title: Topical tenofovir protects against vaginal simian HIV infection in macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis.
abstract: Chlamydia trachomatis and Trichomonas vaginalis, two prevalent sexually transmitted infections, are known to increase HIV risk in women and could potentially diminish preexposure prophylaxis efficacy, particularly for topical interventions that rely on local protection. We investigated in macaques whether coinfection with Chlamydia trachomatis/Trichomonas vaginalis reduces protection by vaginal tenofovir (TFV) gel.
  
  
  
  Vaginal TFV gel dosing previously shown to provide 100 or 74% protection when applied either 30 min or 3 days before simian HIV(SHIV) challenge was assessed in pigtailed macaques coinfected with Chlamydia trachomatis/Trichomonas vaginalis and challenged twice weekly with SHIV162p3 for up to 10 weeks (two menstrual cycles). Three groups of six macaques received either placebo or 1% TFV gel 30 min or 3 days before each SHIV challenge. We additionally assessed TFV and TFV diphosphate concentrations in plasma and vaginal tissues in Chlamydia trachomatis/Trichomonas vaginalis coinfected (n = 4) and uninfected (n = 4) macaques.
  
  
  
  Chlamydia trachomatis/Trichomonas vaginalis coinfections were maintained during the SHIV challenge period. All macaques that received placebo gel were SHIV infected after a median of seven challenges (one menstrual cycle). In contrast, no infections were observed in macaques treated with TFV gel 30 min before SHIV challenge (P < 0.001). Efficacy was reduced to 60% when TFV gel was applied 3 days before SHIV challenge (P = 0.07). Plasma TFV and TFV diphosphate concentrations in tissues and vaginal lymphocytes were significantly higher in Chlamydia trachomatis/Trichomonas vaginalis coinfected compared with Chlamydia trachomatis/Trichomonas vaginalis uninfected macaques.
  
  
  
  Our findings in this model suggest that Chlamydia trachomatis/Trichomonas vaginalis coinfection may have little or no impact on the efficacy of highly effective topical TFV modalities and highlight a significant modulation of TFV pharmacokinetics.
authors.affiliation: aLaboratory Branch, Division of HIV/AIDS Prevention bDivision of Sexually Transmitted Disease Prevention, Centers of Disease Control and Prevention (CDC) Atlanta, Georgia cTotal Solutions, Inc., Madison, Alabama, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Makarova
authors.forename: Tara
authors.initials: T
authors.lastname: Henning
authors.forename: Andrew
authors.initials: A
authors.lastname: Taylor
authors.forename: Chuong
authors.initials: C
authors.lastname: Dinh
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lipscomb
authors.forename: Rachael
authors.initials: R
authors.lastname: Aubert
authors.forename: Debra
authors.initials: D
authors.lastname: Hanson
authors.forename: Christi
authors.initials: C
authors.lastname: Phillips
authors.forename: John
authors.initials: J
authors.lastname: Papp
authors.forename: James
authors.initials: J
authors.lastname: Mitchell
authors.forename: Janet
authors.initials: J
authors.lastname: McNicholl
authors.forename: Gerardo J
authors.initials: GJ
authors.lastname: Garcia-Lerma
authors.forename: Walid
authors.initials: W
authors.lastname: Heneine
authors.forename: Ellen
authors.initials: E
authors.lastname: Kersh
authors.forename: Charles
authors.initials: C
authors.lastname: Dobard
mesh_terms: D000287:Administration, Topical; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D002690:Chlamydia Infections / Q000150:complications*; D060085:Coinfection / Q000150:complications*; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D005260:Female; D008251:Macaca; D010919:Placebos / Q000008:administration & dosage; D010949:Plasma / Q000737:chemistry; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000068698:Tenofovir / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D014247:Trichomonas Vaginitis / Q000150:complications*; D014621:Vagina / Q000737:chemistry; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage
chemical_list: D019380:Anti-HIV Agents; D010919:Placebos; D014622:Vaginal Creams, Foams, and Jellies; D000068698:Tenofovir