title: Inhibition of vaginal transmission of HIV-1 in hu-SCID mice by the non-nucleoside reverse transcriptase inhibitor TMC120 in a gel formulation.
abstract: OBJECTIVE
  The development of drugs that can be used as topical microbicides is currently recognized as a priority area of research.
  
  
  METHODS
  A preclinical evaluation of the potential effectiveness of TMC120, a non-nucleoside reverse transcriptase inhibitor (NNRTI), as a topical microbicide to prevent vaginal HIV-1 transmission in a humanized severe combined immunodeficient (hu-SCID) mouse model.
  
  
  METHODS
  Reconstituted mice received an intravaginal application of a TMC120-containing gel 20 min prior to a non-invasive vaginal challenge with cell-associated HIV. The possible cytotoxic effect of TMC120-containing-gel on lymphocytes was assessed and their in vivo migration was followed using fluorescently labelled human lymphocytes. Systemic infection was monitored by p24 antigen detection in culture supernatant from cocultured intraperitoneal cells using antigen capture enzyme-linked immunosorbent assay test and by the presence of integrated proviral HIV-1 DNA in DNA extracted from spleen cells. In vivo migration of labelled lymphocytes was examined by analysis of cells isolated from regional lymph nodes.
  
  
  RESULTS
  In this model, systemic infection was successfully inhibited by the presence of TMC120-containing gel at vaginal level. The in vivo migration of human lymphocytes from the vagina to regional lymph nodes, following the deposition of TMC120-containing gel, excluded the possibility that inhibition of systemic infection was a result of NNRTI toxicity.
  
  
  CONCLUSIONS
  Vaginal transmission of HIV was successfully prevented by the application of a gel formulation containing TMC120. This is the first evidence of the in vivo effectiveness of a microbicide preparation containing an NNRTI against cell-associated HIV.
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Di Fabio
authors.forename: Jens
authors.initials: J
authors.lastname: Van Roey
authors.forename: Giacomo
authors.initials: G
authors.lastname: Giannini
authors.forename: Guy
authors.initials: G
authors.lastname: van den Mooter
authors.forename: Massimo
authors.initials: M
authors.lastname: Spada
authors.forename: Andrea
authors.initials: A
authors.lastname: Binelli
authors.forename: Maria F
authors.initials: MF
authors.lastname: Pirillo
authors.forename: Elena
authors.initials: E
authors.lastname: Germinario
authors.forename: Filippo
authors.initials: F
authors.lastname: Belardelli
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: de Bethune
authors.forename: Stefano
authors.initials: S
authors.lastname: Vella
mesh_terms: D000180:Acrylic Resins; D000282:Administration, Intravaginal; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005782:Gels; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D011145:Polyvinyls / Q000008:administration & dosage; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D014621:Vagina / Q000276:immunology; D014783:Viscosity
chemical_list: D000180:Acrylic Resins; D000890:Anti-Infective Agents; D005782:Gels; D011145:Polyvinyls; D018894:Reverse Transcriptase Inhibitors; C006912:carboxypolymethylene; D002482:Cellulose; C002283:hydroxyethylcellulose