Safety and Effectiveness of TFV 1% Gel, TDF Tablets, and FTC/TDF Tablets in Preventing HIV in Women

Phase 2B Safety and Effectiveness Study of Tenofovir 1% Gel, Tenofovir Disproxil Fumarate Tablet and Emtricitabine/Tenofovir Disoproxil Fumarate Tablet for the Prevention of HIV Infection in Women

A new approach to HIV prevention currently being studied includes the use of microbicides, substances that kill microbes. Tenofovir disoproxil fumarate (TDF) and emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) are oral, FDA-approved, anti-HIV drugs, and tenofovir gel is an experimental microbicide. The purpose of this study is to determine the safety and effectiveness of daily tenofovir 1% gel compared to a vaginal placebo gel, and the safety and effectiveness of oral TDF and oral FTC/TDF compared to an oral placebo in preventing HIV infection among women at risk for sexually transmitted infections.

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 anti-HIV drugs (TDF, FTC/TDF), this study will measure the effectiveness and safety to and blood levels of the three interventions in three regimens given to HIV uninfected women.

The expected duration of participation for each participant ranges from a minimum of 12 months to a maximum of 38 months. Study participants will be randomly assigned into one of five study groups, each with a different regimen. Group 1 participants will take one TDF tablet daily and one FTC/TDF placebo tablet daily. Group 2 participants will take one TDF placebo tablet daily and one FTC/TDF tablet daily. Group 3 participants will take one TDF placebo tablet daily and one FTC/TDF placebo tablet daily. Group 4 participants will apply tenofovir 1% gel vaginally once daily. Group 5 participants will apply tenofovir 1% placebo gel vaginally once daily.

Study visits will occur every 28 days after enrollment. Medical history, a physical exam, behavioral and adherence assessment, urine and blood collection, and counseling will occur at all visits. Blood will also be collected and archived for future research at select visits. Pharmacokinetic studies will occur at some visits. A pap smear will occur at select visits. Some participants may have hair samples collected on an optional basis at study visits every 2 months.

Inclusion Criteria:

• Willing to provide adequate locator information
• Sexually active, defined as having vaginal intercourse at least once in the 3 months prior to screening
• Agree to not participate in other research studies involving drugs, medical devices, or vaginal products for duration of study.
• Agree to use effective method of contraception. More information on this criterion can be found in the protocol.

Exclusion Criteria:

• HIV infected
• Known adverse reaction to any of the study products
• Known adverse reaction to latex
• Pathologic bone fracture not related to trauma
• Non-therapeutic injection drug use in the 12 months prior to screening
• Post-exposure prophylaxis for HIV exposure within 6 months prior to enrollment
• Last pregnancy outcome 42 days or less prior to enrollment
• Gynecologic or genital procedure 42 days or less prior to enrollment
• Participation in any other research study involving drugs, medical devices, or vaginal products 30 days or less prior to enrollment
• Currently using spermicide, interferon or interleukin therapy, or certain medications. More information on this criterion can be found in the protocol.
• Any significant uncontrolled active or chronic disease. More information on this criterion can be found in the protocol.
• Certain abnormal laboratory values. More information on this criterion can be found in the protocol.
• Intends to become pregnant in the 24 months after enrollment
• Plans to relocate or travel away from the study site for more than 8 consecutive weeks in the 24 months after enrollment
• Urinary tract infection
• Pelvic inflammatory disease, an STI, or reproductive tract infection requiring treatment
• Grade 2 or higher pelvic exam finding
• Any condition that, in the opinion of the investigator, would interfere with the study
• Pregnant or breastfeeding