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Viral diversity from next-generation sequencing of HIV-1 samples provides precise estimates of infection recency and time since infection

Louisa A Carlisle, Teja Turk, Katharina Kusejko, Karin J Metzner, Christine Leemann, Corinne Schenkel, Nadine Bachmann, Susana Posada, Niko Beerenwinkel, Jürg Böni, Sabine Yerly, Thomas Klimkait, Matthieu Perreau, Dominique L Braun, Andri Rauch, Alexandra Calmy, Matthias Cavassini, Manuel Battegay, Pietro Vernazza, Enos Bernasconi, Huldrych F Günthard, Roger D Kouyos & Swiss HIV Cohort Study

abstract

BACKGROUND
HIV-1 genetic diversity increases over the course of infection, and can be used to infer time since infection (TSI) and consequently also infection recency, crucial quantities 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. Fraction of ambiguous nucleotides (FAN) obtained by population sequencing were available for 207 samples. We assessed whether average pairwise diversity (APD) calculated using NGS sequences provided a more exact prediction of TSI and classification of infection recency (<1 year post-infection) compared to FAN.

RESULTS
NGS-derived APD classifies an infection as recent with a sensitivity of 88% and specificity of 85%. When considering only the 207 samples for which FAN were available, NGS-derived APD exhibited a higher sensitivity (90% vs 78%) and specificity (95% vs 67%) than FAN. Additionally, APD can estimate TSI with a mean absolute error of 0.84 years, compared to 1.03 years for FAN.
   
citation Carlisle L A, Turk T, Kusejko K, Metzner K J, Leemann C, Schenkel C, Bachmann N, Posada S, Beerenwinkel N, Böni J, Yerly S, Klimkait T, Perreau M, Braun D L, Rauch A, Calmy A, Cavassini M, Battegay M, Vernazza P, Bernasconi E, Günthard H F, Kouyos R D, Swiss HIV Cohort Study . Viral diversity from next-generation sequencing of HIV-1 samples provides precise estimates of infection recency and time since infection. J Infect Dis 2019;.
   
type journal paper/review (English)
date of publishing 04-03-2019
journal title J Infect Dis
ISSN electronic 1537-6613
PubMed 30835266
DOI 10.1093/infdis/jiz094