Humanized mice reconstituted with human lymphoid cells provide rapid, reliable, reproducible experimental systems for testing the efficacy of ABX464 in vivo. In the initial setting, SCID mice are reconstituted with PBMCs and then infected with the HIV-1 strain JR-CSF. Mice are treated twice a day (b.i.d) for 15 days by oral gavage with 20 mg/kg of ABX464. Measures of viral RNA show that the oral treatment with ABX464 is able to significantly reduce the viral load over a period of 15 days of treatment. FACS analysis of blood samples show that treatment with ABX464 prevents depletion of CD4+ cells following infection of reconstituted mice and thereby restores the CD8+/CD4+ ratio back to that of non-infected mice[1].
In Vitro
ABX464 inhibits HIV-1 production in PBMC- and macrophages-infected cells. ABX464 has a strong inhibitory effect for all HIV-1 subtypes tested including subtype B, C and recombinant viruses. ABX464 also very efficiently inhibits the replication of viral strains harbouring mutations that confer resistance to different therapeutic agents in vitro. While the antiviral drug 3TC is not highly active on K65R and M184V mutant strains, both strains are inhibited by ABX464. To generalize the effect of ABX464 on HIV-1 replication in other primary cells, cells are treated with between 0.01 μM up to 30 μM concentrations of ABX464 and p24 antigen levels are monitored in culture supernatants over a 12 days period. ABX464 efficiently blocks virus replication in a dose-dependent manner with an IC50 ranging between 0.1 μM and 1 μM[1].
Kinase Assay
Cell Assay
Animal Administration
References
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