Cross-Border Circulation and Molecular Surveillance of HIV-1 in the Azov and Donbas Regions: A Study of Genetic Diversity and Drug Resistance

As critical geopolitical and migratory hubs in Eastern Europe, the Azov and Donbas regions represent an epidemiological melting pot for HIV-1 trafficking, exacerbating the global trend of rising dolutegravir (DTG) resistance through the cross-border dissemination of drug-resistant strains. This study presents a comprehensive molecular epidemiological analysis of HIV-1 in these regions in 2025 (N = 1666), focusing on drug resistance and cross-border transmission networks using phylogenetic and molecular network approaches. The study cohort was predominantly female (53.33%) and had heterosexual transmission (78.77%). Most patients (87.64%) received antiretroviral therapy (ART). Sub-subtype A6 predominated, with the radiation’s origin traced to September 1994. Molecular network analysis identified the study area as a significant node, demonstrating viral exports towards the Russian Federation and Belarus, alongside multiple imports from Ukraine, Poland, and Russia. The overall resistance prevalence was 4.49% to integrase strand transfer inhibitors (INSTIs), 2.49% to protease inhibitors (PIs), 12.19% to nucleoside reverse transcriptase inhibitors (NRTIs), and 16.07% to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Surveillance drug resistance mutations in treatment-naive individuals stood at 0.89% (INSTIs), 4.90% (PIs), 4.90% (NRTIs), and 8.82% (NNRTIs). Crucially, intermediate or high-level DTG resistance and key mutations (G118R, R263K, and Y143R) were detected in individuals without prior DTG exposure. This 4.49% integrase inhibitor resistance cannot be considered low; combined with intense cross-border viral dissemination, it may indicate the formation of a stable pool of resistant variants, potentially posing a risk of dolutegravir-based regimen failure and highlighting the need for enhanced regional molecular surveillance.