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/m2 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−1·h−1 (0.01–0.50 L·kg−1·h−1) at week 2 to 0.18 L·kg−1·h−1 (0.01–0.78 L·kg−1·h−1) 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.
*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.
Correspondence to: Elaine Lau, BScPhm, PharmD, MSc, Department of Pharmacy, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada (e-mail: email@example.com).
Supported by the Canadian Foundation for AIDS Research (CANFAR) grant # 023 505.
Presented in part at the 23rd Canadian Conference on HIV/AIDS Research (CAHR Meeting); May 1–4, 2014, St. John's, Newfoundland, Canada (abstract no. P074), the 6th International HIV Pediatrics Workshop, Melbourne, Australia; July 18–19, 2014, and the 25th Canadian Conference on HIV/AIDS Research (CAHR Meeting); May 12–16, 2016, Winnipeg, Manitoba, Canada (abstract no. CSP11.01).
The authors have no conflicts of interest to disclose.
Received August 12, 2016
Accepted January 11, 2017