The global transmission network of HIV-1

Abstract

Human immunodeficiency virus type 1 (HIV-1) is pandemic, but its contemporary global transmission network has not been characterized. A better understanding of the properties and dynamics of this network is essential for surveillance, prevention, and eventual eradication of HIV. Here, we apply a simple and computationally efficient network-based approach to all publicly available HIV polymerase sequences in the global database, revealing a contemporary picture of the spread of HIV-1 within and between countries. This approach automatically recovered well-characterized transmission clusters and extended other clusters thought to be contained within a single country across international borders. In addition, previously undescribed transmission clusters were discovered. Together, these clusters represent all known modes of HIV transmission. The extent of international linkage revealed by our comprehensive approach demonstrates the need to consider the global diversity of HIV, even when describing local epidemics. Finally, the speed of this method allows for near-real-time surveillance of the pandemic's progression.

Keywords: human immunodeficiency virus; molecular epidemiology; transmission network.

Figure 1.

Partial human immunodeficiency virus type 1 global transmission network inferred from pol locus. All clusters containing between 3 and 125 nodes are depicted (n = 1038). Edge lengths are optimized for visual presentation and do not represent genetic distances between potential transmission partners. All nodes are of equal size. Colors correspond to geographic regions.

Figure 2.

Large international transmission clusters. A, Southeast Asian transmission cluster, CRF01_AE, primarily from Thailand and Vietnam. Additional isolates from Belgium, Cambodia, China, Czech Republic, France, Greece, Indonesia, Japan, Luxembourg, Malaysia, Singapore, Sweden, Taiwan, United Kingdom, and United States. B, Former Soviet Union transmission cluster, subtype A1, primarily from the former Soviet Union. Isolates from Azerbaijan, Belarus, Cyprus, Czech Republic, Denmark, Georgia, Israel, Kazakhstan, Latvia, Moldova, Portugal, Russia, Slovenia, Spain, Sweden, Ukraine, United Kingdom, and Uzbekistan. Edge lengths are optimized for visual presentation and do not represent genetic distances between potential transmission partners. All nodes are of equal size, and colors correspond to geographic regions in Figure 1.

Figure 3.

Examples of transmission clusters inferred from the global network shown in Figure 1. Node size is proportional to relative degree (number of edges per node). Edge lengths are optimized for visual presentation and do not represent genetic distances between potential transmission partners. Colors correspond to geographic regions in Figure 1.

Figure 4.

Global transmission patterns of human immunodeficiency virus type 1. There are 211 putative transmission links between countries/regions. Green countries/regions are sampled in the network; gray indicates absence of sampling. Connections for each country/region originate in the centroid of its map region.

Figure 5.

Properties of the human immunodeficiency virus type 1 global transmission network. A, Relationship between cluster size and maximum pairwise divergence within a cluster. B, Number of years separating viral sequence isolation from potential transmission partners in the global transmission network. C, Network characteristic exponent ρ (black squares) stabilizes as number of clusters (gray circles) increases. Dashed line shows ρ inferred from the complete network. D, Effect of distance cutoff for potential transmission partners on network characteristic exponent ρ (black squares) and the number of clusters (gray circles).