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Background: In HIV infection, dysregulation of cytokines, including interleukin 18 (IL-18), has been linked to poor clinical outcomes in studies mainly conducted in resource-rich countries. This phenomenon has not been well-studied in resource-limited settings where outcomes could be confounded by exposure to endemic infections and genetic factors., Objectives: Therefore, the influence of immunological and virological status of HIV-infected, antiretroviral therapy (ART)-naïve patients on serum IL-18 levels at baseline (pretreatment) and 24 weeks following initiation of combination ART (cART24) in a resource-limited setting was investigated., Methods: Using the cross-sectional and longitudinal mixed method design, a total of Forty-four (44) newly diagnosed consenting HIV patients were consecutively recruited during routine clinic visits at the Nasara Treatment & Care Centre of the Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria between December 2016 to January 2018, and followed up for 24 weeks on initiation of first-line cART., Results: Serum IL-18 concentrations, CD4+ T-cell counts (CD4+) counts, and HIV1 RNA levels were determined at baseline and cART24. There was little CD4 + count gain in both <200 and ≥ 200 cell/mm 3 subgroups despite the high proportion of subjects having virological suppression (n = 35, [80%]) at cART24. However, at cART24 there was a more than a threefold decrease in the level of IL-18 concentration compared to baseline in patients with <200 cells/mm 3 and a significant decrease in the median plasma IL-18 concentration in patients with HIV1 RNA <1000 cp/mL at cART24. A multivariate logistic regression model shows IL-18 intermediate quartile to be more related to immunological poor gain as compared to the highest quartile., Conclusion: Our study found high baseline and significantly low levels of IL-18 at cART24 in virologically suppressed subjects but not among virological non-suppressed responders despite comparable IL-18 levels by CD4+ T cell count strata at cART24. These findings have implications for risk stratification and treatment outcomes in HIV-positive persons., Competing Interests: Conflict of interest The authors declare that they have no conflict of interests., (© the Author(s).)