Off-label dosing of long-acting injectable cabotegravir and rilpivirine during pregnancy: A case study with therapeutic drug monitoring

Authors

Natella Rakhmanina, Division of Infectious Diseases, Children's National Hospital, Washington, District of Columbia, USA.
Justin Unternaher, Division of Infectious Diseases, Children's National Hospital, Washington, District of Columbia, USA.
Tierra Williams, Division of Infectious Diseases, Children's National Hospital, Washington, District of Columbia, USA.
Kevin J. Ryan, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Kedria Walker, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Edward P. Acosta, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
John Van Den Anker, Center for Health Outcomes Research and Delivery Science, Children's National Research Institute, Children's National Hospital, Washington, DC, USA.
Rachel K. Scott, School of Medicine, Georgetown University, Washington, District of Columbia, USA.

Document Type

Journal Article

Publication Date

12-16-2025

Journal

British journal of clinical pharmacology

DOI

10.1002/bcp.70424

Keywords

HIV; cabotegravir/rilpivirine; off‐label dose; pharmacokinetics; pregnancy

Abstract

We report individualized off-label monthly use of a high dose of long-acting intramuscular cabotegravir/rilpivirine (CAB/RPV = 600 mg/900 mg) co-administered preconceptionally and throughout pregnancy with subcutaneous lenacapavir to a young woman with perinatally acquired HIV, multiple comorbidities, and class III obesity. Therapeutic drug monitoring for CAB and RPV was performed throughout the pregnancy and postpartum. At 7 weeks gestation, the plasma CAB and RPV C were 16 (2.58 mg/L) and 9 (0.11 mg/L) times above the respective protein adjusted (PA)-IC. From 7 to 32 weeks of gestation, plasma CAB and RPV C decreased to 1.28 and to 0.08 mg/L, respectively, but remained above PA-IC for both drugs. After receiving one monthly high-dose CAB/RPV injection after delivery at 7 weeks postpartum, the plasma CAB and RPV C were 4.02 and 0.19 mg/L, 56% and 73% higher than at 7 weeks of gestation. Despite a decrease in cabotegravir (50%) and rilpivirine (27%) concentrations between first and third trimesters, plasma exposures remained above therapeutic thresholds and viral load <20 copies/mL was maintained throughout pregnancy. Higher CAB and RPV exposures did not result in adverse maternal, pregnancy or infant safety outcomes. At 7 weeks postpartum, CAB/RPV was switched to standard bimonthly dosing. At 33 weeks postpartum, the patient remained undetectable on standard CAB/RPV bimonthly dose, although subsequent pregnancies might require long-acting CAB/RPV dosing adjustments. Our case of empiric use of high-dose CAB/RPV with monthly injections and therapeutic drug monitoring during pregnancy in a complex patient with class III obesity provides novel insights into pharmacokinetics of long-acting CAB/RPV.

APA Citation

Rakhmanina, Natella; Unternaher, Justin; Williams, Tierra; Ryan, Kevin J.; Walker, Kedria; Acosta, Edward P.; Van Den Anker, John; and Scott, Rachel K., "Off-label dosing of long-acting injectable cabotegravir and rilpivirine during pregnancy: A case study with therapeutic drug monitoring" (2025). GW Authored Works. Paper 8397.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8397

Department

Pediatrics