Journal Article

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

Mohammad-Ali Jenabian, Héla Saïdi, Charlotte Charpentier, Yven Van Herrewege, Jong Chan Son, Dominique Schols, Jan Balzarini, Guido Vanham and Laurent Bélec

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 64, issue 6, pages 1192-1195
Published in print December 2009 | ISSN: 0305-7453
Published online October 2009 | e-ISSN: 1460-2091 | DOI: https://dx.doi.org/10.1093/jac/dkp380
In vitro synergistic activity against CCR5-tropic HIV-1 with combinations of potential candidate microbicide molecules HHA, KRV2110 and enfuvirtide (T20)

More Like This

Show all results sharing these subjects:

  • Medical Oncology
  • Critical Care

GO

Show Summary Details

Preview

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

Journal Article.  1915 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content. subscribe or login to access all content.