Background
Early ART within 3 months of birth has dramatically improved long-term outcomes in children living with perinatal HIV. However, these children face decades of HIV-associated immune dysregulation and chronic inflammation. Neither the long-term inflammatory profile nor the risk of long-term non-communicable diseases are well understood. We assessed biomarkers associated with inflammation (monocyte and lymphocyte), metabolic and cardiovascular damage and response markers in early-treated children compared to controls unexposed to HIV.
Methods
175 children (66 with HIV, 109 unexposed to HIV) aged 7-12 years and previously part of CHER and P1060 trials were followed at Tygerberg Children’s Hospital, South Africa. Children with HIV initiated ART within 3 months of birth, were seen 3-monthly for clinical care, were virologically suppressed (>90% suppression), had preserved CD4+ cell counts and were asymptomatic. Unexposed children arose from the same communities and socio-economic background. Each child had 1 blood measurement. We measured 26 inflammatory proteins in blood serum using ELISA and Luminex™ multiplex immunoassays, comprising monocyte-derived biomarkers (IL-18, IL-6, TNF-α, MCP1, IL-1a, S100A9, IL1-ra, S100A8), lymphocyte-derived markers (IL-17, IFNγ, IL-12p70, IP-10, IL-10), response markers (CRP, sCD14, E-selectin), metabolic markers (leptin, adiponectin, resistin, LBP, IL-18, FABP4), and cardiovascular markers (VEGF, E-selectin, IP-10, MCP1, P-selectin, sCD163, VCAM1, ICAM1). We used linear regression to compare the effect of HIV group on each biomarker, adjusting for age, sex and ethnicity. Results are Holm adjusted.
Results
Mean age of children with HIV was 8.5 years (unexposed: 9.2 years). After adjusting for age, sex and ethnicity, MCP1, S100A9, IL-6, sCD14, Adiponectin, VEGF and P-selectin levels were significantly higher in early treated children compared to unexposed, whilst IP10 was significantly lower in children with HIV (p<0.05). All other biomarkers showed no significant difference between groups.
Conclusions
Despite early ART and sustained viral suppression, early treated children on ART displayed extensive immune marker elevations, clustered around monocyte activation and markers associated with cardio-metabolic disease. These children remain at risk of premature vascular disease events (heart attacks/ strokes).