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

Phase 4

Completed

• Conditions: Herpes Simplex Type II
• Interventions: Drug: TDF; Drug: Vaginal TFV Gel; Drug: Placebo Vaginal Gel; Drug: Placebo Tablets

• Registration Number: NCT01448616
• Lead Sponsor: University of Washington

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.

Study Timeline

• Study First Submitted: 2011-09-14
• Study First Submitted QC: 2011-10-06
• Study First Posted: 2011-10-07
• Study Start: 2012-02
• Primary Completion: 2015-06
• Study Completion: 2015-06
• Results First Submitted: 2015-08-05
• Results First Submitted QC: 2015-12-02
• Results First Posted: 2016-01-12
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-14
• Last Update Posted: 2023-02-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 73

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Study Drug Phase: TDF	TDF	Participants will take tenofovir disoproxil fumarate (TDF) tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
Study Drug Phase: Vaginal TFV Gel	Vaginal TFV Gel	Participants will take oral placebo tablets and apply a tenofovir 1% (TFV) vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
Study Drug Phase: TDF	Placebo Vaginal Gel	Participants will take tenofovir disoproxil fumarate (TDF) tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
Study Drug Phase: Double Placebo	Placebo Vaginal Gel	Participants will take oral placebo tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
Study Drug Phase: Vaginal TFV Gel	Placebo Tablets	Participants will take oral placebo tablets and apply a tenofovir 1% (TFV) vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.
Study Drug Phase: Double Placebo	Placebo Tablets	Participants will take oral placebo tablets and apply a placebo vaginal gel. Participants will begin treatment and swab the genital region twice daily for 5 more weeks. Study drugs will be administered once daily.

Primary Outcome Measures

Name	Time	Method
HSV Shedding Rate in Those Receiving Oral TDF, Vaginal TFV, or Double Placebo	Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase	The within-person changes in rate of HSV shedding during study drug administration (treatment phase) compared with the rate of HSV shedding during lead-in observation phase in the same participants. We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment. This is analyzed separately for each treatment arm and not compared between arms.

Secondary Outcome Measures

Name	Time	Method
Within-person Changes in Log-copy Numbers of HSV	Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase	The within-person changes in mean log-copy numbers of HSV shed during treatment phase (oral TDF, vaginal TFV, or double placebo) compared with the lead-in (observation) phase in the same participants. Each treatment arm is analyzed separately without comparison between arms.; We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment.
Asymptomatic Shedding (Shedding on Days Without Genital Lesions)	Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase	Within person changes in shedding on days without lesions between the lead-in (observational) phase and the study drug (treatment) phase. Each arm is evaluated separately and no inter arm comparisons are made.; We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment.
Genital Lesion Rate	Comparison of 4 weeks of treatment phase with 4 weeks of lead-in phase	The within person change in proportion of days with lesions between the lead-in (observational) and study drug (treatment) phase for each arm separately. No between arm comparisons were performed. We include intent to treat with all randomized participants as well as per protocol (persons receiving study drug for at least 30 days with 90% or better reported compliance per returned product counts).; We evaluated only weeks 2-5 of HSV shedding during the treatment phase in comparison with the 4 weeks of the lead-in phase. We excluded the first week of samples from the treatment phase in order to allow for physiologic run-in of the treatment.

Trial Locations

Locations (1)

University of Washington Virology Research Clinic; 🇺🇸 Seattle, Washington, United States