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Bridging dolutegravir clinical viral response across doses and formulations using model-based exposure-response

Hardik Chandasana1, Siobhán Hayes2, Ann M Buchanan3

  • 1Clinical Pharmacology Modeling & Simulation, GSK, Collegeville, Pennsylvania, USA.

AIDS (London, England)
|May 20, 2024
PubMed

Insights

Dolutegravir (DTG) exposure in children with HIV-1 is generally above the level needed for virologic response. This supports using adult dosing guidelines for pediatric DTG formulations.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Pediatrics

Background:

  • Dolutegravir (DTG) is an integrase inhibitor for HIV-1 treatment in adults and children.
  • Pediatric dosing relies on exposure matching to adults, but variability raises efficacy concerns.
  • This study evaluates DTG exposure-response in pediatric HIV-1 patients.

Purpose of the Study:

  • To assess the relationship between dolutegravir (DTG) exposure and virologic response in children with HIV-1.
  • To determine if current pediatric dosing strategies for DTG are adequate for achieving virologic suppression.
  • To identify factors influencing virologic response to DTG in pediatric populations.

Main Methods:

  • Population pharmacokinetic-pharmacodynamic (PK/PD) analysis using logistic regression.
  • Data from 146 pediatric participants (age ≥4 weeks to <18 years) in the IMPAACT P1093 study.
  • Analysis of DTG exposure metrics and covariates over 48 weeks of treatment.

Main Results:

  • No DTG exposure metric predicted virologic response within the observed range.
  • Higher baseline viral load (≥100,000 copies/mL) was associated with a lower probability of virologic response.
  • Baseline viral load significantly predicted virologic response at week 48.

Conclusions:

  • Pediatric DTG exposures appear to be above the exposure-response plateau.
  • Matching adult pharmacokinetic exposures for DTG dosing in children is a reasonable approach.
  • Baseline viral load is a key factor influencing virologic outcomes in pediatric HIV-1 treatment with DTG.
Abstract

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