Background: There are insufficient data on pediatric antiretroviral therapy (ART) pharmacokinetics (PK), particularly for children in low and middle-income countries.
Methods: We conducted a prospective nevirapine (NVP) PK study among HIV-infected Kenyan children aged 3-13 years initiating an NVP-based ART regimen. NVP dose timing was measured through medication event monitors (MEMS(R)). Participants underwent 2 inpatient assessments; one at 4 to 8 weeks after ART initiation and one 3 to 4 months after ART initiation. Allometric scaling of oral clearance (CL)/bioavailability (F) and volume of distribution (Vd)/F values were computed. Nonlinear mixed effects modeling using the First Order Conditional Estimation with Interaction method was performed with covariates. The impact of adherence on time below minimum effective concentration (MEC) was assessed in the final PK model using MEMS(R) data and model-estimated individual parameters.
Results: Among 21 children enrolled, mean age was 5.4 years and 57% were female. CL/F was 1.67 L/h and Vd/F was 3.8 L for a median child weighing 15 kg. Participants' age had a significant impact on CL/F (p <0.05), with an estimated decrease in CL of 6.2% for each one-year increase in age. Total body water percentage was significantly associated with Vd/F (p <0.001). No children had >10% of time below MEC when the PK model assumed perfect adherence compared to 10 children when adherence data were used.
Conclusions: Age and body composition were significantly associated with children's NVP PK parameters. ART adherence significantly impacted drug exposure over time, revealing sub-therapeutic windows that may lead to viral resistance.
(C) 2014 by Lippincott Williams & Wilkins