Safety and Acceptability of a Vaginal Microbicide

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH)

The purpose of this study is to determine the safety and acceptability of a vaginal microbicide in HIV uninfected sexually active women. Study hypothesis: The vaginal microbicide 1% tenofovir will be safe and well tolerated in HIV uninfected women who are in good general health.

While the male condom is effective in preventing sexual transmission of HIV, its use is hampered by deeply rooted cultural and social barriers. About half of all HIV infections worldwide occur in women, yet the only available female-controlled method of HIV prevention is the female condom. Alternative prevention tools, such as vaginal microbicides, are urgently needed to slow the rapid spread of heterosexual HIV infection. This study will last 24 weeks, with an additional 10 weeks of follow-up for participants with chronic hepatitis B virus (HBV) infection. Participants will be randomly assigned to one of four arms. Arm A participants will insert a vaginal tenofovir 1% gel two hours prior to vaginal intercourse for a maximum of two daily applications. Arm B participants will insert a vaginal placebo gel two hours prior to vaginal intercourse for a maximum of two daily applications. Arm C participants will insert a vaginal tenofovir 1% gel once daily at bedtime or during the longest period of daily rest. Arm D participants will insert a vaginal placebo gel once daily at bedtime or during the longest period of daily rest. A medical and menstrual history update, pregnancy test, HIV and sexually transmitted infections (STI) risk reduction counseling, and interview to assess behaviors toward vaginal gel use will occur during all study visits. HIV/STI counseling and testing, urinalysis, and blood collection will occur at study entry and at Week 24. Pelvic exam with colposcopy and vaginal swab collection will occur at study entry and Weeks 4, 12, and 24. For participants with chronic HBV, additional blood will be collected to monitor hepatitis B infection at study entry and Weeks 12, 24, 28, 32, and 36.

Anti-Infective Agents, Local, HIV Seronegativity, Tenofovir, Vaginal gel, Microbicide, Vaginal Microbicide, PMPA

Macroscopic evidence of damage to the cervical, vulvar, or vaginal epithelium, including ulceration and other lesions, severe erythema, or severe edema, related or not related to the study gel or applicator

Inclusion Criteria: HIV uninfected Good general health Sexually active Willing to use acceptable methods of contraception, including male latex condoms for all acts of intercourse Willing to undergo all study-related assessments and adhere to the requirements of the study Exclusion Criteria: Menopausal or postmenopausal Hysterectomy Abnormal screening results for several gynecologic exams Taking or planning to take tenofovir, adefovir, or any other medication for chronic HBV infection History of latex allergy History of adverse reaction to tenofovir or adefovir Use of a diaphragm or spermicide for contraception Prior participation in the study Prior participation in any vaginal microbicide, spermicide, or other drug study within 30 days of study entry Gynecologic surgical procedure within 90 days of study entry Illicit injection drug use within 12 months of study entry History of vaginal intercourse more than an average of two times per day in the two weeks prior to study screening Any other criteria that, in the investigator's opinion, may interfere with the study Current pregnancy or previous pregnancy within 90 days of study entry Breastfeeding

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