Identification of Plasma Immune markers Associated with Latent Tuberculosis Conversion in HIV-Infected Individuals who received isoniazid preventive therapy.

Tuberculosis remains a major risk for people living with HIV, even those on antiretroviral therapy, due to increased susceptibility to latent TB infection. Identifying immune signatures that distinguish progression from resistance is critical for developing predictive biomarkers and targeted prevention strategies. In this study, 80 HIV-infected adults on antiretroviral therapy who received isoniazid preventive therapy (IPT) were followed for six months and categorized as Progressors, Sustainers, Converters, or Resisters based on serial QuantiFERON-TB results. Plasma levels of cytokines, chemokines, and growth factors were analyzed using a Luminex assay, alongside machine learning and pathway analyses. Progressors and Sustainers exhibited elevated proinflammatory cytokines, chemokines, and growth factors, while Resisters showed dynamic immune modulation following preventive therapy. Key predictors of progression included PD-L1, TNF-α, IL-17A, and FGF2. Network and pathway analyses highlighted persistent inflammatory signaling in Progressors and adaptive immune regulation in Resisters. Findings suggest distinct immune profiles associated with TB risk, offering potential for improved prediction and targeted interventions.