Antiretroviral drug exposure and response in obese and morbidly obese people with HIV: a study combining modelling and Swiss HIV Cohort data.
HIV
antiretrovirals
drug exposure
drug response
obesity
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
21 Aug 2023
21 Aug 2023
Historique:
received:
20
06
2023
revised:
07
08
2023
accepted:
17
08
2023
medline:
21
8
2023
pubmed:
21
8
2023
entrez:
21
8
2023
Statut:
aheadofprint
Résumé
Obesity is increasingly prevalent among people with HIV (PWH) and can possibly result in suboptimal antiretroviral drug (ARV) exposure and response. However, this has not been thoroughly evaluated given that obese PWH are underrepresented in clinical trials. We performed virtual trials using physiologically based pharmacokinetic (PBPK) modelling combined with observed clinical data to provide ARV dosing guidance in obese individuals. Each trial included a cohort of virtual adults with a body mass index (BMI) between 18.5-60 kg/m2. Therapeutic drug monitoring data from the Swiss HIV Cohort Study (SHCS) were used to verify the predictive performance of the model. The model was applied to predict the pharmacokinetics of ARVs for different obesity classes. The association between ARV plasma concentrations and virological response was investigated in obese and non-obese individuals. The PBPK model predicted an average reduction in ARVs exposure of ∼20% and trough concentrations of ∼6% in obese (BMI ≥30 kg/m2) compared to non-obese (BMI 18.5-25 kg/m2) consistent with observed clinical data. Etravirine and rilpivirine were the most impacted especially in individuals with BMI >40 kg/m2 whose trough concentrations were below the clinical target threshold. Obese PWH in the SHCS did not have a higher rate of unsuppressed viral load compared to non-obese PWH. The concentrations of ARVs are modestly reduced in obese with no negative impact on the virological response. Our data provide reassurance that standard dose of ARVs is suitable in obese PWH including those who gained substantial weight with some of the first-line ARVs.
Sections du résumé
BACKGROUND
BACKGROUND
Obesity is increasingly prevalent among people with HIV (PWH) and can possibly result in suboptimal antiretroviral drug (ARV) exposure and response. However, this has not been thoroughly evaluated given that obese PWH are underrepresented in clinical trials. We performed virtual trials using physiologically based pharmacokinetic (PBPK) modelling combined with observed clinical data to provide ARV dosing guidance in obese individuals.
METHODS
METHODS
Each trial included a cohort of virtual adults with a body mass index (BMI) between 18.5-60 kg/m2. Therapeutic drug monitoring data from the Swiss HIV Cohort Study (SHCS) were used to verify the predictive performance of the model. The model was applied to predict the pharmacokinetics of ARVs for different obesity classes. The association between ARV plasma concentrations and virological response was investigated in obese and non-obese individuals.
RESULTS
RESULTS
The PBPK model predicted an average reduction in ARVs exposure of ∼20% and trough concentrations of ∼6% in obese (BMI ≥30 kg/m2) compared to non-obese (BMI 18.5-25 kg/m2) consistent with observed clinical data. Etravirine and rilpivirine were the most impacted especially in individuals with BMI >40 kg/m2 whose trough concentrations were below the clinical target threshold. Obese PWH in the SHCS did not have a higher rate of unsuppressed viral load compared to non-obese PWH.
CONCLUSIONS
CONCLUSIONS
The concentrations of ARVs are modestly reduced in obese with no negative impact on the virological response. Our data provide reassurance that standard dose of ARVs is suitable in obese PWH including those who gained substantial weight with some of the first-line ARVs.
Identifiants
pubmed: 37602428
pii: 7246547
doi: 10.1093/cid/ciad495
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.