Evaluation of an immunoassay for determination of plasma efavirenz concentrations in resource-limited settings

INTRODUCTION: Therapeutic drug monitoring (TDM) may improve antiretroviral efficacy through adjustment of individual drug administration. This could result in reduced toxicity, prevent drug resistance, and aid management of drug–drug interactions. However, most measurement methods are too costly to be implemented in resource-limited settings. This study evaluated a commercially available immunoassay for measurement of plasma efavirenz. METHODS: The immunoassay-based method was applied to measure efavirenz using a readily available Humastar 80 chemistry analyzer. We compared plasma efavirenz concentrations measured by the immunoassay with liquid chromatography tandem mass spectrometry (LC-MS/MS) (reference method) in 315 plasma samples collected from HIV patients on treatment. Concentrations were categorized as suboptimal<1 µg/ml, normal 1–4 µg/ml or high>4 µg/ml. Agreement between results of the methods was assessed via Bland-Altman plot and κ statistic values. RESULTS: The median Interquartile range (IQR) efavirenz concentration was 2.8 (1.9; 4.5) µg/ml measured by the LC–MS/MS method and 2.5 (1.8; 3.9) µg/ml by the immunoassay and the results were well correlated (ρ=0.94). The limits of agreement assessed by Bland–Altman plots were −2.54; 1.70 µg/ml. Although immunoassay underestimated high concentrations, it had good agreement for classification into low, normal or high concentrations (K=0.74). CONCLUSIONS: The immunoassay is a feasible alternative to determine efavirenz in areas with limited resources. The assay provides a reasonable approximation of efavirenz concentration in the majority of samples with a tendency to underestimate high concentrations. Agreement between tests evaluated in this study was clinically satisfactory for identification of low, normal and high efavirenz concentrations.