Optimizing pediatric dosing recommendations and treatment management of antiretroviral drugs utilizing therapeutic drug monitoring data in children living with HIV

INTRODUCTION: This review summarises the current dosing recommendations for antiretroviral drugs (ARVs) in the international pediatric guidelines of the World Health Organisation (WHO), US Department of Health and Human Services (DHHS), and Paediatric European Network for Treatment of AIDS (PENTA) and evaluates the research that informed these approaches. We further explore the role of data generated through therapeutic drug monitoring (TDM) in optimizing the dosing of ARVs in children. METHODS: A PubMed search was conducted for literature on ARV dosing published in English. Additionally, the registration documentation of European Medicines Agency and the US Food and Drug Administration for currently used ARVs and studies referenced by WHO, DHHS and EMA guidelines were screened. Resulting publications were screened for papers containing data on the area under the concentration-time curve, trough concentration, and peak concentration. Studies with enrolled participants with median or mean age of >/=18 years were excluded. No restriction on publishing date was applied. DISCUSSION & CONCLUSION: Pediatric ARV dosing is frequently based on data obtained from small studies and is often simplified to facilitate dosing in the context of a public health approach. Pharmacokinetic (PK) parameters of pediatric ARVs are subject to high inter-patient variation and this leads to a potential risk for under or overdosing when drugs are used in real life. To ensure optimal use of ARVs and validate dosing recommendations for children, it is essential to monitor ARV dosing more thoroughly with larger sample sizes and to include diverse sub-populations. TDM data generated in children, where available and affordable, has the potential to enhance our understanding of the appropriateness of simplified paediatric dosing strategies recommended using a public health approach and to uncover suboptimal dosing or other unanticipated issues post-marketing, further facilitating the ultimate goal of optimizing pediatric antiretroviral treatment.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal

• Population(s)
  • Children or Youth (less than 18 years old)
  • General HIV+ population
• Engagement and Care Cascade
  • Treatment
• Prevention
  • Biomedical interventions