Longitudinal assessment of inflammatory biomarkers among youth with perinatal HIV infection and HIV exposure.
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OBJECTIVES: To compare changes in inflammatory biomarkers among youth with perinatally-acquired HIV (PHIV) and perinatal HIV-exposure without infection (PHEU), and to examine their associations with antiretroviral therapy (ART) and HIV disease status. DESIGN: A substudy within a longitudinal cohort study conducted across 14 U.S. sites. METHODS: We measured inflammatory biomarkers at baseline and ~11 years later in 99 PHIV participants receiving ART and 59 PHEU participants. Univariable and multivariable linear regression models evaluated changes within and between groups and associations between biomarker concentrations at follow-up and ART regimens, CD4 + cell count, and viral loads (VL). RESULTS: At baseline, the median ages of PHIV and PHEU were 13 and 11 years. Median baseline concentrations of interleukin-18 (IL-18) and tumor necrosis factor alpha (TNF-α) were significantly higher in PHIV than PHEU. At follow-up, only the median sTNF-R2 concentration was significantly higher in PHIV than PHEU. In both groups, median biomarker concentrations decreased from baseline to follow-up except for TNF-α (increased in PHEU) and hsCRP (increased in both). A greater decrease in IL-10 in PHIV than PHEU was the only significant difference between groups. At follow-up, a nadir CD4 + <15% was associated with lower IL-8 concentrations; CD4 + cell count ≤500 cells/mm 3 was associated with higher IL-18 concentrations; and VL ≥400 copies/ml was associated with higher sTNF-R2 concentrations. Longer duration of integrase inhibitor (INSTI) use was associated with increases in IL-6, IL-8, and IL-10. CONCLUSIONS: Among PHIV on ART, inflammation decreases over time, associated with better HIV disease control, and likely reduces the risk of HIV-related comorbidities. However, inflammation may increase with INSTI exposure.