Bictegravir (GS-9883) is a potent inhibitor of HIV-1 integrase with an IC50 value of 7.5 nM.

HIV-1 integrase:7.5 nM

Bictegravir potently inhibits HIV-1 replication in both MT-2 and MT-4 cells with EC50s of 1.5 and 2.4 nM, respectively. Bictegravir inhibits the strand transfer activity with an IC50 of 7.5 nM. Relative to its inhibition of strand transfer activity, Bictegravir is a much weaker inhibitor of the 3′-processing activity of HIV-1 IN, with an IC50 of 241 nM. Bictegravir enhances the accumulation of 2-LTR circles ~5-fold relative to the mock-treated control and reduces the number of authentic integration products in infected cells by 100-fold. Bictegravir exhibits potent antiviral effects in both primary CD4+ T lymphocytes and monocyte-derived macrophages, with EC50s of 1.5 nM and 6.6 nM, respectively, which are comparable to values obtained in T-cell lines[1].

MT-2 cells are infected in bulk culture with HIV-1 IIIb at a cell density of 2×10^6 cells/mL for 3 h at 37°C. Infected MT-2 cells receive either DMSO (mock-treated control) or Bictegravir at a final concentration greater than or equal to 20 times their respective antiviral EC50. These plates are incubated at 37°C for either 12 h (for late reverse transcription product quantification) or 24 h (for 2-LTR circle and Alu-LTR product quantification), after which time the cells are harvested for total DNA isolation. DNA is extracted from each well using the DNA minikit and collected as a 100-μL eluate. TaqMan real-time PCR-quantified 2-LTR junctions, late reverse transcription products, and integration junctions (Alu-LTR) are normalized to the level of host globin gene in each sample[1].