Modifiers of Tenofovir in the Female Genital Tract

Study Overview
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Brief Summary
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Two-armed, single visit, pharmacokinetic study to compare tenofovir diphosphate concentrations in cervical tissues of women on Depo-Provera contraception vs non-hormonal contraception.

Official Title
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Modifiers of Tenofovir Exposure in the Female Genital Tract of African Women on Depo-provera

Conditions
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HIV/AIDS, Contraception

Intervention / Treatment
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* Drug: Tenofovir Disoproxil Fumarate
* Drug: Depo-Provera


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female, or transgender female with a cervix, aged 18-35 years old HIV-positive Stable on antiretroviral regimen containing TDF 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. Exclusion Criteria: Currently pregnant or previous pregnancy within 3 months of enrollment Currently breast feeding Symptomatic vaginal infection within 2 weeks prior to enrollment Unexplained, undiagnosed abnormal bleeding per vagina, bleeding per vagina during or following vaginal intercourse, or gynecologic surgery within 90 days prior to enrollment History of vulvar/vaginal/ cervical dysplasia, neoplasia or cancer, atypical squamous cells of undetermined significance, condyloma, or human papilloma virus (HPV) in the past year Use of oral and/or vaginal preparations of antibiotic or antifungal medications within 30 days prior to the enrollment visit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Depo-Provera<br> | Drug: Tenofovir Disoproxil Fumarate<br>* Two cervical biopsies, blood plasma, PBMC, urine, and two cervicovaginal swabs will be collected at a single study visit<br>Drug: Depo-Provera<br>* Two cervical biopsies, blood plasma, PBMC, urine, and two cervicovaginal swabs will be collected at a single study visit<br>|
| Non-hormonal contraception<br> | Drug: Tenofovir Disoproxil Fumarate<br>* Two cervical biopsies, blood plasma, PBMC, urine, and two cervicovaginal swabs will be collected at a single study visit<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cervical Tissue Concentrations | Assess the influence of hormonal contraception on tenofovir concentrations in cervical tissues | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proinflammatory cytokines | To determine relationship between local inflammation and drug disposition in the female genital tract | Day 1 | 
| Gene expression of drug metabolizing enzymes and transporters | To assess the influence of hormonal contraception on the expression of drug metabolizing enzymes and transporters in cervical tissue | Day 1 | 
| Vaginal microbiome | 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, microbiome, inflammation