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Comparison of cluster-based and source-attribution methods for estimating transmission risk using large HIV sequence

Stéphane Le Vu1, Oliver Ratmann2, Valerie Delpech3

  • 1Department of Infectious Disease Epidemiology and the NIHR HPRU on Modeling Methodology, Imperial College London, United Kingdom.

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Summary

Phylogenetic clustering methods for HIV transmission can be misleading. Source attribution methods are more accurate for identifying HIV transmission risk factors, though quantitative estimates may require population genetic modeling.

Keywords:
Cluster analysisComputer simulationHIV epidemiologyPhylodynamicsPhylogenetic analysis

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Area of Science:

  • Epidemiology
  • Virology
  • Computational Biology

Background:

  • Phylogenetic clustering of HIV sequences can reveal transmission patterns.
  • Interpretation is limited by poor theoretical support and understanding of statistical properties.
  • Source attribution methods offer an alternative for quantifying disease transmission.

Purpose of the Study:

  • To assess the error rates of phylogenetic clustering methods in identifying HIV transmission risk factors.
  • To compare the performance of clustering methods with source attribution methods.
  • To evaluate the ability of both approaches to identify patient attributes associated with transmission.

Main Methods:

  • A simulation study was conducted using modeled HIV epidemics among men who have sex with men.
  • Generated phylogenies comparable to UK HIV surveillance data.
  • Applied both clustering and source attribution methods to identify transmission risk factors.

Main Results:

  • Commonly used clustering methods show misleading associations between cluster characteristics and covariates correlated with time since infection.
  • Clustering methods exhibit higher error rates and lower sensitivity compared to source attribution methods.
  • Neither method provides robust estimates of transmission risk ratios.

Conclusions:

  • Source attribution methods can mitigate drawbacks of phylogenetic clustering for identifying transmission risk factors.
  • Formal population genetic modeling may be necessary for accurate quantitative estimation of transmission risk factors.
  • Careful interpretation of phylogenetic clustering is needed due to potential biases.