title: Patterns of hepatitis C virus RNA levels during acute infection: the InC3 study.
abstract: BACKGROUND
  Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV) infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection.
  
  
  METHODS
  Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study). Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels ≤ 120 days) were categorised by a priori-defined patterns of HCV RNA levels: i) spontaneous clearance, ii) partial viral control with persistence (≥ 1 log IU/mL decline in HCV RNA levels following peak) and iii) viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak). Factors associated with HCV RNA patterns were assessed using multinomial logistic regression.
  
  
  RESULTS
  Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%), partial viral control with persistence (27%), and viral plateau with persistence (41%). HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P = 0.018). In the two groups with persistence, Interferon lambda 3 (IFNL3) CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02). In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83).
  
  
  CONCLUSIONS
  Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female sex is associated with ultimate spontaneous clearance.
authors.affiliation: The Kirby Institute, UNSW Australia (University of New South Wales), Sydney, NSW, Australia.
authors.forename: Behzad
authors.initials: B
authors.lastname: Hajarizadeh
authors.affiliation: Cluster Infectious Diseases, GGD Public Health Service of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Grady
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Page
authors.affiliation: Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Arthur Y
authors.initials: AY
authors.lastname: Kim
authors.affiliation: Tufts Medical School, Boston, Massachusetts, United States of America; Abbvie, Chicago, Illinois, United States of America.
authors.forename: Barbara H
authors.initials: BH
authors.lastname: McGovern
authors.affiliation: Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Cox
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Rice
authors.affiliation: Burnet Institute, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Sacks-Davis
authors.affiliation: CRCHUM, Université de Montréal, Montreal, QC, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.affiliation: Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Meghan
authors.initials: M
authors.lastname: Morris
authors.affiliation: The Kirby Institute, UNSW Australia (University of New South Wales), Sydney, NSW, Australia.
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Janke
authors.initials: J
authors.lastname: Schinkel
authors.affiliation: The Kirby Institute, UNSW Australia (University of New South Wales), Sydney, NSW, Australia.
authors.forename: Tanya
authors.initials: T
authors.lastname: Applegate
authors.affiliation: The Kirby Institute, UNSW Australia (University of New South Wales), Sydney, NSW, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Maher
authors.affiliation: Burnet Institute, Melbourne, VIC, Australia; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: Margaret
authors.initials: M
authors.lastname: Hellard
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, UNSW Australia, Sydney, NSW, Australia.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Lloyd
authors.affiliation: Cluster Infectious Diseases, 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: The Kirby Institute, UNSW Australia (University of New South Wales), Sydney, NSW, Australia.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dore
authors.affiliation: The Kirby Institute, UNSW Australia (University of New South Wales), Sydney, NSW, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Grebely
mesh_terms: D000208:Acute Disease; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000235:genetics / Q000276:immunology / Q000821:virology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D000069078:Seroconversion; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000410:Alanine Transaminase; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
references.citation: Science. 2000 Apr 14;288(5464):339-44
references.pmid: 10764648
references.citation: J Infect Dis. 2009 Oct 15;200(8):1216-26
references.pmid: 19764883
references.citation: Stat Med. 1989 May;8(5):551-61
references.pmid: 2657958
references.citation: Gastroenterology. 2011 Mar;140(3):818-29
references.pmid: 21167831
references.citation: Hepatology. 2012 Aug;56(2):444-54
references.pmid: 22331604
references.citation: J Med Virol. 2014 Oct;86(10):1722-9
references.pmid: 25042465
references.citation: J Hepatol. 2009 Oct;51(4):667-74
references.pmid: 19646773
references.citation: Transfus Clin Biol. 2001 Jun;8(3):200-6
references.pmid: 11499958
references.citation: Immune Netw. 2013 Oct;13(5):168-76
references.pmid: 24198741
references.citation: Gastroenterology. 2010 Nov;139(5):1586-92, 1592.e1
references.pmid: 20637200
references.citation: Hepatology. 2012 Jul;56(1):86-94
references.pmid: 22331649
references.citation: Nature. 2009 Oct 8;461(7265):798-801
references.pmid: 19759533
references.citation: Hepatology. 2014 Jan;59(1):109-20
references.pmid: 23908124
references.citation: Gastroenterology. 2010 Dec;139(6):1865-76
references.pmid: 20950615
references.citation: Nature. 2005 Aug 18;436(7053):946-52
references.pmid: 16107834
references.citation: J Viral Hepat. 2007 Mar;14(3):213-20
references.pmid: 17305887
references.citation: J Infect Dis. 2010 Dec 15;202(12):1770-9
references.pmid: 21067369
references.citation: J Infect Dis. 2007 Nov 15;196(10):1474-82
references.pmid: 18008226
references.citation: J Viral Hepat. 2006 Jan;13(1):34-41
references.pmid: 16364080
references.citation: J Gen Virol. 2011 Oct;92(Pt 10):2227-36
references.pmid: 21775583
references.citation: Clin Infect Dis. 2005 Apr 1;40(7):951-8
references.pmid: 15824985
references.citation: Hepatology. 2012 Jun;55(6):1684-91
references.pmid: 22234804
references.citation: Semin Liver Dis. 2005 Feb;25(1):7-17
references.pmid: 15731994
references.citation: J Virol. 1999 Apr;73(4):2938-46
references.pmid: 10074143
references.citation: J Viral Hepat. 2012 Nov;19(11):766-74
references.pmid: 23043383
references.citation: Gut. 2011 Jun;60(6):837-45
references.pmid: 21139063
references.citation: J Viral Hepat. 2015 Sep;22(9):708-17
references.pmid: 25580520
references.citation: J Virol. 2008 Oct;82(20):10017-31
references.pmid: 18667516
references.citation: Nat Rev Gastroenterol Hepatol. 2011 May;8(5):265-74
references.pmid: 21423258
references.citation: Transfusion. 2005 Jun;45(6):994-1002
references.pmid: 15934999
references.citation: JAMA. 2000 Jul 26;284(4):450-6
references.pmid: 10904508
references.citation: J Clin Virol. 2014 Nov;61(3):430-4
references.pmid: 25256151
references.citation: Lancet Infect Dis. 2012 May;12(5):408-14
references.pmid: 22541630
references.citation: J Clin Microbiol. 2008 Feb;46(2):499-506
references.pmid: 18032621
references.citation: PLoS Pathog. 2011 Sep;7(9):e1002243
references.pmid: 21912520
references.citation: J Viral Hepat. 2015 Mar;22(3):263-71
references.pmid: 25174990
references.citation: Clin Infect Dis. 2009 Oct 1;49(7):1051-60
references.pmid: 19725787
references.citation: Eur J Gastroenterol Hepatol. 2011 Nov;23(11):997-1003
references.pmid: 21915057
references.citation: Clin Infect Dis. 2005 Apr 1;40(7):959-61
references.pmid: 15824986
references.citation: Hepatology. 1999 Mar;29(3):908-14
references.pmid: 10051497
references.citation: Hepatology. 2010 Oct;52(4):1216-24
references.pmid: 20803561
references.citation: Int J Epidemiol. 2013 Dec;42(6):1649-59
references.pmid: 23203695
references.citation: Blood. 2006 Feb 1;107(3):892-7
references.pmid: 16204310
references.citation: Hepatology. 2003 Jan;37(1):60-4
references.pmid: 12500189
references.citation: Nat Rev Gastroenterol Hepatol. 2013 Sep;10(9):553-62
references.pmid: 23817321
references.citation: PLoS One. 2011;6(11):e27555
references.pmid: 22110669