Effect of Tenofovir on Genital Herpes Simplex Virus (HSV) Shedding

The investigators propose a randomized, double-blind, placebo-controlled, cross-over study
of 55 adult, healthy women who are HSV-2 seropositive and HIV-1 seronegative. Women will
first participate in a run-in phase with twice daily swabbing. Following 4 weeks of
swabbing, participants will be randomized 2:2:1 to one of three groups: 1) oral tenofovir
and placebo gel, 2) oral placebo and tenofovir gel, or 3) oral placebo and placebo gel.
Participants will begin treatment and swab the genital region twice daily for 5 more weeks.
Study drug will be administered daily.

Inclusion Criteria:

- Women age 18-50

- HSV-2 seropositive by the University of Washington (UW) Western blot

- History of recurrent genital herpes, with more than 4 recurrences but less than 10 in
the last year or, if currently on suppressive therapy, with more than 4 recurrences
but less than 10 in the year prior to starting suppressive therapy

- HIV negative

- General good health

- Willing to not use antiviral therapy (other than the study drug) for the duration of
the study

- Willing to obtain a swab from genital secretions twice daily for the duration of the
study

- Willing to use effective birth control

- Able to provide written informed consent at screening and enrollment

Exclusion Criteria:

- HIV positive or at high risk for HIV acquisition (intravenous drug user or HIV+ sex
partner)

- Hepatitis B (HepB) antigen (Ag) positive, or at high risk for HepB acquisition and
not vaccinated

- Have a history of adverse reaction to tenofovir and/or adefovir

- Immunosuppressive medications, except for intranasal or topical (not high potency)
steroids.

- Any kidney disease, or renal insufficiency, defined as serum creatinine >1.5 mg/dl.
Participants with a prior history of a single episode of pyelonephritis will be
eligible.

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times upper
limit of normal

- Pregnancy, as confirmed by a urine pregnancy test, planning to become pregnant during
the course of the trial, or breast-feeding.

- Serious medical conditions or active infections

- Any other conditions that in the judgment of the investigator would preclude
successful completion of the clinical trial.