Simeprevir (TMC435) with pegylated interferon/ribavirin in patients coinfected with HCV genotype 1 and HIV-1: a phase 3 study.
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.
['Dieterich|Douglas|D|', 'Rockstroh|Jürgen Kurt|JK|', 'Orkin|Chloe|C|', 'Gutiérrez|Félix|F|', 'Klein|Marina B|MB|', 'Reynes|Jacques|J|', 'Shukla|Umesh|U|', 'Jenkins|Alan|A|', 'Lenz|Oliver|O|', 'Ouwerkerk-Mahadevan|Sivi|S|', 'Peeters|Monika|M|', 'De La Rosa|Guy|G|', 'Tambuyzer|Lotke|L|', 'Jessner|Wolfgang|W|']
D000293:Adolescent D000328:Adult D000368:Aged D000998:Antiviral Agents D005260:Female D015658:HIV Infections D015497:HIV-1 D016174:Hepacivirus D019698:Hepatitis C, Chronic D006575:Heterocyclic Compounds, 3-Ring D006801:Humans D016898:Interferon-alpha D008297:Male D008875:Middle Aged D011092:Polyethylene Glycols D011994:Recombinant Proteins D012254:Ribavirin D000069616:Simeprevir D013449:Sulfonamides D016896:Treatment Outcome D055815:Young Adult
simeprevir coinfection hepatitis C virus human immunodeficiency virus type 1