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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Effects of rifampin-based antituberculosis therapy on plasma efavirenz concentrations in children vary by CYP2B6 genotype
AIDS, Volume 27, No. 12, Year 2013
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Description
Objectives: An 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. Design: Plasma 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. Results: Compared 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 intermediatemetabolizer 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. Conclusion: Antituberculosis 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. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Authors & Co-Authors
McIlleron, Helen Margaret
United States, Atlanta
Division of Clinical Research
South Africa, Observatory
Institute of Infectious Disease and Molecular Medicine
Schomaker, Michael
South Africa
Center for Infectious Disease Epidemiology and Research
Ren, Yuan
United States, Atlanta
Division of Clinical Research
Sinxadi, Phumla Zuleika
United States, Atlanta
Division of Clinical Research
Nuttall, James J.C.
South Africa, Cape Town
University of Cape Town
South Africa, Cape Town
Red Cross War Memorial Children's Hospital
Gous, Hermien
South Africa, Johannesburg
University of the Witwatersrand Faculty of Health Sciences
Moultrie, Harry
South Africa, Johannesburg
University of the Witwatersrand Faculty of Health Sciences
Eley, Brian S.
South Africa, Cape Town
University of Cape Town
South Africa, Cape Town
Red Cross War Memorial Children's Hospital
Merry, Concepta
Uganda, Kampala
Makerere University
Ireland, Dublin
Trinity College Dublin
Smith, Peter John
United States, Atlanta
Division of Clinical Research
Haas, David William
United States, Nashville
Vanderbilt University School of Medicine
Maartens, Gary Tuberculosis
United States, Atlanta
Division of Clinical Research
South Africa, Observatory
Institute of Infectious Disease and Molecular Medicine
Statistics
Citations: 57
Authors: 12
Affiliations: 9
Identifiers
Doi:
10.1097/QAD.0b013e328360dbb4
e-ISSN:
14735571
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Noncommunicable Diseases
Study Design
Randomised Control Trial