A lipid index for risk of hyperlipidemia caused by anti-retroviral drugs.

HIV-associated lipodystrophy has been reported in people taking anti-retroviral therapy (ART). Lipodystrophy can cause cardiovascular diseases, affecting the quality of life of HIV-infected individuals. In this study, we propose a pharmacological lipid index to estimate the risk of hyperlipidemia caused by anti-retroviral drugs. Lipid droplets were stained in cells treated with anti-retroviral drugs and cyclosporin A. Signal intensities of lipid droplets were plotted against the drug concentrations to obtain an isodose of 10 μM of cyclosporin A, which we call the Pharmacological Lipid Index (PLI). The PLI was then normalized by EC 50. PLI/EC 50 values were low in early proteinase inhibitors and the nucleoside reverse transcriptase inhibitor, d4T, indicating high risk of hyperlipidemia, which is consistent with previous findings of hyperlipidemia. In contrast, there are few reports of hyperlipidemia for drugs with high PLI/EC 50 scores. Data suggests that PLI/EC 50 is a useful index for estimating the risk of hyperlipidemia. • We generated a lipid index, PLI/EC50 score, for estimating the risk of hyperlipidemia caused by anti-retroviral drugs. • The index was determined by calculating the pharmacological lipid index (PLI) of drugs and dividing it by its EC50 values. • Lower PLI/EC50 were seen in drugs with high frequently reported risk of hyperlipidemia in clinical settings. • PLI is a suitable for drug development that can be performed in 48 h with culture cells using small amount of drug. • The PLI/EC50 score should serve as a valuable indicator for evaluating the lipotoxicity of antiviral drugs. [ABSTRACT FROM AUTHOR]