A Population Pharmacokinetic Model Based on HPTN 077 of Long-acting
Injectable Cabotegravir for HIV PrEP
Abstract
Background 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. Aim 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 analyzed
CAB-LA PK data using nonlinear mixed-effects modeling 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-occasional variability (BOV, i.e., differences in PK within one
individual from one injection to the next) as a significant covariate
affecting the absorption rate. 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. 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.