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

Role of Exogenous and Endogenous Sex Hormones on Tenofovir and Emtricitabine

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.

Study Overview

• Status: Completed
• Conditions: HIV/AIDS; Menopause; Inflammation Vagina
• Intervention / Treatment: Drug: Tenofovir; Drug: Emtricitabine

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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

Description

Inclusion Criteria:

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assess the influence of exogenous and endogenous sex hormones on tenofovir and emtricitabine concentrations in cervical tissues	Day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: American College of Clinical Pharmacy

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2017
• Primary Completion (Actual): February 15, 2024
• Study Completion (Actual): February 15, 2024

Study Registration Dates

• First Submitted: July 10, 2017
• First Submitted That Met QC Criteria: July 13, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: tenofovir; prevention; inflammation; cytokines; microbiome; biopsy; pharmacology; cervicovaginal; swab
• Additional Relevant MeSH Terms: Pathologic Processes; Vaginal Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Inflammation; Vaginitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Emtricitabine
• Other Study ID Numbers: PHARM-2016-24820

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No