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

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 Ctroughs were 16 (2.58 mg/L) and 9 (0.11 mg/L) times above the respective protein adjusted (PA)-IC90. From 7 to 32 weeks of gestation, plasma CAB and RPV Ctroughs decreased to 1.28 and to 0.08 mg/L, respectively, but remained above PA-IC90 for both drugs. After receiving one monthly high-dose CAB/RPV injection after delivery at 7 weeks postpartum, the plasma CAB and RPV Ctroughs 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.