Inhibition of vaginal transmission of HIV-1 in hu-SCID mice by the non-nucleoside reverse transcriptase inhibitor TMC120 in a gel formulation
作者:
Simonetta Di Fabio,
Jens Van Roey,
Giacomo Giannini,
Guy van den Mooter,
Massimo Spada,
Andrea Binelli,
Maria Pirillo,
Elena Germinario,
Filippo Belardelli,
Marie-Pierre de Bethune,
Stefano Vella,
期刊:
AIDS
(OVID Available online 2003)
卷期:
Volume 17,
issue 11
页码: 1597-1604
ISSN:0269-9370
年代: 2003
出版商: OVID
关键词: cell-associated HIV;sexual transmission;huSCID mice;microbicides
数据来源: OVID
摘要:
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 theirin vivomigration 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 vivomigration 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. Thein vivomigration 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 thein vivoeffectiveness of a microbicide preparation containing an NNRTI against cell-associated HIV.
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