Safety, Pharmacokinetics, Pharmacodynamics, and Disintegration Time of Vaginal Tablets Containing Tenofovir and/or Emtricitabine

Objectives:

Primary:

- To assess genital safety after a single use (consisting of one tablet in half of
participants and one tablet followed by a second tablet two hours later in the other
half) and during and after two weeks of daily tablet use

- To assess systemic safety after two weeks of daily tablet use

- To assess the pharmacokinetics (PK) of TFV and FTC after a single use (as defined
above) and during and after two weeks of daily tablet use

Secondary:

- To estimate the time needed for tablet disintegration and the time needed for full
tablet disappearance

- To assess acceptability of the tablet

- To assess indicators of the pharmacodynamics (PD) of TFV and FTC in vitro using
biological samples (fluids) from study participants obtained before use, after a single
(use as define above), and after two weeks of daily tablet use

Inclusion Criteria:

- 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)

- Currently having regular menstrual cycles of 25 - 35 days by participant report

- History of Pap smears and follow-up consistent with American Congress of
Obstetricians and Gynecologist (ACOG) practice guidelines #99 and #109 or willing to
undergo a Pap smear at Visit 1

- Protected from pregnancy

- Willing to abstain from vaginal activity as follows:

Starting 48 hours before Visit 2 until the sixth day after Visit 2 Starting 48 hours
before Visit 3 until the sixth day after Visit 3 Starting 48 hours before Visit 4 until
the sixth day after Visit 6

- Willing to abstain from the use of any vaginal product other than the study product
including spermicides, lubricants, and douches starting 48 hours before Visit 2 until
the sixth day after Visit 6 (tampons may be used, but for menses only)

- Vaginal and cervical anatomy that, in the opinion of the investigator, lends itself
to easy colposcopy and genital tract sample collection

- Negative urine pregnancy test

- Willing to give voluntary consent, sign an informed consent form and comply with
study procedures as required by the protocol

Exclusion Criteria:

- History of hysterectomy

- Currently pregnant or within two calendar months from the last pregnancy outcome.
Note: If recently pregnant must have had at least two spontaneous menses since
pregnancy outcome

- Use of any hormonal contraceptive method in the last 30 days (oral, transdermal,
transvaginal, implant, or hormonal intrauterine contraceptive device)

- Injection of Depo-Provera in the last 6 months

- Current use of IUD

- Currently breastfeeding or having breastfed an infant in the last two months, or
planning to breastfeed during the course of the study

- History of sensitivity/allergy to any component of the study products, topical
anesthetic, or allergy to both silver nitrate and Monsel's solution

- In the last six months, diagnosed with or treated for any STI or pelvic inflammatory
disease. Note: Women with a history of genital herpes or condylomata who have been
asymptomatic for at least six months may be considered for eligibility

- Nugent score greater than or equal to 7 at Visit 1 or symptomatic bacterial vaginosis
(BV) as defined by Amsel's criteria at Visit 1 or 2

- Symptomatic vulvovaginal candidiasis or symptomatic urinary tract infection (UTI)

- Positive test for Trichomonas vaginalis, Neisseria gonorrhea or Chlamydia trachomatis

- Deep epithelial genital findings such as abrasions, ulcerations, and lacerations, or
vesicles suspicious for an STI

- Positive test for HIV

- Positive test for Hepatitis B surface antigen (HBsAg)

- Known bleeding disorder that could lead to prolonged or continuous bleeding with
biopsy

- Chronic or acute vulvar or vaginal symptoms (pain, irritation, spotting, etc.)

- Known current drug or alcohol abuse which could impact study compliance

- 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)

- Systemic use in the last two weeks or anticipated use during the study of any of the
following: corticosteroids, antibiotics, antifungals, antivirals (e.g., acyclovir or
valacyclovir) or antiretrovirals (e.g., Viread, Atripla, Emtriva, Complera). Note:
Participants should avoid non-steroidal anti-inflammatory drugs (NSAIDs) except for
treatment of dysmenorrhea during menses. Participants may use Tylenol® on an
as-needed but not daily basis during the study.

- Participation in any other investigational trial (device, drug, or vaginal trial)
within the last 30 days or planned participation in any other investigational trial
during the study

- History of gynecological procedures (including genital piercing) on the external
genitalia, vagina or cervix within the last 14 days

- Abnormal finding on laboratory or physical examination or a social or medical
condition which, in the opinion of the investigator, would make participation in the
study unsafe or would complicate interpretation of data