Cervicovaginal Secretions in Young Women with Bacterial Vaginosis Enhance HIV Infection

Abstract

Background Bacterial vaginosis (BV) is a major health problem associated with increased HIV risk. To explore underlying mechanisms, we assessed the cervicovaginal mucosal immune environment before and after metronidazole treatment in women with BV and healthy controls. Methods Women with BV diagnosed clinically by Amsel criteria were treated with oral or intravaginal metronidazole. Vaginal swabs and cervicovaginal lavage (CVL) were obtained at enrollment and approximately two and four weeks later for assessment of immune mediators, antiviral activity, and 16s rRNA gene sequencing. Healthy controls had sampling at enrollment and four weeks. Results Vaginal pH, Nugent score, Shannon alpha diversity index, and vaginal community state types (CST) differed significantly at enrollment comparing women with clinical BV (n=19) and controls (n=13) (p<0.001). BV cases had significantly higher CVL IL-1α and TNF-α, but lower IgG at enrollment compared to controls, which improved following treatment. Similar results were observed if participants with discordant molecular results (n=3) were excluded. Most notably, CVL from BV cases enhanced whereas control CVL inhibited HIV infection of cells relative to buffer (138.4 ± 109.8% vs 30.9 ±37.9%, p=0.001). There was a transient reduction in HIV enhancement following treatment, which was not sustained. Enhancement correlated with CST and markers of dysbiosis. Specifically, decreases in lactobacilli and increases in Prevotella, Dialister micraerophilus, and Peptoniphilus lacrimalis were associated with enhancement. Conclusions These findings provide a potential mechanistic link that may contribute to the increased risk of HIV in association with BV and highlight the importance of early diagnosis and improved treatments.