Babakazo, P. | Search bioRxiv

bioRxiv2026

Compartment-specific soluble immune profiles associated with preterm birth, perinatal death, and low birthweight in pregnant individuals living with HIV

BackgroundHuman immunodeficiency virus (HIV) infection in pregnancy is associated with preterm birth (PTB), low birthweight (LBW), and perinatal death (PND). Although antiretroviral therapy (ART) suppresses viral load it does not prevent HIV-associated adverse pregnancy outcomes or resolve inflammation. As circulating maternal immune factors may not fully capture maternal-fetal interface immune dysregulation, this observational cohort study aimed to identify localized and systemic immune factors associated with PTB, LBW and PND in ART-treated pregnant people living with HIV (PPLWH). MethodsWe enrolled 118 PPLWH in Kinshasa, Democratic Republic of the Congo, during the second or third trimester. We collected maternal peripheral plasma (at enrollment, 1-3 days post-delivery, and postpartum) alongside umbilical cord and placental plasma at delivery. Concentrations of 45 immune factors were measured via LegendPlex and ELISAs and associations analyzed using Kruskal-Wallis tests with Dunns correction or Mann-Whitney tests. ResultsPlacental plasma exhibited the highest overall concentrations of immune factors, highlighting a distinct localized microenvironment. Among 118 pregnancies, 35 (30%) resulted in PTB, 10 (9%) in PND, and 9 (8%) in LBW. Compared to term births, PTB was associated with higher levels of the chemokines CCL20, CXCL9, and CXCL10 in cord and/or postdelivery plasma (p<0.01), while placental CCL20 levels were lower (p<0.05). Compared to live births, PND was associated with higher postdelivery CXCL1, cord IL-8, placental MPO and NGAL (p<0.05); higher postdelivery CXCL5 (p<0.01); and higher S100A8/A9 levels in cord and postdelivery plasma (p<0.01 and p<0.001, respectively). Finally, LBW was associated with higher enrollment IL-18 and S100A8/A9 levels (p<0.05 and p<0.01, respectively); as well as higher SAA levels in postdelivery and postpartum plasma (p<0.05). ConclusionsIn ART-treated PPLWH, distinct adverse birth outcomes are driven by time- and compartment-specific immune pathways. PTB is associated with localized T-cell chemokine responses, PND with neutrophil recruitment and activation, and LBW with pro-inflammatory cytokine and acute-phase protein responses. These pathways provide mechanistic insights into pregnancy complications in PPLWH and highlight potential compartment-specific biomarkers for risk stratification.

microbiology↗

bioRxiv2025

The cervicovaginal microbiome of pregnant people living with HIV on antiretroviral therapy in the Democratic Republic of Congo: A Pilot Study and Global Meta-analysis.

Recent studies are revealing that a suboptimal cervicovaginal microbiome (CVMB), including enrichment of anaerobic bacteria associated with multiple female genital disorders, and adverse pregnancy and birth outcomes in pregnant people. Problematically, however, the majority of the available data to date are biased towards highly developed, Global North countries, leaving underrepresented populations like the Democratic Republic of Congo (DRC) poorly characterised. Here, we investigate the CVMB from a cohort of 82 pregnant people living with HIV (PLWH) on antiretroviral therapy (ART) from the DRC. Specifically, we explore the associations between the CVMB via 16S rRNA gene sequencing and maternal peripheral immune factors. Additionally, we compare the CVMB of PLWH-ART from DRC to publicly available CVMB data (5 studies, 1861 samples) in a meta-analysis to elucidate the impact of HIV on the CVMB. Combined, these analyses revealed differences in community structure and predicted function of the microbiota between PLWH-ART and pregnant people without HIV (PWoH). Taxonomically, the CVMB of DRC PLWH-ART were enriched for Lactobacillus iners-dominated CVMBs (53%) or a diverse, polymicrobial CVMB, i.e., bacterial vaginosis (BV) (43%). Functional predictions made from these taxa suggested that protein-coupled receptors, amino sugar and nucleotide sugar metabolism, fatty acid metabolism, and polycyclic aromatic hydrocarbon degradation pathways were differentially abundant between communities. Correlation with host plasma immune factors revealed putative links between some CVMB metrics (e.g., alpha diversity and species abundance) that have been linked to adverse pregnancy and birth outcomes. ImportanceHIV remains prevalent in sub-Saharan Africa, where it has been linked to adverse birth outcomes. . Suboptimal CVMBs have shown similar links. This pilot study fills critical gaps in understanding how HIV interacts with the pregnant CVMB in populations underrepresented in microbiome research, like the Democratic Republic of Congo. We identified maternal systemic immune factors associated with suboptimal CVMBs that have been linked to poor birth outcomes. In a global meta-analysis, we found significant taxonomic and functional difference in the CVMBs between pregnant people living with and without HIV, revealing potential biomarkers that for increased risks for adverse birth outcomes. These findings provide crucial insights into CVMB features that may influence pregnancy health in pregnant people living with HIV, guiding future research and tailored interventions to support safer pregnancies in the DRC and similar populations.

microbiology↗