OBJECTIVE: HIV infection is associated with elevated risk of cardiovascular disease. The effect of antiretroviral drugs on metabolism of atherogenic very low and low density lipoproteins is well studied, but a possible effect of these drugs on reverse cholesterol transport is still unclear. The objective of this study was to assess the effect of various classes of anti-HIV drugs on cellular cholesterol efflux. METHODS: The effect of pharmacological concentrations of seven commonly used antiretroviral compounds, Stavudine, Efavirenz, Nevirapine, Lopinavir, Amprenavir, Nelfinavir and Ritonavir, on cholesterol efflux from RAW 264.7 mouse macrophages and human monocyte-derived macrophages to apolipoprotein A-I and high density lipoprotein was tested. RESULTS: At high pharmacological concentration Nelfinavir and Ritonavir inhibited cholesterol efflux, while other compounds had no effect. However, the same concentrations of Nelfinavir and Ritonovir induced apoptosis, suggesting that the effect of these compounds on cholesterol efflux most likely resulted from their cytotoxicity. When tested in non-cytotoxic concentrations, Nelfinavir and Ritonavir did not affect cholesterol efflux from RAW 264.7 cells, human monocyte-derived macrophages, or human macrophages infected with HIV-1. CONCLUSIONS: We conclude that tested antiretroviral compounds do not have a specific effect on cholesterol efflux.
OBJECTIVE:HIV infection is associated with elevated risk of cardiovascular disease. The effect of antiretroviral drugs on metabolism of atherogenic very low and low density lipoproteins is well studied, but a possible effect of these drugs on reverse cholesterol transport is still unclear. The objective of this study was to assess the effect of various classes of anti-HIV drugs on cellular cholesterol efflux. METHODS: The effect of pharmacological concentrations of seven commonly used antiretroviral compounds, Stavudine, Efavirenz, Nevirapine, Lopinavir, Amprenavir, Nelfinavir and Ritonavir, on cholesterol efflux from RAW 264.7mouse macrophages and human monocyte-derived macrophages to apolipoprotein A-I and high density lipoprotein was tested. RESULTS: At high pharmacological concentration Nelfinavir and Ritonavir inhibited cholesterol efflux, while other compounds had no effect. However, the same concentrations of Nelfinavir and Ritonovir induced apoptosis, suggesting that the effect of these compounds on cholesterol efflux most likely resulted from their cytotoxicity. When tested in non-cytotoxic concentrations, Nelfinavir and Ritonavir did not affect cholesterol efflux from RAW 264.7 cells, human monocyte-derived macrophages, or human macrophages infected with HIV-1. CONCLUSIONS: We conclude that tested antiretroviral compounds do not have a specific effect on cholesterol efflux.
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