Skip Navigation LinksHome > August 24, 2013 - Volume 27 - Issue 13 > Is nevirapine dose-escalation appropriate in young, African,...
doi: 10.1097/QAD.0b013e3283620811
Clinical Science: Concise Communication

Is nevirapine dose-escalation appropriate in young, African, HIV-infected children?

Fillekes, Quirinea; Mulenga, Veronicab; Kabamba, Desiréb; Kankasa, Chipepob; Thomason, Margaret J.c; Cook, Adrianc; Chintu, Chifumbeb; Gibb, Diana M.c; Walker, A. Sarahc; Burger, David M.a; on behalf of the CHAPAS-1 trial team

Collapse Box


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.

© 2013 Lippincott Williams & Wilkins, Inc.


Article Tools


Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.