Effect of Bacterial Vaginosis on HIV Susceptibility and Female Genital Immunology

University of Toronto

Status and phase: Completed; Phase 1

Conditions: Bacterial Vaginosis; HIV Infections

Treatments: Drug: Metronidazole

Study type: Interventional

Funder types: Other

Identifiers

NCT02527941

UTorontoBV

Details and patient eligibility

About

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

Full 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.

Enrollment: 50 patients

Sex: Female

Ages: 18 to 49 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

metronidazole

Experimental group

Description:

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).

Treatment:

Drug: Metronidazole