Publication
HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection
Journal Paper/Review - Oct 31, 2020
Carlisle Louisa A, Günthard Huldrych F, Bernasconi Enos, Vernazza Pietro, Stoeckle Marcel, Cavassini Matthias, Nguyen Aude, Yerly Sabine, Rauch Andri, Salazar-Vizcaya Luisa, Fehr Jan, Braun Dominique L, Huber Michael, Böni Jürg, Shah Cyril, Mbunkah Herbert A, Metzner Karin J, Turk Teja, Kouyos Roger D
Units
PubMed
Doi
Citation
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Journal
Publication Date
Issn Electronic
Brief description/objective
HIV-1 genetic diversity can be used to infer time since infection (TSI) and infection recency. We adapted this approach for HCV and identified genomic regions with informative diversity. We included 72 HCV/HIV-1 coinfected participants of the Swiss HIV Cohort Study, for whom reliable estimates of infection date and viral sequences were available. Average pairwise diversity (APD) was calculated over each codon position for the entire open reading frame of HCV. Utilizing cross validation, we evaluated the correlation of APD with TSI, and its ability to infer TSI via a linear model. We additionally studied the ability of diversity to classify infections as recent (infected for <1 year) or chronic, using receiver-operator-characteristic area under the curve (ROC-AUC) in 50 patients whose infection could be unambiguously classified as either recent or chronic. Measuring HCV diversity over third or all codon positions gave similar performances, and notable improvement over first or second codon positions. APD calculated over the entire genome enabled classification of infection recency (ROC-AUC = 0.76). Additionally, APD correlated with TSI (R = 0.33) and could predict TSI (mean absolute error = 1.67 years). Restricting the region over which APD was calculated to - further improved accuracy (ROC-AUC = 0.85, R = 0.54, mean absolute error = 1.38 years) Genetic diversity in HCV correlates with TSI and is a proxy for infection recency and TSI, even several years post-infection.