Dose Proportionality of TFV-DP After a Single Dose of GS-7340 in Women

Participants:

This study will consist of approximately 24 premenopausal healthy volunteer women between
18-49 years of age with an intact cervix, uterus, and gastrointestinal tract. Women will be
enrolled in the study within 42 days of screening depending on the timing of their menstrual
cycle in comparison to the screening visit, and then will be on study for 14 days, with
follow-up 1-14 days after the end of study sampling. All study visits will be conducted in
the North Carolina Translational and Clinical Sciences (NCTraCS) Clinical Translational
Research Center (CTRC) at the University of North Carolina at Chapel Hill.

Procedures (methods):This is a Phase 1, single center, open-label, dose-ranging
pharmacokinetic study of TFV and TFV-DP mucosal tissue concentrations measured after a
single dose of GS-7340. Each arm is divided into three dosing groups: 5, 10, or 25mg.
Participants will take a single dose of study drug within 7-14 days following the end of the
subjects' menstrual period. Participants will be sequentially assigned to one of the three
TAF doses and four biopsy schedules. Two women from each of the dosing groups will be
assigned to one of four biopsy schedules for a total of 8 women per dosing group. Samples of
blood plasma, cervicovaginal fluid (CVF), cervical tissue, vaginal tissue, and rectal tissue
will be collected from participants at varying time points over the 14 days post-dose.
Subjects will return to clinic within 14 days after the last sampling to complete a
follow-up safety visit.

Inclusion Criteria

1. Healthy pre-menopausal female subjects between the ages of 18 and 49 years, inclusive
on the date of screening, with an intact gastrointestinal tract, uterus, and cervix.

2. All subjects must have an estimated calculated creatinine clearance (eCcr) of at
least 80 mL/min

3. All subjects must have negative pregnancy tests, and be using an acceptable form of
birth control

4. Body Mass Index (BMI) of approximately 18 to 34 kg/m²; and a total body weight > 45
kg (99 lbs).

5. Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the trial.

6. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other trial procedures.

7. Subject must have documentation of a normal pap smear within 36 months of the
screening visit, no procedures for abnormal cervical/vaginal pathology in the last
six months, at least one prior gynecological visit as part of subject's routine
medical history.

8. Subject must be willing to abstain from sexual intercourse, douching, and all
intravaginal and intrarectal objects and products for at least 72 hours prior to Day
1 until study completion.

9. Subject must be HIV-1 and Hepatitis B surface antigen negative

10. Subject must not be actively involved in the conception process.

11. Subject must be able to swallow pills and have no allergies to any component of the
study products

Exclusion Criteria

1. Evidence or history of clinically significant hematological, renal, endocrine,
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or
allergic disease (including documented drug allergies, but excluding untreated,
asymptomatic, seasonal allergies at time of dosing).

2. Subjects with a history of hysterectomy

3. Subjects who are pregnant, possibly pregnant or lactating

4. Subjects with a presence of vaginal discharge or genital bleeding at screening

5. History of febrile illness within five days prior to first dose.

6. Any condition possibly affecting drug absorption (eg, gastrectomy).

7. A positive urine drug screen.

8. A positive result for HIV, Hepatitis B or C

9. An untreated-positive test for syphilis, gonorrhea, Chlamydia, or trichomonas at
screening, or symptomatic bacterial vaginosis.

10. Any laboratory chemistry or hematology result Grade 2 or greater according to the
Division of Acquired Immunodeficiency Syndrome (DAIDS) Laboratory Grading Tables

11. Treatment with an investigational drug within 4 months preceding the first dose of
trial medication.

12. History of regular alcohol consumption exceeding study limits

13. Participation in a clinical trial involving vaginal or rectal biopsies within 6
months preceding the first dose of trial medication.

14. Use of prescription or nonprescription drugs, vitamins, and dietary supplements
within 7 days or 5 half-lives (whichever is longer) prior to the first dose of trial
medication and unable to avoid use during the study period until after the last
sample is collected.

15. Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing.

16. History of sensitivity to heparin or heparin-induced thrombocytopenia.

17. Allergy to lidocaine or Monsel's solution.

18. Allergy to latex.

19. Abnormal pap smear in the past 36 months

20. Any degree of ectopy or abnormality evident during the pelvic exam at screening.

21. Any condition which, in the opinion of the investigator, is likely to interfere with
follow-up or ability to take the study medication appropriately.

22. Unwilling or unable to comply with the dietary and concomitant drug restrictions in
regard to study drug administration as outlined in the study procedures and
prohibited medications sections.