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

## TL;DR

This study finds that cytokine imbalance and exhausted T-cells in HIV-HBV coinfected patients in Nigeria are linked to worse liver disease outcomes.

## Contribution

The study identifies specific immunological markers predicting disease progression in HIV-HBV coinfection in an African population.

## Key findings

- HBV reactivation is common in coinfected patients, with genotype E predominating.
- Elevated IL-6 and reduced IFN-γ are associated with higher HBV viral load and liver disease progression.
- Reduced polyfunctional CD8+ T-cells correlate with worse outcomes in coinfected patients.

## Abstract

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.

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.

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).

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.