Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Immunology, Infectious Diseases, phylogenetic analysis, acute hepatitis C, HIV/HCV coinfection, transmission networks, natural resistance, RESISTANCE-ASSOCIATED VARIANTS, PROTEASE INHIBITOR-RESISTANCE, VIRUS-INFECTION, DRUG-RESISTANCE, NS5A, SEX, MEN, NS3, SUBSTITUTIONS, PREVALENCE, Adult, Cluster Analysis, Disease Transmission, Infectious, Drug Resistance, Viral, Female, Genotype, HIV Infections, Hepacivirus, Hepatitis C, Homosexuality, Male, Humans, Male, Molecular Epidemiology, Poland, Prevalence, Sequence Analysis, DNA, Sequence Homology, Viral Nonstructural Proteins, 1103 Clinical Sciences, 1117 Public Health and Health Services, Virology, 3202 Clinical sciences, 4202 Epidemiology, 4206 Public health

Abstract:

BACKGROUND: Hepatitis C virus (HCV) resistance-associated variants (RAVs) have been shown to adversely affect treatment response of direct-acting antivirals (DAAs). 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 DAA-naive G1 patients (45 G1a, 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 to 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 to 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 to G1b (50.0% vs. 25.9%, p=0.02). The identified clusters contained sequences originating from up to five 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 AHC patients form a national transmission network, including clusters enriched with the NS3 Q80K polymorphism.