Is Routine Therapeutic Drug Monitoring of Anti-Retroviral Agents Warranted in Children Living with HIV?

Jennifer Tam; Elaine Lau; Stanley Read; Ari Bitnun

doi:10.5863/1551-6776-27.6.551

Is Routine Therapeutic Drug Monitoring of Anti-Retroviral Agents Warranted in Children Living with HIV?

J Pediatr Pharmacol Ther. 2022;27(6):551-557. doi: 10.5863/1551-6776-27.6.551. Epub 2022 Aug 19.

Authors

Jennifer Tam^{1

2

3}, Elaine Lau^{2

4}, Stanley Read^{1

2}, Ari Bitnun^{1

2}

Affiliations

¹ Division of Infectious Diseases, Department of Pediatrics (JT, SR, AB), The Hospital for Sick Children, Toronto, ON, Canada.
² University of Toronto (JT, EL, SR, AB), Toronto, ON, Canada.
³ Division of Infectious Diseases, Department of Pediatrics (JT), BC Children's Hospital, Vancouver, BC, Canada.
⁴ Department of Pharmacy (EL), The Hospital for Sick Children, Toronto, ON, Canada.

Abstract

Objective: The utility of routine therapeutic drug monitoring (TDM) in children living with HIV has not been extensively studied. The purpose of this study was to assess this strategy.

Methods: This was a single-center, prospective observational study of routine TDM for protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and integrase strand transfer inhibitors (INSTIs) in children living with HIV who were receiving antiretroviral therapy (ART) between February and December 2014. Outcome measures included the proportion of serum antiretroviral (ARV) medication concentrations in the therapeutic range (target values extrapolated from adult data) and the effect of serum concentrations on virologic control, medication adherence, and toxicity.

Results: Forty-eight children with a median age of 13 years (interquartile range, 3-18) were included. Median viral load (VL) and CD4% were <40 copies/mL (range, <40-124) and 37.4% (range, 8.4-47.9), respectively. Adherence was considered excellent in 95.8% of patients. Of the 50 serum trough concentrations (PI n = 19 [38%]; NNRTI n = 27 [54%]; INSTI n = 4 [8%]), 66% (n = 33) were in the therapeutic range, 12% (n = 6) were subtherapeutic, and 22% (n = 11) were supratherapeutic. There was no statistically significant correlation between serum ARV concentrations and patient demographics, VL, CD4%, or adherence. No clinically significant adverse events were noted. One dose adjustment was made for a subtherapeutic serum raltegravir concentration, likely attributable to interaction with ritonavir.

Conclusions: This study does not support routine TDM in healthy children living with HIV who are well controlled on antiretroviral medication regimens. A more targeted strategy, such as when adherence is questioned or when there are suspected drug interactions, may be more appropriate.

Keywords: HIV; pediatrics; therapeutic drug monitoring.