The spread of hepatitis C virus genotype 1a in North America: a retrospective phylogenetic study

Summary Background The timing of the initial spread of hepatitis C virus genotype 1a in North America is controversial. In particular, how and when hepatitis C virus reached extraordinary prevalence in specific demographic groups remains unclear. We quantified, using all available hepatitis C virus sequence data and phylodynamic methods, the timing of the spread of hepatitis C virus genotype 1a in North America. Methods We screened 45 316 publicly available sequences of hepatitis C virus genotype 1a for location and genotype, and then did phylogenetic analyses of available North American sequences from five hepatitis C virus genes ( E1, E2, NS2, NS4B, NS5B ), with an emphasis on including as many sequences with early collection dates as possible. We inferred the historical population dynamics of this epidemic for all five gene regions using Bayesian skyline plots. Findings Most of the spread of genotype 1a in North America occurred before 1965, and the hepatitis C virus epidemic has undergone relatively little expansion since then. The effective population size of the North American epidemic stabilised around 1960. These results were robust across all five gene regions analysed, although analyses of each gene separately show substantial variation in estimates of the timing of the early exponential growth, ranging roughly from 1940 for NS2 , to 1965 for NS4B . Interpretation The expansion of genotype 1a before 1965 suggests that nosocomial or iatrogenic factors rather than past sporadic behavioural risk (ie, experimentation with injection drug use, unsafe tattooing, high risk sex, travel to high endemic areas) were key contributors to the hepatitis C virus epidemic in North America. Our results might reduce stigmatisation around screening and diagnosis, potentially increasing rates of screening and treatment for hepatitis C virus. Funding The Canadian Institutes of Health Research, Michael Smith Foundation for Health Research, and BC Centre for Excellence in HIV/AIDS.