Antiretroviral drug exposure and response in obese and morbidly obese people with human immunodeficiency virus (HIV): A study combining modelling and Swiss HIV Cohort Data Clinical Infectious Diseases
Several physiological changes impact drug exposure in individuals with obesity. Increased liver blood flow or higher glomerular filtration rate can accelerate metabolic clearance, and drugs accumulated in the tissue may redistribute to the blood, impacting drug trough concentrations. How these changes can lead to ineffective antiretroviral (ARV) drug levels in obese individuals remains unclear.
In this article published in Clinical Infectious Diseases, Berton et al. performed virtual trials to assess the impact of obesity on current ARV drug exposure among people with HIV from the Swiss HIV Cohort Study (SHCS). During these virtual trials, predictions from physiologically based pharmacokinetic (PBPK) modeling were validated with available drug plasma levels from the SHCS database. The validated models were then used to extrapolate pharmacokinetics across obesity classes (up to a BMI of 60 kg/m2).
Compared to individuals without obesity, individuals with a BMI ≥30 kg/m2 had an average reduction in ARV exposure of 20%, and a decrease in trough concentrations of 6%. Trough concentrations were above the efficacy threshold for most drugs, except for etravirine and rilpivirine, in which approximately 40% of individuals with a BMI >40 kg/m2 did not reach the target. However, these lower trough levels were not accompanied by increased rates of detectable HIV viral loads in the cohort.
In summary, the present study provides evidence that the efficacy of current antiretroviral drugs are unlikely to be affected by obesity. This is reassuring particularly given the increasing rates of obesity among people with HIV worldwide. Nevertheless, therapeutic drug monitoring should be considered among obese individuals who receive drugs such as etravirine and rilpivirine to prevent suboptimal drug exposure.