title: Real-World Efficacy of Daclatasvir and Sofosbuvir, With and Without Ribavirin, in HIV/HCV Coinfected Patients With Advanced Liver Disease in a French Early Access Cohort.
abstract: Efficacious, well-tolerated, direct antiviral agents have drastically changed the prognosis of hepatitis C virus (HCV) disease, but real-world data for oral treatments are limited in key populations such as HIV/HCV coinfection with advanced liver disease. Daclatasvir (DCV) efficacy and safety was assessed in the French "Autorisation Temporaire d'Utilisation" (ATU) program, providing DCV ahead of market authorization to patients with advanced HCV disease without other treatment options.
  
  
  
  This was a subanalysis of HIV/HCV coinfected ATU patients treated with DCV plus sofosbuvir (SOF). Recommended duration was 24 weeks; addition of ribavirin (RBV) and/or shorter treatment was at the physician's discretion. The primary efficacy analysis was sustained virologic response at posttreatment week 12 (SVR12; modified intention-to-treat). Safety was assessed by spontaneous adverse event reporting.
  
  
  
  The efficacy population (N = 407) was mostly cirrhotic (72%, of whom 18% were decompensated), HCV treatment-experienced (82%), and infected with genotypes 1 (69%), 3 (12%), or 4 (19%). Median CD4 was 555 cells/mm; 95% had HIV RNA <50 copies/mL. Most (74%) were treated for 24 weeks; 14% received RBV. SVR12 was 92% overall (95% confidence interval: 88.6% to 94.0%); 90% (86.4% to 93.2%) in patients with cirrhosis; 95% (88.9% to 97.5%) in patients without cirrhosis. SVR12 was consistent across HCV genotypes and antiretroviral regimens. Among 617 patients with safety data, 7 discontinued for an adverse event and 10 died.
  
  
  
  DCV+SOF±RBV achieved high SVR12 and was well tolerated in this large real-world cohort of HIV/HCV coinfected patients with advanced liver disease.
authors.affiliation: 1Department of Infectious and Tropical Diseases, Hôpitaux Universitaires Saint-Antoine, Assistance Publique Hôpitaux de Paris (APHP), Paris, France; 2Sorbonne Universités, INSERM, UPMC Univ Paris 06, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP UMRS 1136), Paris, France; 3Hepatology Unit, Cochin Hospital, APHP, INSERM USM20, Pasteur Institute, Paris, France; 4Department of Infectious Diseases, CHU de la Conception, Marseilles, France; 5Department of Hepato-gastroenterology, CHU Purpan, Toulouse, France; 6Department of Internal Medicine and COREVIH PACA-EST, CHU Archet, Nice, France; 7Hepatobiliary Centre, CHU Paul-Brousse, Villejuif, France; 8Department of Infectious and Tropical Diseases, CHU Pitié-Salpêtrière, Paris, France; 9Department of Infectious and Tropical Diseases, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France; 10Department of Infectious and Tropical Diseases, Bichat-Claude Bernard Hospital, Paris, France; 11Department of Clinical Immunology, Georges-Pompidou European Hospital, Paris, France; 12Department of Hepato-gastroenterology, CHU de Montpellier, Montpellier, France; 13Department of Infectious and Tropical Diseases, Hôpitaux Universitaires Tenon, APHP, Paris, France; 14Department of Infectious and Tropical Diseases, CHU Perpignan, Perpignan, France; 15Department of Clinical Immunology, CHU Henri Mondor, Créteil, France; 16Department of Hemato-oncology, CH Aix-en-Provence, Aix-en-Provence, France; 17Department of Infectious Diseases, CHU Toulon, Toulon, France; 18Department of Infectious and Tropical Diseases, CHU Hôtel Dieu, Nantes, France; 19Department of Infectious Diseases, Raymond Poincaré Hospital, APHP, Garches, France; 20Department of Internal Medicine, CHD La Roche-sur-Yon, La Roche-sur-Yon, France; 21Department of Hepato-gastroenterology, CHU Grenoble Alpes, Grenoble, France; 22Hepatic Fibrosis Investigation Centre, Haut-Lévêque Hospital, CHU de Bordeaux, Pessac, France; 23INSERM U1223, Pasteur Institute, Paris-Descartes University and Hepatology Department, Cochin Hospital, Paris, France; 24INSERM U1219, ISPED University of Bordeaux, Bordeaux, France; 25Bristol-Myers Squibb Research and Development, Princeton, NJ; 26Bristol-Myers Squibb Research and Development, Rueil-Malmaison, Paris, France; and 27Paris Descartes University, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Lacombe
authors.forename: Hélène
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authors.lastname: Fontaine
authors.forename: Catherine
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authors.forename: Sophie
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authors.forename: Eric
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authors.forename: Patrick
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authors.lastname: Miailhes
authors.forename: Stanislas
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authors.forename: Dominique
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authors.lastname: Batisse
authors.forename: Georges-Philippe
authors.initials: GP
authors.lastname: Pageaux
authors.forename: Julie
authors.initials: J
authors.lastname: Chas
authors.forename: Hugues
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authors.lastname: Aumaitre
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dominguez
authors.forename: Thierry
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authors.lastname: Allegre
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authors.lastname: Lafeuillade
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authors.lastname: Billaud
authors.forename: Pierre
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authors.lastname: De Truchis
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authors.forename: Vincent
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authors.forename: Victor
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authors.lastname: De Ledinghen
authors.forename: Philippe
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authors.lastname: Sogni
authors.forename: François
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authors.lastname: Dabis
authors.forename: Yue
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authors.lastname: Zhao
authors.forename: Anne
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authors.lastname: Filipovics
authors.forename: Larysa
authors.initials: L
authors.lastname: Fedchuk
authors.forename: Raoudha
authors.initials: R
authors.lastname: Akremi
authors.forename: Yacia
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authors.forename: Dominique
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authors.lastname: Salmon Ceron
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002219:Carbamates; D060085:Coinfection / Q000188:drug therapy; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005602:France; D015658:HIV Infections / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D000069474:Sofosbuvir / Q000008:administration & dosage* / Q000009:adverse effects; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012254:Ribavirin; D014633:Valine; C549273:daclatasvir; D000069474:Sofosbuvir