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/μL, median duration on ART was 18 months, and median (interquartile range)
efavirenz concentration was 2.23 (1.66 to 4.10) μg/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.