Combination Treatment with Ombitasvir, Paritaprevir/Ritonavir, Dasabuvir, and Sofosbuvir in Patients with Genotype 1 HCV Infection

MAY 25, 2016
Katherine Hasal
“Optimal retreatment strategies for patients with chronic hepatitis C virus (HCV) infection who have failed treatment with direct-acting antiviral (DAA) regimens are not yet clearly defined,” said Fred Poordad, MD, PhD, of the Texas Liver Institute/University of Texas Health Science Center in San Antonio, at a presentation at Digestive Disease Week 2016, a joint meeting of the American Academy for the Study of Liver Diseases (AASLD), American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
 
Prior treatment with NS5A inhibitors, such as ledipasvir, ombitasvir, daclatasvir, and elbasvir, increases the risk for the emergence of resistance-associated variants (RAVs), which can persist up to 96 weeks after treatment. Consequently, patients who fail regimens with NS5A inhibitor are likely to require a multi-targeted approach to effective treat their infection.
 
High sustained virologic response rates have been achieved with the 3-DAA (3D) regimen of ombitasvir (OMV) co-formulated with paritaprevir (with the pharmaco-enhancer ritonavir [PTV/r]) and dasabuvir (DSV) with or without ribavirin (RBV) in adults with chronic HCV genotype 1 infection. Sofosbuvir (SOF) is a nucleoside NS5B polymerase inhibitor with potent pangenotypic activity and no cross-resistance with the components of the 3D regimen. There are no meaningful drug-drug interactions between 3D and sofosbuvir. The multi-targeted combination of 3D and sofosbuvir may offer a treatment option for patients who have previously failed DAA combination therapy.
 
The QUARTZ-I study was a phase 2, open-label, multicenter study designed to investigate the safety and efficacy of OBV/PTV/r plus DSV plus SOF in DAA-experienced patients with HCV genotype 1 infection. Patients with genotype 1a infection without cirrhosis received OBV/PTV/r (25/150/100 mg once daily) plus DSV (250 mg twice daily) plus SOF (400 mg once daily) with weight-based ribavirin for 12 weeks. Patients with genotype 1a infection with cirrhosis received the same regimen but for 24 weeks. Patients with genotype 1b infection with or without cirrhosis received the same regimen without ribavirin for 12 weeks. All patients had a history of DAA treatment failure either due to on-treatment breakthrough or relapse. The presence of RAVs was assessed by deep sequencing.
 


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