Dolutegravir

S/GSK1349572 (GSK 1349572) is a novel potent integrase inhibitor with an IC50 of 2.7 nM in vitro. S/GSK1349572 (GSK 1349572) is a compound for the treatment of HIV infection. S/GSK1349572 (GSK 1349572) exhibited in vitro activity against most clinical isolates obtained from patients failing RAL-based therapy. In PBMC cell assay, S/GSK1349572 inhibited HIV integrase with the antiviral IC50=0.51 and IC90=2.0 nM. In MT-4 antiviral assays, potency shift extrapolated to 100% human serum was 75-fold providing PA-IC90=152 nM in PBMCs. S/GSK1349572 (GSK 1349572) had a markedly different resistance profile as evidenced by limited cross-resistance to RAL-resistant molecular clones, by its in vitro activity against clinical isolates obtained from patients failing RAL-based therapy, and in selecting different mutations with low level FC during serial passage. In vitro experiments support the potential for S/GSK1349572 (GSK 1349572) to have a higher genetic barrier to resistance when compared to 1st generation integrase inhibitors.