemic immune activation markers (sCD163, IL-6, IP-10) in all three cohorts. Multivariate mixed-effects models will examine whether immune activation parameters predict HBV DNA suppression rates and fibrosis progression at 24 months. This study generates an original mechanistic understanding of HIV-HBV co-infection immunopathology in a predominantly genotype E HBV, subtype A HIV-1 co-infection setting typical of Nigeria, directly informing optimised dual-infection management guidelines. Keywords: HIV-HBV co-infection, immune activation, HBV pathogenesis, treatment response, Nigeria