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JAC Advance Access originally published online on October 29, 2009
Journal of Antimicrobial Chemotherapy 2009 64(6):1192-1195; doi:10.1093/jac/dkp380
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

In vitro synergistic activity against CCR5-tropic HIV-1 with combinations of potential candidate microbicide molecules HHA, KRV2110 and enfuvirtide (T20)

Mohammad-Ali Jenabian1, Héla Saïdi1, Charlotte Charpentier1, Yven Van Herrewege2, Jong Chan Son3, Dominique Schols4, Jan Balzarini4, Guido Vanham2, Laurent Bélec1,* on behalf of the ANRS Multi-Micro Project Study Group

1 Université Paris Descartes (Paris V), and Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris, France 2 Virology Unit, Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium 3 Korea Research Institute of Clinical Technology, Daejeon, Korea 4 Rega Institute for Medical Research, Leuven, Belgium

Received 21 January 2009; returned 8 May 2009; revised 1 June 2009; accepted 29 September 2009

* Corresponding author. Tel: +33-1-56-09-39-58; Fax: +33-1-56-09-24-47; E-mail: prbelecl{at}yahoo.fr

Objectives: To block the different mechanisms of HIV mucosal transmission, it is likely that use of several microbicide molecules will lead to the best protection against HIV transmission. Indeed, the combination of microbicides with complementary mechanisms of action is expected to increase the antiviral potency of the formulation.

Methods: The gp120-interacting plant lectin HHA (‘Hippeastrum hybrid agglutinin’), the non-nucleoside reverse transcriptase inhibitor KRV2110 and the fusion inhibitor enfuvirtide (T20) were combined in 12 drug associations by using the Ray combination design method. Their activity against HIV-1BaL was assessed by the lymphocyte infectivity reduction assay and by the single-cycle BaL pseudovirus (PV) assay. In addition, their cell tolerance was evaluated for HEC-1 and HeLa epithelial cell lines, both originating from genital tissue.

Results: All evaluated combinations showed synergistic activity in both lymphocyte infectivity reduction and single-cycle BaL PV assays. The combination HHA + KRV2110 resulted in the highest cell viability, whereas the combinations including T20 exhibited a dose-dependent decrease in cell viability, demonstrating the differential tolerance of epithelial cell lines to the combinations.

Conclusions: These observations provide a rational basis for in vitro testing of microbicide candidate molecule combinations, including anti-HIV-1 and cytotoxic cellular assays.

Keywords: AIDS , vaginal microbicide , pre-clinical evaluation


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