Title
**In vitro** synergistic activity against CCR5-tropic HIV-1 with combinations of potential candidate microbicide molecules HHA, KRV2110 and enfuvirtide (T20) **In vitro** synergistic activity against CCR5-tropic HIV-1 with combinations of potential candidate microbicide molecules HHA, KRV2110 and enfuvirtide (T20)
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
London ,
Subject
Human medicine
Source (journal)
The journal of antimicrobial chemotherapy. - London, 1975, currens
Volume/pages
64(2009) :6 , p. 1192-1195
ISSN
0305-7453
1460-2091
ISI
000271816800012
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
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.
E-info
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