A Phase 1 interventional study of Metronidazole in Bacterial Vaginosis and HIV Infections, sponsored by University of Toronto. Completed at 1 site in Kenya. Open to female participants aged 18 Years to 49 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2016-02-10.
Sponsored by University of Toronto · Phase 1, Interventional, and Basic science
A non-randomized, interventional, longitudinal clinical study to quantify the impact of bacterial vaginosis treatment on HIV susceptibility and genital immunology in Kenyan women.
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.
220 studies on the registry are indexed under Vaginosis, Bacterial; 36 are open to participants now.
This study's enrollment of 50 is below the median of 100 across 187 interventional studies indexed under Vaginosis, Bacterial.
Browse Vaginosis, Bacterial studies →University of Toronto is the lead sponsor of 397 studies on the registry; 59 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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).
Drug: Metronidazole
Participants will be provided with oral metronidazole 400mg po tid for one week, and followed up one month after treatment initiation.
Also known as: flagyl
Percent HIV pseudovirus entry into cervical CD4+ T cells.
The percentage of cervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct will be quantified by flow cytometry.
Time frame: up to 8 months
Total number of cervical CD4+ T cells infected ex vivo with HIV.
The total number of cervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct will be quantified by flow cytometry.
Time frame: up to 8 months
A genital inflammation score based on genital levels of pro-inflammatory cytokines and chemokines.
Level of 14 genital cytokines/chemokines (GM-CSF, IL-1a, IL-8, MCP-1, MIG, MIP-3a, RANTES, IL-10, IL-17, IL-1b, IL-6, IP-10, MIP-1b, TNF-a) will be combined into a genital inflammation score \[Arnold K et al, Muc Immunol, 2015\].
Time frame: up to 8 months
The cervico-vaginal microbiome.
The cervico-vaginal microbiome will be assessed by 16s rRNA sequencing before and after metronidazole therapy.
Time frame: up to 8 months
Genital proteome analysis.
The genital proteome will be assessed by mass spectroscopy before and after metronidazole therapy.
Time frame: up to 8 months
CD4+ expression of pre-defined HIV susceptibility markers
Surface expression of CCR5, CD69, a4b7 and a4b1 by endocervical CD4 T cells before and after metronidazole therapy.
Time frame: up to 8 months
This study is completed, as verified in Feb 2016. You cannot join it, but the record below documents what was studied.
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