Identifying pre-existing Ns3 and Ns5a resistance-associated variants and transmission chains in the Polish Hiv/hcv genotype 1 epidemic: impact on prevention and treatment

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. 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. 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. 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.