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.