High soluble CD163 levels correlate with disease progression and inflammation in Kenyan children with perinatal HIV-infection

Abstract

Objectives: CD163 is a hemoglobin scavenger receptor on monocytes and macrophages, cleaved to soluble CD163 (sCD163) in the plasma following activation. In HIV+ adults, sCD163 is linked to non-AIDS morbidity and predicts mortality, but there is limited data in children. We investigated sCD163 levels in HIV+ children and their correlations with disease progression, immune activation and gut mucosal damage. Design and methods: We quantified sCD163 levels in Kenyan children aged 0–20 years with perinatal HIV infection, including 74 antiretroviral treatment (ART)-naïve (ART−) and 64 virally suppressed on ART (ART+), and 79 HIV unexposed-uninfected controls (HIV−). The cohort was divided into age groups 0–5 (younger) and 5–20 (older) years. Correlations between sCD163 and HIV viral load, %CD8+, CD4+ : CD8+ ratio, markers of T-cell activation and proliferation, and gut mucosal damage were also assessed. Results: ART− children have higher sCD163 levels compared with HIV− and ART+ children (P ≤ 0.01); ART+ have equivalent sCD163 levels to HIV− children. In a prospective analysis, sCD163 levels decreased in older ART− children after 12 months of treatment (P < 0.0001). Regardless of age, sCD163 levels correlate with clinical disease progression measured by %CD4+ T cells, CD4+ : CD8+ T-cell ratios and HIV viral load. sCD163 levels directly correlate with T-cell activation markers CD38, human leukocyte antigen-DR isotype, and Ki67 (P ≤ 0.01). Conclusion: High plasma sCD163 levels in HIV+ children correlate with advancing disease and T-cell activation. ART initiation normalizes sCD163 levels and may alleviate HIV-related morbidities and improve long-term pediatric outcomes.