title: Frequent longitudinal sampling of hepatitis C virus infection in injection drug users reveals intermittently detectable viremia and reinfection.
abstract: BACKGROUND
  Detection of hepatitis C virus (HCV) reinfection and intercalation (ie, intermittent recurrent bouts of viremia with homologous virus interspersed with aviremic periods) requires extensive and frequent evaluation and viral sequencing.
  
  
  METHODS
  HCV infection outcomes were studied prospectively in active injection drug users with recurrent HCV RNA-positive tests after serial negative results. HCV viremia and viral sequences (Core/E1) were assessed from monthly blood samples.
  
  
  RESULTS
  Viral clearance, reinfection, and intercalating infection were all detected. Among 44 participants with apparently resolved HCV (26 incident HCV clearers and 18 enrolled with already resolved infection), 36 (82%) remained persistently HCV RNA negative, but 8 demonstrated intermittent recurrent viremia. Four of these (50%) had confirmed reinfection with a heterologous virus; 3 demonstrated viral intercalation, and 1 was not classifiable as either. Estimated incidence of first reinfection was 5.4 per 100 person-years (95% confidence interval, 2.0-14.5). Six (75%) participants, including 3 of 4 with reinfection, demonstrated sustained viral clearance for a median of 26 months since last HCV RNA test.
  
  
  CONCLUSIONS
  These results show that frequent monitoring and viral sequencing are required to correctly assess HCV outcomes and estimate incidence of reinfection (which was previously overestimated). Sustained clearance may take many months and occur after episodes of reinfection and viral intercalation. Three of 4 subjects who had confirmed reinfection showed evidence of long-term clearance. Viral intercalation occurs with significant frequency. Further studies of these events, especially immunological, are needed to inform HCV clinical care and vaccine development.
authors.affiliation: University of California, San Francisco, San Francisco, CA 94105, USA. kpage@psg.ucsf.edu
authors.forename: Kimberly
authors.initials: K
authors.lastname: Page
authors.forename: William
authors.initials: W
authors.lastname: Osburn
authors.forename: Jennifer
authors.initials: J
authors.lastname: Evans
authors.forename: Judith A
authors.initials: JA
authors.lastname: Hahn
authors.forename: Paula
authors.initials: P
authors.lastname: Lum
authors.forename: Alice
authors.initials: A
authors.lastname: Asher
authors.forename: Eric
authors.initials: E
authors.lastname: Delwart
authors.forename: Leslie
authors.initials: L
authors.lastname: Tobler
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Cox
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
mesh_terms: D000328:Adult; D055030:Drug Users; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000276:immunology / Q000821:virology*; D006801:Humans; D007267:Injections / Q000009:adverse effects; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D015819:Substance Abuse, Intravenous / Q000276:immunology / Q000821:virology*; D014766:Viremia / Q000276:immunology / Q000821:virology*; D055815:Young Adult
chemical_list: D012367:RNA, Viral