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

• Published in: Antiviral research Vol. 92; no. 2; pp. 255 - 261
• Main Authors: Scopelliti, Fernanda, Pollicita, Michela, Ceccherini-Silberstein, Francesca, Di Santo, Fabiola, Surdo, Matteo, Aquaro, Stefano, Perno, Carlo-Federico
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01-11-2011; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral activity; Antiviral agents; Apoptosis; Biological and medical sciences; Cells, Cultured; HIV; HIV Core Protein p24 - analysis; HIV Integrase Inhibitors - pharmacology; HIV Integrase Inhibitors - toxicity; HIV-1 - drug effects; HIV-1 - growth & development; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Integrase inhibitors; Lymphocytes; Lymphocytes - virology; Macrophages; Macrophages - virology; Medical sciences; Microbial Sensitivity Tests; PBMC; Pharmacology. Drug treatments; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; HIV; Integrase inhibitors; Macrophages; Lymphocytes; PBMC; Antiretroviral agent; Pharmacotherapy; Integrase inhibitor; Antiviral; Human; Drug; Immunopathology; Monocyte; Treatment efficiency; Retroviridae; AIDS; Immune deficiency; Lentivirus; Biological activity; Infection; Virus; Treatment; Viral disease; Human immunodeficiency virus; Lymphocyte; Comparative study; Raltegravir; Macrophage
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2011.08.008

► 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.
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.