{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T13:51:08Z","timestamp":1772632268140,"version":"3.50.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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-\u03b1 with reduced IFN-\u03b3 compared with HIV-monoinfected controls (all p &amp;lt; 0.001). The IL-6\/IFN-\u03b3 ratio correlated with HBV viral load (r = 0.74), APRI score (r = 0.71), and CD4+ count (r = \u22120.64; all p &amp;lt; 0.001). HBV-specific polyfunctional CD8+ T-cells were markedly reduced (median 0.08% vs 3.8% in controls; p &amp;lt; 0.001). In multivariable Cox regression, IL-6\/IFN-\u03b3 ratio &amp;gt;4.0 (HR 4.12, 95% CI 1.86\u20139.14), CD4+ &amp;lt;200 cells\/\u00b5L (HR 3.24, 95% CI 1.58\u20136.64), and APRI &amp;gt;1.0 (HR 2.86, 95% CI 1.34\u20136.11) independently predicted progression, whilst preserved T-cell polyfunctionality was protective (HR 0.32, 95% CI 0.15\u20130.68).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  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