| Summary: | 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.
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