Markov-Based Model of Cervicovaginal Bacterial Dynamics Predicts Community Equilibrium States in Young South African Women

Abstract

Commensal cervicovaginal bacteria modulate female genital tract (FGT) inflammation and HIV acquisition risk. High diversity communities with low Lactobacillus abundance are associated with more activated cervical HIV target cells and an increased risk of HIV acquisition. While Lactobacillus colonization of the genital tract is believed to be beneficial for reproductive health, the dynamics of cervicovaginal bacteria are not well understood. In this thesis, I construct a Markov-based model of bacterial community transitions in a South African cohort of young healthy women living in a region with high HIV incidence and prevalence. I found that while Lactobacillus crispatus colonization was relatively stable, Lactobacillus iners colonization was unstable with high frequency transitions to Prevotella-rich, high diversity communities. Because of this, the cohort experienced numerous transitions toward more diverse communities that are associated with increased rates of HIV acquisition. Based upon the model, I predict that blocking the FGT colonization transition from L. crispatus to L. iners will most effectively increase the amount of L. crispatus dominant, low-inflammation, bacterial communities that are associated with lower risk of HIV acquisition. These observations may be used to develop more effective methods to prevent HIV acquisition in young women living in sub-Saharan Africa.