Obesity leads to suboptimal antiretroviral drug responses in people with HIV
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Key takeaways:
- Obesity led to reduced exposures across all antiretroviral drugs.
- Etravirine showed the highest change in exposure, and doravirine showed the lowest.
Using physiologically based pharmacokinetic modeling combined with observed clinical data, researchers determined that obesity can lead to reduced exposure and response to antiretroviral drugs.
“Obesity (BMI greater than 30 kg/m2) is not only increasing in the general population, but recent articles observed the same trend among people with HIV. Additionally, it is well documented in the literature and in our recent published articles that obesity is associated with physiological changes that can modify drug disposition, resulting in suboptimal antiretroviral drug (ARV) exposure and response,” Mattia Berton, a PhD student in the division of infectious diseases and hospital epidemiology at University Hospital Basel, told Healio.
“Because obese people with HIV are underrepresented in clinical trials, this question has not been thoroughly evaluated and, therefore, represents an important knowledge gap. Furthermore, there is an increasing interest around obesity in the HIV field because several first-line ARVs have been associated with weight gain,” Berton said.
Using physiologically based pharmacokinetic (PBPK) modeling combined with observed clinical data from the Swiss HIV Cohort Study (SHCS), Berton and colleagues conducted virtual trials to provide ARV dosing guidance in obese patients with HIV.
According to the study, each trial assessed a cohort of virtual adults with a BMI between 18.5 and 60 kg/m2. The model was applied to predict the pharmacokinetics of ARVs for different obesity classes and therapeutic drug-monitoring data from the SHCS were used to verify the predictive performance of the model.
Overall, the researchers found that obesity led to reduced exposures in all ARVs. Specifically, the PBPK model predicted an average reduction in ARV exposure of approximately 20% and trough concentrations of approximately 6% in obese patients (BMI 30 kg/m2 or greater) compared with patients who were not obese (BMI 18.5 to 25 kg/m2).
Berton added that some differences were observed among the various ARVs, with etravirine showing the highest change and doravirine showing the lowest. or most of the evaluated ARVs, he said, the trough concentrations were maintained above the minimal target threshold across a large BMI range with the exception of rilpivirine and etravirine for BMI greater than 40 kg/m2.
“Altogether, our findings suggest that a dose adjustment of ARVs is a priori not required in obese people with HIV, but therapeutic drug monitoring should be considered in morbidly obese people with HIV for rilpivirine and etravrine,” Berton said.
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