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

Mari Shimura, Nobuyo Higashi-Kuwata, Asuka Fujiwara, Mai Taniguchi,Takayuki Ichinose, Fumie Hamano,Masaaki Uematsu, Takato Inoue, Satoshi Matsuyama, Takahiro Suzuki,Arun K. Ghosh, Hideo Shindou, Takao Shimuzu,Hiroaki Mitsuya

ANTIVIRAL RESEARCH(2024)

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摘要
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 mu M of cyclosporin A, which we call the Pharmacological Lipid Index (PLI). The PLI was then normalized by EC50. PLI/EC50 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/EC50 scores. Data suggests that PLI/EC50 is a useful index for estimating the risk of hyperlipidemia.
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关键词
HIV,Anti-retroviral drugs,Hyperlipidemia,Lipid droplets,EC50,X-ray fluorescence microscopy
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