title: Low Efficacy of Pegylated Interferon plus Ribavirin plus Nitazoxanide for HCV Genotype 4 and HIV Coinfection.
abstract: BACKGROUND
  Nitazoxanide (NTZ) plus pegylated interferon and ribavirin (Peg-IFN/RBV) improved the sustained virological response (SVR) achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4)-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV)/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients.
  
  
  METHODS
  This was an open-label, single arm, multicenter phase II pilot clinical trial (NCT01529073) enrolling HIV-infected individuals with HCV-4 chronic infection, naïve to HCV therapy. Patients were treated with NTZ 500 mg bid for 4 weeks, followed by NTZ 500 mg bid plus Peg-IFN alpha-2b 1.5 μg/kg/week plus weight-adjusted RBV during 48 weeks. Analyses were done by intention-to-treat (ITT, missing = failure). A historical cohort of HIV/HCV-4-infected patients treated with Peg-IFN alpha-2b and RBV at the same area was used as control.
  
  
  RESULTS
  Two (9.5%) of 21 patients included in the trial compared with 5 (21.7%) of 23 patients included in the historical cohort achieved SVR (SVR risk difference, -12.2%; 95% confidence interval, -33.2% to 8.8%; p = 0.416). Virological failure was due to lack of response in 13 (62%) individuals recruited in the trial. Two (9.5%) patients included in the trial and two (9.5%) individuals from the historical cohort discontinued permanently due to adverse events.
  
  
  CONCLUSIONS
  No increase in SVR was observed among HIV/HCV-4-coinfected patients receiving Peg-IFN/RBV plus NTZ compared with a historical cohort treated with Peg-IFN/RBV. Interruptions due to adverse events of Peg-IFN/RBV plus NTZ were similar to those of dual therapy.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01529073.
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Sevilla, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Macías
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain.
authors.forename: Luis F
authors.initials: LF
authors.lastname: López-Cortés
authors.affiliation: Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Hospital de La Línea de la Concepción, AGS Campo de Gibraltar, Cádiz, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Téllez
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Sevilla, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Recio
authors.affiliation: Unidad de Gestión Clínica de Enfermedades Infecciosas, Hospital Virgen de la Victoria, Complejo Hospitalario de Málaga, Málaga, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ojeda-Burgos
authors.affiliation: Unidad de Enfermedades Infecciosas, Hospital Universitario Virgen Macarena, Sevilla, Spain.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Ríos
authors.affiliation: Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero-Juárez
authors.affiliation: Servicio de Enfermedades Infecciosas, Hospital Regional de Málaga, Malaga, Spain.
authors.forename: Marcial
authors.initials: M
authors.lastname: Delgado
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain.
authors.lastname: Rivas-Jeremías
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Sevilla, Spain.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Pineda
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D060085:Coinfection / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009574:Nitro Compounds; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D013844:Thiazoles / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009574:Nitro Compounds; D012367:RNA, Viral; D011994:Recombinant Proteins; D013844:Thiazoles; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C041747:nitazoxanide