Use of an Ethinyl Estradiol/Etonogestrel Vaginal Ring Alters Vaginal Microbial Communities in Women with HIV.

Abstract

HIV-1 antiretroviral therapy (ART) alters hormonal contraceptive levels delivered via intravaginal ring (IVR) in a regimen specific manner. We explored the role of the IVR on vaginal microbial communities, vaginal short chain fatty acids (SCFAs), vaginal HIV shedding, and the effect of vaginal microbes on hormone concentrations in cisgender women with HIV (WWH). Vaginal microbes were assessed by 16S RNA sequencing of weekly vaginal swabs, vaginal SCFA by mass spectrometry, HIV-1 shedding by nucleic acid amplification on vaginal aspirates, and bacterial vaginosis by Nugent scoring from 74 participants receiving an etonorgestrel/ethinyl estradiol (ENG/EE) intravaginal ring while on no ART (N=25), efavirenz-based ART (N=25), or atazanavir-based ART (N=24). At baseline, microbial communities of the 64 substudy eligible participants robustly classified as Lactobacillus crispatus--dominant (n=8), L. gasseri-dominant (n=2), L. iners-dominant (n=17), or mixed anaerobic communities (n=37). During IVR therapy, there was an increased probability of Lactobacillus-dominant community state types (CSTs) (odds-ratio=1.61, p=0.04). Vaginal CSTs were associated with Nugent scores. Bacterial vaginosis-associated bacteria were associated with significantly higher and L. iners with lower Nugent Scores (all p adj <0.1). Lactic acid levels were correlated with the relative abundance of Lactobacillus species (r2=0.574; p<0.001). Vaginal shedding of HIV-1 was less common in women with L. crispatus-dominant microbiomes (p=0.04). Mixed anaerobic vaginal communities modulated EE concentrations in a regimen-specific manner. Combined ENG/EE IVR therapy was associated with an increase in Lactobacillus-dominant vaginal microbial communities in WWH and may benefit those with bacterial vaginosis. EE levels were altered by the vaginal microbiota.