TH17/TREG AND IL-17/IL-10 ratio profiles in people living with HIV on long-term cART in Western Kenya

Abstract

Background: Despite sustained viral suppression following combination antiretroviral therapy (cART), a substantial proportion of people living with HIV (PLWHIV) on cART fail to achieve adequate immune reconstitution. Increasing evidence suggests that immune regulatory imbalance involving CD3⁺CD4⁺IL-17⁺ T helper 17 (Th17) cells, CD4⁺CD25^highCD127^low Treg cells, and corresponding cytokines interleukin-17 (IL-17) and interleukin-10 (IL-10), may contribute to persistent dysfunction in immune recovery.

Objective: To evaluate CD3⁺CD4⁺IL-17⁺ T helper 17 (Th17) and CD4⁺CD25^highCD127^low Treg cells dynamics and IL-17/IL-10 balance as associated with immune reconstitution among PLWHIV on long-term cART in western Kenya.

Methods: A cross-sectional study with retrospective clinical data abstraction was conducted at Moi Teaching and Referral Hospital (MTRH). Sixty-four virologically suppressed PLWHIV on cART for 1-6 years were categorized as 32 immunological responders (IRs) or 32 non-responders (INRs) based on CD4⁺ T cell counts and compared with 32 HIV-negative individuals. CD3⁺CD4⁺IL-17⁺ T helper 17 (Th17) cells and CD4⁺CD25^highCD127^low Treg cells were quantified by flow cytometry, while IL-17 and IL-10 were measured using enzyme-linked immunosorbent assay. Data were analyzed using non-parametric tests, Spearman’s correlation, and multivariable logistic regression.

Results: Ninety-six participants (32 per group) were enrolled. Age differed significantly across groups (p=0.026), while other demographics were comparable. Significant differences were observed in CD3⁺CD4⁺IL-17⁺ T helper 17 (Th17) cells, CD4⁺CD25^highCD127^low Treg cells, Th17/Treg ratio, IL-17, IL-10, and IL-17/IL-10 ratio (all p<0.0001). INRs were characterized with lower CD3⁺CD4⁺IL-17⁺ T helper 17 (Th17) cells, IL-17 levels, Th17/Treg and IL-17/IL-10 ratios and but higher CD4⁺CD25^highCD127^low Treg cells and IL-10 levels. Th17/Treg and IL-17/IL-10 ratios positively correlated with CD4⁺ T cell counts. In logistic regression analysis, higher Th17/Treg ratio (AOR = 0.05) and IL-17/IL-10 ratio (AOR = 0.60) were independently associated with lower odds of immunological non-response. Age (AOR = 1.05) and cART duration (AOR = 0.55) were not significantly associated.

Conclusion: Inadequate immune reconstitution is associated with reduced Th17/Treg ratio and IL-17/IL-10 imbalances.