In vitro synergistic activity against CCR5-tropic HIV-1 with combinations of potential candidate microbicide molecules HHA, KRV2110 and enfuvirtide (T20).
OBJECTIVE
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-1(BaL) 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.
Jenabian
Mohammad-Ali
MA
Université Paris Descartes (Paris V), and Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris, France.
Saïdi
Héla
H
Charpentier
Charlotte
C
Van Herrewege
Yven
Y
Son
Jong Chan
JC
Schols
Dominique
D
Balzarini
Jan
J
Vanham
Guido
G
Bélec
Laurent
L
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000077560:Enfuvirtide; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019668:Liliaceae / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D010446:Peptide Fragments / Q000494:pharmacology*; D037121:Plant Lectins / Q000494:pharmacology*; D055815:Young Adult
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D037121:Plant Lectins; D000077560:Enfuvirtide