Nationwide Molecular Epidemiology of HIV‐1 in Uruguay (2007–2021): Lineage Diversity, BF1 Recombinant Complexity and Epidemiological Patterns

INTRODUCTION: Uruguay has one of the highest HIV incidence rates in Latin America, yet its molecular epidemiology remains underexplored. Characterizing the diversity, temporal and geographic dynamics of circulating HIV-1 lineages is essential to detect lineage-specific patterns across population groups and regions, inform tailored prevention and surveillance strategies, and understand cross-border connectivity. METHODS: HIV-1 pol (PR/RT) genotyping data from 1268 people living with HIV, generated during 2007-2021 through nationwide routine genotyping, were analysed. Viral lineages and recombinants were classified using automated subtyping tools, maximum-likelihood phylogenies and recombination analyses. Associations with demographic and exposure characteristics were evaluated using Z-tests and Fisher's exact tests, and temporal trends were assessed using Pearson correlations. RESULTS: Sixteen recognized HIV-1 lineages were identified, including four subtypes/sub-subtypes (B, C, A1 and F1) and twelve circulating recombinant forms (CRFs). Subtype B was the most frequent lineage (39.3%), followed by CRFs 12_BF (27.8%) and 38_BF1 (12.9%). An additional 8.5% of sequences formed a well-supported B/F1 recombinant clade, provisionally designated BF1.UY and not assignable to any known CRF. Temporal analyses showed opposing trends, with a significant decline in subtype B and an increasing contribution of BF1 recombinants within the genotyped dataset. Subtype B was associated with men and transmission among men who have sex with men; 38_BF1 was enriched among women and people reporting injection-related exposures; and BF1.UY predominate in reported heterosexual transmission. Geographic patterns suggested regional connectivity: 12_BF predominated in the West and the Atlantic coastal East, consistent with Argentina-linked border and tourism-related mobility, whereas Brazilian-associated variants (subtype C, 31_BC and F1) were more frequent in the Northeast and East. CONCLUSIONS: In Uruguay, HIV-1 molecular diversity was largely shaped by sustained circulation of subtype B and BF1 recombinants, which showed distinct associations with gender, transmission-route category and geography. These lineage-specific patterns are consistent with partially overlapping transmission networks among Uruguayan subpopulations and viral exchange across border areas. The growing contribution of BF1 recombinants within the genotyped dataset, together with geographically structured diversity in areas connected to Argentina and Brazil, highlights the need for sustained molecular surveillance integrated with epidemiological data and regional collaboration to track HIV-1 diversification and spread.