ArticleJournal of acquired immune deficiency syndromes (1999)2012
Safety, tolerability, and pharmacokinetic interactions of the antituberculous agent TMC207 (bedaquiline) with efavirenz in healthy volunteers: AIDS Clinical Trials Group Study A5267.
Article in Journal of acquired immune deficiency syndromes (1999), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06253715 (Shortened Regimen for Drug-susceptible TB in Children), which is not on this map. Cited by 39 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Shortened Regimen for Drug-susceptible TB in Children
Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Pharmacokinetics of antiretroviral and tuberculosis drugs in children with HIV/TB co-infection: a systematic review.The Journal of antimicrobial chemotherapy · 2020Pooled it
- Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2B6 and Efavirenz-Containing Antiretroviral Therapy.Clinical pharmacology and therapeutics · 2019Guideline
- QT effects of bedaquiline, delamanid, or both in patients with rifampicin-resistant tuberculosis: a phase 2, open-label, randomised, controlled trial.The Lancet. Infectious diseases · 2021Trial
- Impact of Rifabutin or Rifampin on Bedaquiline Safety, Tolerability, and Pharmacokinetics Assessed in a Randomized Clinical Trial with Healthy Adult Volunteers.Antimicrobial agents and chemotherapy · 2018Trial
- Bedaquiline, Pretomanid, Linezolid, and Moxifloxacin: Mechanisms of Action, Drug Interactions, Adverse Effects and Use in Special Situations.Microorganisms · 2026Review
- An Update on the Clinical Management of HIV and Tuberculosis Co-Infection in Pregnancy: TB Preventative Therapy, Long-Acting ARVs, and Bedaquiline-Based Regimens.Current HIV/AIDS reports · 2025Review
- Bedaquiline Delivery Innovations: A Review on Advancing MDR-TB Treatment Strategies.Recent advances in anti-infective drug discovery · 2025Review
- Drug-Drug Interactions Between HIV Antivirals and Concomitant Drugs in HIV Patients: What We Know and What We Need to Know.Pharmaceutics · 2024Review
- Acceleration of infectious disease drug discovery and development using a humanized model of drug metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Bioanalysis of bedaquiline in human plasma by liquid chromatography-tandem mass spectrometry: Application to pharmacokinetic study.Journal of mass spectrometry and advances in the clinical lab · 2024Article
- QT Interval Prolongation with One or More QT-Prolonging Agents Used as Part of a Multidrug Regimen for Rifampicin-Resistant Tuberculosis Treatment: Findings from Two Pediatric Studies.Antimicrobial agents and chemotherapy · 2023Observational
- Advances of new drugs bedaquiline and delamanid in the treatment of multi-drug resistant tuberculosis in children.Frontiers in cellular and infection microbiology · 2023Review
- Evidence for Implementation: Management of TB in HIV and Pregnancy.Current HIV/AIDS reports · 2022Review
- A Scoping Review of the Clinical Pharmacokinetics of Bedaquiline.Clinical pharmacokinetics · 2022Article
- Pharmacodynamics and Bactericidal Activity of Bedaquiline in Pulmonary Tuberculosis.Antimicrobial agents and chemotherapy · 2022Article
- Review
- Treatment of Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis in Children: The Role of Bedaquiline and Delamanid.Microorganisms · 2021Review
- Chemical Classes Presenting Novel Antituberculosis Agents Currently in Different Phases of Drug Development: A 2010-2020 Review.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Are We There Yet? Short-Course Regimens in TB and HIV: From Prevention to Treatment of Latent to XDR TB.Current HIV/AIDS reports · 2020Review
- Safety implications of combined antiretroviral and anti-tuberculosis drugs.Expert opinion on drug safety · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundDrug-drug interactions complicate management of coinfection with HIV-1 and Mycobacterium tuberculosis. Bedaquiline (formerly TMC207), an investigational agent for the treatment of tuberculosis, is metabolized by cytochrome P450 (CYP) 3A which may be induced by the antiretroviral drug efavirenz.
methodsThis was a phase 1 pharmacokinetic drug interaction trial. Each healthy volunteer received two 400 mg doses of bedaquiline, the first alone and the second with concomitant steady-state efavirenz. Plasma pharmacokinetic sampling for bedaquiline and its N-monodesmethyl metabolite was performed over 14 days after each bedaquiline dose. Steady-state efavirenz pharmacokinetics were also determined. Efavirenz metabolizer status was based on CYP2B6 composite 516/983 genotype.
resultsThirty-three of 37 enrolled subjects completed the study. Geometric mean of ratios for bedaquiline with efavirenz versus bedaquiline alone were 0.82 [90% confidence interval (CI): 0.75 to 0.89] for the 14-day area under the concentration-time curve (AUC0-336 h) and 1.00 (90% CI: 0.88 to 1.13) for the maximum concentration (Cmax). For N-monodesmethyl metabolite, the geometric mean of ratios was 1.07 (90% CI: 0.97 to 1.19) for AUC0-336 h and 1.89 (90% CI: 1.66 to 2.15) for C(max). There were no grade 3 or 4 clinical adverse events. One subject developed asymptomatic grade 3 serum transaminase elevation, prompting study drug discontinuation. Efavirenz concentrations stratified by CYP2B6 genotype were similar to historical data.
conclusionsSingle-dose bedaquiline was well tolerated alone and with steady-state efavirenz. The effect of efavirenz on bedaquiline concentrations is unlikely to be clinically significant.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.