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Effect of Rifampicin and CYP2B6 Genotype on Long-Term Efavirenz Autoinduction and Plasma Exposure in HIV Patients With or Without Tuberculosis

2011; Wiley; Volume: 90; Issue: 3 Linguagem: Inglês

10.1038/clpt.2011.129

1532-6535

Eliford Ngaimisi, Sabina Mugusi, Omary Minzi, Philip Sasi, K. Riedel, Akira Suda, N. Ueda, Mohammed Janabi, Ferdinand Mugusi, Walter E. Haefeli, Leif Bertilsson, Jürgen Burhenne, Eleni Aklillu,

HIV Research and Treatment

We performed a prospective comparative study to examine, from a pharmacogenetics perspective, the effect of rifampicin (RIF) on long-term efavirenz (EFV) autoinduction and kinetics. In a study population of patients with HIV receiving EFV with RIF (arm 2, n = 54) or without RIF (arm 1, n = 128 controls), intraindividual and interindividual plasma EFV and 8-hydroxyefavirenz levels were compared at weeks 4 and 16 of EFV therapy. In arm 2, RIF was initiated 4 weeks before starting EFV. In controls (arm 1), the plasma EFV was significantly lower whereas 8-hydroxyefavirenz was higher at week 16 as compared to week 4. By contrast, there were no significant differences in plasma EFV and 8-hydroxyefavirenz concentrations over time in arm 2. At week 4, the plasma EFV concentration was significantly lower in arm 2 as compared to arm 1, but no significant differences were observed by week 16. When stratified by CYP2B6 genotype, significant differences were observed only with respect to CYP2B6*1/*1 genotypes. Ours is the first report of the CYP2B6 genotype-dependent effect of RIF on long-term EFV autoinduction. Clinical Pharmacology & Therapeutics (2011) 90 3, 406–413. doi:10.1038/clpt.2011.129