New article: BJCP - Therapeutic drug monitoring of dolutegravir in children and adolescents living with HIV: A retrospective study

Background:
Dolutegravir (DTG)-based antiretroviral therapy is recommended as both first-line and salvage treatment for HIV across all age groups. However, achieving therapeutic DTG plasma levels in children can be difficult due to individual variability and adherence issues. The role of therapeutic drug monitoring (TDM) in pediatric patients is not well established. This study aimed to evaluate the use and effectiveness of DTG TDM in children.

Materials and Methods:
Researchers retrospectively analyzed TDM data from the Québec Antiretroviral Therapeutic Drug Monitoring Program (2011–2022). Children under 18 with at least one DTG TDM were included. Samples with unknown or early post-dose timing were excluded. Trough concentrations (Ctau) were estimated using average half-lives based on age or weight. Thresholds for efficacy and toxicity were set at ≥0.32 and ≥1.47 mg/L, respectively. Viral suppression was defined as <50 copies/mL. Variability was assessed, and mean Ctau values were compared between suppressed and non-suppressed patients.

Results:
Fifty-three children (55% female) provided 249 samples (average 8.6 per child). At first TDM, the average age was 11.1 years and weight 43.6 kg; 86% had viral suppression. TDM was mostly requested for pediatric or control purposes. Mean Ctau was 2.07 mg/L: 21% therapeutic, 4.8% subtherapeutic, 55% supratherapeutic. Pharmacists recommended taking DTG without food in 17.3% of cases and dose reduction due to CNS side effects in 45.8%, though no dose reductions were implemented. All children weighing 6 to <14 kg had supratherapeutic levels, as did many in higher weight bands. Interindividual variability was high (CV 65.4%), intra-individual lower (median CV 25.6%). No significant difference in Ctau was found between suppressed and non-suppressed patients. Viral suppression improved from 86% to 93% over the first four TDMs, with more therapeutic Ctau levels and fewer supratherapeutic ones. Among those with subtherapeutic levels, most reached therapeutic levels by their final TDM.

Conclusions:
There was high interindividual variability and frequent supratherapeutic DTG levels in pediatric patients. The clinical relevance of these high levels remains uncertain. However, improved virologic outcomes over time suggest potential benefit from TDM. Current weight-based dosing guidelines may need refinement to avoid unnecessarily high drug concentrations.

Additional information to the following link: Therapeutic drug monitoring of dolutegravir in children and adolescents living with HIV: A retrospective study - Pilote - 2025 - British Journal of Clinical Pharmacology - Wiley Online Library