Antiretroviral drug exposure and response in obese and morbidly obese people with HIV: a study combining modelling and Swiss HIV Cohort data.

Berton, Mattia; Bettonte, Sara; Stader, Felix; Decosterd, Laurent; Tarr, Philip E; Livio, Françoise; Cavassini, Matthias; Braun, Dominique L; Kusejko, Katharina; Hachfeld, Anna; Bernasconi, Enos; Calmy, Alexandra; Schmid, Patrick; Battegay, Manuel; Marzolini, Catia (2024). Antiretroviral drug exposure and response in obese and morbidly obese people with HIV: a study combining modelling and Swiss HIV Cohort data. Clinical infectious diseases, 78(1), pp. 98-110. Oxford University Press 10.1093/cid/ciad495

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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

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

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

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.

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