This prospective, randomized, single-blinded, placebo controlled trial will examine the
safety and pharmacokinetics (PK) of a polyurethane tenofovir disoproxil fumarate (TDF)
vaginal ring when used continuously for 14 consecutive days.
The primary objective is to assess the safety of TDF vaginal rings when used continuously
for 14 days by healthy, HIV-uninfected, sexually abstinent women, as compared with a placebo
- General good health (by volunteer history and per investigator discretion) without
any clinically significant systemic disease (including, but not limited to
significant liver disease/hepatitis, gastrointestinal disease, kidney disease,
thyroid disease, osteoporosis or bone disease, and diabetes)
- Willing to give voluntary consent, sign an informed consent form and comply with
study procedures as required by the protocol
- HIV-uninfected based on testing performed by study staff during screening procedures
- Using low dose combined (estrogen and progesterone-containing) oral contraceptive
pills (does not include extended-cycle, 24 and 28-day active pill regimens). Per
participant report must be using this contraceptive method with no change in the
prior 3 months and intending to use same method for the duration of study
- Currently have a regular 28-day menstrual cycle on combined oral contraceptive pills.
- Normal Pap test at screening or appropriately documented history of Pap test and
completed follow-up of any abnormal pap tests consistent with American Congress of
Obstetricians and Gynecologists (ACOG) practice guidelines #99 and #109.
- Agrees not to participate in other research studies involving drugs, medical devices,
or vaginal products for the duration of study participation.
- Able and willing to refrain from inserting any non-study vaginal products or objects
into the vagina for the 48 hours prior to Visit 2 throughout the duration of the
- Able and willing to abstain from oral, vaginal and anal sex for 48 hours prior to
Visit 2 throughout the duration of the study.
Women must meet none of the following criteria prior to genital sampling at Visit 2:
- Known adverse reaction to polyurethane or to any components of the study product or
allergy to both silver nitrate and Monsel's solution.
- Hepatitis B infection (defined as positive hepatitis B surface antigen).
- Chronic, recurrent, and/or acute vulvar or vaginal symptoms (pain, irritation,
- Known bleeding disorder that could lead to prolonged or continuous bleeding with
- Pregnant or intending to become pregnant during the period of study participation.
- Currently breastfeeding or having breastfed an infant in the last two months, or
planning to breastfeed during the course of the study.
- History of unexplained or unresolved intermenstrual bleeding in the 3 months prior to
- History of gynecological procedures (including genital piercing) on the external
genitalia, vagina or cervix in the last 14 days.
- Use and/or anticipated use during the study period of an intravaginal or intrauterine
- Systemic use in the last 2 weeks or anticipated use during the study period of any of
the following: corticosteroids, antibiotics, antifungals, antivirals, anticoagulants
- Grade 1 or higher laboratory abnormality, per the August 2009 update of the Division
of AIDS, National Institute of Allergy and Infectious Disease (DAIDS) Table for
Grading the Severity of Adverse Events (AEs).
- In the last six months, diagnosed with or treated for any sexually transmitted
- Reproductive tract infection (RTI) or pelvic inflammatory disease (PID) requiring
treatment per current CDC guidelines at Screening or Enrollment.
- Positive test for Trichomonas vaginalis, Neisseria gonorrhea or Chlamydia trachomatis
- Reactive test for syphilis at screening.
- At Screening or Enrollment, has a clinically apparent Grade 1 or higher pelvic exam
finding (observed by study clinician or designee) per the Division of AIDS Table for
Grading the Severity of Adult and Pediatric Adverse Events, Addendum 1, Female
Genital Grading Table for Use in Microbicide Studies.