Abstract
Background: No evidence-based optimal dosing guidance is available for abacavir liquid formulation use from birth. We used abacavir pharmacokinetic data from neonates and infants to determine an exact abacavir dosing strategy (mg/kg) for infants aged 0–3 months and to propose dosing by WHO weight band for neonates. Methods: Abacavir pharmacokinetic and safety data were pooled from three completed studies (1997–2020): PACTG 321 (USA), the Tygerberg Cohort (South Africa), and IMPAACT P1106 (South Africa). PACTG 321 and the Tygerberg Cohort were performed in neonates exposed to HIV receiving a single dose of abacavir. IMPAACT P1106 included predominantly low birthweight (<2500 g) infants on antiretroviral therapy enrolled when they were younger than 3 months. We developed a population pharmacokinetic model and performed simulations to achieve abacavir exposures (area under the curve for 0–12 h) within the target range of 3·2–25·2 μg·h/mL, previously reported in older children. Findings: 45 infants contributed 308 abacavir concentrations; 21 neonates were younger than 15 days. At first pharmacokinetic assessment, median postnatal age for PACTG 321 was 1 day and median bodyweight was 3·1 kg; for the Tygerberg Cohort it was 10 days and 3·3 kg; and for IMPAACT P1106 it was 73 days and 3·8 kg. Our model predicted a slow abacavir clearance of 2·51 mL/min per kg at birth, which doubled by 4 weeks of age. Therapeutic targets were achieved with exact abacavir doses of 2·0 mg/kg twice daily from 0 weeks to 4 weeks and 4·0 mg/kg twice daily from 4 weeks to 12 weeks. A fixed weight-band dosing strategy of 8 mg (for 2–3 kg), 10 mg (3–4 kg), and 12 mg (4–5 kg) abacavir twice daily achieved target exposures throughout the first 4 weeks of life without the need for dose adjustment due to age or bodyweight changes. No adverse events of grade 3 or higher were related to abacavir. Interpretation: Integration of these dosing recommendations into National and International guidelines for the abacavir liquid formulation will expand antiretroviral options from birth and simplify the clinical management of neonates with HIV.