| Online-Ressource |
Verfasst von: | Aklillu, Eleni [VerfasserIn]  |
| Zumla, Alimuddin [VerfasserIn]  |
| Habtewold, Abiy [VerfasserIn]  |
| Amogne, Wondwossen [VerfasserIn]  |
| Makonnen, Eyasu [VerfasserIn]  |
| Yimer, Getnet [VerfasserIn]  |
| Burhenne, Jürgen [VerfasserIn]  |
| 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 |
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 |
Early or deferred initiation of efavirenz during rifampicin-based TB therapy has no significant effect on CYP3A induction in TB-HIV infected patients / Aklillu, Eleni [VerfasserIn]; August 2021 (Online-Ressource)