title: Mid-dosing interval efavirenz plasma concentrations in HIV-1-infected children in Rwanda: treatment efficacy, tolerability, adherence, and the influence of CYP2B6 polymorphisms.
abstract: This study evaluated mid-dosing interval efavirenz plasma concentrations and the influence of CYP2B6 polymorphisms in relation to efficacy, tolerability, and adherence in 97 Rwandan HIV-infected children (3-16 years). Plasma drug concentrations and CYP2B6 polymorphisms were determined. Ten children were excluded for nonadherence. Large intersubject variability in efavirenz plasma concentrations was found. Of the 87 remaining, efavirenz concentrations were therapeutic, supratherapeutic, and subtherapeutic in 67%, 20%, and 14%, respectively. No associations were found between efavirenz concentrations and central nervous system disturbances or virologic failure. Minor allele frequencies were 0.32 (516G>T), 0.33 (785A>G), and 0.09 (983T>C). Polymorphisms in CYP2B6 were strongly associated with high efavirenz levels.
authors.affiliation: Department of Pediatrics, Kigali University Teaching Hospital (KUTH), Kigali, Rwanda. mutwaph@gmail.com
authors.forename: Philippe R
authors.initials: PR
authors.lastname: Mutwa
authors.forename: Quirine
authors.initials: Q
authors.lastname: Fillekes
authors.forename: Marie
authors.initials: M
authors.lastname: Malgaz
authors.forename: Diane
authors.initials: D
authors.lastname: Tuyishimire
authors.forename: Rianne van de
authors.initials: Rv
authors.lastname: Kraats
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Boer
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
authors.forename: Narcisse
authors.initials: N
authors.lastname: Muganga
authors.forename: Sibyl P M
authors.initials: SP
authors.lastname: Geelen
mesh_terms: D000293:Adolescent; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D005260:Female; D005787:Gene Frequency; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D010949:Plasma / Q000737:chemistry*; D011110:Polymorphism, Genetic; D012432:Rwanda; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; C098320:efavirenz