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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
High prevalence of subtherapeutic plasma concentrations of efavirenz in children
Journal of Acquired Immune Deficiency Syndromes, Volume 45, No. 2, Year 2007
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Description
OBJECTIVE: Efavirenz-containing regimens using concentration-controlled dosing have been shown to provide potent antiretroviral activity in children. In many settings, concentration-controlled dosing is not available. In this study, efavirenz plasma concentrations were evaluated in South African HIV-infected children receiving efavirenz-based antiretroviral treatment. METHODS: Three consecutive blood samples were drawn between 12 and 24 hours after dosing in 15 HIV-infected children receiving the recommended daily doses of efavirenz. Validated liquid chromatography tandem mass spectrometry methods were used to determine plasma levels of efavirenz. The trough concentration (Cmin) of efavirenz was estimated by extrapolation of the log-linear regression line of the 3 concentration versus time points to 24 hours. RESULTS: The estimated Cmin was <1 mg/L in 6 (40%) of the children. Three of the 5 children with detectable viral loads had low efavirenz concentrations. Marked bimodality in efavirenz concentrations was observed. CONCLUSIONS: Our findings, together with those of previous studies, indicate that many children dosed according to the current guidelines do not achieve adequate efavirenz exposure. Because low efavirenz concentrations are associated with the rapid emergence of efavirenz-resistant mutations and treatment failure, the current recommended efavirenz doses should be re-evaluated, especially in developing countries, where therapeutic drug monitoring is seldom available. © 2007 Lippincott Williams & Wilkins, Inc.
Authors & Co-Authors
Ren, Yuan
South Africa, Cape Town
University of Cape Town
Nuttall, James J.C.
South Africa, Cape Town
University of Cape Town
Egbers, Claire
South Africa, Johannesburg
Chris Hani Baragwanath Hospital
South Africa, Johannesburg
University of the Witwatersrand
Eley, Brian S.
South Africa, Cape Town
University of Cape Town
Meyers, Tammy M.M.
South Africa, Johannesburg
Chris Hani Baragwanath Hospital
South Africa, Johannesburg
University of the Witwatersrand
Smith, Peter J.D.
South Africa, Cape Town
University of Cape Town
Maartens, Gary Tuberculosis
South Africa, Cape Town
University of Cape Town
McIlleron, Helen Margaret
South Africa, Cape Town
University of Cape Town
South Africa, Observatory
Groote Schuur Hospital
Statistics
Citations: 75
Authors: 8
Affiliations: 4
Identifiers
Doi:
10.1097/QAI.0b013e31805c9d52
ISSN:
15254135
Research Areas
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study