The Q80K polymorphism is a naturally occurring resistance-associated variant (RAV) in the hepatitis C virus (HCV) 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 (MRCA) was estimated with a coalescent-based model within a Bayesian statistical framework.
Study participants (n = 150) were either men who have sex with men (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% CI 28-44%) of patients throughout the sample collection period (2000-2015) and was most prevalent in MSM (52%, 95% CI 38-65%). Five MSM-specific transmission clusters were identified, of which 3 exclusively contained sequences with Q80K. The HCV-1a MRCA in the Netherlands was estimated in 1914 (95% higher posterior density (HPD) 1879-1944) and Q80K originated in 1957 (95% HPD 1942-1970) within HCV-1a clade I. All Q80K lineages could be traced back to this single origin.
Q80K is a highly stable and transmissible RAV 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.