Unraveling HIV-1 spread in Southwest China: a phylogenetic and molecular network approach

Guangxi is one of the regions most affected by HIV-1 in China, yet the fine-scale transmission dynamics and molecular epidemiology remain incompletely characterized. In this study, we integrated molecular transmission network analysis, phylogenetic inference, and spatial analysis to elucidate HIV-1 dispersal patterns and inform precision public health interventions. We analyzed 10, 199 HIV-1 pol sequences collected from all 14 cities in Guangxi, encompassing major subtypes including CRF01AE, CRF07BC, CRF08BC, and CRF55₀1B. Molecular networks were constructed using a 1. 5% TN93 genetic-distance threshold, and logistic regression was applied to identify factors associated with network clustering. Bayesian phylogenetic and phylogeographic analyses were used to characterize spatiotemporal dissemination patterns. Overall, 75. 6% (7, 706/10, 199) of individuals clustered within molecular networks, with clustering proportions exceeding 60% in every city. Factors independently associated with clustering included viral load 10, 000 copies/mL (OR = 1. 23, 95% CI: 1. 10–1. 39), education level of junior high school or below (OR = 1. 67, 95% CI: 1. 30–2. 14), age ≥50 years (OR = 1. 38, 95% CI: 1. 16–1. 63), Zhuang ethnicity (OR = 1. 18, 95% CI: 1. 08–1. 30), and syringe sharing (OR = 1. 65, 95% CI: 1. 14–2. 38). Intercity connections accounted for 48. 2% of inferred genetic linkages, with CRF55₀1B showing the highest intercity connectivity (60. 4%). CRF01AE displayed the broadest geographic distribution, Nanning and Qinzhou emerged as key connectivity hubs. Phylogeographic analyses suggested that Qinzhou was a major source of dispersal for CRF01AE and CRF08BC, whereas Nanning played a central role in the dissemination of CRF07BC, CRF08BC, and CRF55₀1B. HIV-1 transmission in Guangxi is characterized by high network clustering and pronounced spatial heterogeneity, with distinct hub cities contributing to regional connectivity. These findings provide actionable evidence to support targeted, location-specific HIV prevention and control strategies at both local and regional levels.