Adherence and Acceptability to and Blood Levels of Tenofovir Gel and Tablets in HIV Uninfected Women

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 2

Conditions: HIV Infections

Treatments: Drug: Tenofovir disoproxil fumarate; Drug: Tenofovir gel

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00592124

MTN-001

10617 (Registry Identifier)

1U01AI068633-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

A new approach to HIV prevention currently being studied includes the use of microbicides, substances that kill microbes. Tenofovir disoproxil fumarate (TDF) is an oral, FDA-approved, anti-HIV drug, and tenofovir gel is an experimental microbicide. The purpose of this study is to determine the adherence and acceptability to and blood levels of three daily regimens of tenofovir in both oral and gel form.

Full description

It is necessary to monitor both the adherence and blood levels of microbicides in order to gauge its efficacy in a study population. Utilizing an experimental microbicide (tenofovir gel) and an anti-HIV drug (TDF), this study will measure the adherence and acceptability to and blood levels of the two interventions in three separate regimens given to HIV-uninfected women.

The expected duration of participation for each participant is 21 weeks. Study participants will be randomly assigned into one of six study groups, each with a different regimen sequence. Each sequence will consist of three study periods and three wash-out periods. Each study period lasts 6 weeks, followed by a 1 week wash-out period. The regimen assigned for a given study period will include either oral TDF, tenofovir vaginal gel, or both. All participants will be prescribed all three regimens in the order designated by their randomized assignment.

Study visits will occur at Weeks 1, 3, 6, 7, 10, 13, 14, 17, 20, and 21. Medical history, a physical exam, behavioral assessment, and urine, blood, pelvic sample collection, and counseling will occur at all visits. At some study sites rectal swabs may be performed. Counseling will include information regarding contraception, protocol adherence, HIV, HIV/Sexually Transmitted Infection risk reduction, and male condom use. Pharmacokinetic (PK) studies, to be determined by the study site, will occur during all three study periods. These studies may involve additional procedures.

Enrollment: 168 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• General good health
• HIV-uninfected
• Normal menstrual cycle. More information can be found in the protocol.
• Creatinine clearance greater than 70 ml/min
• Sexually active. More information can be found in the protocol.
• Normal Pap smear result within 12 months prior to study entry
• Agrees to not participate in other investigational studies
• Willing to use effective forms of contraception. More information can be found in the protocol.

Exclusion criteria

• Adverse reaction to either of the study products
• Adverse reaction to latex
• Currently sexually active with a partner with history of adverse reaction to latex
• More than three sexual partners in the month prior to screening
• Pathologic bone fracture not related to trauma
• Last pregnancy outcome within 90 days or less prior to enrollment
• Gynecologic or genital procedure within 90 days of study entry
• Enrollment in other investigational study within 30 days of study entry
• Nontherapeutic injection drug use within 12 months of screening
• Any social or medical condition that, in the opinion of the investigator, would interfere with the study
• Abnormal laboratory values
• Grade 2 or higher genital lesions, erythema, and/or edema or has any other abnormal physical or pelvic exam finding that, in the opinion of the investigator, would interfere with the study
• Kidney, reproductive, or urinary tract infection requiring treatment. More information on this criterion can be found in the protocol.
• Pregnant, breastfeeding, or intend to become pregnant
• Unwilling to comply with study participation requirements, including attendance at all scheduled study visits
• Per participant report, use of the following at enrollment, and/or anticipated use during the period of study participation - use of a diaphragm, vaginal ring, and/or spermicide for contraception, acyclovir or valacyclovir, post-exposure prophylaxis for HIV exposure, TDF/emtricitabine, non-study vaginal products

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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168 participants in 6 patient groups

1

Experimental group

Description:

Oral tenofovir disoproxil fumarate (TDF) for Weeks 1 through 6, vaginal tenofovir gel application for Weeks 8 through 13, and oral TDF and vaginal tenofovir gel application for Weeks 15 through 20

Treatment:

Drug: Tenofovir gel

Drug: Tenofovir disoproxil fumarate

2

Experimental group

Description:

Vaginal tenofovir gel application for Weeks 1 through 6, oral TDF for Weeks 8 through 13, and oral TDF and vaginal tenofovir gel application for Weeks 15 through 20

Treatment:

Drug: Tenofovir gel

Drug: Tenofovir disoproxil fumarate

3

Experimental group

Description:

Oral TDF and vaginal tenofovir gel application for Weeks 1 through 6, oral TDF for Weeks 8 through 13, and vaginal tenofovir gel application for Weeks 15 through 20

Treatment:

Drug: Tenofovir gel

Drug: Tenofovir disoproxil fumarate

4

Experimental group

Description:

Oral TDF and vaginal tenofovir gel application for Weeks 1 through 6, vaginal tenofovir gel application for Weeks 8 through 13, and oral TDF for Weeks 15 through 20

Treatment:

Drug: Tenofovir gel

Drug: Tenofovir disoproxil fumarate

5

Experimental group

Description:

Oral TDF for Weeks 1 through 6, oral TDF and vaginal tenofovir gel application for Weeks 8 through 13, and vaginal tenofovir gel application for Weeks 15 through 20

Treatment:

Drug: Tenofovir gel

Drug: Tenofovir disoproxil fumarate

6

Experimental group

Description:

Vaginal tenofovir gel application for Weeks 1 through 6, oral TDF and vaginal tenofovir gel application for Weeks 8 through 13, and oral TDF for Weeks 15 through 20

Treatment:

Drug: Tenofovir gel

Drug: Tenofovir disoproxil fumarate