Valint D J, Fiedler Tina L, Liu Congzhou, Srinivasan Sujatha, Fredricks David N
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Department of Medicine, University of Washington, Seattle, Washington, USA.
mBio. 2024 Dec 11;15(12):e0111024. doi: 10.1128/mbio.01110-24. Epub 2024 Nov 21.
Several bacterial vaginosis (BV)-associated bacteria have been associated with elevated risk of human immunodeficiency virus (HIV) acquisition; however, susceptibility of these bacteria to antibiotics is poorly understood. Vaginal samples were collected from 22 persons daily for 2 weeks following BV diagnosis. Metronidazole treatment was prescribed for 5-7 days. Changes in bacterial concentrations were measured with taxon-specific 16S rRNA gene quantitative PCR (qPCR) assays. A culture-based antimicrobial assay confirmed presence of antibiotics in vaginal swab samples. Bacterial DNA concentrations decreased during antibiotic administration for all 13 bacterial taxa tested. Comparison of bacterial DNA concentrations in samples before administration of antibiotics to samples taken on the last day of antimicrobial assay-confirmed antibiotic presence showed a 2.25-4.78 log10-fold decrease across all taxa. Concentrations were frequently reduced to the qPCR assay's limit of detection, suggesting eradication of bacteria. Mean clearance time varied across taxa (1.2-7.9 days), with several bacteria (e.g., spp., Vaginal TM7, and -like sp.) taking >7 days to suppress. Metronidazole reduces quantities of bacterial taxa associated with increased HIV acquisition risk.IMPORTANCEHuman immunodeficiency virus (HIV) transmission through sex remains a major public health challenge despite efforts at risk reduction and use of anti-retroviral pre-exposure prophylaxis. Many bacterial vaginosis (BV)-associated vaginal bacteria have been associated with increased HIV infection risk among women. If these bacteria help mediate HIV infection risk, then eradication of these bacteria is one potential strategy to reduce this risk. However, the best approach to eradicate HIV-high risk bacteria from the vagina is not known. We analyzed vaginal swabs collected daily from women with BV to determine the impact of metronidazole treatment on 13 vaginal bacterial taxa linked to elevated risk of HIV infection through use of taxon-directed quantitative PCR assays. We conclude that eradication of high-risk vaginal bacteria using metronidazole is one promising avenue for reducing HIV acquisition risk, and we provide evidence that a 5-7-day treatment course may not be sufficient to suppress all bacteria.
几种与细菌性阴道病（BV）相关的细菌与人类免疫缺陷病毒（HIV）感染风险升高有关；然而，这些细菌对抗生素的敏感性却知之甚少。在BV诊断后的2周内，每天从22人身上采集阴道样本。开出甲硝唑治疗处方，疗程为5 - 7天。用分类群特异性16S rRNA基因定量PCR（qPCR）检测方法测量细菌浓度的变化。基于培养的抗菌检测证实阴道拭子样本中存在抗生素。在给予抗生素期间，所有13种被测细菌类群的细菌DNA浓度均下降。将抗生素给药前样本中的细菌DNA浓度与抗菌检测确认有抗生素存在的最后一天所采集样本中的细菌DNA浓度进行比较，结果显示所有类群的细菌DNA浓度下降了2.25 - 4.78个log10倍。浓度常常降至qPCR检测的检测限，提示细菌被根除。平均清除时间因类群而异（1.2 - 7.9天），几种细菌（如某些菌属、阴道TM7菌属和某类似菌属）需要超过7天才能被抑制。甲硝唑可减少与HIV感染风险增加相关的细菌类群数量。
尽管在降低风险和使用抗逆转录病毒暴露前预防方面做出了努力，但通过性行为传播的人类免疫缺陷病毒（HIV）仍然是一项重大的公共卫生挑战。许多与细菌性阴道病（BV）相关的阴道细菌与女性HIV感染风险增加有关。如果这些细菌有助于介导HIV感染风险，那么根除这些细菌是降低这种风险的一种潜在策略。然而，从阴道中根除HIV高风险细菌的最佳方法尚不清楚。我们分析了每天从患有BV的女性身上采集的阴道拭子，通过使用分类群定向定量PCR检测方法来确定甲硝唑治疗对13种与HIV感染风险升高相关的阴道细菌类群的影响。我们得出结论，使用甲硝唑根除高风险阴道细菌是降低HIV感染风险的一个有前景的途径，并且我们提供的证据表明5 - 7天的疗程可能不足以抑制所有细菌。
