Abstract / Summary
Abstract Pregnant people living with human immunodeficiency virus (PPLWH) face elevated risks of preterm birth (PTB), perinatal death (PND), and low birthweight (LBW). While antiretroviral therapy (ART) effectively suppresses viral load, it neither prevents these adverse pregnancy outcomes nor resolves underlying inflammation. Since circulating maternal markers may not fully capture local immune dysregulation, this observational cohort study identified compartmentalized immune factors associated with adverse outcomes. We analyzed 45 immune factors in paired maternal, placental, and cord plasma from 118 ART-treated PPLWH in Kinshasa, Democratic Republic of the Congo. Among these pregnancies, 30% resulted in PTB, 9% in PND, and 8% in LBW. Compared to term births, PTB ( n = 35) was associated with discordant spatio-temporal signaling of T-cell-associated chemokines CCL20, CXCL9, and CXCL10. PND ( n = 10) correlated with the largest inflammatory signature and was associated with factors that signal neutrophil recruitment and activation, including CXCL1, CXCL5, MPO and S100A8/A9. LBW ( n = 9) was associated with higher concentrations of inflammatory factors at enrollment IL-18 and S100A8/A9, alongside increased postdelivery and postpartum SAA. In ART-treated PPLWH, distinct outcomes were characterized by time- and compartment-specific immune pathways. These pathways may provide mechanistic insights into adverse birth outcomes in PPLWH and highlight potential compartment-specific biomarkers for risk stratification.