Simeprevir (TMC435) With Pegylated Interferon/Ribavirin in Patients Coinfected With HCV Genotype 1 and HIV-1: A Phase 3 Study

• Published in: Clinical infectious diseases Vol. 59; no. 11; pp. 1579 - 1587
• Main Authors: Dieterich, Douglas, Rockstroh, Jürgen Kurt, Orkin, Chloe, Gutiérrez, Félix, Klein, Marina B., Reynes, Jacques, Shukla, Umesh, Jenkins, Alan, Lenz, Oliver, Ouwerkerk-Mahadevan, Sivi, Peeters, Monika, De La Rosa, Guy, Tambuyzer, Lotke, Jessner, Wolfgang
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-12-2014
• Subjects: Adolescent; Adult; Aged; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretrovirals; Antiviral agents; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; ARTICLES AND COMMENTARIES; Biological and medical sciences; Coinfection; Female; Genotype & phenotype; Genotypes; Hepacivirus; Hepacivirus - genetics; Hepatitis; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Heterocyclic Compounds, 3-Ring - adverse effects; Heterocyclic Compounds, 3-Ring - therapeutic use; HIV; HIV 1; HIV infections; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - isolation & purification; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Interferon; Interferon-alpha - adverse effects; Interferon-alpha - therapeutic use; Interferons; Male; Medical sciences; Middle Aged; Patients; Pharmacology. Drug treatments; Polyethylene Glycols - adverse effects; Polyethylene Glycols - therapeutic use; Prescription drugs; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Ribavirin - adverse effects; Ribavirin - therapeutic use; RNA; Simeprevir; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; Young Adult; Human; Immunopathology; Mixed infection; Typing; HIV-1 virus; Cytokine; Retroviridae; Genotype; AIDS; Immune deficiency; Lentivirus; Ribavirin; Infection; Virus; Microbiological investigation; Viral disease; Nucleoside analog; Antiviral; Interferon; Human immunodeficiency virus; Flaviviridae; Pegylated form; Hepatitis C virus; Hepacivirus; hepatitis C virus; human immunodeficiency virus type 1; simeprevir; coinfection
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciu675

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 responseguided 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.