Miłosz Parczewski1, Iwona Cielniak2, Justyna Kordek1, Bogusz Aksak-Wąs1, Anna Urbańska1, Magdalena Leszczyszyn-Pynka1, Ewa Siwak2, Monika Bociąga-Jasik3, Anna Nowak3, Aleksandra Szymczak4, Małgorzata Zalewska4, Władysław Łojewski5, Anne-Mieke Vandamme6,7, Nadine Lübke8, Lize Cuypers6,9. 1. Department of Infectious, Tropical Diseases and Immune Deficiency, Pomeranian Medical University, Szczecin, Poland. 2. Hospital for Infectious Diseases, HIV Out-Patient's Clinic, Warsaw, Poland. 3. Department of Infectious Diseases, Hepatology and Acquired Immune Deficiencies, Wrocław Medical University, Wrocław, Poland. 4. Department of Infectious Diseases, Jagiellonian University Medical College, Kraków, Poland. 5. Department of Infectious Diseases, Regional Hospital in Zielona Gora, Zielona Góra, Poland. 6. Department of Microbiology and Immunology, RegaInstitute for Medical Research, Clinical and Epidemiological Virology, KU Leuven-University of Leuven, Leuven, Belgium. 7. Microbiology Unit, Center for Global Health and Tropical Medicine, Institute for Hygiene and Tropical Medicine, University Nova de Lisboa, Lisbon, Portugal. 8. Institute of Virology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. 9. Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
Abstract
BACKGROUND: Hepatitis C virus (HCV) resistance-associated variants (RAVs) have been shown to adversely affect treatment response of direct-acting antivirals. Identifying pre-existing RAVs and transmission networks among HIV/HCV genotype 1 (G1)-infected patients from Poland will assist in shaping surveillance strategies for HCV. METHODS: NS3 and NS5A sequences were obtained from samples of 112 direct-acting antiviral-naive G1 patients (45 G1a and 67 G1b), of which 74 were chronically infected and 38 were diagnosed with acute hepatitis C (AHC). RAVs were identified using geno2pheno, and 98 concatenated NS3/NS5A alignments were constructed to identify transmission clusters using a maximum likelihood approach. RESULTS: G1a was notably more prevalent compared with G1b among men-having-sex-with-men (MSM) (60.0% vs. 31.3%, P = 0.004), AHC cases (46.7% vs. 25.4%, P = 0.019), and patients diagnosed with syphilis (52.2% vs. 24.5%, P = 0.009). The overall NS3/NS5A RAVs frequency was 14.3% with variants occurring more often in G1a compared with G1b (27.5% vs. 5.2%, P = 0.005), mostly for NS3 due to the high prevalence of polymorphism Q80K. NS5A RAVs were only found in 2.9% of sequences. Significant clustering was observed for 73.5% of the Polish sequences, however, more common in G1a MSM compared with G1b (50.0% vs. 25.9%, P = 0.02). The identified clusters contained sequences originating from up to 5 Polish cities, located within a mean distance of 370 km. CONCLUSIONS: Close clustering of Polish strains suggests the presence of compartmentalized epidemics of MSM that fuel the spread of G1a variants. Particularly patients with AHC form a national transmission network, including clusters enriched with the NS3 Q80K polymorphism.
BACKGROUND: Hepatitis C virus (HCV) resistance-associated variants (RAVs) have been shown to adversely affect treatment response of direct-acting antivirals. Identifying pre-existing RAVs and transmission networks among HIV/HCV genotype 1 (G1)-infected patients from Poland will assist in shaping surveillance strategies for HCV. METHODS: NS3 and NS5A sequences were obtained from samples of 112 direct-acting antiviral-naive G1 patients (45 G1a and 67 G1b), of which 74 were chronically infected and 38 were diagnosed with acute hepatitis C (AHC). RAVs were identified using geno2pheno, and 98 concatenated NS3/NS5A alignments were constructed to identify transmission clusters using a maximum likelihood approach. RESULTS: G1a was notably more prevalent compared with G1b among men-having-sex-with-men (MSM) (60.0% vs. 31.3%, P = 0.004), AHC cases (46.7% vs. 25.4%, P = 0.019), and patients diagnosed with syphilis (52.2% vs. 24.5%, P = 0.009). The overall NS3/NS5A RAVs frequency was 14.3% with variants occurring more often in G1a compared with G1b (27.5% vs. 5.2%, P = 0.005), mostly for NS3 due to the high prevalence of polymorphism Q80K. NS5A RAVs were only found in 2.9% of sequences. Significant clustering was observed for 73.5% of the Polish sequences, however, more common in G1a MSM compared with G1b (50.0% vs. 25.9%, P = 0.02). The identified clusters contained sequences originating from up to 5 Polish cities, located within a mean distance of 370 km. CONCLUSIONS: Close clustering of Polish strains suggests the presence of compartmentalized epidemics of MSM that fuel the spread of G1a variants. Particularly patients with AHC form a national transmission network, including clusters enriched with the NS3 Q80K polymorphism.
Authors: Ana Belen Pérez; Bram Vrancken; Natalia Chueca; Antonio Aguilera; Gabriel Reina; Miguel García-Del Toro; Francisco Vera; Miguel Angel Von Wichman; Juan Ignacio Arenas; Francisco Téllez; Juan A Pineda; Mohamed Omar; Enrique Bernal; Antonio Rivero-Juárez; Elisa Fernández-Fuertes; Alberto de la Iglesia; Juan Manuel Pascasio; Philippe Lemey; Féderico Garcia; Lize Cuypers Journal: Euro Surveill Date: 2019-02
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