title: Comparative antiviral activity of integrase inhibitors in human monocyte-derived macrophages and lymphocytes.
abstract: 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 EC(50) was 0.4, 0.9, 11.5 nM in macrophages, in PBMCs and T cells, respectively; for L870,810, the EC(50) was 1.5, 14.3, and 10.6 nM, respectively; for IN5 the EC(50) was 0.5, 13.7, and 5.7 nM, respectively.
authors.affiliation: University of Rome Tor Vergata, Rome, Italy.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Scopelliti
authors.forename: Michela
authors.initials: M
authors.lastname: Pollicita
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
authors.forename: Fabiola
authors.initials: F
authors.lastname: Di Santo
authors.forename: Matteo
authors.initials: M
authors.lastname: Surdo
authors.forename: Stefano
authors.initials: S
authors.lastname: Aquaro
authors.forename: Carlo-Federico
authors.initials: CF
authors.lastname: Perno
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000032:analysis; D019428:HIV Integrase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008214:Lymphocytes / Q000821:virology*; D008264:Macrophages / Q000821:virology*; D008826:Microbial Sensitivity Tests
chemical_list: D016655:HIV Core Protein p24; D019428:HIV Integrase Inhibitors