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Antimicrobial Agents and Chemotherapy, January 2004, p. 337-339, Vol. 48, No. 1
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.1.337-339.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vitro Evaluation of Nonnucleoside Reverse Transcriptase Inhibitors UC-781 and TMC120-R147681 as Human Immunodeficiency Virus Microbicides

Laboratory of Immunology,¹ AIDS Reference Laboratory, Department of Microbiology, Institute of Tropical Medicine, Antwerp,³ Tibotec-Virco NV, Mechlin,² Laboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Leuven,⁴ Center for Molecular Design, Janssen Pharmaceutica, Vosselaar, Belgium⁵

Received 11 June 2003/ Returned for modification 26 August 2003/ Accepted 23 September 2003

The nonnucleoside reverse transcriptase inhibitors UC-781 and TMC120-R147681 (Dapivirine) effectively prevented human immunodeficiency virus (HIV) infection in cocultures of monocyte-derived dendritic cells and T cells, representing primary targets in sexual transmission. Both drugs had a favorable therapeutic index. A 24-h treatment with 1,000 nM UC-781 or 100 nM TMC120-R147681 prevented cell-free HIV infection, whereas 10-fold-higher concentrations blocked cell-associated HIV.

This work is dedicated to the memory of Paul A. J. Janssen, founder of Janssen Pharmaceutica and the Center for Molecular Design.

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