title: Postcoital bioavailability and antiviral activity of 0.5% PRO 2000 gel: implications for future microbicide clinical trials.
abstract: BACKGROUND
  The pharmacokinetics and pharmacodynamics of vaginal microbicides are typically assessed among sexually abstinent women. However, the physical act of sex may modulate gel distribution, and preclinical studies demonstrate seminal plasma interferes with the antiviral activity of several microbicides. This study compared the biological activity and concentration of PRO 2000 in cervicovaginal lavage (CVL) collected in the absence or following coitus.
  
  
  METHODS
  CVL samples were collected from ten heterosexual couples at baseline, after sex, after a single dose of 0.5% PRO 2000 gel and sex, and after gel application without sex. The impact of CVL on HIV-1 infection of TZM-bl cells and HSV-2 infection of CaSki cells was monitored by luciferase and plaque assay, respectively. PRO 2000 concentrations were measured by fluorescence.
  
  
  RESULTS
  CVL collected after PRO 2000 application significantly inhibited HIV-1 and HSV-2 (p = 0.01). However, the antiviral activity was reduced following sex and no significant protective effect was observed in postcoital CVL obtained in the presence compared to the absence of PRO 2000 for HIV (p = 0.45) or HSV-2 (p = 0.56). Less PRO 2000 was recovered in postcoital CVL, which, in conjunction with interference by seminal plasma, may have contributed to lower antiviral activity.
  
  
  CONCLUSIONS
  Postcoital responses to PRO 2000 differ from precoital measures and the results obtained may provide insights into the clinical trial findings in which there was no significant protection against HIV-1 or HSV-2. Postcoital studies should be incorporated into clinical studies before embarking on large-scale efficacy trials.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Marla J
authors.initials: MJ
authors.lastname: Keller
authors.forename: Pedro M M
authors.initials: PM
authors.lastname: Mesquita
authors.forename: N Merna
authors.initials: NM
authors.lastname: Torres
authors.forename: Sylvia
authors.initials: S
authors.lastname: Cho
authors.forename: Gail
authors.initials: G
authors.lastname: Shust
authors.forename: Rebecca P
authors.initials: RP
authors.lastname: Madan
authors.forename: Hillel W
authors.initials: HW
authors.lastname: Cohen
authors.forename: Julie
authors.initials: J
authors.lastname: Petrie
authors.forename: Tara
authors.initials: T
authors.lastname: Ford
authors.forename: Lydia
authors.initials: L
authors.lastname: Soto-Torres
authors.forename: Albert T
authors.initials: AT
authors.lastname: Profy
authors.forename: Betsy C
authors.initials: BC
authors.lastname: Herold
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D002986:Clinical Trials as Topic; D003075:Coitus; D005782:Gels; D015497:HIV-1 / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans
chemical_list: D000998:Antiviral Agents; D005782:Gels