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Protease, Polymerase, and Assembly Inhibitors for the Treatment of Hepatitis C Virus Infection
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Marianne Martinello, Jason Grebely, Gregory Dore
Boceprevir is primarily eliminated by the liver. After a single 800-mg oral dose of 14C-boceprevir, approximately 79% (8% unchanged) and 9% (3% unchanged) of the dose was excreted in feces and urine, respectively.
Treatment of hepatitis C virus infection in people with opioid use disorder: a real-world study of elbasvir/grazoprevir in a US Department of Veterans Affairs population
Published in The American Journal of Drug and Alcohol Abuse, 2022
Jennifer R. Kramer, Amy Puenpatom, Yumei Cao, Xian Yu, Hashem B. El-Serag, Fasiha Kanwal
Use of any medication for opioid use disorder (MOUD)/naloxone was defined as a prescription for buprenorphine/naloxone, naloxone, naltrexone, or methadone within 1 year prior to initiation of direct-acting antiviral (DAA) therapy and continuing until the end of treatment. Comorbid conditions, such as cirrhosis (including ascites, varices, and hepatic encephalopathy), diabetes, hypertension, depression, anxiety, history of alcohol and/or any illicit drug use, and HIV coinfection, were identified by ICD-9/10-CM codes or corresponding laboratory data. Staging of CKD was evaluated based on two estimated glomerular filtration rate (eGFR) values at least 90 days apart (no/mild CKD, eGFR ≥60 mL/min/1.73 m2; stage 3 CKD, eGFR 30–59 mL/min/1.73 m2; stage 4/5 CKD, eGFR <30 mL/min/1.73 m2). eGFR was measured using the Modification of Diet in Renal Disease equation (18). Demographic covariates included age, sex, race/ethnicity (White, Black, Hispanic, Asian, others), and body mass index. The use of concomitant psychiatric medications (ie, benzodiazepines, mood stabilizers, stimulants, antidepressants, and antipsychotics) was recorded during the treatment course. Prior HCV treatment was defined as prior use of an interferon-based regimen (± ribavirin), boceprevir, telaprevir, simeprevir, or sofosbuvir. Patients who had received >1 previous treatment regimen were classified based on the most recent regimen received.
Managing hepatitis C therapy failures and chronic kidney disease
Published in Expert Review of Clinical Pharmacology, 2018
Fabrizio Fabrizi, Piergiorgio Messa
The understanding of the life cycle of HCV has helped the development of novel therapies toward HCV. In 2011, boceprevir and telaprevir were the first drugs provided with direct antiviral activity and approved for the treatment of chronic HCV. Boceprevir and telaprevir were NS3/4a non-structural protease inhibitors and were combined with peg-IFN interferon and ribavirin (RBV) to prevent the occurrence of resistances, a major concern commonly observed when these agents were used in mono-therapy. The SVR rates obtained with triple antiviral regimens (pegIFN, RBV, and telaprevir of boceprevir) increased to approximately 75% in some patient subgroups with the potential to shorten treatment duration. However, adverse events continued to be common due to the need to use both IFNs and RBV in combination. The data in the medical literature regarding these antiviral regimens in the CKD population are extremely limited [10].
Personalized treatment of hepatitis C genotype 1a in Norway and Sweden 2014–2016: a study of treatment outcome in patients with or without resistance-based DAA-therapy
Published in Scandinavian Journal of Gastroenterology, 2018
Hege Kileng, Midori Kjellin, Dario Akaberi, Assar Bergfors, Ann-Sofi Duberg, Lars Wesslén, Astrid Danielsson, Magnhild Gangsøy Kristiansen, Tore Gutteberg, Rasmus Goll, Anders Lannergård, Johan Lennerstrand
In the control group, only 30% of the patients were treated with simeprevir + sofosbuvir combination compared to 50% in the intervention group, possibly due to new treatment guidelines introduced in February (Sweden) and March (Norway) 2015, which recommended treatment with the fixed combination of ledipasvir plus sofosbuvir. Thus, these guidelines recommended NS5A inhibitor-based regimens for previous treatment failures of boceprevir/telaprevir, without regard to baseline resistance analysis. Of note, the only patient in the control group with Q80K at baseline that failed treatment was one out of four patients with such RAS that were treated with simeprevir plus sofosbuvir (i.e., SVR 75%). Furthermore, the single patient with baseline R155K that underwent simeprevir plus sofosbuvir treatment in the control group also failed to attain SVR.