Donahue Carlson Renee, Sheth Anandi N, Read Timothy D, Frisch Michael B, Mehta C Christina, Martin Amy, Haaland Richard E, Patel Anar S, Pau Chou-Pong, Kraft Colleen S, Ofotokun Igho
Department of Medicine, Division of Infectious Diseases, School of Medicine.
Department of Human Genetics, School of Medicine.
J Infect Dis. 2017 Nov 15;216(8):990-999. doi: 10.1093/infdis/jix420.
The female genital tract (FGT) microbiome may affect vaginal pH and other factors that influence drug movement into the vagina. We examined the relationship between the microbiome and antiretroviral concentrations in the FGT.
Over one menstrual cycle, 20 human immunodeficiency virus (HIV)-infected women virologically suppressed on tenofovir (TFV) disoproxil fumarate/emtricitabine and ritonavir-boosted atazanavir (ATV) underwent serial paired cervicovaginal and plasma sampling for antiretroviral concentrations using high-performance liquid chromatography-tandem mass spectrometry. Analysis of 16S ribosomal RNA gene sequencing of cervicovaginal lavage clustered each participant visit into a unique microbiome community type (mCT).
Participants were predominantly African American (95%), with a median age of 38 years. Cervicovaginal lavage sequencing (n = 109) resulted in a low-diversity mCT dominated by Lactobacillus (n = 40), and intermediate-diversity (n = 28) and high-diversity (n = 41) mCTs with abundance of anaerobic taxa. In multivariable models, geometric mean FGT:plasma ratios varied significantly by mCT for all 3 drugs. For both ATV and TFV, FGT:plasma was significantly lower in participant visits with high- and low-diversity mCT groups (all P < .02). For emtricitabine, FGT:plasma was significantly lower in participant visits with low- vs intermediate-diversity mCT groups (P = .002).
Certain FGT mCTs are associated with decreased FGT antiretroviral concentrations. These findings are relevant for optimizing antiretrovirals used for biomedical HIV prevention in women.
女性生殖道（FGT）微生物群可能会影响阴道pH值以及其他影响药物进入阴道的因素。我们研究了FGT微生物群与抗逆转录病毒药物浓度之间的关系。
在一个月经周期内，对20名感染人类免疫缺陷病毒（HIV）且病毒学抑制的女性进行研究，她们正在服用富马酸替诺福韦二吡呋酯/恩曲他滨，并使用利托那韦增强阿扎那韦（ATV）。采用高效液相色谱-串联质谱法对她们进行连续配对的宫颈阴道和血浆采样，以检测抗逆转录病毒药物浓度。对宫颈阴道灌洗样本进行16S核糖体RNA基因测序分析，将每个参与者的就诊情况聚类为独特的微生物群社区类型（mCT）。
参与者主要为非裔美国人（95%），中位年龄为38岁。宫颈阴道灌洗测序（n = 109）结果显示，微生物群多样性较低的mCT以乳酸杆菌为主（n = 40），微生物群多样性中等（n = 28）和较高（n = 41）的mCT中厌氧类群丰富。在多变量模型中，所有3种药物的FGT:血浆几何平均比值因mCT不同而有显著差异。对于ATV和替诺福韦（TFV），微生物群多样性高和低的mCT组参与者就诊时FGT:血浆比值均显著较低（所有P < 0.02）。对于恩曲他滨，微生物群多样性低与中等的mCT组参与者就诊时FGT:血浆比值显著较低（P = 0.002）。
某些FGT的mCT与FGT抗逆转录病毒药物浓度降低有关。这些发现对于优化用于女性生物医学HIV预防的抗逆转录病毒药物具有重要意义。
