Is dose adjustment of dolutegravir necessary in Chinese adults living with HIV across different body weight levels? A population pharmacokinetics analysis.

Abstract

Background: Dolutegravir (DTG) is an integrase strand transfer inhibitor indicated for human immunodeficiency virus (HIV) infection. Although intrinsic factors show no ethnic-specific impact on DTG pharmacokinetics, extrinsic factors may modulate its pharmacokinetic profile.

Research design and methods: This study developed a population pharmacokinetic model for DTG in Chinese adults living with HIV and identified key covariates influencing its pharmacokinetics using nonlinear mixed-effects modeling.

Results: A total of 302 DTG concentrations from 293 Chinese patients receiving once-daily 50 mg DTG were analyzed. A one-compartment model with first-order absorption and elimination characterized the data. The estimated parameters were as follows: an absorption rate constant of 0.222 h^-1, an apparent clearance of 0.843L·h^-1, and a volume of distribution of 9.32 L. Body weight (WT) was identified as a significant (p < 0.01) covariate influencing apparent clearance. Monte Carlo simulations indicated that under the standard 50 mg once-daily regimen, DTG exposure was comparable across the WT range of 40-100 kg.

Conclusion: The findings may contribute to more personalized and effective treatment for Chinese adults living with HIV. In this predominantly male cohort, WT-based dose adjustment was generally not warranted among patients weighing 40-100 kg who received DTG 50 mg once daily.