Spatiotemporal analysis of HIV-1 subtype B transmission networks in Uruguay

To reconstruct the evolutionary and demographic history of HIV-1 subtype B in Uruguay and characterize the establishment, persistence, and regional connectivity of its major transmission lineages.

Nationwide molecular epidemiological and phylodynamic study of 491 HIV-1 subtype B pol sequences derived from routine resistance genotyping in Uruguay between 2007 and 2021.

Maximum-likelihood and Bayesian phylogenetic approaches were used to classify pandemic and Caribbean subtype B lineages, identify viral introductions and local transmission clusters, estimate their times of emergence, reconstruct the demographic dynamics of major Uruguayan lineages, and assess their regional origins and transmission tempo.

Pandemic subtype B accounted for 96.3% of sequences. We identified 229 independent introductions, of which only 52 (22.7%) generated detectable local transmission clusters, revealing marked heterogeneity in lineage establishment. The two largest country-specific lineages, B_PAN-UY-I (n = 37) and B_PAN-UY-II (n = 30), emerged independently in the mid-to-late 1980s and underwent sustained expansion until approximately 2010, followed by stabilization and recent declines in effective reproductive number. The median estimated maximum interval between successive infections was 25.4 months, with 49.3% of intervals <2 years and 21.5% >5 years. Among South American lineages with inferred regional ancestry, Brazil was the predominant source of both clustered and sporadic introductions.

HIV-1 subtype B in Uruguay represents a mature, highly compartmentalized epidemic shaped by recurrent viral introductions but sustained predominantly by a small number of early-established founder lineages. These findings highlight the enduring effects of historical contingency, transmission-network structure, and regional connectivity on contemporary HIV epidemic dynamics.