Abstract

Objective: To investigate the association between 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity and antiretroviral therapy (ART)-induced increase in low-density lipoprotein cholesterol (LDL). Materials and methods: We enrolled 62 patients and used liquid chromatography-tandem mass spectrometry to measure 11β-HSD1 activity, which was expressed as a ratio of the sum of urinary tetrahydrocortisol and allo-tetrahydrocortisol concentrations to urinary tetrahydrocortisone concentration. Patient data, including baseline laboratory values, were extracted from medical records for logistic regression analyses of factors associated with LDL increase during ART. The cutoff 11β-HSD1 activity ratio associated with the LDL increase during ART was determined using receiver operator characteristic (ROC) curve analysis. Results: The LDL level increased significantly from 88.8 mg/dL before ART to 106.7 mg/dL during ART (p = 0.04). Additionally, patients with increased LDL tended to have a higher 11β-HSD1 activity ratio (1.59 vs. 1.21, p = 0.06) and longer duration of ART (13.9 vs. 10.2 months, p = 0.07) than patients with unchanged or decreased LDL. The cutoff 11β-HSD1 activity ratio was 1.226. Results of the univariate logistic regression analysis suggested that 11β-HSD1 activity ratio ≥ 1.226 was associated with LDL increase during ART (p = 0.011), with an odds ratio of 8.000. Conclusion: This study revealed the possible association between 11β-HSD1 activity and ART-induced LDL increase. The findings of this study suggest that 11β-HSD1 could be a useful drug target for the treatment of ART-induced hyperlipidemia.

Author Details

Authors

• Kazuyuki Niki¹
• Kazuo Harada²
• Shinich Hikasa³
• Mamiko Tsugane¹
• Mikiko Ueda¹
• Satoshi Higasa⁴
• Takeshi Kimura³
• Tatsuya Takagi⁵
• Etsuko Uejima¹


Departments

• ¹ Department of Clinical Pharmacy Research and Education,
• ² Department of Applied Environmental Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka,
• ³ Department of Pharmacy, The Hospital of Hyogo College of Medicine,
• ⁴ Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, and
• ⁵ Department of Pharmainformatics and Pharmacometrics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan

Address

Kazuyuki Niki, BP

Department of Clinical Pharmacy Research and Education
Graduate School of Pharmaceutical Sciences
Osaka University
1-6 Yamadaoka, Suita, Osaka, Japan
Email: [email protected]

Citation