Population Pharmacokinetics of Bictegravir During Pregnancy and Postpartum: Role of Adherence in Maintaining Therapeutic Exposure
Year: 2025
Type: article
Abstract: Bictegravir is an integrase strand transfer inhibitor available in fixed-dose combination with emtricitabine and tenofovir alafenamide for HIV treatment. The objectives of this study were to develop a population pharmacokinetic model for bictegravir during pregnancy and postpartum, identify main drivers of between-subject variability, and evaluate the role of adherence patterns in maintaining therapeutic exposure. Intensive bictegravir concentration-time data were used from IMPAACT 2026, a pharmacokinetic study of selected antiretroviral drugs during pregnancy and postpartum. Five hundred and eight bictegravir plasma concentrations from 27 participants during the second and third trimesters of pregnancy and postpartum were utilized for model development. A one-compartment structural model best described bictegravir PK. Pregnancy increased bictegravir apparent clearance (CL/F) by 61% compared to postpartum, while Black/African American race was associated with a 32% increase in apparent volume of distribution (Vd/F). Plasma albumin concentrations were associated with a 43% decrease in CL/F and body weight was associated with a 120% increase in Vd/F over the range of observed values. Monte Carlo simulations predicted median (90% prediction interval) pre-dose bictegravir concentrations of 920 ng/mL (265-2081) during the third trimester and 3399 ng/mL (1423-6391) postpartum, exceeding the protein-adjusted 95% effective concentration (162 ng/mL). Adherence simulations predicted a single missed dose at steady-state during the third trimester results in 43.7% of virtual subjects with concentrations below pharmacodynamic target, while two consecutive missed doses result in 90.4% with concentrations below target. These results show that while standard bictegravir dosing is effective during pregnancy, consistent adherence is critical to maintain effective therapeutic exposures.
DOI: 10.1002/jcph.70134
Institutions: University of California San Diego, Boston University, Boston Medical Center, Harvard University, Massachusetts General Hospital, Johns Hopkins University, Johns Hopkins Medicine, University of Southern California, Gilead Sciences (United States), Chiang Mai University, University of Colorado Anschutz
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: University of Southern California, University of Miami, Emory University, Johns Hopkins University, Rush University, International Maternal Pediatric Adolescent AIDS Clinical Trials Network, Mahidol University, National Institutes of Health, University of California, Los Angeles, School of Medicine, Emory University, University of California, San Diego, Faculty of Medicine Siriraj Hospital, Mahidol University, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1039780002, G1524427083, G1654426238, G1857750563, G2384456196, G3045663399, G3262353703, G32641939, G3342746445, G3665517470, G4853082081, G4927240118, G5602729146, G6585143688, G7093710796, G7445317512, G7502524018, G803170016, G8500352392, G8536071820, G8709470907, G876279366, G8922259349, SDMC - IMPAACT Leadership Group
OpenAlex ID: W4417430216