Effect of Bacterial Vaginosis and Its Treatment on HIV Susceptibility and Female Genital Immunology
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Percent HIV pseudovirus entry into cervical CD4+ T cells.
研究概览
简要总结
A non-randomized, interventional, longitudinal clinical study to quantify the impact of bacterial vaginosis treatment on HIV susceptibility and genital immunology in Kenyan women.
详细描述
Bacterial Vaginosis (BV), defined as an alteration in the normal vaginal bacteria ("microbiome"), is characterized by a reduction of hydrogen peroxide-producing gram-positive lactobacilli and overgrowth of gram-negative and anaerobic bacteria. BV is more prevalent in SSA and usually recurs soon after treatment. BV is associated with vaginal inflammation, an increased HIV acquisition risk among uninfected women, and increased HIV transmission to the male sexual partner of a co-infected woman. Therefore, BV may be responsible for up to 17% of HIV transmission events in SSA.
There are several hypotheses for the mechanisms by which BV may increase the risk of HIV acquisition. These include the disruption of mucosal barrier, alteration of protective innate immunity, and increased number and/or susceptibility of HIV target cells in the genital mucosa. Longitudinal studies that address the mechanisms by which the vaginal microbiota alters host mucosal immunology and HIV risk will help us better understand the impact of BV and it's treatment on mucosal immunology and HIV susceptibility. The goal of this non-randomized, interventional, longitudinal clinical study is to use a novel ex vivo HIV infectivity assay developed in the Kaul lab to quantify the effect of BV and its treatment on HIV susceptibility and genital immunology in HIV-uninfected women from Nairobi, Kenya. Fifty HIV, STI-uninfected women with bacterial vaginosis on Nugent scoring will be provided with one week of metronidazole 400mg po three times daily (as per Kenyan National Guidelines). Cytobrush and vaginal SoftCup sampling will be performed at baseline and 4 weeks after treatment initiation, at the same stage of the menstrual cycle. The primary endpoint will be pseudovirus entry into cervix-derived CD4+ T cells. Secondary endpoints will include a pre-defined cervico-vaginal inflammation score; genital CD4+ T cell immune characteristics; the genital microbiome; the genital proteome.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Participants are over 18 years of age, not pregnant and willing to give informed consent, and answer short questionnaires on economic status, and sexual risk behavior.
- •Willing to comply with the requirements of the protocol
- •HIV and classical STI (see below) negative
- •test positive for BV, defined as Nugent score from 7-10
- •willing to take oral metronidazole twice a day for 7 days
- •willing to abstain from alcohol during and for 48 hours after metronidazole treatment
排除标准
- •HIV infected
- •Deemed by physician to be unlikely to complete study protocol.
- •Irregular menstrual cycle, or actively menstruating at the time of genital sampling.
- •Tested positive for classical STIs or having genital ulcers
- •Prior hysterectomy
- •Contraindication, allergy or intolerance to use of metronidazole
研究组 & 干预措施
metronidazole
50 women who test negative for HIV and classical sexually transmitted infections but test positive for Bacterial Vaginosis will be treated with metronidazole at a dosage of 400mg/dose, 3 doses per day, for 7 days (as per Kenyan National Guidelines).
干预措施: Metronidazole (Drug)
结局指标
主要结局
Percent HIV pseudovirus entry into cervical CD4+ T cells.
时间窗: up to 8 months
The percentage of cervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct will be quantified by flow cytometry.
Total number of cervical CD4+ T cells infected ex vivo with HIV.
时间窗: up to 8 months
The total number of cervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct will be quantified by flow cytometry.
次要结局
- A genital inflammation score based on genital levels of pro-inflammatory cytokines and chemokines.(up to 8 months)
- The cervico-vaginal microbiome.(up to 8 months)
- Genital proteome analysis.(up to 8 months)
- CD4+ expression of pre-defined HIV susceptibility markers(up to 8 months)
研究者
Rupert Kaul
Professor
University of Toronto