Efficacy and safety of daclatasvir plus pegylated-interferon alfa 2a and ribavirin in previously untreated HCV subjects coinfected with HIV and HCV genotype-1: a Phase III, open-label study

• Published in: Hepatology international Vol. 11; no. 2; pp. 188 - 198
• Main Authors: Sulkowski, Mark S., Fessel, Walford J., Lazzarin, Adriano, Berenguer, Juan, Zakharova, Natalia, Cheinquer, Hugo, Côté, Pierre, Dieterich, Douglas, Gadano, Adrian, Matthews, Gail, Molina, Jean-Michel, Moreno, Christophe, Pineda, Juan Antonio, Pulido, Federico, Rivero, Antonio, Rockstroh, Jurgen, Hernandez, Dennis, McPhee, Fiona, Eley, Timothy, Liu, Zhaohui, Mendez, Patricia, Hughes, Eric, Noviello, Stephanie, Ackerman, Peter
• Format: Journal Article
• Language: English
• Published: New Delhi Springer India 01.03.2017; Springer Nature B.V
• Subjects: Adult; Aged; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Coinfection - drug therapy; Coinfection - virology; Colorectal Surgery; Drug Therapy, Combination; Female; Hepacivirus - drug effects; Hepacivirus - genetics; Hepatitis C virus; Hepatitis C, Chronic - complications; Hepatitis C, Chronic - drug therapy; Hepatology; HIV Infections - complications; HIV Infections - drug therapy; Humans; Imidazoles - administration & dosage; Imidazoles - adverse effects; Imidazoles - therapeutic use; Interferon-alpha - administration & dosage; Interferon-alpha - adverse effects; Interferon-alpha - therapeutic use; Lentivirus; Male; Medicine; Medicine & Public Health; Middle Aged; Original Article; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - adverse effects; Polyethylene Glycols - therapeutic use; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; Retroviridae; Ribavirin - administration & dosage; Ribavirin - therapeutic use; Surgery; Treatment Outcome; Young Adult; Daclatasvir; HIV/HCV coinfection; Peginterferon alfa-2a/ribavirin; HCV GT-1
• ISSN: 1936-0533; 1936-0541; 1936-0541
• DOI: 10.1007/s12072-017-9788-z

Background Daclatasvir (DCV) is a potent, pangenotypic, hepatitis C virus (HCV) non-structural protein 5A inhibitor with low potential for drug interactions with antiretroviral therapy (ART). We evaluated the safety and efficacy of DCV plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in HIV-1/HCV genotype-1-coinfected patients. Methods AI444043 (NCT01471574), an open-label, Phase III, single-arm, response-guided treatment (RGT) study included 301 patients. They received DCV doses of 30, 60 or 90 mg once daily (depending on concomitant ART), plus weight-based RBV (<75 kg, 1000 mg/day; or ≥75 kg, 1200 mg/day), and once-weekly PegIFN 180 μg, for 24 weeks. If required by RGT, PegIFN/RBV without DCV was extended for an additional 24 weeks of therapy. The primary endpoint was the proportion of patients with sustained virologic response at post-treatment Week 12 (SVR12). Results Overall, 224 (74%) patients achieved SVR12 and the lower bound of the 95% confidence interval was higher than the historic SVR rate with PegIFN/RBV alone (70 vs. 29%). Most common adverse events (AEs) were fatigue, neutropenia, anemia, asthenia and headache. On-treatment serious AEs occurred in 24/301 (8%) patients; 18/301 (6%) discontinued treatment due to AE. Conclusions DCV + PegIFN/RBV led to sustained HCV virologic response in the majority of HIV-1-HCV-coinfected patients, regardless of concomitant ART. HIV control was not compromised and no new safety signals were identified. This study supports DCV use in HIV-1-HCV-coinfected patients, while allowing the vast majority of patients to remain on their existing ART regimen.