Assessment of Nevirapine Prophylactic and Therapeutic Dosing Regimens for Neonates

• Main Authors: Tim R. Cressey, Baralee Punyawudho, Sophie Le Coeur, Gonzague Jourdain, Chalermpong Saenjum, Edmund V. Capparelli, Kanokwan Jittayanun, Siriluk Phanomcheong, Anita Luvira, Thitiporn Borkird, Achara Puangsombat, Leon Aarons, Pra Ornsuda Sukrakanchana, Saik Urien, Marc Lallemant, Suraphan Sangsawang, Jullapong Achalapong, Kanchana Preedisripipat, Chaiwat Putiyanun, Vanichaya Wanchaitanawong, Prapap Yuthavisuthi, Chaiwat Ngampiyaskul, Prateep Kanjanavikai, Nantasak Chotivanich, Suchat Hongsiriwon, Weerapong Suwankornsakul, Phantip Sreshthatat, Annop Kanjanasing, Ratchanee Kwanchaipanich, Boonsong Rawangban, Sadhit Santadusit, Tapnarong Jarupanich, Boonyarat Warachit, Thitiporn Siriwachirachai, Pornpimon Rojanakarin, Kraisorn Vivatpatanakul, Sansanee Hanpinitsak, Phaiboon Wanasiri, Sakulrat Srirojana, Rucha Kongpanichkul, Suthunya Bunjongpak, Prapan Sabsanong, Prateung Liampongsabuddhi, Kultida Pongdetudom, Prayoon Khamja, Noppadon Akarathum, Supha Arth Phonin, Wannee Limpitikul, Jantana Jungpipun, Ratikorn Petprakorp, Sukit Mahattanan, Somsri Kotchawet, Toranong Pilalai
• Format: Journal
• Published: 2018
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85025687300&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/47079
• Institution: Chiang Mai University

© Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved. Background: Nevirapine (NVP) is a key component of antiretroviral prophylaxis and treatment for neonates. We evaluated current World Health Organization (WHO) weight-band NVP prophylactic dosing recommendations and investigated optimal therapeutic NVP dosing for neonates. Methods: 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 pharmacokinetics (PK) parameters were estimated using nonlinear 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. Results: 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 1-compartment PK model. Infant weight and postnatal age influenced NVP PK parameters. Based on simulations for a 3-kg infant, ≥92% would have an 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. Conclusion: 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.