Soluble CD163 and monocyte populations in response to antiretroviral therapy and in relationship with neuropsychological testing among HIV-infected children

BACKGROUND Monocytes play a central role in HIV neuropathogenesis, but there are limited data on monocyte subsets and markers of monocyte activation in perinatally HIV-infected children. OBJECTIVE To determine the relationship between monocyte subsets, the sCD163 monocyte activation marker, and neuropsychological performance among perinatally HIV-infected children initiating antiretroviral therapy (ART). METHODS ART-naïve children from the PREDICT study were categorised into two groups: those on ART for ≥24 weeks (ART group, n =201) and those untreated (no ART group, n =79). This analysis used data from the baseline and week 144 including sCD163 and frequencies of activated monocytes (CD14+/CD16+/HLA-DR+), perivascular monocytes (CD14+/CD16+/CD163+ and CD14low/CD16+/CD163+), and neuropsychological testing scores: Verbal and Performance Intelligence Quotient (VIQ and PIQ), Beery Visuomotor Integration (VMI) and Children's Color Trails 2 (CT2). RESULTS Baseline demographic and HIV disease parameters were similar between groups. The median age was 6 years, CD4 was 20% (620 cells/mm3), and HIV RNA was 4.8 log10. By week 144, the ART vs the no ART group had significantly higher CD4 (938 vs 552 cells/mm3) and lower HIV RNA (1.6 vs 4.38 log10 copies/mL, P <0.05). sCD163 declined in the ART vs no ART group (median changes -2533 vs -159 ng/mL, P <0.0001). Frequencies of all monocyte subsets declined in the treated but not the untreated group (P <0.05). Higher CD14+/CD16+/HLA-DR+ percentage was associated with higher VIQ, Beery VMI and CT2 scores. Higher percentages of CD14+/CD16+/CD163+ and CD14low/CD16+/CD163+ were associated with higher CT2 and VIQ, respectively. CONCLUSION ART significantly reduced sCD163 levels and frequencies of activated and perivascular monocytes. Higher frequencies of these cells correlated with better neuropsychological performance suggesting a protective role of monocyte-macrophage immune activation in perinatal HIV infection in terms of neuropsychological function.