Delineating the “Who-Where-How” of Persistent HIV Epidemics: A 23-Year Longitudinal Genetic Network, Phylodynamic, and Spatial Analysis for Precise Intervention in Rural China

Despite "Treat All" strategies, HIV outbreaks persist among the elderly in rural Southwest China. To identify the core drivers ("Who"), geographic foci ("Where"), and socio-behavioral mechanism ("How") of sustained transmission in the post-"Treat All" era, we triangulated longitudinal genetic networks, phylodynamic and spatial analysis, and behavioral surveys using multi-source 1999-2021 data (N = 5,094). Although antiretroviral therapy reduced community-level transmission risk by 21.0%, 107 molecular super-spreaders, predominantly males aged 50-69, were identified across four phases. These individuals exhibited poor treatment retention, with dropout rates reaching 28.2% and 38.5% having unsuppressed or missing viral loads by Phase 4. Notably, 94.4% of super-spreaders resided within 2 km of transportation arteries, exceeding 77.9% population baseline. Townships within this buffer exhibited significantly higher cumulative HIV cases independently of population metrics (adjusted Incidence Rate Ratio =1.43, 95% CI: 1.14-1.78). Characterized as infrastructure-anchored "risk hubs", these areas facilitate sustained viral dispersal through a "double-proximity" mechanism. Older men frequent nearby periodic markets along transit corridors for commercial sex, while female sex workers exhibit linear mobility across townships, effectively aligning their service cycles with the temporal rhythm of the periodic markets. Our methodology facilitates targeted node-level testing and interventions, bridging clinical treatment and public health prevention to mitigate aging-driven epidemics in resource-limited regions.