The vaginal 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 reveal that a suboptimal vaginal microbiome (VMB), including the enrichment of anaerobic bacteria associated with multiple female genital disorders, is linked to adverse pregnancy and birth outcomes in pregnant people. Problematically, however, the majority of the available data, to date, is biased toward highly developed, Global North countries, leaving underrepresented populations like the Democratic Republic of the Congo (DRC) poorly characterized. Here, we investigate the VMB from a cohort of 82 pregnant people living with human immunodeficiency virus (PLWH) on antiretroviral therapy (ART) from the DRC. Specifically, we explore the associations between the VMB via 16S rRNA gene sequencing and maternal peripheral immune factors. Additionally, we compare the VMB of pregnant PLWH-ART from DRC with publicly available VMB data (5 studies, 1861 samples) in a meta-analysis to elucidate the impact of HIV on the VMB. Combined, these analyses revealed the differences in community structure and predicted function of the microbiota between pregnant PLWH-ART and pregnant people without HIV (PWoH). Taxonomically, the VMB of DRC PLWH-ART were enriched for IMPORTANCE: Human immunodeficiency virus (HIV) remains prevalent in sub-Saharan Africa, where it has been linked to adverse birth outcomes. Suboptimal vaginal microbiomes (VMBs) have shown similar links. This pilot study fills critical gaps in understanding how HIV interacts with the pregnant VMB in populations underrepresented in microbiome research, like the Democratic Republic of the Congo (DRC). We identified maternal systemic immune factors associated with suboptimal VMBs that have been linked to poor birth outcomes. In a global meta-analysis, we found significant taxonomic and functional differences in the VMBs between pregnant people living with and without HIV, revealing potential biomarkers that increase the risk of adverse birth outcomes. These findings provide crucial insights into VMB features that may influence pregnancy health in PLWH-ART, guiding future research and tailored interventions to support safer pregnancies in the DRC and similar populations.This study is registered with NCT03048669.