Plasma Efavirenz Concentrations Are Associated With Lipid and Glucose Concentrations.

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Sinxadi PZ, McIlleron HM, Dave JA, Smith PJ, Levitt NS, Haas DW, Maartens G

Plasma Efavirenz Concentrations Are Associated With Lipid and Glucose Concentrations.

Medicine (Baltimore). 2016 Jan;95(2):e2385. doi: 10.1097/MD.0000000000002385.

PubMed ID

26765416 [ View in PubMed

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Abstract

Efavirenz-based antiretroviral therapy (ART) has been associated with dyslipidemia and dysglycemia, risk factors for cardiovascular disease. However, the pathogenesis is not well understood. We characterized relationships between plasma efavirenz concentrations and lipid and glucose concentrations in HIV-infected South Africans.Participants on efavirenz-based ART were enrolled into a cross-sectional study. The oral glucose tolerance test was performed after an overnight fast, and plasma drawn for mid-dosing interval efavirenz, fasting total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglycerides concentrations.Among 106 participants (77 women), median age was 38 years, median CD4 + T-cell count was 322 cells/muL, median duration on ART was 18 months, and median (interquartile range) efavirenz concentration was 2.23 (1.66 to 4.10) mug/mL. On multivariable analyses (adjusting for age, sex, body mass index, and ART duration) doubling of efavirenz concentrations resulted in mean changes in mmol/L (95%CI) of: total cholesterol (0.40 [0.22 to 0.59]), LDL cholesterol (0.19 [0.04 to 0.30]), HDL cholesterol (0.14 [0.07 to 0.20]), triglycerides (0.17 [0.03 to 0.33]), fasting glucose (0.18 [0.03 to 0.33]), and 2-h glucose concentrations (0.33 [0.08 to 0.60]). Among 57 participants with CYP2B6 genotype data, associations between slow metabolizer genotypes and metabolic profiles were generally consistent with those for measured efavirenz concentrations.Higher plasma efavirenz concentrations are associated with higher plasma lipid and glucose concentrations. This may have implications for long-term cardiovascular complications of efavirenz-based ART, particularly among populations with high prevalence of CYP2B6 slow metabolizer genotypes.

DrugBank Data that Cites this Article

Pharmaco-metabolomics

Drug	Drug Groups	Metabolite	Change	Description
Efavirenz	Approved Investigational	HDL cholesterol	increased	Efavirenz increases the level of HDL cholesterol in the blood
Efavirenz	Approved Investigational	LDL cholesterol	increased	Efavirenz increases the level of LDL cholesterol in the blood
Efavirenz	Approved Investigational	Glucose	increased	Efavirenz increases the level of Glucose in the blood
Efavirenz	Approved Investigational	Total cholesterol	increased	Efavirenz increases the level of Total cholesterol in the blood