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.
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].
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%).
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: firstname.lastname@example.org).
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