BACKGROUND: Guidelines for the treatment of human immunodeficiency virus (HIV) infection consistently recommend initiation of antiretroviral therapy in patients with hepatitis C virus (HCV)/HIV-1 coinfection. Therefore, potential drug interactions between antiretroviral drugs and HCV direct-acting antiviral agents (DAAs) must be carefully considered. The objective of this investigation was to evaluate the compatibility of a novel combination of DAAs (the 3D regimen) with commonly prescribed HIV-1 protease inhibitors (PIs). METHODS: Five phase 1, multiple-dose, open-label pharmacokinetic studies were performed in 144 healthy volunteers. Participants in each study were randomly assigned 1:1 into cohorts assessing the effects of the steady-state 3D regimen on steady-state HIV-1 PIs or vice versa. The 3D regimen comprised ombitasvir (25 mg once daily), paritaprevir/ritonavir (150/100 mg once daily), and dasabuvir (250 or 400 mg twice daily). The HIV-1 PIs assessed included atazanavir, darunavir, and lopinavir (administered with ritonavir). Safety, tolerability, and pharmacokinetic parameters were assessed to evaluate the compatibility of the drug regimens. RESULTS: Coadministration of the 3D regimen with the evaluated HIV-1 PIs was generally well tolerated in healthy volunteers. Morning administration of atazanavir (300 mg once daily) and darunavir regimens exhibited no clinically meaningful drug interactions with the 3D regimen. However, owing to higher paritaprevir and/or ritonavir exposures, evening administration of atazanavir (300 mg) plus ritonavir (100 mg) or lopinavir/ritonavir (800/200 mg) with the 3D regimen is not recommended. CONCLUSIONS: The 3D regimen can be coadministered with morning atazanavir and darunavir regimens. However, evening atazanavir plus ritonavir and lopinavir/ritonavir regimens are not recommended in combination with the 3D regimen.
RCT Entities:
BACKGROUND: Guidelines for the treatment of human immunodeficiency virus (HIV) infection consistently recommend initiation of antiretroviral therapy in patients with hepatitis C virus (HCV)/HIV-1 coinfection. Therefore, potential drug interactions between antiretroviral drugs and HCV direct-acting antiviral agents (DAAs) must be carefully considered. The objective of this investigation was to evaluate the compatibility of a novel combination of DAAs (the 3D regimen) with commonly prescribed HIV-1 protease inhibitors (PIs). METHODS: Five phase 1, multiple-dose, open-label pharmacokinetic studies were performed in 144 healthy volunteers. Participants in each study were randomly assigned 1:1 into cohorts assessing the effects of the steady-state 3D regimen on steady-state HIV-1 PIs or vice versa. The 3D regimen comprised ombitasvir (25 mg once daily), paritaprevir/ritonavir (150/100 mg once daily), and dasabuvir (250 or 400 mg twice daily). The HIV-1 PIs assessed included atazanavir, darunavir, and lopinavir (administered with ritonavir). Safety, tolerability, and pharmacokinetic parameters were assessed to evaluate the compatibility of the drug regimens. RESULTS: Coadministration of the 3D regimen with the evaluated HIV-1 PIs was generally well tolerated in healthy volunteers. Morning administration of atazanavir (300 mg once daily) and darunavir regimens exhibited no clinically meaningful drug interactions with the 3D regimen. However, owing to higher paritaprevir and/or ritonavir exposures, evening administration of atazanavir (300 mg) plus ritonavir (100 mg) or lopinavir/ritonavir (800/200 mg) with the 3D regimen is not recommended. CONCLUSIONS: The 3D regimen can be coadministered with morning atazanavir and darunavir regimens. However, evening atazanavir plus ritonavir and lopinavir/ritonavir regimens are not recommended in combination with the 3D regimen.