Cytokines in HIV-1 patients on combination antiretroviral therapy with persistent low-level viremia at a tertiary hospital in Western Kenya

Abstract

Introduction: persistent low-level viremia (pLLV) in HIV-1 participants on combination antiretroviral therapy (cART) is a significant predictor of immune activation and virologic rebound. Elevated cytokine levels are linked to pLLV, yet the roles of pro- and anti-inflammatory cytokines remain unclear in settings such as Kenya. This study assessed IL-17, IFN-γ, IL-10, and TGF-β in HIV-1 pLLV and virally suppressed participants at Moi Teaching and Referral Hospital (MTRH) to explore alternative biomarkers for virologic monitoring in resource- limited settings. Methods: cross-sectional study of 82 age- and gender-matched HIV-1 participants on first-line cART, -41 pLLV (50-500 copies/ml), and 41 virally suppressed (<50 copies/ml) was conducted using MTRH database data. Plasma cytokines (IL- 17, IFN-γ, IL-10, TGF-β) were measured by ELISA (Zeptometrix, USA), and viral loads by RT-PCR (Abbott, USA). Data were analyzed using Mann- Whitney U, Chi-squared, and logistic regression tests. Results: the median (IQR) levels of IL-17, IFN- γ, IL-10, and TGF-β (pg/ml) were significantly higher in pLLV participants on first-line cART compared to virally suppressed participants: 23.8 (21.3-25.8) vs. 15.5 (12.7-18.2); 28.3 (23.5-31.2) vs. 11.4 (8.8-14.8); 45.2 (34.0-53.7) vs. 28.4 (22.6- 31.6); and 56.9 (50.0-67.8) vs. 27.7 (19.5-34.7) p<.001. The odds (95% CI) of being suppressed were reduced by TGF-β 0.329 (0.035-0.361), IFN-γ, 0.360 (0.270-1.501, and IL-17 0.938 (0.691-1.273), but increased by IL-10 1.106 (0.675-1.811), though not statistically significant. Conclusion: persistent low-level viremia (pLLV) presents with elevated pro-inflammatory (IL-17, IFN-γ) and anti- inflammatory cytokines (IL-10, TGF-β) levels. Recommendation: exploring other cytokines in pLLV could enhance understanding of cytokine levels and viral suppression and may help refine HIV-1 treatment