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Eligible women (n\u2009=\u200927; 18\u201334\u00a0years; negative for HIV, sexually transmitted infections, and Amsel-bacterial vaginosis) were randomized 2:2:1 to use of IVRs containing TFV, TFV\/LNG, or placebo. Using vaginal wall and IVR swabs at IVR insertion and removal, the genital microbial composition was determined using 16S rRNA gene sequencing. The presence of<jats:italic>Candida<\/jats:italic>spp. was determined using qPCR. The vaginal total bacterial burden appeared to decrease with TFV and TFV\/LNG IVR use (log<jats:sub>10<\/jats:sub>0.57 and log<jats:sub>10<\/jats:sub>0.27 decrease respectively; p\u2009&gt;\u20090.05). The TFV\/LNG IVR was more \u2018stabilizing\u2019: 50% of the participants\u2019 microbiota community state types remained unchanged and 50% shifted towards higher<jats:italic>Lactobacillus<\/jats:italic>abundance. Specifically, TFV\/LNG IVR use was accompanied by increased abundances of<jats:italic>Lactobacillus gasseri\/hominis\/johnsonii\/taiwanensis<\/jats:italic>(16.3-fold) and<jats:italic>L. fermentum\/reuteri\/vaginalis<\/jats:italic>(7.0-fold; all p\u2009&lt;\u20090.01). A significant shift in the overall microbial \u03b1-diversity or \u03b2-diversity was not observed for either IVR, and IVR use did not influence<jats:italic>Candida<\/jats:italic>spp. prevalence. TFV\/LNG and TFV IVRs did not adversely affect the genital microbiota and are safe to use. Our findings support further studies assessing their efficacy in preventing HIV\/HSV-2 and unintended pregnancies.<\/jats:p>","DOI":"10.1038\/s41598-022-13475-9","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T15:05:17Z","timestamp":1657811117000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Genital microbiota of women using a 90 day tenofovir or tenofovir and levonorgestrel intravaginal ring in a placebo controlled randomized safety trial in 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