Lactobacillus-Deficient Cervicovaginal Bacterial Communities are Associated with Increased HIV Acquisition in Young South African Women

&NA; Elevated inflammation in the female genital tract is associated with increased HIV risk. Cervicovaginal bacteria modulate genital inflammation; however, their role in HIV susceptibility has not been elucidated. In a prospective cohort of young, healthy South African women, we found that individuals with diverse genital bacterial communities dominated by anaerobes other than Gardnerella were at over 4‐fold higher risk of acquiring HIV and had increased numbers of activated mucosal CD4+ T cells compared to those with Lactobacillus crispatus‐dominant communities. We identified specific bacterial taxa linked with reduced (L. crispatus) or elevated (Prevotella, Sneathia, and other anaerobes) inflammation and HIV infection and found that high‐risk bacteria increased numbers of activated genital CD4+ T cells in a murine model. Our results suggest that highly prevalent genital bacteria increase HIV risk by inducing mucosal HIV target cells. These findings might be leveraged to reduce HIV acquisition in women living in sub‐Saharan Africa. Graphical Abstract Figure. No caption available. HighlightsWomen with high‐diversity genital bacterial communities acquire HIV at 4× higher ratesActivated mucosal CD4+ T cell numbers are elevated in women with high‐risk bacteriaSpecific genital bacterial taxa are linked with reduced or elevated HIV acquisitionI.vag administered Prevotella increases activated genital CD4+ T cell numbers in mice &NA; The potential impact of cervicovaginal bacteria on HIV susceptibility is not well‐defined. Gosmann et al. (2017) identify anaerobic cervicovaginal bacterial communities and specific taxa highly prevalent in young healthy South African women that increase their HIV risk. These findings might be leveraged to reduce HIV acquisition in women.