High prevalence of subtherapeutic plasma concentrations of efavirenz in children.
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.
Ren
Yuan
Y
Pharmacokinetic Research Unit, Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Nuttall
James J C
JJ
Egbers
Claire
C
Eley
Brian S
BS
Meyers
Tammy M
TM
Smith
Peter J
PJ
Maartens
Gary
G
McIlleron
Helen M
HM
D000293:Adolescent; D000480:Alkynes; D019380:Anti-HIV Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D048588:Benzoxazines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D019562:Viral Load
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz