Background:  We previously reported 12-hour pharmacokinetic profiles of nevirapine (NVP), stavudine (d4T), and lamivudine (3TC) in HIV-infected African children after taking fixed-dose combination antiretroviral tablets (Triomune Baby—50 mg NVP, 6 mg d4T, 30 mg 3TC) and Junior (double Baby dose). However, this study included only 2 children with body weight 3 to 6 kg; we therefore undertook pharmacokinetic evaluations in 14 additional children weighing 3 to 6 kg.

Methods:  We included 16 HIV-infected children aged 1 month or older, weighing 3 to 6 kg, and fulfilling WHO criteria for initiating treatment. Children were admitted for a 12-hour pharmacokinetic sampling session at least 4 weeks after starting treatment. Samples were taken at t = 0, 2, 6, and 12 hours after observed intake of 1 tablet Triomune Baby. NVP plasma concentrations were determined using high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters (AUC, C_max, C_min) were determined using noncompartmental methods.

Results:  One child was excluded because of nonadherence. The median (interquartile range) age, body weight and daily NVP dose of the remaining 15 children (8 girls; 7 boys) were 5.3 (4.1 to 8.4) months, 5.3 (4.2 to 5.5) kg, and 348 (324-386) mg/m², respectively. The mean (standard deviation) NVP AUC_0-12h, C_max and C_min were 78.7 (30.2) h.mg/L, 8.1 (2.4) mg/L, and 4.9 (2.6) mg/L, respectively. These values are higher than reported in adults, but are 15 to 20% lower than observed previously in Zambian children with body weight >6 kg taking these pediatric fixed-dose combinations. Of some concern, 4 of the 15 (27%) children with body weight 3 to 6 kg had a subtherapeutic NVP C_min (defined as <3.0 mg/L) compared to only 3 of 63 (5%) children with body weight >6 kg (p = 0.02, Exact Test). While children aged <5 months appeared to have a higher risk for a subtherapeutic NVP C_min than those 5 months or older, numbers were too small to reach statistical significance—3 of 6 (50%) vs 1 of  9 (11%), p = 0.24; note, dose range in those <5 months was 324 to 406 mg/m².

Conclusions:  Exposure to NVP in African HIV-infected children with low body weight taking fixed-dose combination tablets appears on average to be adequate, but due to large intersubject variability a relatively high proportion of children had subtherapeutic NVP C_min levels, particularly those aged <5 months. As infants <5 months may be at risk for low NVP exposure for only a short time after initiating treatment, the clinical consequences of such low C_min may be minor, but require further evaluation.