Berton, Mattia 
ORCID: 0000-0001-9450-2228, Bettonte, Sara, Stader, Felix, Decosterd, Laurent ORCID: 0000-0002-9840-1325, Tarr, Philip E, Livio, Françoise, Cavassini, Matthias, Braun, Dominique L, Kusejko, Katharina, Hachfeld, Anna et al (show 6 more authors)
(2024)
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 : an official publication of the Infectious Diseases Society of America, 78 (1).
pp. 98-110.
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Abstract
<h4>Background</h4>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.<h4>Methods</h4>Each trial included a cohort of virtual adults with a body mass index (BMI) between 18.5 and 60 kg/m2. Therapeutic drug-monitoring data from the Swiss HIV Cohort Study (SHCS) were used to verify the predictive performance of the model. Subsequently, 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 nonobese individuals.<h4>Results</h4>The PBPK model predicted an average reduction in ARV exposure of ∼20% and trough concentrations of ∼6% in obese (BMI ≥30 kg/m2) compared with nonobese (BMI: 18.5-25 kg/m2) individuals, 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 than nonobese PWH.<h4>Conclusions</h4>The concentrations of ARVs are modestly reduced in obese individuals, with no negative impact on the virological response. Our data provide reassurance that standard doses of ARVs are suitable in obese PWH, including those who gained substantial weight with some of the first-line ARVs.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Swiss HIV Cohort Study, Humans, HIV, HIV Infections, Obesity, Morbid, Anti-Retroviral Agents, Cohort Studies, Adult, Switzerland |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 29 Feb 2024 08:21 |
| Last Modified: | 09 Apr 2024 13:28 |
| DOI: | 10.1093/cid/ciad495 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178969 |
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