Population pharmacokinetics of bictegravir in real-world people with HIV
Bictegravir is a widely prescribed integrase strand transfer inhibitor, yet its pharmacokinetic profile has not been characterized in real-world clinical settings. In a study published in the Journal of Antimicrobial Chemotherapy, Ekobena et al. investigated bictegravir population pharmacokinetics and covariates affecting its exposure among participants of the Swiss HIV Cohort Study.
The study included 572 people with HIV who underwent therapeutic drug monitoring at the Lausanne University Hospital between July 2019 and July 2024, contributing 708 steady-state plasma concentrations. Demographic and clinical data, and co-medications were recorded during routine SHCS visits. A population pharmacokinetic model was developed using a non-linear mixed-effect approach.
A one-compartment model with first-order absorption and elimination best characterized bictegravir pharmacokinetics. Body weight and age were found to significantly affect bictegravir clearance: Higher body weight led to lower bictegravir exposure, while older age led to higher exposure. Compared to an individual aged 51 years and 70 kg (typical individual in the cohort), those aged 51 years weighing 100 kg showed a 13% increase in clearance, and those aged 80 years weighing 70 kg showed an 11% decrease. Notably, simulations predicted that younger individuals with high body weight (e.g. 20 years, 135 kg) could experience a median 43% decrease in trough concentrations, with nearly 5% of values falling below the minimum recommended concentration for efficacy (760 ng/mL).
In summary, bictegravir pharmacokinetics show moderate variability influenced by body weight and age. However, given the wide safety margin of the drug, routine therapeutic drug monitoring is of limited value and should be reserved for specific scenarios where individuals are at risk of insufficient drug exposure. The findings highlight that altered pharmacokinetics might be particularly relevant among obese or older individuals.