OA10.05
Background: Bacterial vaginosis (BV), a highly prevalent alteration of vaginal flora, has been linked to an increased risk of HIV acquisition and transmission in observational studies, but the underlying biologic mechanisms are not known. We measured markers of subclinical vaginal inflammation, endogenous antimicrobial activity, and vaginal flora in women with BV and repeated sampling 1 week and 1 month after completion of metronidazole therapy.
Methods: Longitudinal, open label study (ClinicalTrials.gov #NCT01347632) of 33 women with a Nugent score of 4 or higher. All women had genital swabs, cervicovaginal (CV) fluid lavage (CVL) and vaginal biopsies obtained at enrollment (active BV) and received 7 days of metronidazole treatment. Repeat sampling was performed approximately 1 week and 1 month after completion of therapy.
Results: The CVL from women with resolved BV (Nugent 0 - 3) had significantly higher anti-HIV activity compared to women with abnormal microbiota (Nugent 4 - 10). The mean anti-HIV activity of women with BV was<0, indicating that their CVL enhanced HIV infection of TZMbl cells in vitro. Genital tract interleukins IL-1β and ICAM-1 levels were significantly higher (p<0.05) and SLPI levels were lower (p=0.02) in the presence of BV compared to normal microbiota. Anti-HIV activity of CVL was significantly associated with the Nugent score and genital IL-1β and IL-8 levels in a multivariate model controlling for participant race and visit. Although women with BV had significantly lower numbers of CD45+, CD3+ and CD8+ vaginal immune cells compared to racially matched women without BV, they had significantly greater numbers of CCR5+ cells and increased numbers CD4+ cells and CD4/CD8 ratios.
Conclusions: These data support that BV is associated with changes in select soluble immune mediators, an increase in mucosal HIV target cells and a reduction in endogenous CV antiviral activity, which may contribute to the increased risk of HIV acquisition.
