Astrid M Newsum1, Cynthia K Y Ho, Faydra I Lieveld, Thijs J W van de Laar, Sylvie M Koekkoek, Sjoerd P Rebers, Jan T M van der Meer, Anne M J Wensing, Greet J Boland, Joop E Arends, Karel J van Erpecum, Maria Prins, Richard Molenkamp, Janke Schinkel. 1. aDepartment of Infectious Diseases Research and Prevention, Public Health Service of Amsterdam bDepartment of Internal Medicine, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center cDepartment of Medical Microbiology, Section of Clinical Virology, Academic Medical Center, Amsterdam dDepartment of Gastroenterology and Hepatology eDepartment of Internal Medicine and Infectious Diseases, University Medical Center Utrecht fDepartment of Blood-Borne Infections, Division of Research, Sanquin Blood Supply Foundation, Amsterdam gDepartment of Medical Microbiology, University Medical Center Utrecht, the Netherlands.
Abstract
OBJECTIVES: The Q80K polymorphism is a naturally occurring resistance-associated variant in the hepatitis C virus (HCV) nonstructural protein 3 (NS3) region and is likely transmissible between hosts. This study describes the Q80K origin and prevalence among HCV risk groups in the Netherlands and examines whether Q80K is linked to specific transmission networks. DESIGN AND METHODS: Stored blood samples from HCV genotype 1a-infected patients were used for PCR and sequencing to reconstruct the NS3 maximum likelihood phylogeny. The most recent common ancestor was estimated with a coalescent-based model within a Bayesian statistical framework. RESULTS: Study participants (n = 150) were either MSM (39%), people who inject drugs (17%), or patients with other (15%) or unknown/unreported (29%) risk behavior. Overall 45% was coinfected with HIV. Q80K was present in 36% (95% confidence interval 28-44%) of patients throughout the sample collection period (2000-2015) and was most prevalent in MSM (52%, 95% confidence interval 38-65%). Five MSM-specific transmission clusters were identified, of which three exclusively contained sequences with Q80K. The HCV-1a most recent common ancestor in the Netherlands was estimated in 1914 (95% higher posterior density 1879-1944) and Q80K originated in 1957 (95% higher posterior density 1942-1970) within HCV-1a clade I. All Q80K lineages could be traced back to this single origin. CONCLUSION: Q80K is a highly stable and transmissible resistance-associated variant and was present in a large part of Dutch HIV-coinfected MSM. The introduction and expansion of Q80K variants in this key population suggest a founder effect, potentially jeopardizing future treatment with simeprevir.
OBJECTIVES: The Q80K polymorphism is a naturally occurring resistance-associated variant in the hepatitis C virus (HCV) nonstructural protein 3 (NS3) region and is likely transmissible between hosts. This study describes the Q80K origin and prevalence among HCV risk groups in the Netherlands and examines whether Q80K is linked to specific transmission networks. DESIGN AND METHODS: Stored blood samples from HCV genotype 1a-infectedpatients were used for PCR and sequencing to reconstruct the NS3 maximum likelihood phylogeny. The most recent common ancestor was estimated with a coalescent-based model within a Bayesian statistical framework. RESULTS: Study participants (n = 150) were either MSM (39%), people who inject drugs (17%), or patients with other (15%) or unknown/unreported (29%) risk behavior. Overall 45% was coinfected with HIV. Q80K was present in 36% (95% confidence interval 28-44%) of patients throughout the sample collection period (2000-2015) and was most prevalent in MSM (52%, 95% confidence interval 38-65%). Five MSM-specific transmission clusters were identified, of which three exclusively contained sequences with Q80K. The HCV-1a most recent common ancestor in the Netherlands was estimated in 1914 (95% higher posterior density 1879-1944) and Q80K originated in 1957 (95% higher posterior density 1942-1970) within HCV-1a clade I. All Q80K lineages could be traced back to this single origin. CONCLUSION:Q80K is a highly stable and transmissible resistance-associated variant and was present in a large part of Dutch HIV-coinfected MSM. The introduction and expansion of Q80K variants in this key population suggest a founder effect, potentially jeopardizing future treatment with simeprevir.
Authors: Stephanie Popping; Rosanne Verwijs; Lize Cuypers; Mark A Claassen; Guido E van den Berk; Anja De Weggheleire; Joop E Arends; Anne Boerekamps; Richard Molenkamp; Marion P Koopmans; Annelies Verbon; Charles A B Boucher; Bart J Rijnders; David A M C van de Vijver Journal: Clin Infect Dis Date: 2020-11-05 Impact factor: 9.079