Influence of Reproductive Cycle and Menopause on HIV-1 Infection and TFV Gel Activity

Influence of Female Reproductive Cycle and Menopause on Cervicovaginal Tissue Susceptibility to HIV-1 Infections and Tenofovir 1% Gel Activity

Purpose of the study is to assess tenofovir (TFV) PK and PD endpoints, cervicovaginal safety parameters, susceptibility to HIV-1 infection, and objective measures of vaginal applicator use in premenopausal and postmenopausal women.

Study Overview

• Status: Completed
• Conditions: HIV Prevention
• Intervention / Treatment: Drug: TFV 1% gel; Drug: Estradiol vaginal cream

Detailed Description

Premenopausal women: Baseline blood and genital samples will be taken in the follicular and luteal phase (visits 2 and 3). The participant will be given TFV gel and instructed to insert two doses, separated by 2 hours, and return to the clinic 3 hours after the second insertion for blood and genital samples (visits 4/4a and 5/5a).

Postmenopausal women: Premenopausal women: Baseline blood and genital samples will be taken (visit 2). The participant will be given TFV gel and instructed to insert two doses, separated by 2 hours, and return to the clinic 3 hours after the second insertion for blood and genital samples (visit 3/3a). Estradiol cream will be distributed at visit 4. Post estradiol blood and genital samples will be taken at Visit 5. The participant will given TFV gel and instructed to insert 2 doses as before, while continuing to use the estradiol cream. Post TFV gel and estradiol cream blood and genital samples will be taken (visit 6/6a).

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Clinical Research Center, Eastern Virginia Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria: All volunteers

• In good healthsignificant systemic disease
• Not at risk of an STI, meaning: In a monogamous heterosexual or same sex relationship for at least the last four months with a partner who is not known to be HIV positive and has no known risks for STIs OR sexually abstinent
• Willing and able to comply with study procedures
• Normal Pap smear (by written report) in the past year.

Inclusion Criteria: Premenopausal volunteers

• 21-to-45 years of age
• Not at risk for pregnancy, meaning:
• Regular menstrual cycles (every 24 - 35 days)
• Luteal phase P level of greater than or equal to 3 ng/ml

Inclusion Criteria: Postmenopausal volunteers

• 46-89 years of age OR both ovaries removed at least 30 days prior to Visit 1
• No menstrual periods/vaginal bleeding in the past 12 months OR both ovaries removed at least 30 days prior to Visit 1
• FSH level of greater than or equal to 20 MIU/ml

Exclusion Criteria: All volunteers

• Clinically significant history of an abnormal Pap smear in the past year
• Surgery or biopsy of the vagina or cervix within 30 days
• Current STI or lower genital tract infection
• Current use of chronic immunosuppressants
• Current presence of vulvar, anal and/or vaginal genital warts
• Current tobacco use of any amount
• History of sensitivity/allergy to any component of the study product, topical anesthetic, or allergy to silver nitrate and/or Monsel's solution
• Known bleeding disorder that could lead to prolonged or continuous bleeding
• Grade 1 or higher laboratory abnormality, per the August 2009 update of the DAIDS Table for Grading the Severity of Adverse Events
• Systemic use in the last two weeks or anticipated use during the study of any of the following: corticosteroids, antibiotics, anticoagulants or other drugs known to prolong bleeding and/or clotting, antifungals, antivirals or antiretrovirals.
• Investigator discretion
• Current participation in any other drug or device study

Exclusion Criteria: Premenopausal women

• Use of DMPA in last six months
• Use of any other hormonal contraceptive method without 2 subsequent, normal menses since stopping hormonal contraceptives
• Current use of copper IUD
• Currently pregnant or pregnancy within the past 3 months
• Currently breastfeeding/having breastfed an infant in the last 2 months

Exclusion Criteria: Postmenopausal women

• Use of any hormonal medications in the past 30 days
• Contraindications to vaginal estrogen cream

Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Baseline; Premenopausal women will undergo baseline sampling in each the follicular and luteal phase. Postmenopausal women will undergo baseline sampling one time.
Experimental: TFV 1% Gel; Participants will vaginally insert 1 applicator of TFV gel followed by a 2nd applicator 2 hours later. Each applicator contains 4.4 gm of TFV 1% gel. Premenopausal women will undergo sampling after TFV gel use in each the follicular and luteal phase. Postmenopausal women will undergo sampling after TFV gel use one time.	Drug: TFV 1% gel
Experimental: Estradiol Vaginal Cream; Post menopausal women only: Participants will insert 2 grams of estradiol cream into the vagina every night for 14 days and then one gram of estradiol cream into the vagina every other night	Drug: Estradiol vaginal cream
Experimental: TFV 1% gel and estradiol cream; Postmenopausal women only: Participants will vaginally insert 1 applicator of TFV gel followed by a 2nd applicator 2 hours later. Each applicator contains 4.4 gm of TFV 1% gel. In addition, participants will one gram of estradiol cream into the vagina every other night.	Drug: TFV 1% gel; Drug: Estradiol vaginal cream

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Concentrations of tenofovir in plasma, vaginal aspirate, and genital tissue	3 hours after dosing
Concentrations of TFV-DP in genital tissue	3 hours after dosing

Collaborators and Investigators

• Sponsor: CONRAD

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: March 11, 2013
• First Submitted That Met QC Criteria: March 11, 2013
• First Posted (Estimate): March 13, 2013

Study Record Updates

• Last Update Posted (Estimate): April 10, 2015
• Last Update Submitted That Met QC Criteria: April 9, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: A12-124