Role of Exogenous and Endogenous Sex Hormones on Tenofovir and Emtricitabine Disposition in Female Genital Tract

NCT03218085 | Completed FDA Drug

• 1 other identifier: PHARM-2016-24820
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Cervical biopsies will be collected from women aged 18 and over whom are virally suppressed and taking tenofovir as part of their antiretroviral therapy regimen. Blood plasma, peripheral blood mononuclear cells (PBMC), and cervicovaginal swabs will also be collected. Drug concentrations, hormone concentrations, inflammatory cytokines, and vaginal microbiome will be evaluated to understand the role of hormones, inflammation, and the microbiome in modulating drug efficacy in the female genital tract.

Conditions

HIV/AIDS; Menopause; Inflammation Vagina

Keywords

tenofovir; prevention; microbiome; cervicovaginal; biopsy; swab; cytokines; inflammation; pharmacology

Outcome Measures

Primary Outcomes (1)

• Assess the influence of exogenous and endogenous sex hormones on tenofovir and emtricitabine concentrations in cervical tissues

  Day 1

Secondary Outcomes (5)

• To assess the influence of endogenous and exogenous sex hormones on the expression of drug metabolizing enzymes and transporters in cervical tissue

  Day 1

• To determine the influence of endogenous and exogenous sex hormones on the endogenous nucleotide pool in cervical tissues

  Day 1

• To discriminate between local and systemic effects of hormonal use on antiretroviral disposition.

  Day 1

• To determine relationship between local inflammation and drug disposition in the female genital tract

  Day 1

• To identify potential role of the vaginal microbiome in local drug disposition,

  Day 1

Interventions

Tenofovir DRUG

Two cervical biopsies, blood plasma, PBMC, and two cervicovaginal swabs will be collected at a single study visit

Emtricitabine DRUG

Two cervical biopsies, blood plasma, PBMC, and two cervicovaginal swabs will be collected at a single study visit

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

1. Currently pregnant or previous pregnancy within 3 months of enrollment 2. Currently breast feeding 3. Symptomatic vaginal infection within 2 weeks prior to enrollment 4. Unexplained, undiagnosed abnormal bleeding per vagina, bleeding per vagina during or following vaginal intercourse, or gynecologic surgery within 90 days prior to enrollment 5. Use of oral and/or vaginal preparations of antibiotic or antifungal medications within 30 days prior to the enrollment visit

You may qualify if:

• Female, or transgender female with a cervix, age 18 years or older
• HIV-positive
• Stable on antiretroviral regimen containing tenofovir or emtricitabine for at least 2 weeks at time of enrollment.
• Virally suppressed (HIV-RNA copies \<50 copies/mL) for at least 6 months at time of enrollment.
• Willing to refrain from vaginal intercourse and use of vaginal devices such as douches and sex toys within 72 hours of the biopsy visit.
• Willing and able to give signed informed consent.

Sponsors & Collaborators

• University of Minnesota: lead
• American College of Clinical Pharmacy: collaborator

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Vaginitis; Inflammation

Interventions

Tenofovir; Emtricitabine

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Vaginal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2017
• First Posted: July 14, 2017
• Study Start: July 14, 2017
• Primary Completion: February 15, 2024
• Study Completion: February 15, 2024
• Last Updated: April 16, 2024

Record last verified: 2024-04

Locations

US (1)