Effect of ageing on antiretroviral drug pharmacokinetics using clinical data combined with modelling and simulation. British Journal of Clinical Pharmacology
Stader et al. aimed to investigate age-related pharmacokinetic changes of HIV drugs by using a previously developed and verified physiologically based pharmacokinetic (PBPK) framework in combination with clinically observed data sampled as part of the Swiss HIV Cohort Study in ageing people living with HIV (PLWH).
Plasma concentrations for 10 first-line antiretrovirals were obtained in PLWH ≥55 years, participating in the Swiss HIV Cohort Study, and used to proof the predictive performance of the PBPK model. The verified PBPK model predicted the continuous effect of ageing on HIV drug pharmacokinetics across adulthood (20–99 years). The impact of ethnicity on age-related pharmacokinetic changes between whites and other races was statistically analyzed.
Clinically observed concentration-time profiles of all investigated antiretrovirals were generally within the 95% confidence interval of the PBPK simulations, demonstrating the predictive power of the modelling approach used. The predicted decline in drug clearance drove age-related pharmacokinetic changes of antiretrovirals, resulting in a maximal 70% [95% confidence interval: 40%, 120%] increase in antiretrovirals exposure across adulthood. Peak concentration, time to peak concentration and apparent volume of distribution were predicted to be unaltered by ageing. There was no statistically significant difference of age-related pharmacokinetic changes between studied ethnicities.
In conclusion, the impact of advanced ageing on antiretroviral drug pharmacokinetics is not clinically relevant considering the large therapeutic index of the current first-line treatment. In the current study, neither sex nor ethnicity appear to impact age-related pharmacokinetic changes. Overall, antiretroviral drug dose adjustment is a priori not necessary in ageing male and female PLWH in the absence of severe comorbidities.