A population pharmacokinetic model based on HPTN 077 of long‐acting injectable cabotegravir for HIV PrEP. Issue 10 (14th August 2022)

• Record Type: Journal Article
• Authors: Yu, Yifan; Bigos, Kristin L.; Marzinke, Mark A.; Landovitz, Raphael J.; McCauley, Marybeth; Ford, Susan; Hendrix, Craig W.; Bies, Robert R.; Weld, Ethel D.
• Other Names: Gacia‐Bournissen Facundo guestEditor.; Rieder Michael guestEditor.
• Is Part Of: British journal of clinical pharmacology. Volume 88:Issue 10(2022)
• Page Start: 4623
• Page End: 4632
• Publication Date: 2022-08-14
• Subjects: antiretrovirals -- HIV/AIDS -- infectious diseases -- pharmacometrics; Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/bcp.15477
• Languages: English
• ISSNs: 0306-5251

Abstract

Abstract : Aims: Cabotegravir delivered as a long‐acting intramuscular injection has shown superior efficacy to oral tenofovir‐emtricitabine as pre‐exposure prophylaxis (PrEP) for HIV. Cabotegravir pharmacokinetics (PK), like those of other long‐acting depot preparations, exhibit variability between individuals and between injection occasions. The aim of this study is to describe the population pharmacokinetics of long‐acting cabotegravir (CAB‐LA). Methods: Using available PK measurements from 133 participants in the HIV Prevention Trials Network (HPTN) 077 trial, we analysed CAB‐LA PK data using nonlinear mixed‐effects modelling to develop a population PK model. Results: A two‐compartment model with first order absorption best described the CAB‐LA PK. The analysis identified between‐occasion variability (BOV, i.e., differences in PK within one individual from one injection to the next) as a significant covariate affecting the absorption rate, with an estimated contribution of BOV to PK variability on the absorption rate (ka ) of 38.5%. Sex and body weight were identified as significant covariates influencing the absorption rate and apparent clearance of CAB‐LA after intramuscular injection at various doses and frequencies. Male participants had 67% higher ka than female participants. Serially adding to the model body weight on clearance, sex on ka, and BOV on ka led to a decrease in the objective function value (OFV) of 24.4, 36 and 321.4, respectively. Conclusion: The public availability of this model will facilitate and enable a wide variety of future clinically relevant simulations to inform the optimal use of CAB‐LA.