Inference of direction, diversity, and frequency of HIV-1 transmission using approximate Bayesian computation

Abstract

ABSTRACTDiversity of the founding population of Human Immunodeficiency Virus Type 1 (HIV-1) transmissions raises many important biological, clinical, and epidemiological issues. In up to 40% of sexual infections there is clear evidence for multiple founding variants, which can influence the efficacy of putative prevention methods and the reconstruction of epidemiologic histories. To measure the diversity of the founding population and to compute the probability of alternative transmission scenarios, while explicitly taking phylogenetic uncertainty into account, we created an Approximate Bayesian Computation (ABC) method based on a set of statistics measuring phylogenetic topology, branch lengths, and genetic diversity. We applied our method to a heterosexual transmission pair showing a complex paraphyletic-polyphyletic donor-recipient phylogenetic topology. We found evidence identifying the donor that was consistent with the known facts of the case (Bayes factor >20). We also found that while the evidence for ongoing transmission between the pair was as good or better than the singular transmission event model, it was only viable when the rate of ongoing transmission was implausibly high (~1/day). We concluded that the singular transmission model, which was able to estimate the diversity of the founding population (mean 7% substitutions/site), was more biologically plausible. Our study provides a formal inference framework to investigate HIV-1 direction, diversity, and frequency of transmission. The ability to measure the diversity of founding populations in both simple and complex transmission situations is essential to understanding the relationship between the phylogeny and epidemiology of HIV-1 as well as in efforts developing new prevention technologies.