Prediction of plasma efavirenz concentrations among HIV-positive patients taking efavirenz-containing combination antiretroviral therapy

Abstract

We investigated the predictors of plasma mid-dose concentrations (C12) of efavirenz by enrolling 456 HIV-positive patients who had received 2 nucleos(t)ide reverse-transcriptase inhibitors plus efavirenz (600 mg daily) for 2 weeks or longer and had their CYP2B6 516G>T polymorphism and efavirenz C12 determined. The median efavirenz C12 was 2.41 mg/L (IQR, 1.93-3.14). In analysis of covariance models, patients with CYP2B6 516GT and TT genotypes compared to those with GG genotype had higher efavirenz C12 (for GT genotype, an increase by 0.976 mg/L [95%CI, 0.765-1.188], and TT genotype, 4.871 mg/L [95%CI, 4.126-5.616]), while per 10-kg increment in weight decreased C12 by 0.199 mg/L (95%CI, 0.111-0.287). Models incorporating CYP2B6 516G>T polymorphism and weight had moderate predictive values in predicting efavirenz C12 ≥ 2 mg/L (ROC area under curve = 0.706 [95%CI, 0.656-0.756]). In the absence of CYP2B6 516G>T polymorphism, weight ≤58 kg provided better predictabilities for efavirenz C12 ≥ 2 mg/L (probability, 77.1% [95%CI, 69.0-83.5%] for weight = 50 kg and 70.6% [95%CI, 64.1-76.4%] for weight = 58 kg).

Figure 1

Scattered diagram and linear models for prediction of mid-dose plasma efavirenz concentration. (a) The model with CYP2B6 516G>T polymorphism and (b) the model without CYP2B6 516G>T polymorphism.

Figure 2

Area-under-the-curves (AUCs) of the receiver-operating-characteristic (ROC) curves of the models predicting plasma mid-dose efavirenz concentration ≥2 mg/L. (Solid line indicating the models with CYP2B6 516G>T genotype and the dashed line indicating the models without CYP2B6 516G>T genotype).

Figure 3

Predicted probability of plasma mid-dose efavirenz concentrations ≥2 mg/L in different weights by binary logistic regression model.

Figure 4

Plasma mid-dose efavirenz concentrations in (a) weight quartile groups and (b) 10-kg increment groups.