Effect of Bacterial Vaginosis on HIV Susceptibility and Female Genital Immunology
|ClinicalTrials.gov Identifier: NCT02527941|
Recruitment Status : Completed
First Posted : August 19, 2015
Last Update Posted : February 10, 2016
|Condition or disease||Intervention/treatment||Phase|
|Bacterial Vaginosis HIV Infections||Drug: Metronidazole||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Effect of Bacterial Vaginosis and Its Treatment on HIV Susceptibility and Female Genital Immunology|
|Study Start Date :||August 2015|
|Actual Primary Completion Date :||November 2015|
|Actual Study Completion Date :||November 2015|
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).
Participants will be provided with oral metronidazole 400mg po tid for one week, and followed up one month after treatment initiation.
Other Name: flagyl
- Percent HIV pseudovirus entry into cervical CD4+ T cells. [ Time Frame: 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. [ Time Frame: 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.
- A genital inflammation score based on genital levels of pro-inflammatory cytokines and chemokines. [ Time Frame: up to 8 months ]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].
- The cervico-vaginal microbiome. [ Time Frame: up to 8 months ]The cervico-vaginal microbiome will be assessed by 16s rRNA sequencing before and after metronidazole therapy.
- Genital proteome analysis. [ Time Frame: up to 8 months ]The genital proteome will be assessed by mass spectroscopy before and after metronidazole therapy.
- CD4+ expression of pre-defined HIV susceptibility markers [ Time Frame: up to 8 months ]Surface expression of CCR5, CD69, a4b7 and a4b1 by endocervical CD4 T cells before and after metronidazole therapy.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02527941
|Kenya AIDS Vaccine Initiative Clinic|
|Principal Investigator:||Rupert Kaul, MD/PhD||University of Toronto|