title: Addition of nitazoxanide to PEG-IFN and ribavirin to improve HCV treatment response in HIV-1 and HCV genotype 1 coinfected persons naïve to HCV therapy: results of the ACTG A5269 trial.
abstract: BACKGROUND
  We hypothesized that nitazoxanide (NTZ) added to pegylated interferon alfa-2a (PEG-IFN) and weight-based ribavirin (WBR) would improve hepatitis C virus (HCV) virologic responses in HCV treatment-naïve HIV-1/HCV genotype 1 coinfected persons.
  
  
  METHODS
  Prospective, single-arm study in which subjects received 4-week lead-in (NTZ 500 mg twice daily) followed by 48 weeks of NTZ, PEG-IFN, and WBR. We compared the HCV virologic responses of these subjects to historical controls from the completed ACTG study A5178 who received PEG-IFN and WBR and had similar subject characteristics. Primary endpoints were early virologic response and complete early virologic response (EVR and cEVR).
  
  
  RESULTS
  Among 67 subjects (78% male; 48% Black; median age, 50 years), EVR was achieved in 65.7% (90% CI, 55.0%-75.3%), cEVR in 38.8% (28.8%-49.6%). and SVR in 32.8% (23.4%-43.5%). EVR was higher with NTZ (51.4% in A5178; P = .03), but the sustained virologic response (SVR) proportion was similar (27.3% in A5178; P = .24). In contrast to A5178, SVR was similar across IL28B genotypes. Overall, NTZ was safe and well-tolerated.
  
  
  CONCLUSIONS
  Whereas EVR proportion improved significantly in this pilot study, the addition of NTZ to PEG-IFN/WBR did not significantly improve SVR compared to historical controls. NTZ may be associated with an attenuation of the effect of IL28B on HCV treatment response.
authors: Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors: Valerianna K
authors: VK
authors: Amorosa
authors: University of California at San Francisco, San Francisco, California.
authors: Anne
authors: A
authors: Luetkemeyer
authors: Harvard School of Public Health, Boston, Massachusetts.
authors: Minhee
authors: M
authors: Kang
authors: Birmingham Veterans Affairs Medical Center, Birmingham, Alabama University of Alabama School of Medicine, Birmingham, Alabama.
authors: Victoria A
authors: VA
authors: Johnson
authors: Harvard School of Public Health, Boston, Massachusetts.
authors: Triin
authors: T
authors: Umbleja
authors: Vanderbilt School of Medicine, Nashville, Tennessee.
authors: David W
authors: DW
authors: Haas
authors: ACTG Operations Center, Silver Spring, Maryland.
authors: Suria
authors: S
authors: Yesmin
authors: Romark Laboratories LC, Tampa, Florida.
authors: Matthew C
authors: MC
authors: Bardin
authors: Harvard Medical School, Boston, Massachsetts.
authors: Ray T
authors: RT
authors: Chung
authors: Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors: Beverly
authors: B
authors: Alston-Smith
authors: University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
authors: Pablo
authors: P
authors: Tebas
authors: University of California at San Francisco, San Francisco, California.
authors: Marion G
authors: MG
authors: Peters
mesh_terms: D000328:Adult; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009574:Nitro Compounds; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009574:Nitro Compounds; D011994:Recombinant Proteins; D013844:Thiazoles; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a; C041747:nitazoxanide
keywords: HIV; genotype 1; hepatitis C; nitazoxanide; pegylated interferon; ribavirin