Effect of Tenofovir on Genital Herpes Simplex Virus (HSV) Shedding
Condition: Herpes Simplex Type II
MeSH terms: Herpes Simplex
Intervention: TDF; Placebo Vaginal Gel; Vaginal TFV Gel; Placebo Tablets
Intervention description: Oral tenofovir will be administered as tablets. TDF (Viread®) tablets contain 300 mg of tenofovir disoproxil fumarate, which is equivalent to 245 mg of tenofovir disoproxil. Study participants are instructed to take the one tablet, by mouth, once each day without regard to meals.; Study participants are instructed to insert one dose (the entire contents of one applicator) of product into the vagina once each day. They are instructed to insert their gel as close to the same time each day as possible.
The placebo gel (known as the 'universal' placebo gel) is formulated to minimize any possible effects - negative or positive - on study endpoints.; Tenofovir 1% gel (w/w) is a gel formulation of tenofovir. Study participants are instructed to insert one dose (the entire contents of one applicator) of product into the vagina once each day. They are instructed to insert their gel as close to the same time each day as possible.; TDF placebo tablets are film-coated and contain denatonium benzoate, a bittering agent, in addition to other inactive ingredients. Study participants are instructed to take the one tablet, by mouth, once each day without regard to meals.
Intervention MeSH terms: Tenofovir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 73.0
Sex: Female
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      The investigators propose a randomized, double blind, placebo-controlled, cross-over trial to
      evaluate the effect of oral and topical (vaginal gel) tenofovir on genital herpes simplex
      virus (HSV) shedding among herpes simplex virus type-2 (HSV-2) seropositive, human
      immunodeficiency virus (HIV) seronegative women. The investigators hypothesize that tenofovir
      will reduce genital HSV shedding compared to placebo.
    

Eligibility criteria:

        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.