Drug Interactions between betibeglogene autotemcel and darunavir

ADJUST DOSING INTERVAL: Antiretroviral medications may interfere with the manufacturing of apheresed cells used for autologous gene therapy that undergo transduction by a lentiviral vector (LVV) (e.g., atidarsagene autotemcel, betibeglogene autotemcel, elivaldogene autotemcel, lovotibeglogene autotemcel). Following hematopoietic stem cell (HSC) mobilization and apheresis, CD34+ cells are genetically modified with a replication-incompetent, self-inactivating LVV carrying functional copies of deoxyribonucleic acid (DNA). Lentiviruses are retroviruses which possess short spans of genetic information identical to that of the human immunodeficiency virus (HIV) and may therefore be susceptible to inactivation by antiretroviral medications. Clinical data examining the use of antiretroviral medication(s) during the mobilization and apheresis process are not available.

MANAGEMENT: Antiretroviral medications should be avoided for at least one month, or the expected duration of elimination of the antiretroviral medication, prior to HSC mobilization and until all cycles of apheresis have been completed. Some manufacturers of atidarsagene autotemcel suggest continuing to avoid antiretroviral medications for at least 7 days after its infusion. If antiretroviral therapy is being considered for HIV or human T-lymphotropic virus (HTLV) prophylaxis, serology testing should be conducted to rule out infection before initiating mobilization and apheresis. Delaying gene therapy treatment until an HIV/HTLV western blot and viral load assay have been performed at 6-months postexposure may be appropriate. In addition, after the administration of autologous gene therapies that undergo the LVV transduction process, use of non-polymerase chain reaction (PCR)-based assays are recommended when screening for HIV, due to the risk of a false positive result with PCR-based assays.