Effect of Bacterial Vaginosis on HIV Susceptibility and Female Genital Immunology

HIV Infections Clinical Trial

Official title:

Effect of Bacterial Vaginosis and Its Treatment on HIV Susceptibility and Female Genital Immunology

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02527941
• Other study ID #: UTorontoBV
• Status: Completed
• Phase: Phase 1
• First received: August 14, 2015
• Last updated: February 9, 2016
• Start date: August 2015
• Est. completion date: November 2015

Study information

• Verified date: February 2016
• Source: University of Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Canadian Institutes of Health Research
• Study type: Interventional

Clinical Trial Summary

A non-randomized, interventional, longitudinal clinical study to quantify the impact of bacterial vaginosis treatment on HIV susceptibility and genital immunology in Kenyan women.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

1. 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.

2. Willing to comply with the requirements of the protocol

3. HIV and classical STI (see below) negative

4. test positive for BV, defined as Nugent score from 7-10

5. willing to take oral metronidazole twice a day for 7 days

6. willing to abstain from alcohol during and for 48 hours after metronidazole treatment

Exclusion Criteria:

1. HIV infected

2. Deemed by physician to be unlikely to complete study protocol.

3. Pregnant.

4. Irregular menstrual cycle, or actively menstruating at the time of genital sampling.

5. Tested positive for classical STIs or having genital ulcers

6. Prior hysterectomy

7. Contraindication, allergy or intolerance to use of metronidazole

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Bacterial Vaginosis
• Disease Susceptibility
• HIV Infections
• Vaginal Diseases
• Vaginosis, Bacterial

Intervention

Drug:
• Metronidazole
Participants will be provided with oral metronidazole 400mg po tid for one week, and followed up one month after treatment initiation.

Locations

Country	Name	City	State
Kenya	Kenya AIDS Vaccine Initiative Clinic	Nairobi

Sponsors (1)

Lead Sponsor	Collaborator
University of Toronto

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	up to 8 months	No
Primary	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.	up to 8 months	No
Secondary	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].	up to 8 months	No
Secondary	The cervico-vaginal microbiome.	The cervico-vaginal microbiome will be assessed by 16s rRNA sequencing before and after metronidazole therapy.	up to 8 months	No
Secondary	Genital proteome analysis.	The genital proteome will be assessed by mass spectroscopy before and after metronidazole therapy.	up to 8 months	No
Secondary	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.	up to 8 months	No