title: Early HCV dynamics on Peg-interferon and ribavirin in HIV/HCV co-infection: indications for the investigation of new treatment approaches.
abstract: OBJECTIVE
  To describe the 28-day hepatitis C virus (HCV) kinetics under Pegylated-interferon (Peg-IFN) + ribavirin (RBV) therapy in HIV/HCV co-infected patients. To evaluate the predictive value of early virological response (EVR) of achieving a sustained virological response (SVR). To investigate the baseline mutations in the interferon sensitivity determining region (ISDR)2209-2248 in the non-structural 5A protein of HCV according to genotype.
  
  
  METHODS
  Open, prospective trial including 28 co-infected patients with directly observed treatment with Peg-IFN + RBV. We assessed the predictive values of EVR (> or = 2 log10 of HCV decay or a negative qualitative test) at days 1, 7, 28 and in week 12 of the SVR.
  
  
  RESULTS
  The SVR in an intention-to-treat analysis was 28.6% (genotype 1, 1/13; genotype 3, 6/10; genotype 4, 1/5). Patients who reached SVR presented a significantly faster HCV plasma viral load reduction compared to non-responders from the first 24 h [-1.06 log10 (interquartile range, -1.7 to -0.4) versus -0.05 log10 (interquartile range, -0.4 to +0.14) respectively; P = 0.002]. The median HCV viral load at week 12 was significantly different from that at baseline in responder and transient responders but not in non-responder patients. The positive predictive value was 100% within the first month and the best negative predictive value was 92% and 88.8% at weeks 4 and 12 respectively. The only genotype 1 responder patient had eight mutations in ISDR2209-2248.
  
  
  CONCLUSIONS
  A very early HCV viral decay is observed in responder patients. An early virological response assessment at week 4 and 12 might be a useful tool in the clinical management of the co-infected population.
authors.affiliation: HIV Clinical Unit, University Hospital Germans Trias i Pujol, Universitat Autónoma de Barcelona, Barcelona, Spain.
authors.forename: Angel Luis
authors.initials: AL
authors.lastname: Ballesteros
authors.forename: Sandra
authors.initials: S
authors.lastname: Franco
authors.forename: Daniel
authors.initials: D
authors.lastname: Fuster
authors.forename: Ramón
authors.initials: R
authors.lastname: Planas
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Martínez
authors.forename: Lesly
authors.initials: L
authors.lastname: Acosta
authors.forename: Guillem
authors.initials: G
authors.lastname: Sirera
authors.forename: Anna
authors.initials: A
authors.lastname: Salas
authors.forename: Jordi
authors.initials: J
authors.lastname: Tor
authors.forename: Celestino
authors.initials: C
authors.lastname: Rey-Joly
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Cristina
authors.initials: C
authors.lastname: Tural
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010865:Pilot Projects; D011092:Polyethylene Glycols; D011379:Prognosis; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014779:Virus Replication / Q000502:physiology; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a