Model-informed Dolutegravir Dose Selection in Pediatrics With First-generation INSTI Resistance

Area of Science:

• Pharmacology
• Infectious Diseases
• Pediatrics

Background:

• Dolutegravir is an integrase strand transfer inhibitor used for HIV treatment.
• Current dosing is approved for adults but not for pediatric populations.
• HIV-1 resistance to integrase strand transfer inhibitors is a growing concern.

Purpose of the Study:

• To establish a weight-tiered, twice-daily Dolutegravir dosing regimen for children.
• To predict Dolutegravir exposures in pediatric patients using population pharmacokinetic modeling.
• To evaluate the potential for similar efficacy and safety in children compared to adults.

Main Methods:

• Population pharmacokinetic modeling was employed.
• Simulations were conducted to assess dosing outcomes.
• Weight-tiered dosing strategies were analyzed.

Main Results:

• A weight-tiered, twice-daily Dolutegravir dose was identified for pediatric use.
• Simulations predicted Dolutegravir exposures within the therapeutic window.
• The proposed dosing is expected to provide efficacy and safety comparable to adults.

Conclusions:

• The identified weight-tiered dosing regimen offers a potential solution for pediatric Dolutegravir treatment.
• Pharmacokinetic modeling supports the use of this regimen in children with HIV.
• Further clinical validation is warranted to confirm efficacy and safety in pediatric populations.