Journal of acquired immune deficiency syndromes (1999) 2017 05 09() doi 10.1097/QAI.0000000000001447
Nevirapine (NVP) is a key component of antiretroviral prophylaxis and treatment for neonates. We evaluated current WHO weight-band NVP prophylactic dosing recommendations and investigated optimal therapeutic NVP dosing for neonates.
The PHPT-5 study in Thailand assessed the efficacy of ‘Perinatal Antiretroviral Intensification’ to prevent mother-to-child transmission of HIV in women with <8 weeks of antiretroviral treatment before delivery (NCT01511237). Infants received a 2-week course of zidovudine/lamivudine/NVP [NVP syrup/once daily: 2 mg/kg for 7 days; then 4 mg/kg for 7 days]. Infant samples were assessed during the first 2-weeks of life. NVP population PK parameters were estimated using non-linear mixed-effects models. Simulations were performed to estimate the probability of achieving target NVP trough concentrations for prophylaxis (>0.10 mg/L) and for therapeutic efficacy (>3.0 mg/L) using different infant dosing strategies.
Sixty infants (55% male) were included. At birth, median (range) weight was 2.9 (2.3-3.6) kg. NVP concentrations were best described by a one compartment PK model. Infant weight and post-natal age influenced NVP PK parameters. Based on simulations for a 3-kg infant, ≥92% would have a NVP trough >0.1 mg/L after 48 hours through 2 weeks using the PHPT-5 and WHO-dosing regimens. For NVP-based therapy, a 6 mg/kg twice daily dose produced a trough >3.0 mg/L in 87% of infants at 48 hours and 80% at 2 weeks.
WHO weight-band prophylactic guidelines achieved target concentrations. Starting NVP 6 mg/kg twice daily from birth is expected to achieve therapeutic concentrations during the first 2 weeks of life.