Medroxyprogesterone acetate mediated alteration in the vaginal microbiota and microenvironment in a Kenyan sex worker cohort
AbstractThe hormonal contraceptive Medroxyprogesterone Acetate (MPA) is associated with increased risk of Human Immunodeficiency Virus (HIV), via incompletely understood mechanisms. Increased diversity in the vaginal microbiota modulates genital inflammation and is associated with increased HIV-1 acquisition. However, the effect of MPA on diversity of the vaginal microbiota is relatively unknown. In a cohort of female Kenyan sex workers, negative for sexually transmitted infections (STIs), with Nugent Scores <7 (N=58 of 370 screened), MPA correlated with significantly increased diversity of the vaginal microbiota as assessed by 16S rRNA gene sequencing. MPA was also significantly associated with low vaginal glycogen and -amylase, factors implicated in vaginal colonization by lactobacilli, bacteria believed to protect against STIs. Furthermore, increased diversity of the vaginal microbiota correlated with activation of vaginal HIV-1 target cells. Results were recapitulated in humanized mice where MPA treatment was associated with increased diversity of the vaginal microbiota, low glycogen, and enhanced HIV-1 susceptibility. Together these results suggest MPA-induced hypo-estrogenism may alter key metabolic components necessary for vaginal colonization by certain bacterial species including lactobacilli, and allow for greater bacterial diversity in the vaginal microbiota. Bacterial diversity in the vaginal microbiota correlates with activation of HIV-1 target cells, which might thus contribute to enhanced susceptibility to HIV-1.