Identification of major routes of HIV transmission throughout Mesoamerica

Abstract

Background: Migration and travel are major drivers of the spread of infectious diseases. Geographic proximity and a common language facilitate travel and migration in Mesoamerica, which in turn could affect the spread of HIV in the region.

Methods: 6092 HIV-1 subtype B partial pol sequences sampled from unique antiretroviral treatment-naïve individuals from Mexico (40.7%), Guatemala (24.4%), Honduras (19%), Panama (8.2%), Nicaragua (5.5%), Belize (1.4%), and El Salvador (0.7%) between 2011 and 2016 were included. Phylogenetic and genetic network analyses were performed to infer putative relationships between HIV sequences. The demographic and geographic associations with clustering were analyzed and viral migration patterns were inferred using the Slatkin-Maddison approach on 100 iterations of random subsets of equal number of sequences per location.

Results: A total of 1685/6088 (27.7%) of sequences linked with at least one other sequence, forming 603 putative transmission clusters (range: 2-89 individuals). Clustering individuals were significantly more likely to be younger (median age 29 vs 33years, p<0.01) and men-who-have-sex-with-men (40.4% vs 30.3%, p<0.01). Of the 603 clusters, 30 (5%) included sequences from multiple countries with commonly observed linkages between Mexican and Honduran sequences. Eight of the 603 clusters included >10 individuals, including two comprised exclusively of Guatemalans (52 and 89 individuals). Phylogenetic and migration analyses suggested that the Central and Southern regions of Mexico along with Belize were major sources of HIV throughout the region (p<0.01) with genetic flow southward from Mexico to the other nations of Mesoamerica. We also found evidence of significant viral migration within Mexico.

Conclusion: International clusters were infrequent, suggesting moderate migration between HIV epidemics of the different Mesoamerican countries. Nevertheless, we observed important sources of transnational HIV spread in the region, including Southern and Central Mexico and Belize.

Keywords: Clusters; HIV; Mesoamerica; Migration; Network.

Figure 1

1A. Sampling distribution across Mesoamerica. The number of HIV pol sequences included in the analysis are represented. 1B. Clustering Proportion. Heat map representing the proportion of sampled HIV infected individuals within each geographic subdivision clustering with at least one other individual. Data are presented at the Country level for El Salvador, Belize, Nicaragua and Panama at the state/province level for Guatemala, Honduras, and Mexico.

Figure 2. HIV transmission clusters

The structure and demographic make-up of inferred HIV-1 transmission clusters from the Mesoamerican cohort are illustrated. Nodes (rectangles and circles) represent connected individuals in the overall network, and putative transmission linkages are represented by edges (lines). A. Intra-national clusters. Nodes are color coded by the reported risk behavior. B. Transnational Clusters. Nodes are color coded by the country of origin (left panel) and the reported risk behavior (right panel). Only clusters with ≥3 individuals are presented. Clustering individuals from El Salvador (n=6) are not shown as they are only included in dyads.

Figure 3. Matrix of HIV migration events

An increase in redness represents a stronger migratory signal. Red asterisk indicates significant major sources of viral migration. Viral migration patterns were inferred using the Slatkin-Maddison approach on 100 iteration of random subsets of equal number of sequences per location (see Methods for details).