title: Nevirapine Pharmacokinetics and Safety in Neonates Receiving Combination Antiretroviral Therapy for Prevention of Vertical HIV Transmission.
abstract: BACKGROUND
  Nevirapine (NVP)-based combination antiretroviral therapy is routinely prescribed to infants deemed at high risk of vertical HIV infection in our centers. We evaluated NVP pharmacokinetics and safety of this regimen.
  
  
  METHODS
  Neonates were recruited prospectively between September 2012 and April 2015 or enrolled retrospectively if treated similarly before prospective study initiation. NVP was dosed at 150 mg/m daily for 14 days, then twice daily for 14 days. NVP levels were drawn at weeks 1, 2, and 4 [target trough (NVP-T): 3-8 mg/L].
  
  
  RESULTS
  Thirty-three neonates were included (23 prospectively). Median gestational age (GA) and birth weight were 38 weeks (32-41 weeks) and 2.9 kg (1.5-4.2 kg), respectively. Median NVP-Ts were 8.2 mg/L (1.6-25.1 mg/L), 3.5 mg/L (1.6-6.8 mg/L), and 4.3 mg/L (0.1-19.9 mg/L) at weeks 1, 2, and 4, respectively. The proportions with therapeutic NVP-T were 42%, 61%, and 73% at these same timepoints. Median apparent oral clearance (CL/F) increased from 0.05 L·kg·h (0.01-0.50 L·kg·h) at week 2 to 0.18 L·kg·h (0.01-0.78 L·kg·h) at week 4. Increased drug exposure [area under the curve (AUCτ)] correlated with younger GA (r = 0.459, P = 0.032) and lower birth weight (r = 0.542, P = 0.009). The most common adverse events potentially attributable to combination antiretroviral therapy were transient asymptomatic hyperlactatemia (26%), anemia (24.7%), and neutropenia (22.1%).
  
  
  CONCLUSIONS
  Treatment dose NVP was generally well-tolerated and associated with normalization of trough levels over time in most cases without dose adjustment. Lower empiric dosing is recommended for infants <34 weeks of GA. Routine therapeutic drug monitoring may not be required for infants ≥34 weeks of GA.
authors.affiliation: *Department of Pharmacy, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; †Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada; ‡Department of Paediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada; Departments of §Paediatrics; ‖Obstetrics and Gynecology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; ¶Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; Departments of #Paediatric Laboratory Medicine; and **Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Elaine
authors.initials: E
authors.lastname: Lau
authors.forename: Jason
authors.initials: J
authors.lastname: Brophy
authors.forename: Lindy
authors.initials: L
authors.lastname: Samson
authors.forename: Fatima
authors.initials: F
authors.lastname: Kakkar
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Campbell
authors.forename: Mark H
authors.initials: MH
authors.lastname: Yudin
authors.forename: Kellie
authors.initials: K
authors.lastname: Murphy
authors.forename: Winnie
authors.initials: W
authors.lastname: Seto
authors.forename: David
authors.initials: D
authors.lastname: Colantonio
authors.forename: Stanley E
authors.initials: SE
authors.lastname: Read
authors.forename: Ari
authors.initials: A
authors.lastname: Bitnun
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D018890:Chemoprevention / Q000009:adverse effects / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000517:prevention & control*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D011446:Prospective Studies; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D019829:Nevirapine