Clinical trial NCT01448616: Effect of Tenofovir on Genital Herpes Simplex Virus (HSV) Shedding
Official title: Effect of Tenofovir on Genital HSV Shedding: a Randomized, Double-blind, Placebo-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Herpes Simplex Type II
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: CONRAD
name: Gilead Sciences
First posted: 2011-10-07
Enrollment: 73
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

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.

Primary outcomes:
measure: HSV Shedding Rate in Those Receiving Oral TDF, Vaginal TFV, or Double Placebo
timeFrame: Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase
Secondary outcomes:
measure: Within-person Changes in Log-copy Numbers of HSV
timeFrame: Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase
measure: Genital Lesion Rate
timeFrame: Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase
measure: Asymptomatic Shedding (Shedding on Days Without Genital Lesions)
timeFrame: Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington Virology Research Clinic
state: Washington
Study officials:
affiliation: University of Washington
name: Anna Wald, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Johnston C, Harrington R, Jain R, Schiffer J, Kiem HP, Woolfrey A. Safety and Efficacy of Combination Antiretroviral Therapy in Human Immunodeficiency Virus-Infected Adults Undergoing Autologous or Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies. Biol Blood Marrow Transplant. 2016 Jan;22(1):149-56. doi: 10.1016/j.bbmt.2015.08.006. Epub 2015 Aug 8.
citation: Bender Ignacio RA, Perti T, Magaret AS, Rajagopal S, Stevens CE, Huang ML, Selke S, Johnston C, Marrazzo J, Wald A. Oral and Vaginal Tenofovir for Genital Herpes Simplex Virus Type 2 Shedding in Immunocompetent Women: A Double-Blind, Randomized, Cross-over Trial. J Infect Dis. 2015 Dec 15;212(12):1949-56. doi: 10.1093/infdis/jiv317. Epub 2015 Jun 4.