Abstract
BACKGROUND: Helicobacter pylori (H. pylori) is known to modulate host immunity and sustain chronic inflammation, yet most data come from HIV-negative populations. In people living with HIV, whose T cell compartments are already dysregulated, the way H. pylori shapes peripheral T cell phenotypes, and how those profiles change after eradication therapy, is still unclear. Because both infections are common in Central Ethiopia, we examined peripheral T cell phenotypes in adults with and without HIV according to H. pylori status and assessed the immunologic effects of antibiotic eradication. MATERIALS AND METHODS: We conducted a prospective study in people with and without HIV infection from Ethiopia. H. pylori status was determined by stool-antigen testing; a subset received standard triple therapy and was followed for 12 months. Multiparameter flow cytometry quantified T cell activation, proliferation, exhaustion, and regulatory T cells (T(regs)) at baseline and after therapy. RESULTS: T cell analyses showed that participants with HIV had consistently higher proliferation (Ki67), exhaustion (PD-1, TIM3), and Th17 (CCR6⁺CD161⁺) markers than those without HIV. H. pylori-positive individuals exhibited higher T(reg) levels irrespective of HIV status (HIV-negative: median 2% vs 1.08%, p < 0.0001; HIV-positive: median 2.9% vs 1.62%, p = 0.009). Successful eradication therapy led to a significant reduction in T(regs) in both HIV-positive (median 3.04% → 0.70%, p = 0.031) and HIV-negative (median 2.96% → 1.46%, p = 0.040) groups. A similar decline was also observed in HIV-negative individuals with unsuccessful therapy (median 2.85% vs 1.29%, p = 0.0039). CONCLUSIONS: H. pylori infection was linked to significant differences in T cell profiles in both HIV-negative and HIV-positive individuals. Eradication therapy was followed by a reduction in Tregs-significant in HIV-negative participants irrespective of outcome and in PLWH with successful eradication-with subgroup-specific shifts in activation and differentiation/exhaustion markers, highlighting potential therapeutic avenues for mitigating immune dysregulation in co-infected populations.