Plasma Efavirenz Concentrations Are Associated With Lipid and Glucose Concentrations.

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.

Amiodarone-induced thyroid dysfunction.

BACKGROUND: Little is known about the frequency of thyroid dysfunction (TD) associated with amiodarone therapy in southern Africa. OBJECTIVES: To determine the incidence of TD in a cohort of patients initiated on amiodarone therapy at a cardiac clinic in Cape Town, South Africa, believed to be an iodine-replete area. PATIENTS: Pharmacy records were used to obtain the names of patients who received amiodarone between November 1999 and December 2002. RESULTS: The sample size was 194, but data analysis was limited to the 163 patients for whom there were complete data. The mean age +/- standard deviation (SD) was 59.0 +/- 15.0 years (range 22 - 89 years). There were 67 female and 96 male patients. The indications for amiodarone therapy were supraventricular tachycardias (N = 102, 62.6%), ventricular tachycardia (N = 55, 33.7%), and prophylaxis against tachycardias (N = 3, 1.8%). The indication was uncertain in 3 patients (1.8%). The median duration of amiodarone treatment was 679.0 days (quartile deviation (QD) 1172 days, range 3 - 6425 days) in the whole cohort. The median duration of amiodarone therapy until new TD was 943 days (QD 1185 days), significantly longer than in patients who remained euthyroid (547 days, QD 1135 days) (P = 0.05). There were 45 new TD cases (27.6%): 11 patients (6.7%) were thyrotoxic, 1 (0.6%) transient thyrotoxicosis, 1 (0.6%) subclinical hyperthyroidism, 13 (8.0%) had subclinical hypothyroidism, 12 (7.4%) hypothyroidism and 7 (4.3%) had minor changes in thyroid function. CONCLUSIONS: We found a high incidence of new-onset TD, similar to the highest rates reported internationally. Local factors responsible for this need to be investigated.