Cross-Sectional Analysis of Selected Genital Tract Immunological Markers and Molecular Vaginal Microbiota in Sub-Saharan African Women, with Relevance to HIV Risk and Prevention.

Data on immune mediators in the genital tract and the factors that modulate them in sub-Saharan women are limited. Cervicovaginal lavage (CVL) samples from 430 sexually active women from Kenya, South Africa, and Rwanda were analyzed for 12 soluble immune mediators using Bio-Plex and Meso Scale Discovery multiplex platforms, as well as single enzyme-linked immunosorbent assays. Ten bacterial species were quantified in vaginal swab samples. Bacterial vaginosis (BV) was defined by Nugent scoring. CVL samples from HIV-infected women showed a clear-cut proinflammatory profile. Pregnant women, adolescents, and women engaging in traditional vaginal practices differed in specific soluble markers compared to reference groups of adult HIV-negative women. Cervical mucus, cervical ectopy, abnormal vaginal discharge, and having multiple sex partners were each associated with an increase in inflammatory mediators. The levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12(p70), and IL-8 were elevated, whereas the IL-1RA/IL-1(α+β) ratio decreased in women with BV. The level of gamma interferon-induced protein 10 was lower in BV-positive than in BV-negative women, suggesting its suppression as a potential immune evasion mechanism by BV-associated bacteria. Lactobacillus crispatus and Lactobacillus vaginalis were associated with decreased proinflammatory cytokines and each BV-associated species with increased proinflammatory cytokines. Remarkably, the in vitro anti-HIV activity of CVL samples from BV-positive women was stronger than that of BV-negative women. In conclusion, we found significant associations of factors, including vaginal microbiota, which can influence immune mediators in the vaginal environment in sexually active women. These factors need to be considered when establishing normative levels or pathogenic cutoffs of biomarkers of inflammation and associated risks in African women.