Nevirapine Pharmacokinetics and Safety in Neonates Receiving Combination Antiretroviral Therapy for Prevention of Vertical HIV Transmission.

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.