Evaluation of Drug-Drug Interactions Between Hepatitis C Antiviral Agents Ombitasvir, Paritaprevir/Ritonavir, and Dasabuvir and HIV-1 Protease Inhibitors.

Abstract

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.

• Authors: Amit Khatri, Sandeep Dutta, Haoyu Wang, Thomas Podsadecki, Roger Trinh, Walid Awni, Rajeev Menon
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 62 Issue 8 Pg. 972-9 (Apr 15 2016) ISSN: 1537-6591 [Electronic] United States
• PMID: 26740513 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected].

Chemical References

• Anilides
• Antiviral Agents
• Carbamates
• Cyclopropanes
• HIV Protease Inhibitors
• Lactams, Macrocyclic
• Macrocyclic Compounds
• Sulfonamides
• ombitasvir
• Uracil
• Proline
• 2-Naphthylamine
• dasabuvir
• Valine
• Ritonavir
• paritaprevir

Topics

• 2-Naphthylamine
• Adolescent
• Adult
• Anilides (administration & dosage, pharmacokinetics, therapeutic use)
• Antiviral Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Carbamates (administration & dosage, pharmacokinetics, therapeutic use)
• Coinfection (drug therapy, virology)
• Cyclopropanes
• Drug Administration Schedule
• Drug Interactions
• Drug Therapy, Combination (adverse effects)
• Female
• HIV Infections (complications, drug therapy, virology)
• HIV Protease Inhibitors (administration & dosage, adverse effects, pharmacokinetics)
• HIV-1 (drug effects)
• Healthy Volunteers
• Hepacivirus (drug effects)
• Hepatitis C (complications, drug therapy, virology)
• Hepatitis C, Chronic (complications, drug therapy, virology)
• Humans
• Lactams, Macrocyclic
• Macrocyclic Compounds (administration & dosage, pharmacokinetics, therapeutic use)
• Male
• Middle Aged
• Proline (analogs & derivatives)
• Ritonavir (administration & dosage, pharmacokinetics)
• Sulfonamides (administration & dosage, pharmacokinetics, therapeutic use)
• Uracil (administration & dosage, analogs & derivatives, pharmacokinetics, therapeutic use)
• Valine
• Young Adult