Factors associated with circulating levels of IL-17A in a high HIV-burden population

Interleukin-17A (IL-17A) is a key cytokine in inflammation and autoimmunity. However, its systemic correlates, particularly in a high HIV burden population, are not fully elucidated. This study aimed to identify the sociodemographic, clinical, inflammatory, metabolic, and renal factors independently associated with plasma IL-17A levels. This was a cross-sectional study of 226 adults recruited from Livingstone University Teaching Hospital, Zambia. Sociodemographic and clinical data were collected using standardized methods, and plasma biomarkers were measured using validated assays. Associations with IL-17A were assessed using multivariable linear regression models constructed using a theory-driven approach. A base clinical model was specified a priori, followed by models incorporating metabolic and inflammatory variables. A final parsimonious model was developed, and sensitivity analyses were conducted, separating by HIV status.The cohort was predominantly female (68.6%) and included a high proportion of people living with HIV (64.2%), most of whom were receiving integrase inhibitor-based therapy. In the base clinical model, HIV status was positively associated with IL-17A; however, this association was no longer significant after adjustment for inflammatory markers. In the final model, IL-1 (β: 1.32, 95% CI: 0.60-2.04, p < 0.001) and IL-6 (β: 16.02, 95% CI: 8.19-23.84, p < 0.001) were positively associated with IL-17A, while soluble ST2 (β: -23.86, 95% CI: -41.99 to -5.73, p = 0.010) was inversely associated. Plasma potassium showed a modest positive association (β: 5.83, 95% CI: 0.37-11.29, p = 0.036), but this was not retained in analyses restricted to people living with HIV and in HIV negative individuals. Clinical and metabolic variables were not consistently associated with IL-17A after adjustment. In this high HIV-burden population, IL-17A levels were primarily associated with inflammatory cytokines rather than HIV status or metabolic factors. The attenuation of the HIV association after adjustment suggests that IL-17A was more closely associated with broader inflammatory activity than with HIV status itself. The observed association with plasma potassium was not robust and should be interpreted as exploratory. These findings highlight the role of IL-17A within a coordinated inflammatory network and underscore the need for longitudinal studies to clarify causal pathways.