Abstract

Gender, weight and cytochrome P450 2B6 (CYP2B6) 516G>T genetic data of 61 patients on efavirenz containing highly active anti-retroviral therapy (HAART) was collated and analysed. Multivariate data analysis and correlations between variables were done to determine the relative contributions of gender, weight and CYP2B6 genetic polymorphism. Models were derived to guide dose adjustment in patients predicted to have unsafe drug exposure. The data showed that 44% of patients had concentrations above the minimum safe concentrations. Gender, weight and genetics explain 22% of the variation of therapeutic levels efavirenz drug exposure in the model. The model generated indicates that all patients homozygous for the 516G>T variant, irrespective of gender or weight required dose adjustment to 200 mg/day, whilst patients of the G/G genotype should be given the standard 600 mg/day. Patients of the G/T genotype showed mixed outcomes. Analysis of this group showed that females of weight less than 62 kg need dose adjustment to 400 mg/day whereas their male counterparts did not need dose adjustment.

Key words: Efavirenz, CYP2B6 516G>T, weight, gender, dose adjustment, partial least squares.