Louisa A Carlisle1,2, Teja Turk1,2, Katharina Kusejko1,2, Karin J Metzner1,2, Christine Leemann1,2, Corinne D Schenkel1,2, Nadine Bachmann1,2, Susana Posada3,4, Niko Beerenwinkel3,4, Jürg Böni2,5, Sabine Yerly6, Thomas Klimkait7, Matthieu Perreau8, Dominique L Braun1,2, Andri Rauch9, Alexandra Calmy6, Matthias Cavassini10, Manuel Battegay11, Pietro Vernazza12, Enos Bernasconi13, Huldrych F Günthard1,2, Roger D Kouyos1,2. 1. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich. 2. Institute of Medical Virology, University of Zurich, Zurich. 3. Department of Biosystems Science and Engineering, ETH Zurich. 4. SIB Swiss Institute of Bioinformatics, University of Basel, Basel. 5. Swiss National Center for Retroviruses, University of Zurich, Zurich. 6. Laboratory of Virology and Division of Infectious Diseases, Geneva University Hospital, Geneva. 7. Molecular Virology, Department of Biomedicine-Petersplatz, University of Basel, Basel. 8. Division of Immunology and Allergy, Lausanne University Hospital, Lausanne. 9. Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern. 10. Division of Infectious Diseases, Lausanne University Hospital, Lausanne. 11. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel. 12. Division of Infectious Diseases, Cantonal Hospital St. Gallen, St. Gallen. 13. Division of Infectious Diseases, Regional Hospital Lugano, Lugano, Switzerland.
Abstract
BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) genetic diversity increases over the course of infection and can be used to infer the time since infection and, consequently, infection recency, which are crucial for HIV-1 surveillance and the understanding of viral pathogenesis. METHODS: We considered 313 HIV-infected individuals for whom reliable estimates of infection dates and next-generation sequencing (NGS)-derived nucleotide frequency data were available. Fractions of ambiguous nucleotides, obtained by population sequencing, were available for 207 samples. We assessed whether the average pairwise diversity calculated using NGS sequences provided a more exact prediction of the time since infection and classification of infection recency (<1 year after infection), compared with the fraction of ambiguous nucleotides. RESULTS: NGS-derived average pairwise diversity classified an infection as recent with a sensitivity of 88% and a specificity of 85%. When considering only the 207 samples for which fractions of ambiguous nucleotides were available, the NGS-derived average pairwise diversity exhibited a higher sensitivity (90% vs 78%) and specificity (95% vs 67%) than the fraction of ambiguous nucleotides. Additionally, the average pairwise diversity could be used to estimate the time since infection with a mean absolute error of 0.84 years, compared with 1.03 years for the fraction of ambiguous nucleotides. CONCLUSIONS: Viral diversity based on NGS data is more precise than that based on population sequencing in its ability to predict infection recency and provides an estimated time since infection that has a mean absolute error of <1 year.
BACKGROUND:Human immunodeficiency virus type 1 (HIV-1) genetic diversity increases over the course of infection and can be used to infer the time since infection and, consequently, infection recency, which are crucial for HIV-1 surveillance and the understanding of viral pathogenesis. METHODS: We considered 313 HIV-infected individuals for whom reliable estimates of infection dates and next-generation sequencing (NGS)-derived nucleotide frequency data were available. Fractions of ambiguous nucleotides, obtained by population sequencing, were available for 207 samples. We assessed whether the average pairwise diversity calculated using NGS sequences provided a more exact prediction of the time since infection and classification of infection recency (<1 year after infection), compared with the fraction of ambiguous nucleotides. RESULTS: NGS-derived average pairwise diversity classified an infection as recent with a sensitivity of 88% and a specificity of 85%. When considering only the 207 samples for which fractions of ambiguous nucleotides were available, the NGS-derived average pairwise diversity exhibited a higher sensitivity (90% vs 78%) and specificity (95% vs 67%) than the fraction of ambiguous nucleotides. Additionally, the average pairwise diversity could be used to estimate the time since infection with a mean absolute error of 0.84 years, compared with 1.03 years for the fraction of ambiguous nucleotides. CONCLUSIONS: Viral diversity based on NGS data is more precise than that based on population sequencing in its ability to predict infection recency and provides an estimated time since infection that has a mean absolute error of <1 year.
Authors: Shuntai Zhou; Sabrina Sizemore; Matt Moeser; Scott Zimmerman; Erika Samoff; Victoria Mobley; Simon Frost; Andy Cressman; Michael Clark; Tara Skelly; Hemant Kelkar; Umadevi Veluvolu; Corbin Jones; Joseph Eron; Myron Cohen; Julie A E Nelson; Ronald Swanstrom; Ann M Dennis Journal: J Infect Dis Date: 2021-03-03 Impact factor: 5.226
Authors: Louisa A Carlisle; Teja Turk; Karin J Metzner; Herbert A Mbunkah; Cyril Shah; Jürg Böni; Michael Huber; Dominique L Braun; Jan Fehr; Luisa Salazar-Vizcaya; Andri Rauch; Sabine Yerly; Aude Nguyen; Matthias Cavassini; Marcel Stoeckle; Pietro Vernazza; Enos Bernasconi; Huldrych F Günthard; Roger D Kouyos Journal: Viruses Date: 2020-10-31 Impact factor: 5.048