Comparative antiviral activity of integrase inhibitors in human monocyte-derived macrophages and lymphocytes

The activity of raltegravir and 4 other integrase inhibitors (MK-2048, L870,810, IN2, and IN5) was investigated in primary human macrophages, PBMC and C8166-lymphocytic T cells, in order to determine their relative potency and efficacy in different cellular systems of HIV infection. Raltegravir showed better protective efficacy in all cell types; MK-2048, L870,810 and IN5 showed a potent anti-HIV-1 activity in macrophages, while in lymphocytes only MK-2048 and L870,810 showed an inhibitory effect comparable to raltegravir. IN2 was a poorly effective anti-HIV-1 compound in all cellular systems. All effective integrase inhibitors exhibited a potent antiviral activity against both X4 and R5 HIV-1 strains. In general, raltegravir, MK-2048, L870,810 and IN5 showed anti HIV activity similar or slightly higher in macrophages compared to PBMC and C8166 T cells: for MK-2048, the EC50 was 0.4, 0.9, 11.5 nM in macrophages, in PBMCs and T cells, respectively; for L870,810, the EC50 was 1.5, 14.3, and 10.6 nM, respectively; for IN5 the EC50 was 0.5, 13.7, and 5.7 nM, respectively.

► We investigated the anti HIV activity of integrase inhibitors (INIs) in macrophages, PBMC and C8166 T lymphocytes.
► Raltegravir and the other INIs showed similar or slightly higher efficacy in macrophages compared to PBMC and T cells.
► Raltegravir (and other INIs) may represent a therapy of choice to prevent and control the replication of HIV in the brain.