Publication

HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection

Journal Paper/Review - Oct 31, 2020

Units
PubMed
Doi

Citation
Carlisle L, Günthard H, Bernasconi E, Vernazza P, Stoeckle M, Cavassini M, Nguyen A, Yerly S, Rauch A, Salazar-Vizcaya L, Fehr J, Braun D, Huber M, Böni J, Shah C, Mbunkah H, Metzner K, Turk T, Kouyos R. HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection. Viruses 2020; 12
Type
Journal Paper/Review (English)
Journal
Viruses 2020; 12
Publication Date
Oct 31, 2020
Issn Electronic
1999-4915
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.