University of California San Diego, La Jolla, CA.
University of North Carolina, Durham, NC.
J Acquir Immune Defic Syndr. 2022 Apr 1;89(4):390-395. doi: 10.1097/QAI.0000000000002884.
We evaluated the association of inflammation and dysbosis on cervicovaginal fluid (CVF) tenofovir (TFV) concentrations in women taking oral tenofovir disoproxil fumarate/emtricitable for HIV pre-exposure prophylaxis (PrEP) in the United States.
Thirty-five women in a HIV PrEP implementation study attended their week 24 visit at a San Diego research clinic and provided CVF specimens.
Women in the Adherence Enhancement Guided by Individualized Texting and Drug Levels study had their CVF specimens evaluated for (1) sexually transmitted bacterial (Neisseria gonorrhoeae, Chlamydia trachomatis, Gardnerella, and Trichomonas vaginalis), viral (human papillomavirus, cytomegalovirus and herpes simplex virus-1/2) and fungal (Candida) infections; (2) microbiome composition by 16 S sequencing (V3-V4 region); and (3) cytokine profiles by enzyme-linked immunoassay (Interleukin-8, macrophage Inflammatory protein-1a, macrophage Inflammatory Protein-1b and interferon-γ-inducible protein-10). Univariate statistical analysis was used to determine factors associated with CVF TFV concentrations. CVF TFV of 100-1000 ng/mL benchmarked typical genital concentrations and TFV-diphosphate in dried blood spots of 700 fmol/punch was considered adequate adherence.
Thirty-five women had CVF specimens collected. No factor was associated with CVF TFV concentrations or discordance of blood and vaginal concentrations. Among 27 participants assessed for vaginosis (Candida, Gardnerella or Trichomonas), women with Gardnerella (n = 11) were more likely to have high (>1000 ng/mL) CVF TFV concentrations (82% versus 33%, P = 0.02).
Presence of genital viruses, cytokines, or vaginal community state types were not associated with low CVF TFV concentrations in cisgender women taking oral tenofovir disoproxil fumarate/emtricitable for PrEP. The surprising association observed between presence of Gardnerella and higher vaginal TFV concentrations needs further evaluation.
我们评估了炎症和阴道菌群失调与在美国接受口服替诺福韦二吡呋酯/恩曲他滨（TDF/FTC）进行 HIV 暴露前预防（PrEP）的女性的宫颈阴道液（CVF）替诺福韦（TFV）浓度之间的关联。
35 名参与 HIV PrEP 实施研究的女性在圣地亚哥研究诊所进行了第 24 周就诊，并提供了 CVF 标本。
在通过个体化短信和药物水平增强依从性研究中，对女性的 CVF 标本进行了以下评估：（1）性传播细菌（淋病奈瑟菌、沙眼衣原体、加德纳菌和阴道毛滴虫）、病毒（人乳头瘤病毒、巨细胞病毒和单纯疱疹病毒 1/2）和真菌（念珠菌）感染；（2）通过 16S 测序（V3-V4 区）评估微生物组组成；（3）通过酶联免疫吸附试验（白细胞介素-8、巨噬细胞炎症蛋白-1a、巨噬细胞炎症蛋白-1b 和干扰素-γ诱导蛋白-10）评估细胞因子谱。采用单变量统计分析来确定与 CVF TFV 浓度相关的因素。CVF TFV 的 100-1000ng/mL 为典型的生殖器浓度，700fmol/穿孔的干血斑中 TFV-二磷酸被认为是足够的依从性。
35 名女性采集了 CVF 标本。没有因素与 CVF TFV 浓度或血液和阴道浓度的不一致相关。在评估 27 名阴道病（念珠菌、加德纳菌或阴道毛滴虫）的参与者中，患有加德纳菌（n=11）的女性更有可能具有高（>1000ng/mL）CVF TFV 浓度（82%比 33%，P=0.02）。
在接受口服替诺福韦二吡呋酯/恩曲他滨进行 PrEP 的顺性别女性中，生殖器病毒、细胞因子或阴道群落状态类型的存在与低 CVF TFV 浓度无关。加德纳菌的存在与阴道 TFV 浓度升高之间的惊人关联需要进一步评估。
