title: HIV-1 infection of female genital tract tissue for use in prevention studies.
abstract: OBJECTIVE
  Ex vivo HIV-1 challenge has been proposed as a bioindicator of microbicide product effectiveness. The objective of this study was to establish optimal parameters for use of female genital tract tissue in this model.
  
  
  METHODS
  Ex vivo challenge involves in vivo product use, followed by tissue biopsy, and exposure of the tissue to HIV-1 in the laboratory.
  
  
  METHODS
  Paired ectocervical and vaginal biopsies were collected from 42 women, and 28 women had additional biopsies from each site collected after 5% lidocaine (n = 14) or chlorhexidine (n = 14) treatment. Tissues were transported immediately to the laboratory and exposed to HIV-1. HIV-1 infection was followed by p24 enzyme-linked immunosorbent assay on culture supernatants and at study end after weighing and fixing the tissue for immunohistochemistry to detect p24 expressing cells.
  
  
  RESULTS
  Although both tissue types were equally infected with HIV-1 based on the immunohistochemistry results, ectocervical tissues had significantly higher HIV-1 replication than vaginal tissues (P < 0.005). Lidocaine and chlorhexidine had minimal impact on HIV-1 infection and replication. Point estimates for p24 levels were defined for 95% probability of p24-positive tissues and were 3.43 log10 for ectocervical tissue and 2.50 log10 for vaginal tissue based on the weight-adjusted cumulative p24 end points.
  
  
  CONCLUSIONS
  Although similar proportions of ectocervical and vaginal tissues support HIV-1 infection, higher levels of HIV-1 replication were observed in ectocervical tissues. Defining point estimates for HIV-1 infection in fresh ectocervical and vaginal tissues provides valuable information for the evaluation of HIV-1 preventative treatments during early clinical studies.
authors.affiliation: *Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA; †Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA; ‡Alpha StatConsult, LLC, Damascus, MD; and §University of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Charlene S
authors.initials: CS
authors.lastname: Dezzutti
authors.forename: Kevin
authors.initials: K
authors.lastname: Uranker
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Bunge
authors.forename: Nicola
authors.initials: N
authors.lastname: Richardson-Harman
authors.forename: Ingrid
authors.initials: I
authors.lastname: Macio
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hillier
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001706:Biopsy; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005836:Genitalia, Female / Q000821:virology*; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D016655:HIV Core Protein p24