title: Hepatitis C Virus Reinfection and Spontaneous Clearance of Reinfection--the InC3 Study.
abstract: BACKGROUND
  We aimed to characterize the natural history of hepatitis C virus (HCV) reinfection and spontaneous clearance following reinfection (reclearance), including predictors of HCV reclearance.
  
  
  METHODS
  Data were synthesized from the 9 prospective cohorts of the International Collaboration of Incident Human Immunodeficiency Virus and HCV in Injecting Cohorts study, which evaluated HCV infection outcomes among people who inject drugs. Participants with primary HCV infection were classified as having achieved viral suppression if they had negative results of at least 1 subsequent HCV RNA test. Those with positive results of an HCV RNA test following viral suppression were investigated for reinfection. Viral sequence analysis was used to identify reinfection (defined as detection of heterologous virus with no subsequent detection of the original viral strain).
  
  
  RESULTS
  Among 591 participants with acute primary HCV infection, 118 were investigated for reinfection. Twenty-eight participants were reinfected (12.3 cases/100 person-years; 95% confidence interval [CI], 8.5-17.8). Peak HCV RNA level was lower during reinfection than primary infection (P = .011). The proportion of individuals with reclearance 6 months after reinfection was 52% (95% CI, 33%-73%). After adjustment for study site, females with the IFNL4 (formerly IFNL3 and IL28B) rs12979860 CC genotype detected were more likely to have reclearance (hazard ratio, 4.16; 95% CI, 1.24-13.94; P = .021).
  
  
  CONCLUSIONS
  Sex and IFNL4 genotype are associated with spontaneous clearance after reinfection.
authors.affiliation: Burnet Institute, Monash University, Melbourne Department of Epidemiology and Preventive Medicine, Monash University, Melbourne.
authors.forename: Rachel
authors.initials: R
authors.lastname: Sacks-Davis
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Grebely
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors.forename: William
authors.initials: W
authors.lastname: Osburn
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Cox
authors.affiliation: Department of Epidemiology and Biostatistics, University of California-San Francisco.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Rice
authors.affiliation: Burnet Institute, Monash University, Melbourne Department of Epidemiology and Preventive Medicine, Monash University, Melbourne.
authors.forename: Timothy
authors.initials: T
authors.lastname: Spelman
authors.affiliation: CRCHUM, Université de Montréal, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.affiliation: GGD Public Health Service of Amsterdam, Amsterdam, The Netherlands Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Prins
authors.affiliation: Harvard Medical School, Boston, Massachusetts.
authors.forename: Arthur Y
authors.initials: AY
authors.lastname: Kim
authors.affiliation: Tufts Medical School, Boston, Massachusetts Abbvie, Chicago, Illinois.
authors.forename: Barbara H
authors.initials: BH
authors.lastname: McGovern
authors.affiliation: CRCHUM, Université de Montréal, Canada.
authors.forename: Naglaa H
authors.initials: NH
authors.lastname: Shoukry
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Janke
authors.initials: J
authors.lastname: Schinkel
authors.affiliation: Harvard Medical School, Boston, Massachusetts.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.affiliation: Department of Epidemiology and Biostatistics, University of California-San Francisco.
authors.forename: Meghan
authors.initials: M
authors.lastname: Morris
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Behzad
authors.initials: B
authors.lastname: Hajarizadeh
authors.affiliation: The Kirby Institute, University of New South Wales, Sydney, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Maher
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Lloyd
authors.affiliation: Department of Epidemiology and Biostatistics, University of California-San Francisco.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Page
authors.affiliation: Burnet Institute, Monash University, Melbourne Department of Epidemiology and Preventive Medicine, Monash University, Melbourne.
authors.forename: Margaret
authors.initials: M
authors.lastname: Hellard
mesh_terms: D000208:Acute Disease; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D007378:Interleukins / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000302:isolation & purification; D012008:Recurrence; D012737:Sex Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D007378:Interleukins; D012367:RNA, Viral; C579163:IFNL4 protein, human; D000095022:Interferon Lambda
keywords: IFNL4; cohort study; hepatitis C; injecting drug use; re-infection; sex; viral resolution