ArticleAIDS (London, England)2013
Effects of rifampin-based antituberculosis therapy on plasma efavirenz concentrations in children vary by CYP2B6 genotype.
Article in AIDS (London, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 3 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 3 syntheses or guidelines pooled it, 53 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
- Pharmacokinetics of efavirenz in patients on antituberculosis treatment in high human immunodeficiency virus and tuberculosis burden countries: A systematic review.British journal of clinical pharmacology · 2018Pooled it
- CYP2B6 Genotype and Weight Gain Differences Between Dolutegravir and Efavirenz.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Trial
- CYP2B6 Genotype-Dependent Inhibition of CYP1A2 and Induction of CYP2A6 by the Antiretroviral Drug Efavirenz in Healthy Volunteers.Clinical and translational science · 2019Trial
- Multiphenotype association study of patients randomized to initiate antiretroviral regimens in AIDS Clinical Trials Group protocol A5202.Pharmacogenetics and genomics · 2017Trial
- Rifampin enhances cytochrome P450 (CYP) 2B6-mediated efavirenz 8-hydroxylation in healthy volunteers.Drug metabolism and pharmacokinetics · 2016Trial
- Efavirenz Pharmacokinetics and Pharmacodynamics in HIV-Infected Persons Receiving Rifapentine and Isoniazid for Tuberculosis Prevention.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2015Trial
- Factors associated with variability in rifampin plasma pharmacokinetics and the relationship between rifampin concentrations and induction of efavirenz clearance.Pharmacotherapy · 2014Trial
- Pharmacokinetics, pharmacogenetics, and toxicity of co-administered efavirenz and isoniazid.Southern African journal of HIV medicine · 2025Article
- Pharmacogenetics in Tuberculosis-HIV Coinfected Populations: A Systematic Review of Genetic Variants Influencing Antiretroviral and Anti-Tuberculosis Drug Response.Journal of multidisciplinary healthcare · 2025Review
- Advances in Antiretroviral Therapy for Patients with Human Immunodeficiency Virus-Associated Tuberculosis.Viruses · 2024Review
- Electroencephalography as a diagnostic tool for late-onset efavirenz neurotoxicity syndrome.PloS one · 2023Article
- Pharmacokinetics of Efavirenz 600mg in Combination with Rifampicin in Chinese HIV/TB Co-Infection Patients.Infection and drug resistance · 2023Article
- Late-onset efavirenz toxicity: A descriptive study from Pretoria, South Africa.Southern African journal of HIV medicine · 2023Article
- Concentration-response relationships of dolutegravir and efavirenz with weight change after starting antiretroviral therapy.British journal of clinical pharmacology · 2022Article
- Safety implications of combined antiretroviral and anti-tuberculosis drugs.Expert opinion on drug safety · 2020Review
- Population pharmacokinetics of efavirenz in HIV and TB/HIV coinfected children: the significance of genotype-guided dosing.The Journal of antimicrobial chemotherapy · 2019Article
- Management of active tuberculosis in adults with HIV.The lancet. HIV · 2019Review
- Effect of Rifampin-Isoniazid-Containing Antituberculosis Therapy on Efavirenz Pharmacokinetics in HIV-Infected Children 3 to 14 Years Old.Antimicrobial agents and chemotherapy · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
Abstract
objectivesAn efavirenz-based antiretroviral therapy (ART) regimen is preferred for children more than 3 years of age with tuberculosis. However, rifampin, a key component of antituberculosis therapy, induces CYP2B6. An increased dose of efavirenz is recommended in adults weighing more than 50 kg who require rifampin, but there is scant information in children being treated for tuberculosis.
designPlasma efavirenz concentrations were compared in 40 children during concomitant treatment for tuberculosis and HIV-1, after stopping rifampicin, and in a control group of children without tuberculosis. Associations with antituberculosis treatment, metabolizer genotype (based on CYP2B6 516G→T, 983T→C, and 15582C→T), weight, and time after dose were evaluated.
resultsCompared to children with extensive metabolizer genotypes, efavirenz concentrations were increased 1.42-fold (95% confidence interval, CI 0.94–2.15) and 2.85-fold (95% CI 1.80–4.52) in children with intermediate and slow metabolizer genotypes, respectively. Concomitant antituberculosis treatment increased efavirenz concentrations 1.49-fold (95% CI 1.10–2.01) in children with slow metabolizer genotypes, but did not affect efavirenz concentrations in extensive or intermediate metabolizer genotypes. After adjustment for dose/kg, each kilogram of weight was associated with a 2.8% (95% CI 0.9–4.7) decrease in efavirenz concentrations. Despite higher milligram per kilogram doses, a higher proportion of children in the lowest weight band (10–13.9 kg) had efavirenz concentrations less than 1.0 mg/l than larger children.
conclusionAntituberculosis treatment was not associated with reduced efavirenz concentrations in children, which does not support increased efavirenz doses. Children with slow metabolizer genotype have increased efavirenz concentrations during antituberculosis treatment, likely due to isoniazid inhibiting enzymes involved in accessory metabolic pathways for efavirenz.
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