Clinical trial NCT02527941: Effect of Bacterial Vaginosis on HIV Susceptibility and Female Genital Immunology
Official title: Effect of Bacterial Vaginosis and Its Treatment on HIV Susceptibility and Female Genital Immunology
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bacterial Vaginosis
HIV Infections
Keywords: Genital immunology
HIV susceptibility
Microbiome
Bacterial vaginosis
Virus entry assay
Lead sponsor: University of Toronto
Sponsor class: OTHER
First posted: 2015-08-19
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent HIV pseudovirus entry into cervical CD4+ T cells.
timeFrame: up to 8 months
measure: Total number of cervical CD4+ T cells infected ex vivo with HIV.
timeFrame: up to 8 months
Secondary outcomes:
measure: A genital inflammation score based on genital levels of pro-inflammatory cytokines and chemokines.
timeFrame: up to 8 months
measure: The cervico-vaginal microbiome.
timeFrame: up to 8 months
measure: Genital proteome analysis.
timeFrame: up to 8 months
measure: CD4+ expression of pre-defined HIV susceptibility markers
timeFrame: up to 8 months
Other outcomes:
Locations:
city: Nairobi
country: Kenya
facility: Kenya AIDS Vaccine Initiative Clinic
Study officials:
affiliation: University of Toronto
name: Rupert Kaul, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: