Studies
have shown that when administered using concentration-controlled dosing, efavirenz
produces potent antiretroviral activity in children. Concentration-controlled
dosing, however, is not available in some resource-limited settings, suggesting
that pediatric patients may be receiving doses that are either too low (subtherapeutic)
or too high (with intensified side effects).
In a study reported in the
June 1, 2007 Journal of Acquired Immune Deficiency Syndromes, researchers
evaluated efavirenz plasma concentrations in 15 HIV positive children in South
Africa who were receiving the recommended doses.
To analyze efavirenz
levels, 3 consecutive blood samples were drawn between 12 and 24 hours after dosing
and analyzed using liquid chromatography tandem mass spectrometry. The trough
concentration (Cmin) of efavirenz was estimated by extrapolating the log-linear
regression line of the 3 concentration-versus-time points up to 24 hours.
Results
• The estimated efavirenz Cmin
was below 1 mg/L in 6 (40%) of the children.
•
3 of the 5 children with detectable HIV viral loads had low efavirenz
concentrations.
• Marked
bimodality in efavirenz concentrations was observed.
Conclusion
"Our
findings, together with those of previous studies, indicate that many children
dosed according to the current guidelines do not achieve adequate efavirenz exposure,"
the investigators wrote. "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."
06/29/07
Reference Y
Ren, JJ Nuttall, C Egbers, and others. High Prevalence of Subtherapeutic Plasma
Concentrations of Efavirenz in Children [Rapid Communication]. JAIDS 45(2):
133-136. June 1, 2007.
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