Title: Inhibition of vaginal transmission of HIV-1 in hu-SCID mice by the non-nucleoside reverse transcriptase inhibitor TMC120 in a gel formulation
Authors: Di Fabio, Simonetta ×
Van Roey, Jens
Giannini, Giacomo
Van den Mooter, Guy
Spada, Massimo
Binelli, Andrea
Pirillo, Maria F
Germinario, Elena
Belardelli, Filippo
de Bethune, Marie-Pierre
Vella, Stefano #
Issue Date: Jul-2003
Publisher: Gower Academic Journals
Series Title: AIDS vol:17 issue:11 pages:1597-1604
Abstract: OBJECTIVE: The development of drugs that can be used as topical microbicides is currently recognized as a priority area of research. DESIGN: 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.
ISSN: 0269-9370
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
× corresponding author
# (joint) last author

Files in This Item:
File Description Status SizeFormat
2003-Di Fabio-Inhibition of vaginal transmission of HIV-1...-Aids.pdf Published 1726KbAdobe PDFView/Open Request a copy

These files are only available to some KU Leuven Association staff members


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science