Modifiers of Tenofovir in the Female Genital Tract

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

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

Study Overview

• Status: Completed
• Conditions: HIV/AIDS; Contraception
• Intervention / Treatment: Drug: Tenofovir Disoproxil Fumarate; Drug: Depo-Provera

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• Uganda
  • Kampala, Uganda
    • MU-JHU Care Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women will be recruited from an existing cohort.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Depo-Provera	Drug: Tenofovir Disoproxil Fumarate; Two cervical biopsies, blood plasma, PBMC, urine, and two cervicovaginal swabs will be collected at a single study visit; Drug: Depo-Provera; Two cervical biopsies, blood plasma, PBMC, urine, and two cervicovaginal swabs will be collected at a single study visit
Non-hormonal contraception	Drug: Tenofovir Disoproxil Fumarate; Two cervical biopsies, blood plasma, PBMC, urine, and two cervicovaginal swabs will be collected at a single study visit

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: MU-JHU CARE

Publications and helpful links

General Publications

• Nicol MR, Eneh P, Nakalega R, Kaiser T, Kabwigu S, Isingel E, Beksinska M, Sykes C, Fowler MG, Brown TT, Staley C, Kiweewa Matovu F. Depot Medroxyprogesterone Acetate and the Vaginal Microbiome as Modifiers of Tenofovir Diphosphate and Lamivudine Triphosphate Concentrations in the Female Genital Tract of Ugandan Women: Implications for Tenofovir Disoproxil Fumarate/Lamivudine in Preexposure Prophylaxis. Clin Infect Dis. 2020 Apr 10;70(8):1717-1724. doi: 10.1093/cid/ciz443.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2017
• Primary Completion (Actual): March 29, 2018
• Study Completion (Actual): April 2, 2018

Study Registration Dates

• First Submitted: December 8, 2017
• First Submitted That Met QC Criteria: December 13, 2017
• First Posted (Actual): December 19, 2017

Study Record Updates

• Last Update Posted (Actual): May 1, 2018
• Last Update Submitted That Met QC Criteria: April 30, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: tenofovir; inflammation; microbiome
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Physiological Effects of Drugs; 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; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptive Agents, Male; Tenofovir; Medroxyprogesterone Acetate; Medroxyprogesterone
• Other Study ID Numbers: STUDY00000171

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No