title: Oral and Vaginal Tenofovir for Genital Herpes Simplex Virus Type 2 Shedding in Immunocompetent Women: A Double-Blind, Randomized, Cross-over Trial.
abstract: BACKGROUND
  Tenofovir is a potent anti-human immunodeficiency virus (HIV) agent that decreased risk of herpes simplex virus type 2 (HSV-2) acquisition in HIV pre-exposure prophylaxis trials. Whether tenofovir has utility in established HSV-2 disease is unclear.
  
  
  METHODS
  We randomized immunocompetent women with symptomatic HSV-2 infection to oral tenofovir disoproxil fumarate (TDF)/placebo vaginal gel, oral placebo/tenofovir (TFV) vaginal gel, or double placebo (ratio 2:2:1) in a one-way cross-over trial. Women collected genital swabs twice daily for HSV PCR during 4-week lead-in and 5-week treatment phases. The primary intent-to-treat end point was within-person comparison of genital HSV shedding and lesion rates.
  
  
  RESULTS
  64 women completed the lead-in phase and were randomized. Neither TDF nor TFV gel decreased overall shedding or lesion rate in the primary analysis; TFV gel decreased quantity of HSV DNA by -0.50 (-0.86-0.13) log10 copies/mL. In the per-protocol analysis, TDF reduced shedding (relative risk [RR] = 0.74, P = .006) and lesion rates (RR = 0.75, P = .032); quantity of virus shed decreased by 0.41 log10 copies/mL.
  
  
  CONCLUSIONS
  Oral TDF modestly decreased HSV shedding and lesion rate, and quantity of virus shed when used consistently. Vaginal TFV gel decreased quantity of virus shed by 60%. In contrast to effects on HSV-2 acquisition, tenofovir is unlikely to provide clinically meaningful reductions in the frequency of HSV shedding or genital lesions.
  
  
  BACKGROUND
  NCT01448616.
authors.affiliation: Division of Allergy and Infectious Diseases, Department of Medicine Department of Medicine Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Bender Ignacio
authors.affiliation: Division of Allergy and Infectious Diseases, Department of Medicine Department of Medicine.
authors.forename: Tara
authors.initials: T
authors.lastname: Perti
authors.affiliation: Department of Laboratory Medicine Department of Biostatistics Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Amalia S
authors.initials: AS
authors.lastname: Magaret
authors.affiliation: Department of Epidemiology, University of Washington Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Sharanya
authors.initials: S
authors.lastname: Rajagopal
authors.affiliation: Department of Medicine.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Stevens
authors.affiliation: Department of Laboratory Medicine Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine.
authors.forename: Stacy
authors.initials: S
authors.lastname: Selke
authors.affiliation: Division of Allergy and Infectious Diseases, Department of Medicine Department of Medicine Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Christine
authors.initials: C
authors.lastname: Johnston
authors.affiliation: Division of Allergy and Infectious Diseases, Department of Medicine Department of Medicine.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Marrazzo
authors.affiliation: Division of Allergy and Infectious Diseases, Department of Medicine Department of Medicine Department of Laboratory Medicine Department of Epidemiology, University of Washington Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
mesh_terms: D000282:Administration, Intravaginal; D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000473:pathology; D018258:Herpesvirus 2, Human / Q000302:isolation & purification*; D006801:Humans; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D000068698:Tenofovir / Q000627:therapeutic use*; D016896:Treatment Outcome; D017201:Virus Shedding
chemical_list: D000998:Antiviral Agents; D010919:Placebos; D000068698:Tenofovir
keywords: HIV acquisition; HSV-2 transmission; genital herpes; herpes simplex virus-2 (HSV-2); tenofovir; vaginal microbicide