In developing countries where therapeutic drug level monitoring is not readily available, HIV-infected children taking efavirenz are likely to be undertreated, according to a research team in South Africa.
Guidelines recommend that physicians maintain efavirenz trough concentrations of between 1 and 4 mg/L, Dr. Helen M. McIlleron's team notes in the June 1 issue of the Journal of Acquired Immune Deficiency Syndromes. Doses are determined based on the patient's weight.
Dr. McIlleron, a pharmacologist at the University of Cape Town, and associates evaluated efavirenz plasma concentrations in 15 children on efavirenz-based antiretroviral therapy. Ages ranged from 2.25 to 11.7 years, and subjects weighed more than 10 kg.
Blood samples were drawn three times between 12 and 24 hours after the efavirenz was taken the previous day, and concentrations were determined by liquid chromatography tandem mass spectrometry. The results were used to extrapolate 24-hour trough concentrations. Mid-dosing interval concentration was the mean of the concentrations taken between 16 and 20 hours after dose administration.
The estimated trough concentration was < 1 mg/L in 6 children (40%). Four of these subjects had mid-dosing interval concentrations < 1 mg/L. Moreover, of 5 children with detectable viral load, three had low efavirenz concentrations.
The investigators also observed "marked bimodality," with two subjects having trough concentrations > 4 mg/L and elevated mid-dosing interval concentrations.
Higher body weight was associated with lower efavirenz dose per kilogram, but higher trough concentrations, results indicate.
"Pharmacokinetic studies, including the evaluation of safety and efficacy, are urgently needed in pediatric populations to define optimal dosing strategies," Dr. McIlleron and her associates conclude.
J Acquir Immune Defic Syndr 2007;45:133-136.
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