Rachel Sacks-Davis1, Jason Grebely2, Gregory J Dore2, William Osburn3, Andrea L Cox3, Thomas M Rice4, Timothy Spelman1, Julie Bruneau5, Maria Prins6, Arthur Y Kim7, Barbara H McGovern8, Naglaa H Shoukry5, Janke Schinkel9, Todd M Allen7, Meghan Morris4, Behzad Hajarizadeh2, Lisa Maher2, Andrew R Lloyd10, Kimberly Page4, Margaret Hellard1. 1. Burnet Institute, Monash University, Melbourne Department of Epidemiology and Preventive Medicine, Monash University, Melbourne. 2. The Kirby Institute, University of New South Wales, Sydney, Australia. 3. Department of Medicine, Johns Hopkins University, Baltimore, Maryland. 4. Department of Epidemiology and Biostatistics, University of California-San Francisco. 5. CRCHUM, Université de Montréal, Canada. 6. GGD Public Health Service of Amsterdam, Amsterdam, The Netherlands Academic Medical Center, Amsterdam, The Netherlands. 7. Harvard Medical School, Boston, Massachusetts. 8. Tufts Medical School, Boston, Massachusetts Abbvie, Chicago, Illinois. 9. Academic Medical Center, Amsterdam, The Netherlands. 10. School of Medical Sciences, University of New South Wales, Sydney, Australia.
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.
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: Son T Pham; Rowena A Bull; James M Bennett; William D Rawlinson; Gregory J Dore; Andrew R Lloyd; Peter A White Journal: Hepatology Date: 2010-11 Impact factor: 17.425
Authors: Jason Grebely; Maria Prins; Margaret Hellard; Andrea L Cox; William O Osburn; Georg Lauer; Kimberly Page; Andrew R Lloyd; Gregory J Dore Journal: Lancet Infect Dis Date: 2012-05 Impact factor: 25.071
Authors: Jason Grebely; Kathy Petoumenos; Margaret Hellard; Gail V Matthews; Vijayaprakash Suppiah; Tanya Applegate; Barbara Yeung; Phillipa Marks; William Rawlinson; Andrew R Lloyd; David Booth; John M Kaldor; Jacob George; Gregory J Dore Journal: Hepatology Date: 2010-10 Impact factor: 17.425
Authors: Hans L Tillmann; Alex J Thompson; Keyur Patel; Manfred Wiese; Hannelore Tenckhoff; Hans D Nischalke; Yuliya Lokhnygina; Ulrike Kullig; Uwe Göbel; Emanuela Capka; Johannes Wiegand; Ingolf Schiefke; Wolfgang Güthoff; Kurt Grüngreiff; Ingrid König; Ulrich Spengler; Jeanette McCarthy; Kevin V Shianna; David B Goldstein; John G McHutchison; Jörg Timm; Jacob Nattermann Journal: Gastroenterology Date: 2010-07-14 Impact factor: 22.682
Authors: Kimberly Page; William Osburn; Jennifer Evans; Judith A Hahn; Paula Lum; Alice Asher; Eric Delwart; Leslie Tobler; Andrea L Cox; Michael P Busch Journal: Clin Infect Dis Date: 2012-10-22 Impact factor: 9.079
Authors: Peter Vickerman; Jason Grebely; Gregory J Dore; Rachel Sacks-Davis; Kimberly Page; David L Thomas; William O Osburn; Andrea L Cox; Campbell K Aitken; Matthew Hickman; Margaret Hellard Journal: J Infect Dis Date: 2012-03-29 Impact factor: 5.226
Authors: Emma C Thomson; Vicki M Fleming; Janice Main; Paul Klenerman; Jonathan Weber; Joseph Eliahoo; Jennifer Smith; Myra O McClure; Peter Karayiannis Journal: Gut Date: 2010-12-07 Impact factor: 23.059
Authors: Charlotte H B S van den Berg; Bart P X Grady; Janke Schinkel; Thijs van de Laar; Richard Molenkamp; Robin van Houdt; Roel A Coutinho; Debbie van Baarle; Maria Prins Journal: PLoS One Date: 2011-11-15 Impact factor: 3.240
Authors: Rachel Sacks-Davis; Campbell K Aitken; Peter Higgs; Tim Spelman; Alisa E Pedrana; Scott Bowden; Mandvi Bharadwaj; Usha K Nivarthi; Vijayaprakash Suppiah; Jacob George; Jason Grebely; Heidi E Drummer; Margaret Hellard Journal: PLoS One Date: 2013-11-07 Impact factor: 3.240
Authors: Ramy El-Diwany; Lisa N Wasilewski; Kenneth W Witwer; Justin R Bailey; Kimberly Page; Stuart C Ray; Andrea L Cox; David L Thomas; Ashwin Balagopal Journal: J Virol Date: 2015-07-08 Impact factor: 5.103
Authors: A I Soipe; H Razavi; D Razavi-Shearer; O Galárraga; L E Taylor; B D L Marshall Journal: Epidemiol Infect Date: 2016-08-05 Impact factor: 2.451
Authors: Chaturaka Rodrigo; Melanie R Walker; Preston Leung; Auda A Eltahla; Jason Grebely; Gregory J Dore; Tanya Applegate; Kimberly Page; Sunita Dwivedi; Julie Bruneau; Meghan D Morris; Andrea L Cox; William Osburn; Arthur Y Kim; Janke Schinkel; Naglaa H Shoukry; Georg M Lauer; Lisa Maher; Margaret Hellard; Maria Prins; Fabio Luciani; Andrew R Lloyd; Rowena A Bull Journal: Infect Genet Evol Date: 2017-01-05 Impact factor: 3.342
Authors: A Esmaeili; A Mirzazadeh; G M Carter; A Esmaeili; B Hajarizadeh; H S Sacks; K A Page Journal: J Viral Hepat Date: 2016-10-28 Impact factor: 3.728
Authors: Aryan Esmaeili; Ali Mirzazadeh; Meghan D Morris; Behzad Hajarizadeh; Henry S Sacks; Lisa Maher; Jason Grebely; Arthur Y Kim; Georg Lauer; Andrea L Cox; Margaret Hellard; Paul Dietze; Julie Bruneau; Naglaa H Shoukry; Gregory J Dore; Andrew R Lloyd; Maria Prins; Kimberly Page Journal: Clin Infect Dis Date: 2018-01-06 Impact factor: 9.079
Authors: Zelalem A Mekonnen; Branka Grubor-Bauk; Kieran English; Preston Leung; Makutiro G Masavuli; Ashish C Shrestha; Patrick Bertolino; David G Bowen; Andrew R Lloyd; Eric J Gowans; Danushka K Wijesundara Journal: J Virol Date: 2019-09-12 Impact factor: 5.103