title: SPL7013 Gel (VivaGel®) retains potent HIV-1 and HSV-2 inhibitory activity following vaginal administration in humans.
abstract: SPL7013 Gel (VivaGel(®)) is a microbicide in development for prevention of HIV and HSV. This clinical study assessed retention and duration of antiviral activity following vaginal administration of 3% SPL7013 Gel in healthy women. Participants received 5 single doses of product with ≥5 days between doses. A cervicovaginal fluid (CVF) sample was collected using a SoftCup™ pre-dose, and immediately, or 1, 3, 12 or 24 h post-dose. HIV-1 and HSV-2 antiviral activities of CVF samples were determined in cell culture assays. Antiviral activity in the presence of seminal plasma was also tested. Mass and concentration of SPL7013 in CVF samples was determined. Safety was assessed by reporting of adverse events. Statistical analysis was performed using the Wilcoxon signed-rank test with Bonferroni adjustment; p≤0.003 was significant. Eleven participants completed the study. Inhibition of HIV-1 and HSV-2 by pre-dose CVF samples was negligible. CVF samples obtained immediately after dosing almost completely inhibited (median, interquartile range) HIV-1 [96% (95,97)] and HSV-2 [86% (85,94)], and activity was maintained in all women at 3 h (HIV-1 [96% (95,98), p = 0.9]; HSV-2 [94% (91,97), p = 0.005]). At 24 h, >90% of initial HIV-1 and HSV-2 inhibition was maintained in 6/11 women. SPL7013 was recovered in CVF samples obtained at baseline (46% of 105 mg dose). At 3 and 24 h, 22 mg and 4 mg SPL7013, respectively, were recovered. More than 70% inhibition of HIV-1 and HSV-2 was observed if there was >0.5 mg SPL7013 in CVF samples. High levels of antiviral activity were retained in the presence of seminal plasma. VivaGel was well tolerated with no signs or symptoms of vaginal, vulvar or cervical irritation reported. Potent antiviral activity was observed against HIV-1 and HSV-2 immediately following vaginal administration of VivaGel, with activity maintained for at least 3 h post-dose. The data provide evidence of antiviral activity in a clinical setting, and suggest VivaGel could be administered up to 3 h before coitus.
  
  
  BACKGROUND
  The study is registered at ClinicalTrials.gov under identifier: NCT00740584.
authors.affiliation: Starpharma Pty Ltd, Melbourne, Victoria, Australia. clare.price@starpharma.com
authors.forename: Clare F
authors.initials: CF
authors.lastname: Price
authors.forename: David
authors.initials: D
authors.lastname: Tyssen
authors.forename: Secondo
authors.initials: S
authors.lastname: Sonza
authors.forename: Ashley
authors.initials: A
authors.lastname: Davie
authors.forename: Sonya
authors.initials: S
authors.lastname: Evans
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Lewis
authors.forename: Shirley
authors.initials: S
authors.lastname: Xia
authors.forename: Tim
authors.initials: T
authors.lastname: Spelman
authors.forename: Peter
authors.initials: P
authors.lastname: Hodsman
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Moench
authors.forename: Andrew
authors.initials: A
authors.lastname: Humberstone
authors.forename: Jeremy R A
authors.initials: JR
authors.lastname: Paull
authors.forename: Gilda
authors.initials: G
authors.lastname: Tachedjian
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D018592:Cross-Over Studies; D050091:Dendrimers / Q000737:chemistry*; D005260:Female; D005782:Gels / Q000737:chemistry*; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D018258:Herpesvirus 2, Human / Q000378:metabolism*; D006801:Humans; D010919:Placebos; D011107:Polylysine / Q000737:chemistry*; D013997:Time Factors; D014621:Vagina / Q000473:pathology
chemical_list: D000890:Anti-Infective Agents; D000998:Antiviral Agents; D050091:Dendrimers; D005782:Gels; D010919:Placebos; D011107:Polylysine; C480351:astodrimer