Differential effects of depot medroxyprogesterone acetate administration on vaginal microbiome in Hispanic White and Black women

Liying Yang,Yuhan Hao,Jiyuan Hu,Dervla Kelly,Huilin Li,Stuart Brown,Carley Tasker,Natalie E Roche,Theresa L Chang,Zhiheng Pei

doi:10.1080/22221751.2018.1563458

Abstract

ABSTRACT The use of depot medroxyprogesterone acetate (DMPA), a 3-monthly injectable hormonal contraceptive, is associated with an increased risk of HIV acquisition possibly through alteration of the vaginal microbiome. In this longitudinal interventional study, we investigated the impact of DMPA administration on the vaginal microbiome in Hispanic White and Black women at the baseline (visit 1), 1 month (visit 2), and 3 months (visit 3) following DMPA treatment by using 16S rRNA gene sequencing. No significant changes in the vaginal microbiome were observed after DMPA treatment when Hispanic White and Black women were analysed as a combined group. However, DMPA treatment enriched total vaginosis-associated bacteria (VNAB) and Prevotella at visit 2, and simplified the correlational network in the vaginal microbiome in Black women, while increasing the network size in Hispanic White women. The microbiome in Black women became more diversified and contained more VNAB than Hispanic White women after DMPA treatment. While the Firmicutes to Bacteroidetes (F/B) ratio and Lactobacillus to Prevotella (L/P) ratio were comparable between Black and Hispanic White women at visit 1, both ratios were lower in Black women than in Hispanic White women at visit 2. In conclusion, DMPA treatment altered the community network and enriched VNAB in Black women but not in Hispanic White women. The Lactobacillus deficiency and enrichment of VNAB may contribute to the increased risk of HIV acquisition in Black women. Future studies on the impact of racial differences on the risk of HIV acquisition will offer insights into developing effective strategies for HIV prevention. Abbreviations: DMPA: depot medroxyprogesterone acetate; PCR: polymerase chain reaction; OTU: operational taxonomic unit; STI: sexually transmitted infections; VNAB: vaginosis-associated bacteria

Highlights

Depo-Provera, an injectable form of hormonal contraceptive given every 3 months, is associated with an increased risk of HIV acquisition and transmission [1,2,3]
Our results indicated that depot medroxyprogesterone acetate (DMPA) changed the vaginal microbiome and this change was affected by race and duration of treatment
In an analysis of the effect of DMPA use on α-diversity, we found that α-diversity of the vaginal microbiome in all women did not attain statistical significance among visits 1, 2, and 3 and between any two of the three visits by either observed operational taxonomic unit (OTU), Chao1-predicted OTUs, or Shannon diversity index (Supplementary Table S3)

Summary

Introduction

Depo-Provera (depot medroxyprogesterone acetate, DMPA), an injectable form of hormonal contraceptive given every 3 months, is associated with an increased risk of HIV acquisition and transmission [1,2,3]. Studies on biological mechanisms of heightened HIV transmission by DMPA indicate that DMPA may increase HIV susceptibility by alteration of epithelial permeability [5,6], immune response [4,7,8], and vaginal microbiome [9], the dynamics of vaginal microbiome in response to DMPA are less defined. The vaginal microbiome has been classified into several types based on specific Lactobacillus species and the abundance of Lactobacillus [11]. Studies on microbiome dynamics in the reproductive cycle in different populations indicate that the type of species present in the vaginal microbiome remain constant throughout the cycle, their abundance varies in different

Methods

Results

Conclusion