title: Antiretroviral Use in the CEASE Cohort Study and Implications for Direct-Acting Antiviral Therapy in Human Immunodeficiency Virus/Hepatitis C Virus Coinfection.
abstract: Background.  Interferon-free direct-acting antiviral (DAA) regimens for hepatitis C virus (HCV) provide a major advance in clinical management, including in human immunodeficiency virus (HIV)/HCV coinfection. Drug-drug interactions (DDIs) with combination antiretroviral therapy (cART) require consideration. This study aimed to characterize the cART regimens in HIV/HCV-coinfected individuals and assess the clinical significance of DDIs with DAAs in a real-world cohort. Methods.  This analysis included participants enrolled in CEASE-D, a prospective cohort of HIV/HCV-coinfected individuals in Sydney, Australia, between July 2014 and December 2015. A simulation of potential DDIs between participants' cART and interferon-free DAA regimens was performed using www.hep-druginteractions.org and relevant prescribing information. Results.  In individuals on cART with HCV genotype (GT) 1 and 4 (n = 128), category 3 DDIs (contraindicated or not recommended) were noted in 0% with sofosbuvir/ledipasvir, 0% with sofosbuvir plus daclatasvir, 17% with sofosbuvir/velpatasvir, 36% with ombitasvir/paritaprevir/ritonavir ± dasabuvir, 51% with grazoprevir/elbasvir, and 51% with sofosbuvir plus simeprevir; current cART regimens were suitable for coadministration in 100%, 100%, 73%, 64%, 49%, and 49%, respectively. In individuals with HCV GT 2 or 3 (n = 53), category 3 DDIs were evident in 0% with sofosbuvir plus daclatasvir, 0% with sofosbuvir and ribavirin, and 13% with sofosbuvir/velpatasvir; current cART regimens were suitable in 100%, 100%, and 81%, respectively. Conclusions.  Potential DDIs are expected and will impact on DAA prescribing in HIV/HCV coinfection. Sofosbuvir in combination with an NS5A inhibitor or ribavirin appeared to be the most suitable regimens in this cohort. Evaluation of potential DDIs is required to prevent adverse events or treatment failure.
authors.affiliation: Viral Hepatitis Clinical Research Program, The Kirby Institute, University of New South Wales (UNSW) Australia, Sydney; Department of Infectious Diseases and Immunology, St Vincent's Hospital, Sydney, New South Wales.
authors.forename: Marianne
authors.initials: M
authors.lastname: Martinello
authors.affiliation: Viral Hepatitis Clinical Research Program, The Kirby Institute, University of New South Wales (UNSW) Australia, Sydney; Department of Infectious Diseases and Immunology, St Vincent's Hospital, Sydney, New South Wales.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.affiliation: Viral Hepatitis Clinical Research Program , The Kirby Institute, University of New South Wales (UNSW) Australia , Sydney.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Skurowski
authors.affiliation: The Albion Centre, Sydney, New South Wales; School of Public Health and Community Medicine, UNSW Australia, Sydney, New South Wales.
authors.forename: Rohan I
authors.initials: RI
authors.lastname: Bopage
authors.affiliation: Taylor Square Private Clinic , Sydney, New South Wales.
authors.forename: Robert
authors.initials: R
authors.lastname: Finlayson
authors.affiliation: East Sydney Doctors , New South Wales.
authors.forename: David
authors.initials: D
authors.lastname: Baker
authors.affiliation: Holdsworth House Medical Practice , Sydney, New South Wales , Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Bloch
authors.affiliation: Viral Hepatitis Clinical Research Program, The Kirby Institute, University of New South Wales (UNSW) Australia, Sydney; Department of Infectious Diseases and Immunology, St Vincent's Hospital, Sydney, New South Wales.
authors.forename: Gail V
authors.initials: GV
authors.lastname: Matthews
keywords: HIV; antiretroviral therapy; direct-acting antiviral therapy; drug-drug interactions; hepatitis C