HIV-1 drug resistance transmission cluster dynamics among men who have sex with men across Europe: a multi-regional molecular epidemiological study

Abstract The HIV epidemic among men who have sex with men (MSM) in Europe is sustained by structured transmission networks in which drug resistance mutations (DRMs) spread across geopolitical boundaries. Herein, we applied a systematic molecular epidemiological framework to characterise DRM prevalence, temporal trends, and identify transmission clusters from MSM across European geopolitical regions (Western Europe, Central and Eastern Europe, Southern Europe, and Northern Europe). This was a retrospective molecular epidemiological analysis conducted with 3300 HIV pol sequences from 1983 to 2016. Sequences were aligned with ViralMSA, the maximum likelihood (ML) tree was reconstructed with IQ-TREE, the transmission cluster was inferred with ClusterPicker, and HIVDR was evaluated with Stanford HIVdb. An overall DRM prevalence of 28% (95% CI: 26.5–29.5%) was detected, with NRTIs as the dominant drug class affected (12.8%). A significant decreasing temporal trend was detected (Mann–Kendall τ = − 0.52, p < 0.05), corresponding to an estimated reduction of 1.42 percentage points per year. ML phylogenetic inference followed by transmission cluster detection identified 492 clusters encompassing 49% of sequences; 92% were geographically confined to a single region, while 8% exhibited interregional spread predominantly linking Central and Eastern with Western Europe. Drug-resistant sequences in Western Europe were significantly less likely to belong to a transmission cluster (OR = 0.57; 95% CI: 0.48–0.68; p < 0.001). These findings reveal that resistant variants are actively clustering and spreading across European borders, underscoring the need for coordinated multi-regional molecular surveillance.