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The ability of HIV to persist within latent cellular reservoirs represents a major barrier to cure. The timing of establishment of individual viral reservoirs over the course of an infection may influence their susceptibility to elimination by immune-mediated or therapeutic approaches. However, methods to accurately estimate the age of reservoir sequences remain scarce.
We propose a simple method to date suspected reservoir sequences using phylogenetically informed regression. Our method is as follows: Taking aligned HIV sequences from a single individual sampled over multiple time points, we reconstruct a maximum-likelihood phylogeny. The location of the root in the phylogeny is determined using root-to-tip regression. Finally, the root-to-tip distances of possibly latent sequences are mapped to the optimal regression line to estimate reservoir establishment dates.
To validate our method, we simulated HIV sequence evolution under a standard model and reconstructed phylogenies from these data by maximum likelihood.
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