Cytokine imbalance and HBV-specific T-cell exhaustion predict disease progression in HIV-HBV coinfection

Background HIV-HBV coinfection accelerates liver disease, yet the immunological mechanisms underlying adverse outcomes remain incompletely characterized 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, 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 characterized by HBV reactivation, cytokine imbalance, and T-cell exhaustion, which were associated with disease progression and may inform risk stratification.