Incorporating Within-Host Diversity in Phylogenetic Analyses for Detecting Clusters of New HIV Diagnoses.

BACKGROUND

Phylogenetic analyses of HIV sequences are used to detect clusters and inform public health interventions. Conventional approaches summarize within-host HIV diversity with a single consensus sequence per host of the gene, obtained from Sanger or next-generation sequencing (NGS). There is growing recognition that this approach discards potentially important information about within-host sequence variation, which can impact phylogenetic inference. However, whether alternative summary methods that incorporate intra-host variation impact phylogenetic inference of transmission network features is unknown.

METHODS

We introduce , a method to incorporate within-host NGS sequence diversity into phylogenetic HIV cluster inference. We compare this approach to Sanger- and NGS-derived and near-whole-genome consensus sequences and evaluate its potential benefits in identifying molecular clusters among all newly-HIV-diagnosed individuals over six months at the largest HIV center in Rhode Island.

RESULTS

cluster inference demonstrated that within-host viral diversity impacts phylogenetic inference across individuals, and that consensus sequence approaches can obscure both magnitude and effect of these impacts. Clustering differed between Sanger- and NGS-derived consensus and sequences, and across gene regions.

DISCUSSION

can incorporate within-host HIV diversity captured by NGS into phylogenetic analyses. This additional information can improve robustness of cluster detection.