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Luetkemeyer, A.F., Rosenkranz, S.L., Lu, D., Marzan, F., Ive, P., Hogg, E., Swindells, S., Benson, C.A., Grinsztejn, B., Sanne, I.M., Havlir, D.V. and Aweeka, F. (2013) Relationship between Weight, Efavirenz Exposure, and Virologic Suppression in HIV-Infected Patients on Rifampin-Based Tuberculosis Treatment in the AIDS Clinical Trials Group A5221 STRIDE Study. Clinical Infectious Diseases, 57, 586-593.
http://dx.doi.org/10.1093/cid/cit246

has been cited by the following article:

• TITLE: Influence of CYP2B6 516G > T and Long Term HAART on Population Pharmacokinetics of Efavirenz in Rwandan Adults on HIV and Tuberculosis Cotreatment

  AUTHORS: Emile Bienvenu, Michael Ashton, Angela Äbelö

  KEYWORDS: Clearance, CYP2B6, Efavirenz, HIV, RBT, Tuberculosis

  JOURNAL NAME: Pharmacology & Pharmacy, Vol.6 No.11, November 25, 2015

  ABSTRACT: Aim: To describe the pharmacokinetic parameters of efavirenz and estimate its clearance (CL/F) accounting simultaneously for drug-drug interactions and CYP2B6 genetic polymorphism. Methods: Genotyping of 516G > T single nucleotide polymorphism of CYP2B6 was performed using a PCR-based technology and plasma efavirenz concentrations were measured by high performance liquid chromatography on blood samples from 76 HIV adults co-infected with tuberculosis who had received an efavirenz-based regimen. Data were analyzed using population modeling with NONMEM. Results: The absorption rate constant and the apparent volume of distribution in the final model were 1.9 h-1 and 580 L/70kg, respectively. The CL/F at baseline was 11.8 L/h/70kg, 8.8 L/h/70kg and 3.9 L/h/70kg for patients carrying the G/G, G/T and T/T genotypes of CYP2B6 516G > T, respectively, in patients who were administered tuberculosis (TB) treatment prior to HIV treatment (Group A); and 16.7 L/h/70kg, 10.6 L/h/70kg and 1.8 L/h/70kg for G/G, G/T and T/T genotype patients respectively, in patients with previous exposure to HIV treatment (Group B). The CL/F at baseline and steady state was always higher in Group B compared to Group A patients. Expectedly, carriers of CYP2B6 516G/G and T/T genotypes exhibited higher and lower CL/F, respectively. Conclusion: Our results indicated that the CL/F of efavirenz in the population studied was predictably different due to whether the patients were mono-treated for TB with HAART deferred or for HIV before initiation of TB therapy, and to CYP2B6 516G > T variant, implying that both CYP2B6 genetic polymorphisms and previous efavirenz-based HAART should be taken into account when adjusting efavirenz dose.