ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
Cytokine Imbalance and HBV-Specific T-Cell Exhaustion Predict Disease Progression in HIV-HBV Coinfection
1. Institute of Medical Microbiology and Hygiene, Freiburg University Medical Center, Freiburg, Germany
2. Nigeria Army Reference Hospital Sokoto, Sokoto, Nigeria
3. Federal University Lafia, Lafia, Nigeria
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Abstract
Background: HIV-HBV coinfection accelerates liver disease, yet the immunological mechanisms underlying adverse outcomes remain incompletely characterised in African populations. We investigated relationships between HBV reactivation, cytokine dysregulation, T-cell dysfunction, and disease progression in a Nigerian cohort. Methods: We screened 1,139 participants across four Nigerian states. Of 344 HIV-positive individuals, 53 (15.4%) had HBV coinfection. For detailed immunological and longitudinal analyses, 59 coinfected participants with complete datasets were included in the mechanistic cohort. Comprehensive assessments including HBV DNA quantification, S-gene sequencing, Page 2 cytokine profiling, and HBV-specific T-cell responses were performed on 59 coinfected patients with longitudinal follow-up. Results: Phylogenetic analysis indicated 71.4% (30/42) of cases with rising HBV DNA were consistent with reactivation. HBV genotype E predominated (94.3%). Coinfected patients demonstrated elevated IL-6 and TNF-α with reduced IFN-γ compared with HIV-monoinfected controls (all p < 0.001). The IL-6/IFN-γ ratio correlated with HBV viral load (r = 0.74), APRI score (r = 0.71), and CD4+ count (r = −0.64; all p < 0.001). HBV-specific polyfunctional CD8+ T-cells were markedly reduced (median 0.08% vs 3.8% in controls; p < 0.001). In multivariable Cox regression, IL-6/IFN-γ ratio >4.0 (HR 4.12, 95% CI 1.86–9.14), CD4+ <200 cells/µL (HR 3.24, 95% CI 1.58–6.64), and APRI >1.0 (HR 2.86, 95% CI 1.34–6.11) independently predicted progression, whilst preserved T-cell polyfunctionality was protective (HR 0.32, 95% CI 0.15– 0.68). Conclusions: HIV-HBV coinfection was characterised by HBV reactivation, cytokine imbalance, and T-cell exhaustion, which were associated with disease progression and may inform risk stratification.
Summary
Keywords
Cytokine dysregulation, HBV reactivation, HIV-HBV coinfection, liver fibrosis, Nigeria, T-cell exhaustion
Received
16 January 2026
Accepted
17 February 2026
Copyright
© 2026 Asaga, Ibeh, Ramalan and Bako. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Peter Mac Asaga
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