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

Study Overview
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Brief Summary
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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.

Official Title
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Role of Exogenous and Endogenous Sex Hormones on Tenofovir and Emtricitabine

Conditions
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HIV/AIDS, Menopause, Inflammation Vagina

Intervention / Treatment
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* Drug: Tenofovir
* Drug: Emtricitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tenofovir|Two cervical biopsies, blood plasma, PBMC, and two cervicovaginal swabs will be collected at a single study visit|
|Drug: Emtricitabine|Two cervical biopsies, blood plasma, PBMC, and two cervicovaginal swabs will be collected at a single study visit|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tenofovir, prevention, microbiome, cervicovaginal, biopsy, swab, cytokines, inflammation, pharmacology