Literature DB >> 25192745

Simeprevir (TMC435) with pegylated interferon/ribavirin in patients coinfected with HCV genotype 1 and HIV-1: a phase 3 study.

Douglas Dieterich1, Jürgen Kurt Rockstroh2, Chloe Orkin3, Félix Gutiérrez4, Marina B Klein5, Jacques Reynes6, Umesh Shukla7, Alan Jenkins8, Oliver Lenz9, Sivi Ouwerkerk-Mahadevan10, Monika Peeters9, Guy De La Rosa7, Lotke Tambuyzer9, Wolfgang Jessner9.   

Abstract

BACKGROUND: Simeprevir is an oral, once-daily, hepatitis C virus (HCV) NS3/4A protease inhibitor for the treatment of chronic HCV genotype 1 infection. Human immunodeficiency virus (HIV) coinfection accelerates progression of liver disease. This uncontrolled, open-label trial explored the safety and efficacy of simeprevir in patients with HCV genotype 1/HIV type 1 (HIV-1) coinfection.
METHODS: Patients received simeprevir (150 mg once daily) with pegylated interferon alfa-2a/ribavirin (peg-IFN/RBV) for 12 weeks. Noncirrhotic HCV treatment-naive patients and prior relapsers received response-guided therapy (RGT) with peg-IFN/RBV for 24 or 48 weeks. Prior null responders, prior partial responders, and patients with cirrhosis received peg-IFN/RBV for 48 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12).
RESULTS: One hundred and six patients (93 on antiretroviral therapy) were enrolled and treated. SVR12 rates were 79.2% in HCV treatment-naive patients, 57.1% in prior null responders, 86.7% in prior relapsers, and 70.0% in prior partial responders. Fifty-four of 61 eligible patients (88.5%) met RGT criteria for 24 weeks of peg-IFN/RBV, of whom 87.0% (47/54) achieved SVR12. SVR12 rates were 80.0% (36/45) and 63.6% (14/22) for patients with METAVIR scores of F0-F2 and F3-F4, respectively. Common adverse event (AE) rates were consistent with peg-IFN/RBV therapy (fatigue, headache, nausea, neutropenia). Most AEs were grade 1/2; serious AEs occurred in 5.7% of patients, none of which were fatal.
CONCLUSIONS: Simeprevir was generally well tolerated with safety similar to that observed in HCV-monoinfected patients and high SVR12 rates in HCV treatment-naive patients, prior relapsers, prior partial responders, and prior null responders with HIV-1 coinfection. CLINICAL TRIALS REGISTRATION: NCT01479868.
© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Entities:  

Keywords:  coinfection; hepatitis C virus; human immunodeficiency virus type 1; simeprevir

Mesh:

Substances:

Year:  2014        PMID: 25192745     DOI: 10.1093/cid/ciu675

Source DB:  PubMed          Journal:  Clin Infect Dis        ISSN: 1058-4838            Impact factor:   9.079


  26 in total

Review 1.  Simeprevir.

Authors: 
Journal:  Aust Prescr       Date:  2014-12-19

2.  Recent advances in management of the HIV/HCV coinfected patient.

Authors:  Cindy J Bednasz; Joshua R Sawyer; Anthony Martinez; Patrick G Rose; Samantha S Sithole; Holly R Hamilton; Farzia S Kaufman; Charles S Venuto; Qing Ma; Andrew Talal; Gene D Morse
Journal:  Future Virol       Date:  2015       Impact factor: 1.831

3.  Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection.

Authors: 
Journal:  Clin Infect Dis       Date:  2018-10-30       Impact factor: 9.079

4.  HIV and HCV Medications in End-Stage Renal Disease.

Authors:  Keiko I Greenberg; Mark A Perazella; Mohamed G Atta
Journal:  Semin Dial       Date:  2015-04-06       Impact factor: 3.455

Review 5.  A changing paradigm: management and treatment of the HCV/HIV-co-infected patient.

Authors:  Ameer Abutaleb; Kenneth E Sherman
Journal:  Hepatol Int       Date:  2018-09-20       Impact factor: 6.047

6.  Sofosbuvir and Ribavirin for Treatment of Chronic Hepatitis C in Patients Coinfected With Hepatitis C Virus and HIV: The Impact on Patient-Reported Outcomes.

Authors:  Zobair M Younossi; Maria Stepanova; Mark Sulkowski; Susanna Naggie; Massimo Puoti; Chloe Orkin; Sharon L Hunt
Journal:  J Infect Dis       Date:  2015-01-12       Impact factor: 5.226

7.  Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection.

Authors:  Anu Osinusi; Kerry Townsend; Anita Kohli; Amy Nelson; Cassie Seamon; Eric G Meissner; Dimitra Bon; Rachel Silk; Chloe Gross; Angie Price; Mohammad Sajadi; Sreetha Sidharthan; Zayani Sims; Eva Herrmann; John Hogan; Gebeyehu Teferi; Rohit Talwani; Michael Proschan; Veronica Jenkins; David E Kleiner; Brad J Wood; G Mani Subramanian; Phillip S Pang; John G McHutchison; Michael A Polis; Anthony S Fauci; Henry Masur; Shyam Kottilil
Journal:  JAMA       Date:  2015 Mar 24-31       Impact factor: 56.272

8.  Treatment intensification with boceprevir in HIV-positive patients with acute HCV-genotype 1 infection at high risk for treatment failure.

Authors:  Mattias Mandorfer; Sebastian Steiner; Philipp Schwabl; Berit A Payer; Maximilian C Aichelburg; Katharina Grabmeier-Pfistershammer; Michael Trauner; Thomas Reiberger; Markus Peck-Radosavljevic
Journal:  Wien Klin Wochenschr       Date:  2015-12-10       Impact factor: 1.704

9.  A Conserved Inhibitory Mechanism of a Lycorine Derivative against Enterovirus and Hepatitis C Virus.

Authors:  Yu Guo; Yaxin Wang; Lin Cao; Peng Wang; Jie Qing; Qizhen Zheng; Luqing Shang; Zheng Yin; Yuna Sun
Journal:  Antimicrob Agents Chemother       Date:  2015-11-23       Impact factor: 5.191

Review 10.  New treatment strategies for hepatitis C infection.

Authors:  Fatih Ermis; Elif Senocak Tasci
Journal:  World J Hepatol       Date:  2015-08-18
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