AEGiS-14IAC: Inhibition of vaginal transmission of HIV-1 in hu-SCID mice by a microbicide containing an NNRTI

AEGiS-14IAC: Inhibition of vaginal transmission of HIV-1 in hu-SCID mice by a microbicide containing an NNRTI - Dapivirine. (TMC120).

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Inhibition of vaginal transmission of HIV-1 in hu-SCID mice by a microbicide containing an NNRTI - Dapivirine. (TMC120).

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. WeOrD1315)

Fabio SD, Roey JV, Giannini G, Van den Mooter G, Penta CL, Spada M, Binelli A, Germinario E, Belardelli F, Proietti E, de Bethune MP, Vella S
Laboratory of Virology, Istituto Superiore di Sanita, Rome, Italy

BACKGROUND: The identification of anti-HIV drug as topical microbicides to prevent virus transmission between sexual partners is a priority for controlling the spread of AIDS in both developed and developing countries. We report the successful prevention of vaginal transmission of HIV throug the application of a gel formulation containing Dapivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI).

METHODS: In order to mimic the in vivo transmission that occurs in humans, we used a hu-SCID animal model of vaginal transmission of HIV-1 for the evaluation of vaginal microbicides and for the evaluation of rectal microbicides a hu-SCID animal model of rectal transmission of HIV-1. Gels made up of carbopol 940 or hydroxyethyl cellulose (HEC), two water soluble polymers, were prepared containing TMC120 in different concentrations (0.225mM; 0.0225mM or 0.00225mM). Animals received a single intravaginal application of 25 ml of gel containing Dapivirine, 15-20 minutes prior to a non invasive vaginal challenge with 2x106 human peripheral blood lymphocytes PBL (hu-PBL) previously infected in vitro with a non-syncytium (NSI) strains of HIV-1 (SF162 and 1/BX08). Cell to cell transmission was assessed by p24 production and by quantitative PCR.

RESULTS: Systemic infection was successfully inhibited by Dapivirine - containing gel in this model as shown by p24, and PCR results.

CONCLUSION: We report the successful prevention of a vaginal transmission of HIV throug the application of a gel formulation containing Dapivirine (TMC120), a non-nucleoside reverse transcriptase inhibitor (NNRTI). This is the first evidence of the in vivo effectiveness of an NNRTI as microbicide.

Keywords: AEGIS, HIV-1, Mice, SCID, HIV Infections, Vagina, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Anti-Infective Agents, HIV, Hemolytic-Uremic Syndrome, Lymphocytes, Acquired Immunodeficiency Syndrome, Simian Acquired Immunodeficiency Syndrome, Polymerase Chain Reaction, Mice, Animal, Female, Human, In Vitro, transmission

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