Objectives: Young children metabolize nevirapine faster than older children/adults. We evaluated nevirapine pharmacokinetics with or without dose-escalation in Zambian, HIV-infected infants/children and its relationship with safety/efficacy.
Design: A retrospective pharmacokinetic substudy of the CHAPAS-1 trial.
Methods: HIV-infected, Zambian children were randomized to initiate antiretroviral therapy (ART) with full-dose twice-daily nevirapine versus 2-week nevirapine dose-escalation. Samples taken 3–4 h postmorning-dose 2 weeks after nevirapine initiation were assayed for nevirapine levels. Viral load was measured on available samples at weeks 4 and 48; adverse events were prospectively reported.
Results: Of 162 (77%) children with week-2 samples, 79 (49%) were randomized to nevirapine dose-escalation. At ART initiation, median [interquartile range (IQR)] age, weight and CD4% were 5.2 (1.5–8.7) years, 13.0 (8.1–19.0) kg and 13 (8–18)%, respectively; 81 (50%) were male. With full dose, few children aged less than 2 years (3/23, 13%) or more than 2 years (4/60, 7%) had subtherapeutic nevirapine levels (defined as <3.0 mg/l), but with dose-escalation, seven out of 22 (32%) aged less than 2 years versus seven out of 57 (12%) more than 2 years had subtherapeutic nevirapine levels (P = 0.05). There was no difference between week-2 nevirapine levels in those with viral load more than 250 versus less than 250 copies/ml at week 4 (P = 0.97) or week 48 (P = 0.40). Eleven out of 162 children had grade 1/2 rash; all were more than 2 years of age (P = 0.04), and 10 were randomized to full dose.
Conclusion: Subtherapeutic nevirapine levels 3–4 h postdose were more frequent in young children on dose-escalation. Younger children were at lower risk for rash. To simplify ART initiation and reduce the risk of suboptimal dosing, full-dose nevirapine at ART initiation should be considered for African HIV-infected children less than 2 years of age.
aRadboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
bUniversity Teaching Hospital, Lusaka, Zambia
cMRC Clinical Trials Unit, London, UK.
Correspondence to Quirine Fillekes, MSc, Department of Pharmacy, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Tel: +31 24 3616408; fax: +31 24 3668755; e-mail: Q.Fillekes@akf.umcn.nl
Received 15 March, 2013
Accepted 4 April, 2013