title: The more you look, the more you find: effects of hepatitis C virus testing interval on reinfection incidence and clearance and implications for future vaccine study design.
abstract: BACKGROUND
  Studies have explored whether spontaneous clearance of hepatitis C virus (HCV) infection decreases the likelihood of reinfection or increases the probability of clearance. This analysis investigates whether the conflicting findings from these studies could be due to differences in frequency of HCV RNA testing.
  
  
  METHODS
  A model simulated the dynamics of HCV reinfection and clearance among a cohort of injection drug users. For different reinfection incidence and clearance rates, the model evaluated the accuracy of epidemiological studies that used different HCV testing frequencies.
  
  
  RESULTS
  Experimental estimates for the reinfection incidence and clearance probability will be accurate (<20% error) if the testing interval is less than the reinfection clearance duration. Otherwise, experimental estimates can greatly underestimate the real values (≤66% error if reinfection duration is 1 month and the testing interval is 3 months). Uncertainty in experimental estimates also increases at lower reinfection incidences, whereas for lower clearance probabilities the uncertainty in the estimated clearance probability increases but estimated reinfection incidence decreases.
  
  
  CONCLUSIONS
  Differences in HCV testing interval could account for most between-study variability in the estimated probability of clearing reinfections and is likely to have biased reinfection incidence estimates. Our findings suggest that a high reinfection clearance probability (>75%) is consistent with data.
authors.affiliation: Department of Global Health and Development, London School of Hygiene and Tropical Medicine, UK. peter.vickerman@lshtm.ac.uk
authors.forename: Peter
authors.initials: P
authors.lastname: Vickerman
authors.forename: Jason
authors.initials: J
authors.lastname: Grebely
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.forename: Rachel
authors.initials: R
authors.lastname: Sacks-Davis
authors.forename: Kimberly
authors.initials: K
authors.lastname: Page
authors.forename: David L
authors.initials: DL
authors.lastname: Thomas
authors.forename: William O
authors.initials: WO
authors.lastname: Osburn
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Cox
authors.forename: Campbell K
authors.initials: CK
authors.lastname: Aitken
authors.forename: Matthew
authors.initials: M
authors.lastname: Hickman
authors.forename: Margaret
authors.initials: M
authors.lastname: Hellard
mesh_terms: D015331:Cohort Studies; D055030:Drug Users; D005838:Genotype; D016174:Hepacivirus / Q000472:pathogenicity*; D006526:Hepatitis C / Q000453:epidemiology* / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D015994:Incidence; D016014:Linear Models; D008962:Models, Theoretical; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D012008:Recurrence; D012107:Research Design / Q000639:trends*; D015819:Substance Abuse, Intravenous / Q000453:epidemiology* / Q000821:virology
chemical_list: D012367:RNA, Viral