Early or deferred initiation of efavirenz during rifampicin-based TB therapy has no significant effect on CYP3A induction in TB-HIV infected patients

• Verfasst von: Aklillu, Eleni [VerfasserIn]
• Verfasst von: Zumla, Alimuddin [VerfasserIn]
• Verfasst von: Habtewold, Abiy [VerfasserIn]
• Verfasst von: Amogne, Wondwossen [VerfasserIn]
• Verfasst von: Makonnen, Eyasu [VerfasserIn]
• Verfasst von: Yimer, Getnet [VerfasserIn]
• Verfasst von: Burhenne, Jürgen [VerfasserIn]
• Verfasst von: Diczfalusy, Ulf [VerfasserIn]
• Titel: Early or deferred initiation of efavirenz during rifampicin-based TB therapy has no significant effect on CYP3A induction in TB-HIV infected patients
• Verf.angabe: Eleni Aklillu, Alimuddin Zumla, Abiy Habtewold, Wondwossen Amogne, Eyasu Makonnen, Getnet Yimer, Jürgen Burhenne, Ulf Diczfalusy
• E-Jahr: 2021
• Jahr: August 2021
• Umfang: 15 S.
• Fussnoten: Gesehen am 18.12.2023
• Titel Quelle: Enthalten in: British journal of pharmacology
• Ort Quelle: Malden, MA : Wiley, 1946
• Jahr Quelle: 2021
• Band/Heft Quelle: 178(2021), 16 vom: Aug., Seite 3294-3308
• ISSN Quelle: 1476-5381
• DOI: doi:10.1111/bph.15309
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: 4β-hydroxycholesterol
• Sach-SW: co-infection
• Sach-SW: CYP3A
• Sach-SW: drug-drug interaction
• Sach-SW: efavirenz
• Sach-SW: enzyme induction
• Sach-SW: HIV
• Sach-SW: rifampicin
• Sach-SW: tuberculosis
• K10plus-PPN: 1876311118

Abstract

Background and Purpose In TB-HIV co-infection, prompt initiation of TB therapy is recommended but anti-retroviral treatment (ART) is often delayed due to potential drug-drug interactions between rifampicin and efavirenz. In a longitudinal cohort study, we evaluated the effects of efavirenz/rifampicin co-treatment and time of ART initiation on CYP3A induction. Experimental Approach Treatment-naïve TB-HIV co-infected patients (n = 102) were randomized to efavirenz-based-ART after 4 (n = 69) or 8 weeks (n = 33) of commencing rifampicin-based anti-TB therapy. HIV patients without TB (n = 94) receiving efavirenz-based-ART only were enrolled as control. Plasma 4β-hydroxycholesterol/cholesterol (4β-OHC/Chol) ratio, an endogenous biomarker for CYP3A activity, was determined at baseline, at 4 and 16 weeks of ART. Key Results In patients treated with efavirenz only, median 4β-OHC/Chol ratios increased from baseline by 269% and 275% after 4 and 16 weeks of ART, respectively. In TB-HIV patients, rifampicin only therapy for 4 and 8 weeks increased median 4β-OHC/Chol ratios from baseline by 378% and 576% respectively. After efavirenz/rifampicin co-treatment, 4β-OHC/Chol ratios increased by 560% of baseline (4 weeks) and 456% of baseline (16 weeks). Neither time of ART initiation, sex, genotype nor efavirenz plasma concentration were significant predictors of 4β-OHC/Chol ratios after 4 weeks of efavirenz/rifampicin co-treatment. Conclusion and Implications Rifampicin induced CYP3A more potently than efavirenz, with maximum induction occurring within the first 4 weeks of rifampicin therapy. We provide pharmacological evidence that early (4 weeks) or deferred (8 weeks) ART initiation during anti-TB therapy has no significant effect on CYP3A induction. LINKED ARTICLES This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc