Effect of Obesity on the Exposure of Long-acting Cabotegravir and Rilpivirine: A Modeling Study.
Clin Infect Dis
; 79(2): 477-486, 2024 Aug 16.
Article
in En
| MEDLINE
| ID: mdl-38309958
ABSTRACT
BACKGROUND:
Obesity is increasingly prevalent among people with human immunodeficiency virus (HIV, PWH). Obesity can reduce drug exposure; however, limited data are available for long-acting (LA) antiretrovirals. We performed in silico trials using physiologically based pharmacokinetic (PBPK) modeling to determine the effect of obesity on the exposure of LA cabotegravir and rilpivirine after the initial injection and after multiple injections.METHODS:
Our PBPK model was verified against available clinical data for LA cabotegravir and rilpivirine in normal weight/ overweight (body mass index [BMI] <30â kg/m2) and in obese (BMI >30â kg/m2). Cohorts of virtual individuals were generated to simulate the exposure of LA cabotegravir/rilpivirine up to a BMI of 60â kg/m2. The fold change in LA cabotegravir and rilpivirine exposures (area under the curve [AUC]) and trough concentrations (Cmin) for monthly and bimonthly administration were calculated for various BMI categories relative to normal weight (18.5-25â kg/m2).RESULTS:
Obesity was predicted to impact more cabotegravir than rilpivirine with a decrease in cabotegravir AUC and Cmin of >35% for BMI >35â kg/m2 and in rilpivirine AUC and Cmin of >18% for BMI >40â kg/m2 at steady-state. A significant proportion of morbidly obese individuals were predicted to have both cabotegravir and rilpivirine Cmin below the target concentration at steady-state with the bimonthly administration, but this was less frequent with the monthly administration.CONCLUSIONS:
Morbidly obese PWH are at risk of presenting suboptimal Cmin for cabotegravir/rilpivirine after the first injection but also at steady-state particularly with the bimonthly administration. Therapeutic drug monitoring is advised to guide dosing interval adjustment.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyridones
/
HIV Infections
/
Anti-HIV Agents
/
Rilpivirine
/
Obesity
Type of study:
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Clin Infect Dis
Journal subject:
DOENCAS TRANSMISSIVEIS
Year:
2024
Document type:
Article
Affiliation country:
Switzerland
Country of publication:
United States