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

Abstract 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. Importance HIV 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. Competing Interest Statement The authors have declared no competing interest. Footnotes Added an author (Ann C. Gregory).