Assessing the role of transmission chains in the spread of HIV-1 among men who have sex with men in Quebec, Canada.

BACKGROUND: Phylogenetics has been used to investigate HIV transmission among men who have sex with men. This study compares several methodologies to elucidate the role of transmission chains in the dynamics of HIV spread in Quebec, Canada. METHODS: The Quebec Human Immunodeficiency Virus (HIV) genotyping program database now includes viral sequences from close to 4,000 HIV-positive individuals classified as Men who have Sex with Men (MSMs), collected between 1996 and early 2016. Assessment of chain expansion may depend on the partitioning scheme used, and so, we produce estimates from several methods: the conventional Bayesian and maximum likelihood-bootstrap methods, in combination with a variety of schemes for applying a maximum distance criterion, and two other algorithms, DM-PhyClus, a Bayesian algorithm that produces a measure of uncertainty for proposed partitions, and the Gap Procedure, a fast non-phylogenetic approach. Sequences obtained from individuals in the Primary HIV Infection (PHI) stage serve to identify incident cases. We focus on the period ranging from January 1st 2012 to February 1st 2016. RESULTS AND CONCLUSION: The analyses reveal considerable overlap between chain estimates obtained from conventional methods, thus leading to similar estimates of recent temporal expansion. The Gap Procedure and DM-PhyClus suggest however moderately different chains. Nevertheless, all estimates stress that longer older chains are responsible for a sizeable proportion of the sampled incident cases among MSMs. Curbing the HIV epidemic will require strategies aimed specifically at preventing such growth.

DM-PhyClus: a Bayesian phylogenetic algorithm for infectious disease transmission cluster inference.

BACKGROUND: Conventional phylogenetic clustering approaches rely on arbitrary cutpoints applied a posteriori to phylogenetic estimates. Although in practice, Bayesian and bootstrap-based clustering tend to lead to similar estimates, they often produce conflicting measures of confidence in clusters. The current study proposes a new Bayesian phylogenetic clustering algorithm, which we refer to as DM-PhyClus (Dirichlet-Multinomial Phylogenetic Clustering), that identifies sets of sequences resulting from quick transmission chains, thus yielding easily-interpretable clusters, without using any ad hoc distance or confidence requirement. RESULTS: Simulations reveal that DM-PhyClus can outperform conventional clustering methods, as well as the Gap procedure, a pure distance-based algorithm, in terms of mean cluster recovery. We apply DM-PhyClus to a sample of real HIV-1 sequences, producing a set of clusters whose inference is in line with the conclusions of a previous thorough analysis. CONCLUSIONS: DM-PhyClus, by eliminating the need for cutpoints and producing sensible inference for cluster configurations, can facilitate transmission cluster detection. Future efforts to reduce incidence of infectious diseases, like HIV-1, will need reliable estimates of transmission clusters. It follows that algorithms like DM-PhyClus could serve to better inform public health strategies.

Assessment of Overlap of Phylogenetic Transmission Clusters and Communities in Simple Sexual Contact Networks: Applications to HIV-1.

BACKGROUND: Transmission patterns of sexually-transmitted infections (STIs) could relate to the structure of the underlying sexual contact network, whose features are therefore of interest to clinicians. Conventionally, we represent sexual contacts in a population with a graph, that can reveal the existence of communities. Phylogenetic methods help infer the history of an epidemic and incidentally, may help detecting communities. In particular, phylogenetic analyses of HIV-1 epidemics among men who have sex with men (MSM) have revealed the existence of large transmission clusters, possibly resulting from within-community transmissions. Past studies have explored the association between contact networks and phylogenies, including transmission clusters, producing conflicting conclusions about whether network features significantly affect observed transmission history. As far as we know however, none of them thoroughly investigated the role of communities, defined with respect to the network graph, in the observation of clusters. METHODS: The present study investigates, through simulations, community detection from phylogenies. We simulate a large number of epidemics over both unweighted and weighted, undirected random interconnected-islands networks, with islands corresponding to communities. We use weighting to modulate distance between islands. We translate each epidemic into a phylogeny, that lets us partition our samples of infected subjects into transmission clusters, based on several common definitions from the literature. We measure similarity between subjects' island membership indices and transmission cluster membership indices with the adjusted Rand index. RESULTS AND CONCLUSION: Analyses reveal modest mean correspondence between communities in graphs and phylogenetic transmission clusters. We conclude that common methods often have limited success in detecting contact network communities from phylogenies. The rarely-fulfilled requirement that network communities correspond to clades in the phylogeny is their main drawback. Understanding the link between transmission clusters and communities in sexual contact networks could help inform policymaking to curb HIV incidence in MSMs.

Modeling fetal weight for gestational age: a comparison of a flexible multi-level spline-based model with other approaches.

We present a model for longitudinal measures of fetal weight as a function of gestational age. We use a linear mixed model, with a Box-Cox transformation of fetal weight values, and restricted cubic splines, in order to flexibly but parsimoniously model median fetal weight. We systematically compare our model to other proposed approaches. All proposed methods are shown to yield similar median estimates, as evidenced by overlapping pointwise confidence bands, except after 40 completed weeks, where our method seems to produce estimates more consistent with observed data. Sex-based stratification affects the estimates of the random effects variance-covariance structure, without significantly changing sex-specific fitted median values. We illustrate the benefits of including sex-gestational age interaction terms in the model over stratification. The comparison leads to the conclusion that the selection of a model for fetal weight for gestational age can be based on the specific goals and configuration of a given study without affecting the precision or value of median estimates for most gestational ages of interest.