title: High Cure Rate With 24 Weeks of Daclatasvir-Based Quadruple Therapy in Treatment-Experienced, Null-Responder Patients With HIV/Hepatitis C Virus Genotype 1/4 Coinfection: The ANRS HC30 QUADRIH Study.
abstract: BACKGROUND
  Few direct anti-hepatitis C virus (HCV) agents have been studied in difficult-to-treat null responder and cirrhotic human immunodeficiency virus (HIV)-coinfected patients. Daclatasvir and asunaprevir combined with pegylated interferon/ribavirin (peg-IFN/RBV) have shown promising results in HCV-monoinfected patients.
  
  
  METHODS
  An open-label, single-arm, phase 2 study was conducted in HIV/HCV genotype 1/4-coinfected patients who were null responders to prior peg-IFN/RBV standard therapy and on a raltegravir-based regimen with HIV RNA <400 copies/mL. They received a 4-week lead-in phase with peg-IFN/RBV, followed by 24 weeks of asunaprevir (100 mg twice daily), daclatasvir (60 mg once daily), and peg-IFN/RBV. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12) using intent-to-treat analysis.
  
  
  RESULTS
  Seventy-five patients were included, of whom 27 (36%) had cirrhosis. The median baseline CD4 count was 748 (interquartile range, 481-930) cells/µL. The global SVR12 rate was 96.0% (95% confidence interval [CI], 88.8%-99.2%; n = 72/75), 92.6% (95% CI, 75.7%-99.1%; n = 25/27) in cirrhotic patients, 94.6% (95% CI, 81.8%-99.3%; n = 35/37) in genotype 1 patients, and 97.4% (95% CI, 86.2%-99.9%; n = 37/38) in genotype 4 patients. Six patients (8%) stopped HCV therapy prematurely: 2 due to HCV breakthrough, 4 to adverse events (1 lung cancer, 3 infections). One patient with cirrhosis (with baseline platelet count <150 000 platelets/µL and albuminemia <35 g/L) died from multiorgan failure. Overall, 36 serious adverse events occurred in 21 (28%) patients. No HIV breakthrough was observed.
  
  
  CONCLUSIONS
  In HIV/HCV genotype 1/4-coinfected null responders, a 24-week regimen combining daclatasvir, asunaprevir, and peg-IFN/RBV was associated with a very high cure rate. The safety profile was acceptable, even though cirrhotic patients with low albuminemia and platelets should be monitored closely. This combination is a new option in this difficult-to-treat population.
  
  
  BACKGROUND
  NCT01725542.
authors.affiliation: Infectious Diseases Department, Centre Hospitalo-Universitaire, and Unité Mixte de Recherche (UMR)1347, Université de Bourgogne, Dijon.
authors.forename: Lionel
authors.initials: L
authors.lastname: Piroth
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) SC10-US019, Villejuif.
authors.forename: Hubert
authors.initials: H
authors.lastname: Paniez
authors.affiliation: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Bicêtre, Hôpitaux Universitaires Paris Sud, Clinical Pharmacy.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Taburet
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) SC10-US019, Villejuif.
authors.forename: Corine
authors.initials: C
authors.lastname: Vincent
authors.affiliation: Service de Médecine Interne, Hôpital de l'Archet, and Université de Nice-Sophia Antipolis.
authors.forename: Eric
authors.initials: E
authors.lastname: Rosenthal
authors.affiliation: Sorbonne Universités, Université Pierre et Marie CURIE (UPMC) Paris 06, INSERM UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, and Service de maladies infectieuses, Hôpital Saint-Antoine, AP-HP.
authors.forename: Karine
authors.initials: K
authors.lastname: Lacombe
authors.affiliation: Infectious Diseases Department, Centre Hospitalo-Universitaire, Nantes.
authors.forename: Eric
authors.initials: E
authors.lastname: Billaud
authors.affiliation: Le Trait d'Union, Hôpitaux Universitaires, Strasbourg.
authors.forename: David
authors.initials: D
authors.lastname: Rey
authors.affiliation: Infectious Diseases Department, Hôpital Foch, Suresnes.
authors.forename: David
authors.initials: D
authors.lastname: Zucman
authors.affiliation: Department of Hepatology, Hôpital de la Croix-Rousse, Hospices Civils de Lyon.
authors.forename: François
authors.initials: F
authors.lastname: Bailly
authors.affiliation: INSERM U954, Centre Hospitalier Universitaire de Nancy, Université de Lorraine, Vandoeuvre les Nancy.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.affiliation: Agence Nationale de Recherche sur le Sida et les Hépatites Virales, France REcherche Nord & sud Sida-hiv Hépatites, Paris.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Simony
authors.affiliation: Agence Nationale de Recherche sur le Sida et les Hépatites Virales, France REcherche Nord & sud Sida-hiv Hépatites, Paris.
authors.forename: Alpha
authors.initials: A
authors.lastname: Diallo
authors.affiliation: Department of Virology, INSERM U1043 IFR-BMT, and Université Paul Sabatier, Toulouse.
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) SC10-US019, Villejuif.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Aboulker
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) SC10-US019, Villejuif.
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.affiliation: Infectious Diseases Department, Hôpital Saint-Louis-AP-HP, and Université Paris Diderot, Sorbonne Paris Cité, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002219:Carbamates; D060085:Coinfection / Q000453:epidemiology / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000453:epidemiology / Q000821:virology; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D014633:Valine; C549273:daclatasvir
keywords: HCV; HIV; asunaprevir; cirrhosis; daclatasvir