Fig 1.
Mechanisms mediating risk for HIV acquisition and transmission in menopausal women.
Numbers and corresponding labels indicate potential mechanisms. During menopause there is a loss of epithelial barrier integrity (1) and increase in BV associated species including Atopobium, Prevotella, and Gardnerella (2), which influence release of proinflammatory cytokines e.g. IL-1α, IL-1β and IL-8 (3) promoting recruitment and/or activation of HIV target cells (4) which may increase risk for HIV acquisition and for HIV positive women increase HIV replication (5) and subsequent viral shedding (6). Loss of H202 producing protective lactobacillus species Lactobacillus (L.) crispatus, L jensenii, L. gasseri (7) and decreased protective immune mediators (human beta defensins, SLPI) (8) may also increase risk for HIV acquisition during menopause. In menopausal women with HIV, E. coli antibacterial activity is lower, reflecting a Lactobacillus deficient microbiome and HSV inhibitory activity is higher reflective of inflammation.
Table 1.
Demographic and clinical characteristics for all participants.
Fig 2.
HIV+ postmenopausal participants have significantly lower CVL E. coli and higher HSV inhibitory activity.
CVL E. coli (A), HSV (B) and HIV inhibitory activity (C) in premenopausal and postmenopausal HIV negative and HIV positive participants. The lines represent the median with interquartile range for percent inhibition of E. coli colonies (A) percent inhibition of HSV plaques (B) and percent reduction in relative luciferase units compared with control (C). Comparisons were made between all pairwise groups, only those with p values ≤ 0.05 and those comparing pre and postmenopausal participants are reported. Circle indicates HIV enhancing activity in HIV+ participants on ART.
Fig 3.
Differences in the taxonomic composition of the vaginal microbiome by reproductive status and levels of E. coli and HIV inhibitory activity.
Taxonomic composition of the vaginal microbiome by reproductive status for HIV+ (A) and HIV- (B) participants, by levels of CVL E. coli bactericidal activity for HIV+ (C) and HIV- (D) participants and by levels of CVL HIV inhibitory activity for HIV+ (E) and HIV- (F) participants. Proportion of genera contributing >1% shown. Asterisks (*) indicate taxa with significantly different relative abundances between groups as determined by an LDA score ≥2. Low and high E. coli and HIV inhibition correspond to the bottom and top quartiles.
Table 2.
Associations of antimicrobial activity with select immune mediators and vaginal bacteria among all participants.
Table 3.
Concentrations of mucosal immune mediators in HIV+ and HIV- premenopausal and postmenopausal women.
Table 4.
qPCR concentrations of bacteria from vaginal swabs.