Drug Interactions between efavirenz / lamivudine / tenofovir disoproxil and elivaldogene autotemcel

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.

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.

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.

MONITOR: Coadministration of efavirenz with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Efavirenz has been associated with hepatotoxicity during postmarketing use. Among reported cases of hepatic failure, a few occurred in patients with no preexisting hepatic disease or other identifiable risk factors.

MANAGEMENT: The risk of hepatic injury should be considered when efavirenz is used in combination with other agents that are potentially hepatotoxic (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; other HIV reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Monitoring of liver function tests should occur before and during treatment, especially in patients with underlying hepatic disease (including hepatitis B or C coinfection) or marked transaminase elevations. The benefit of continued therapy with efavirenz should be considered against the unknown risks of significant liver toxicity in patients who develop persistent elevations of serum transaminases greater than five times the upper limit of normal.

MONITOR: Coadministration of efavirenz with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Efavirenz has been associated with hepatotoxicity during postmarketing use. Among reported cases of hepatic failure, a few occurred in patients with no preexisting hepatic disease or other identifiable risk factors.

MANAGEMENT: The risk of hepatic injury should be considered when efavirenz is used in combination with other agents that are potentially hepatotoxic (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; other HIV reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Monitoring of liver function tests should occur before and during treatment, especially in patients with underlying hepatic disease (including hepatitis B or C coinfection) or marked transaminase elevations. The benefit of continued therapy with efavirenz should be considered against the unknown risks of significant liver toxicity in patients who develop persistent elevations of serum transaminases greater than five times the upper limit of normal.