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Status: Bibliographieeintrag

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Verfasst von:Aklillu, Eleni [VerfasserIn]   i
 Zumla, Alimuddin [VerfasserIn]   i
 Habtewold, Abiy [VerfasserIn]   i
 Amogne, Wondwossen [VerfasserIn]   i
 Makonnen, Eyasu [VerfasserIn]   i
 Yimer, Getnet [VerfasserIn]   i
 Burhenne, Jürgen [VerfasserIn]   i
 Diczfalusy, Ulf [VerfasserIn]   i
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
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
DOI:doi:10.1111/bph.15309
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.1111/bph.15309
 kostenfrei: Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/bph.15309
 DOI: https://doi.org/10.1111/bph.15309
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:4β-hydroxycholesterol
 co-infection
 CYP3A
 drug-drug interaction
 efavirenz
 enzyme induction
 HIV
 rifampicin
 tuberculosis
K10plus-PPN:1876311118
Verknüpfungen:→ Zeitschrift

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