title: Efavirenz plasma concentrations at 1, 3, and 6 months post-antiretroviral therapy initiation in HIV type 1-infected South African children.
abstract: The aim of this study was to quantify the plasma efavirenz concentrations over 6 months in black HIV-1-infected South African children (3-14 years), from resource-limited households, attending an outpatient clinic. The children were antiretroviral treatment (ART) naive and received efavirenz in combination with two nucleoside reverse transcriptase inhibitors according to South African national guidelines. Two blood samples were taken between 12 and 20 h after the last efavirenz dose at 1 (n = 58), 3 (n = 54), and 6 (n = 54) months post-ART initiation. A total of 328 efavirenz mid-dose plasma samples from 58 patients was determined with a validated liquid chromatography tandem mass spectrometry method. Viral suppression (<25 copies/ml) was achieved in 95% of the children after 6 months on ART. The median (range) plasma concentration at time points 1 and 2 were 2.06 (0.10-11.14) and 1.80 (0.14-10.70) microg/ml with respective mean (+/-SD) blood sampling times of 15.24 (2.03) and 16.91 (2.03) h post-evening dose. Efavirenz plasma samples within the therapeutic range of 1-4 microg/ml accounted for 58%; 17% were <1 microg/ml and 25% were >4 microg/ml over the 6 months. Efavirenz levels persistently >4 microg/ml were recorded for 13 (23%) children and 3 (5%) children had persistent efavirenz levels <1 microg/ml. Possible reasons for efavirenz plasma levels outside the accepted therapeutic range include genetic variation in drug metabolism, incorrect dosing, drug-drug interactions, and nonadherence. However, these need to be further explored and the importance of sequential plasma levels has been highlighted in this study.
authors.affiliation: Department of Pharmacology, North-West University, Potchefstroom, South Africa. Michelle.Viljoen@nwu.ac.za
authors.forename: Michelle
authors.initials: M
authors.lastname: Viljoen
authors.forename: Hermien
authors.initials: H
authors.lastname: Gous
authors.forename: Herculina S
authors.initials: HS
authors.lastname: Kruger
authors.forename: Alison
authors.initials: A
authors.lastname: Riddick
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Meyers
authors.forename: Malie
authors.initials: M
authors.lastname: Rheeders
mesh_terms: D000293:Adolescent; D000480:Alkynes; D000553:Ambulatory Care; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D010949:Plasma / Q000737:chemistry*; D013019:South Africa; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz