PMID- 28210927 OWN - NLM STAT- MEDLINE DCOM- 20170727 LR - 20211204 IS - 1936-0541 (Electronic) IS - 1936-0533 (Linking) VI - 11 IP - 2 DP - 2017 Mar TI - 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. PG - 188-198 LID - 10.1007/s12072-017-9788-z [doi] AB - 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 mug, 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. FAU - Sulkowski, Mark S AU - Sulkowski MS AD - Divisions of Infectious Diseases and Gastroenterology/Hepatology, Johns Hopkins Hospital, The Johns Hopkins University School of Medicine , Baltimore, MD, USA. msulkowski@jhmi.edu. FAU - Fessel, Walford J AU - Fessel WJ AD - Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA. FAU - Lazzarin, Adriano AU - Lazzarin A AD - Unit of Infectious Diseases, Clinica Malattie Infettive, Institute of Hospitalisation and Scientific Care, Milan, Italy. FAU - Berenguer, Juan AU - Berenguer J AD - Unidad de Enfermedades Infecciosas/VIH (4100), Instituto de Investigacion Sanitaria Gregorio Maranon, Hospital General Universitario Gregorio Maranon, Madrid, Spain. FAU - Zakharova, Natalia AU - Zakharova N AD - St Petersburg AIDS Center, SPT AIDS C 179A OBVODNIY CANAL, Saint Petersburg, Russian Federation. FAU - Cheinquer, Hugo AU - Cheinquer H AD - Servico De Gastroentereologia, Hospital De Clinicas De Porto Alegre, Porto Alegre, Rio Grande Do Sul, Brazil. FAU - Cote, Pierre AU - Cote P AD - Clinique Medicale Du Quartier Latin, Montreal, QC, Canada. FAU - Dieterich, Douglas AU - Dieterich D AD - Institute for Liver Disease, Mount Sinai School of Medicine, New York, NY, USA. FAU - Gadano, Adrian AU - Gadano A AD - Hospital Italiano De Buenos Aires, Buenos Aires, Argentina. FAU - Matthews, Gail AU - Matthews G AD - St Vincent's Hospital (NSW), Darlinghurst, NSW, Australia. FAU - Molina, Jean-Michel AU - Molina JM AD - Hopital Saint Louis, Paris, France. FAU - Moreno, Christophe AU - Moreno C AD - Hospital Erasme, Brussels, Belgium. FAU - Pineda, Juan Antonio AU - Pineda JA AD - Infectious Diseases and Microbiology Unit, Hospital Universitario de Valme, Seville, Spain. FAU - Pulido, Federico AU - Pulido F AD - Hospital Universitario 12 De Octubre, Madrid, Spain. FAU - Rivero, Antonio AU - Rivero A AD - Hospital Universitario Reina Sofia, Cordoba, Spain. FAU - Rockstroh, Jurgen AU - Rockstroh J AD - Universitaetsklinikum Bonn, Medizinische Klinik, Bonn, Germany. FAU - Hernandez, Dennis AU - Hernandez D AD - Department of Virology Discovery Biology, Bristol-Myers Squibb Research and Development, Wallingford, CT, USA. FAU - McPhee, Fiona AU - McPhee F AD - Department of Virology Discovery Biology, Bristol-Myers Squibb Research and Development, Wallingford, CT, USA. FAU - Eley, Timothy AU - Eley T AD - Bristol-Myers Squibb, Princeton, NJ, USA. FAU - Liu, Zhaohui AU - Liu Z AD - Bristol-Myers Squibb, Hopewell, Pennington, NJ, USA. FAU - Mendez, Patricia AU - Mendez P AD - Bristol-Myers Squibb, Princeton, NJ, USA. FAU - Hughes, Eric AU - Hughes E AD - Bristol-Myers Squibb, Lawrenceville, NJ, USA. FAU - Noviello, Stephanie AU - Noviello S AD - Bristol-Myers Squibb, Lawrenceville, NJ, USA. FAU - Ackerman, Peter AU - Ackerman P AD - Bristol-Myers Squibb, Wallingford, CT, USA. LA - eng SI - ClinicalTrials.gov/NCT01471574 PT - Clinical Trial, Phase III PT - Journal Article DEP - 20170216 PL - United States TA - Hepatol Int JT - Hepatology international JID - 101304009 RN - 0 (Antiviral Agents) RN - 0 (Carbamates) RN - 0 (Imidazoles) RN - 0 (Interferon-alpha) RN - 0 (Pyrrolidines) RN - 0 (Recombinant Proteins) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 49717AWG6K (Ribavirin) RN - HG18B9YRS7 (Valine) RN - LI2427F9CI (daclatasvir) RN - Q46947FE7K (peginterferon alfa-2a) SB - IM MH - Adult MH - Aged MH - Antiviral Agents/administration & dosage/adverse effects/*therapeutic use MH - Carbamates MH - Coinfection/*drug therapy/virology MH - Drug Therapy, Combination MH - Female MH - HIV Infections/*complications/drug therapy MH - Hepacivirus/drug effects/genetics MH - Hepatitis C, Chronic/*complications/drug therapy MH - Humans MH - Imidazoles/administration & dosage/adverse effects/*therapeutic use MH - Interferon-alpha/administration & dosage/adverse effects/*therapeutic use MH - Male MH - Middle Aged MH - Polyethylene Glycols/administration & dosage/adverse effects/*therapeutic use MH - Pyrrolidines MH - Recombinant Proteins/administration & dosage/adverse effects/therapeutic use MH - Ribavirin/administration & dosage/*therapeutic use MH - Treatment Outcome MH - Valine/analogs & derivatives MH - Young Adult OTO - NOTNLM OT - Daclatasvir OT - HCV GT-1 OT - HIV/HCV coinfection OT - Peginterferon alfa-2a/ribavirin EDAT- 2017/02/18 06:00 MHDA- 2017/07/28 06:00 CRDT- 2017/02/18 06:00 PHST- 2016/11/18 00:00 [received] PHST- 2017/01/24 00:00 [accepted] PHST- 2017/02/18 06:00 [pubmed] PHST- 2017/07/28 06:00 [medline] PHST- 2017/02/18 06:00 [entrez] AID - 10.1007/s12072-017-9788-z [pii] AID - 10.1007/s12072-017-9788-z [doi] PST - ppublish SO - Hepatol Int. 2017 Mar;11(2):188-198. doi: 10.1007/s12072-017-9788-z. Epub 2017 Feb 16.