title: Topical resiquimod 0.01% gel decreases herpes simplex virus type 2 genital shedding: a randomized, controlled trial.
abstract: BACKGROUND
  Resiquimod, an investigational immune response modifier and Toll-like receptor (TLR) 7 and 8 agonist, stimulates production of cytokines that promote an antigen-specific T helper type 1 (Th1)--acquired immune response. In animal models, induction of Th1-specific responses modifies experimental herpes simplex virus (HSV) infection.
  
  
  METHODS
  We conducted a randomized, double-blind, vehicle-controlled trial to assess the efficacy of resiquimod 0.01% gel for reducing human anogenital HSV-2 mucosal reactivation. Adults with genital HSV-2 applied resiquimod or vehicle topically to herpes lesions 2 times weekly for 3 weeks and then collected daily anogenital swabs for 60 days for HSV DNA polymerase chain reaction. Recurrences during the subsequent 7 months were treated with study gel. During the final treatment-free 60 days, participants again collected daily swabs to assess shedding.
  
  
  RESULTS
  The median lesion and shedding rates were lower for resiquimod compared with vehicle recipients during the initial sampling period (10% vs. 16% [P=.03] and 10% vs. 17% [P=.08], respectively) and during the final sampling period (3% vs. 22% [P<.001] and 10% vs. 26% [P=.009], respectively). Resiquimod did not influence recurrence length.
  
  
  CONCLUSIONS
  These findings suggest that the immunological control of HSV-2 reactivation and lesion clearance may differ and that TLR7 and TLR8 agonists can reduce the frequency of mucosal HSV-2 reactivation.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98104, USA. kmark@u.washington.edu
authors.forename: Karen E
authors.initials: KE
authors.lastname: Mark
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Tze-Chiang
authors.initials: TC
authors.lastname: Meng
authors.forename: Amalia S
authors.initials: AS
authors.lastname: Magaret
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.forename: Stacy
authors.initials: S
authors.lastname: Selke
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Slade
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Tyring
authors.forename: Terri
authors.initials: T
authors.lastname: Warren
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Sacks
authors.forename: Peter
authors.initials: P
authors.lastname: Leone
authors.forename: Vicki A
authors.initials: VA
authors.lastname: Bergland
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012008:Recurrence; D016896:Treatment Outcome; D017201:Virus Shedding
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D007093:Imidazoles; C402365:resiquimod