1Icahn School of Medicine at Mount Sinai, New York, NY, USA.
2Mediz. Universitätsklinik I-Immunologische Ambulanz, Bonn, Germany.
3Royal London Hospital, London, UK.
4Hospital General de Elche and Universidad Miguel Hernández, Alicante, Spain.
5McGill University Health Centre, Montreal, Canada.
6Centre Hospitalier Universitaire Gui De Chauliac, Montpellier, France.
7Janssen Global Services, Titusville, NJ, USA.
8Janssen Research & Development, Raritan, NJ, USA.
9Janssen Infectious Diseases BVBA, Beerse, Belgium.
10Janssen Research & Development, Beerse, Belgium.
Simeprevir is an oral, once-daily (QD), 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-1 coinfection.
Patients received simeprevir (150 mg QD) with peginterferon α-2a/ribavirin (PR) for 12 weeks. Non-cirrhotic HCV treatment-naïve patients and prior relapsers received response-guided therapy (RGT) with PR for 24 or 48 weeks. Prior null responders, prior partial responders and patients with cirrhosis received PR for 48 weeks. The primary endpoint was sustained virologic response 12 weeks after end of treatment (SVR12).
106 patients (93 on antiretroviral therapy) were enrolled and treated. SVR12 rates were 79.2% in HCV treatment-naïve patients, 57.1% in prior null responders, 86.7% in prior relapsers, and 70.0% in prior partial responders. 54/61 eligible patients (88.5%) met RGT criteria for 24 weeks of PR, of whom 87.0% (47/54) achieved SVR12. SVR12 rates were 80.0% (36/45) and 63.6% (14/22) for METAVIR F0-F2 and F3-F4 patients, respectively. Common adverse event (AE) rates were consistent with PR therapy (fatigue, headache, nausea, neutropenia). Most AEs were Grade 1/2; serious AEs occurred in 5.7% of patients, none were fatal.
Simeprevir was generally well-tolerated with safety similar to that observed in HCV monoinfected patients and high SVR12 rates in HCV treatment-naïve patients, prior relapsers, prior partial responders and prior null responders with HIV-1 coinfection.