The hepatitis C virus nonstructural protein 3 Q80K polymorphism is frequently detected and transmitted among HIV-infected MSM in 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 (n150)were eitherMSM(39%), peoplewho inject drugs (17%), or patients with other (15%) or unknown/unreported (29%) risk behavior. Overall 45% was coinfected with HIV.Q80Kwaspresent in36%(95%confidence interval 28-44%)of patients throughout the sample collection period (2000-2015) and wasmost prevalent inMSM(52%, 95%confidenceinterval38-65%). FiveMSM-specific transmission clusterswereidentified,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) andQ80Koriginated in1957(95%higher posterior density1942-1970) withinHCV-1aclade 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.