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 ART-naive (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 to 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. Soluble CD163 levels directly correlate with T cell activation markers CD38, HLA-DR, and Ki67 (p<0.01). Conclusions: 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.

Coordination of inflammatory responses in children with perinatally acquired HIV infection

“…This finding is in agreement with previous studies in adults with HIV [5–8]. Although most studies have been conducted in adults, a few studies in children and adolescents, including participants with PHIV from sub-Saharan Africa, showed similar patterns [11,14,15]. Although our study did not include HIV-uninfected controls, it is reasonable to interpret the collective decrease in inflammatory biomarkers as representing a shift towards age-appropriate and sex-appropriate levels.…”

“…Little is known about the kinetics and health consequences of inflammation in children with perinatal HIV (PHIV). Previous studies demonstrated that older children and adolescents with PHIV have higher levels of inflammatory markers compared with age-matched healthy controls [11,14,15]. Studies also showed an association of inflammation with impaired neurocognitive development and mood disorders in children with PHIV [16][17][18][19].…”

Characteristics and clinical significance of plasma IL‐18, sCD14, and sCD163 levels in patients with HIV‐1 infection

“…High IL‐18 levels are correlated with detectable HIV viremia in people who inject drugs 24 . Both higher levels of sCD14 and sCD163 predict more rapid disease progression and higher mortality in HIV infection 3,25–27 . Liang et al found that plasma levels of sCD14 and sCD163 were upregulated in HIV‐1 infection and were positively associated with viral loads in treatment‐naive patients 28 .…”

“…24 Both higher levels of sCD14 and sCD163 predict more rapid disease progression and higher mortality in HIV infection. 3,[25][26][27] Liang et al found that plasma levels of sCD14 and sCD163 were upregulated in HIV-1 infection and were positively associated with viral loads in treatmentnaive patients. 28 The present study further reveals the relationship between cytokines and early viral suppression after initiating ART.…”

Biological Aging and Immune Senescence in Children with Perinatally Acquired HIV

“…In a cohort of HIV-infected children [136], ART initiation rapidly and persistently reversed T cell activation but failed to normalize CD4/CD8 ratios and plasma sCD14 levels. However, another study on a cohort of perinatally HIV-infected children [137] showed that ART initiation normalized sCD163 (marker of monocyte activation) levels and improved long-term pediatric outcomes. A recent study [138] agreed that immune activation decreases over time in children after starting ART, which does not have adverse effects itself on microbial translocation.…”