Assessment of Nevirapine Prophylactic and Therapeutic Dosing Regimens for Neonates

Research output: Contribution to journalArticle

  • 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
  • the PHPT-5 study team

Abstract

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.

Bibliographical metadata

Original languageEnglish
Pages (from-to)554-560
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume75
Issue number5
DOIs
StatePublished - 15 Aug 2017