Vaginal Lactic Acid and Lactobacillus‐Dominated Microbiota in HIV‐1 Susceptibility: Mechanistic Insights and Implications for Sub‐Saharan African Women

ABSTRACT Women in Sub‐Saharan Africa experience disproportionately high rates of HIV‐1 acquisition, a disparity not fully explained by reported sexual behavior or conventional epidemiological risk factors. Increasing evidence implicates the cervicovaginal microbiome, particularly the presence of a Lactobacillus‐dominated, lactic‐acid‐rich environment, as an important biological determinant of susceptibility. This review synthesizes mechanistic, clinical, and epidemiological evidence linking vaginal lactic acid, Lactobacillus‐dominated microbiota, bacterial vaginosis, and HIV‐1 acquisition, with particular emphasis on evidence from African populations. Lactic acid produced by vaginal Lactobacillus spp. exhibits direct anti‐HIV‐1 activity, suppresses bacterial‐vaginosis‐associated organisms, and contributes to epithelial barrier homeostasis. Conversely, anaerobe‐dominated dysbiosis is associated with reduced lactic acid production, epithelial disruption, heightened inflammatory signaling, and increased availability of HIV‐1 target cells, with African cohorts reporting approximately two‐ to four‐fold greater HIV‐1 acquisition risk among women with dysbiotic microbiota. Emerging interventions targeting vaginal microbiota, including Lactobacillus crispatus‐based live biotherapeutics, demonstrate potential to restore microbiological homeostasis and reduce bacterial vaginosis recurrence. Collectively, the evidence supports vaginal microbial restoration as a biologically plausible adjunct to HIV‐1 prevention. However, regionally validated trials, durable microbiome‐targeted interventions, scalable diagnostics, and integration with established prevention platforms are needed to determine clinical effectiveness and implementation feasibility in high‐burden African settings.