Antiretroviral drug dose adjustment based on age does not appear to be necessary in aging HIV patients, according to a pharmacokinetics study published in the British Journal of Clinical Pharmacology.
To investigate the impact of aging on antiretroviral agents, plasma concentrations for 10 first line antiretroviral agents were obtained in HIV-positive elderly patients (≥55 years) from the Swiss HIV Cohort Study. Patients selected for study had common comorbidities such as declined renal function and hypertension, but did not have severe conditions.
A verified physiologically based pharmacokinetic (PBPK) model was utilized to predict the continuous effect of aging on antiretroviral drug pharmacokinetics across an age range spanning from 20 to 99 years old. Additionally, the effect of ethnicity on age-related pharmacokinetic changes was analyzed.
According to the PBPK simulation model, aging did not alter the peak concentration, time to peak concentration, or volume of distribution of the 10 first line HIV treatments in the study. Age-related pharmacokinetic changes, which resulted in a maximal 70% (95% CI, 40-120) increase in antiretroviral exposure across the 20-99 age range, were driven by the predicted decline in drug clearance. In addition, the study authors found no statistically significant difference in age-related pharmacokinetic changes among the ethnicities evaluated.
“The impact of advanced aging on antiretroviral drug pharmacokinetics is not clinically relevant considering the large therapeutic index of the current first line treatment,” the study authors concluded. They added that future studies should investigate the impact of the combined effects of aging and severe comorbidities.
Stader F, Courlet P, Kinvig H, et al. Effect of ageing on antiretroviral drug pharmacokinetics using clinical data combined with modelling and simulation [published online May 29, 2020]. British Journal of Clinical Pharmacology. doi: 10.1111/bcp.14402.