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

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.