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

CONRAD

Status and phase: Completed; Phase 1

Conditions: HIV Prevention

Treatments: Drug: TFV 1% gel; Drug: Estradiol vaginal cream

Study type: Interventional

Funder types: Other

Identifiers

NCT01810315

A12-124

Details and patient eligibility

About

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.

Full 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).

Enrollment: 40 patients

Sex: Female

Ages: 21 to 89 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

40 participants in 4 patient groups

Baseline

No Intervention group

Description:

Premenopausal women will undergo baseline sampling in each the follicular and luteal phase. Postmenopausal women will undergo baseline sampling one time.

TFV 1% Gel

Experimental group

Description:

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.

Treatment:

Drug: TFV 1% gel

Estradiol Vaginal Cream

Experimental group

Description:

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

Treatment:

Drug: Estradiol vaginal cream

TFV 1% gel and estradiol cream

Experimental group

Description:

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.

Treatment:

Drug: Estradiol vaginal cream

Drug: TFV 1% gel