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

doi:10.1016/j.antiviral.2024.105819

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

Antiviral Res. 2024 Mar:223:105819. doi: 10.1016/j.antiviral.2024.105819. Epub 2024 Jan 23.

Authors

Affiliations

¹ Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan; RIKEN SPring-8 Center, Sayo, Hyogo, Japan. Electronic address: mshimura@ri.ncgm.go.jp.
² Department of Refractory Viral Diseases, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.
³ Inorganic Analysis Laboratories, Toray Research Center, Inc., Otsu, Shiga, Japan.
⁴ Life Sciences Core Facility, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.
⁵ Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan.
⁶ Department of Materials Physics, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan.
⁷ RIKEN SPring-8 Center, Sayo, Hyogo, Japan; Department of Materials Physics, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan.
⁸ Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo, Japan.
⁹ Department of Chemistry & Department of Medicinal Chemistry, Purdue University, West Lafayette, IN, 47907, USA.
¹⁰ Department of Lipid Life Science, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan; Department of Medical Lipid Science, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
¹¹ Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan; Institute of Microbial Chemistry, Shinagawa-ku, Tokyo, Japan.
¹² Department of Refractory Viral Diseases, National Center for Global Health and Medicine, Shinjuku, Tokyo, Japan; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Center Institute, National Institutes of Health, Bethesda, MD, 20893, USA. Electronic address: hmitsuya@hosp.ncgm.go.jp.

PMID: 38272319
DOI: 10.1016/j.antiviral.2024.105819

Abstract

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 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.

Keywords: Anti-retroviral drugs; EC50; HIV; Hyperlipidemia; Lipid droplets; X-ray fluorescence microscopy.

MeSH terms

Cardiovascular Diseases*
Cyclosporine
Humans
Hyperlipidemias* / chemically induced
Lipids
Quality of Life

Substances

Cyclosporine
Lipids