Background 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). Methods 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). Results 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. Conclusions 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.

中文翻译：

---

使用乙炔雌二醇/依托孕烯阴道环可改变 HIV 感染女性的阴道微生物群落


背景 HIV-1 抗逆转录病毒疗法 （ART） 以方案特异性方式改变通过阴道内环 （IVR） 输送的激素避孕药水平。我们探讨了 IVR 对阴道微生物群落、阴道短链脂肪酸 （SCFAs）、阴道 HIV 脱落以及阴道微生物对顺性别 HIV 感染者 （WWH） 激素浓度的影响。方法 通过每周阴道拭子的 16S RNA 测序、质谱阴道 SCFA、阴道抽吸物核酸扩增的 HIV-1 脱落和细菌性阴道病的 Nugent 评分评估阴道微生物，同时接受依托诺孕酮/乙炔雌二醇 （ENG/EE） 阴道环治疗，同时接受无 ART （N=25）、基于依非韦伦的 ART （N=25） 或基于阿扎那韦的 ART （N=24）。结果 在基线时，64 名符合子研究条件的参与者的微生物群落被强有力地归类为以 Lactobacillus crispatus 为主 （n=8）、L. gasseri 为主 （n=2）、L. iners 为主 （n=17） 或混合厌氧群落 （n=37）。在 IVR 治疗期间，乳酸菌显性社区状态类型 （CST） 的可能性增加 （比值比=1.61，p=0.04）。阴道 CST 与 Nugent 评分相关。细菌性阴道病相关细菌与 Nugent 评分显著升高和 L. iners 较低相关 （均 p 调整 <0.1）。乳酸水平与乳酸菌属的相对丰度相关 （r2=0.574;p<0.001）。HIV-1 的阴道脱落在 L. crispatus 优势微生物组的女性中不太常见 （p=0.04）。混合厌氧阴道群落以方案特异性方式调节 EE 浓度。 结论 ENG/EE IVR 联合治疗与 WWH 中乳酸菌为主的阴道微生物群落的增加有关，可能有益于细菌性阴道病患者。EE 水平被阴道微生物群改变。