Leveraging Phylogenetics to Understand HIV Transmission and Partner Notification Networks

Abstract

Background: Partner notification is an important component of public health test and treat interventions. To enhance this essential function, we assessed the potential for molecular methods to supplement routine partner notification and corroborate HIV networks.

Methods: All persons diagnosed with HIV infection in Wake County, NC, during 2012-2013 and their disclosed sexual partners were included in a sexual network. A data set containing HIV-1 pol sequences collected in NC during 1997-2014 from 15,246 persons was matched to HIV-positive persons in the network and used to identify putative transmission clusters. Both networks were compared.

Results: The partner notification network comprised 280 index cases and 383 sexual partners and high-risk social contacts (n = 131 HIV-positive). Of the 411 HIV-positive persons in the partner notification network, 181 (44%) did not match to a HIV sequence, 61 (15%) had sequences but were not identified in a transmission cluster, and 169 (41%) were identified in a transmission cluster. More than half (59%) of transmission clusters bridged sexual network partnerships that were not recognized in the partner notification; most of these clusters were dominated by men who have sex with men.

Conclusions: Partner notification and HIV sequence analysis provide complementary representations of the existent partnerships underlying the HIV transmission network. The partner notification network components were bridged by transmission clusters, particularly among components dominated by men who have sex with men. Supplementing the partner notification network with phylogenetic data highlighted avenues for intervention.

Figure 1. Sexual network showing phylogenetic cluster membership and gender (A), and selected sexual network components showing cluster members and genetic distance statewide (B)

1A) Sexual and social network compiled from contract tracing depicting HIV status and phylogenetic transmission cluster, Wake County, NC during 2012–2013. Graph shows gender (node shape), cluster membership with respect to gene sequence availability and cluster membership of other persons represented in this sexual network (node color), and partnerships disclosed by index cases (lines connecting nodes). The graph is split into quadrants by number of persons in each component: (a) singletons (n=104 persons), (b) dyads (n=75 components), (c) components size 3 (n=22), 4 (n=10), or 5 (n=12), and (d) components size 6 or larger (n=18 components comprising 243 persons). 1B) Selected phylogenetic transmission clusters (F, I, and J) show sexual network components spanned and additional cluster members statewide who were not part of the Wake County-based sexual network. Graph shows gender (node shape), appearance in sexual network or only transmission cluster (diagonal cross in node shape), transmission cluster status (node color), and connections between nodes. Having a named partner tie (i.e., connection in the sociosexual network) is represented by a solid line and being ≤1.5% pairwise genetic distance in the transmission cluster is represented by a dashed line. Component orientation matches Figure 1a. NC, North Carolina

Figure 2. Phylogenetic tree of HIV pol gene sequences showing transmission clusters

Maximum-likelihood tree constructed for display purposes using sequences (n=800) identified in confirmed phylogenetic transmission clusters among 15,246 HIV-1 positive persons sampled in North Carolina 1997–2014. Confirmed clusters had posterior probability >0.98 in the Bayesian analysis and include at least one index or partner case identified during partner notification of new HIV diagnoses in Wake County, 2012–2013. Index cases (new diagnoses in 2012–2013) are indicated by red circles and partner cases are indicated with blue circles at the tips of the tree. Clusters in grey boxes involve ≥2 cases from the partner notification network. Clusters with letters (A–S) are the Wake clusters that meet these criteria and also include ≥5 persons statewide. Branch support, using the Shimodaira-Hasegawa-like test values, is included for the Wake clusters.