Trial reportBritish journal of pharmacology2021
Early or deferred initiation of efavirenz during rifampicin-based TB therapy has no significant effect on CYP3A induction in TB-HIV infected patients.
Trial report in British journal of pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Early or deferred initiation of efavirenz during rifampicin-based TB therapy has no significant effect on CYP3A induction in TB-HIV infected patients.British journal of pharmacology · 2021Trial
- Variability in plasma rifampicin concentrations and role ofInfectious diseases (London, England) · 2024Article
- The Role of Pharmacogenomics Studies for Precision Medicine Among Ethiopian Patients and Their Clinical Implications: A Scoping Review.Pharmacogenomics and personalized medicine · 2024Article
- Genetic and non-genetic factors influencing efavirenz population pharmacokinetics among human immunodeficiency virus-1-infected children in Ethiopia.CPT: pharmacometrics & systems pharmacology · 2023Article
- Pregnancy Increases CYP3A Enzymes Activity as Measured by the 4β-Hydroxycholesterol/Cholesterol Ratio.International journal of molecular sciences · 2022Article
- Article
- Predictors of Efavirenz Plasma Exposure, Auto-Induction Profile, and Effect of Pharmacogenetic Variations among HIV-Infected Children in Ethiopia: A Prospective Cohort Study.Journal of personalized medicine · 2021Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeIn 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
resultsIn 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.
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