Future of phylogeny in HIV prevention

Abstract

The success of the HIV Prevention Trials Network 052 trial has led to revisions in HIV-1 treatment guidelines. Antiretroviral therapy may reduce the risk of HIV-1 transmissions at the population level. The design of successful treatment as prevention interventions will be predicated on a comprehensive understanding of the spatial, temporal, and biological dynamics of heterosexual men who have sex with men and intravenous drug user epidemics. Viral phylogenetics can capture the underlying structure of transmission networks based on the genetic interrelatedness of viral sequences and cluster networks that could not be otherwise identified. This article describes the phylogenetic expansion of the Montreal men who have sex with men epidemic over the last decade. High rates of coclustering of primary infections are associated with 1 infection leading to 13 onward transmissions. Phylogeny substantiates the role of primary and recent stage infection in transmission dynamics, underlying the importance of timely diagnosis and immediate antiretroviral therapy initiation to avert transmission cascades.

Fig. 1. Phylogenetic inferences on the expansion of the MSM epidemic in Montreal (2002–2012)

Phylogeny shows three patterns of clustering of primary infections. A. A short region in the Maximum-Likelihood tree shows three small clusters, one large cluster, and 13 transmissions. B. The cumulative increase of unique transmissions, small clusters and large clusters over the 2001–2005, 2001–2009, and 2001–2012 periods. C. The cumulative number of infections in the three cluster groups depict the rising role of large clustered transmissions representing 30%, 43% and 54% of transmissions in 2005, 2009, and 2012, respectively.

Fig. 2. The temporal expansion of small and large clusters

A frequency histogram plot shows the temporal spread of primary infections associated with small and large clusters, estimated by calculating the branch length (distance in months) of individual primary infections from the median dates of their respective clusters. The overall temporal interval was 4.75 months (1–11.5 month interquartile range) for small clusters and 11.0 months (3.5–25.5 month interquartile range) for large transmission chains.