Molecular footprints of a traveling epidemic: CRF01_AE-cluster 5 (01_C5) might spread across Northeast and South China via middle-aged MSM

HIV-1 CRF01_AE exhibits multiple distinct sub-subtypes (01_C1-C8) with different transmission dynamics across China. Understanding their geographical distribution, transmission patterns, and key affected populations is critical for optimizing targeted interventions.
We conducted a comprehensive molecular epidemiological study analyzing 4,011 partial pol sequences and demographic data from newly diagnosed CRF01_AE cases (2016–2019) in Shenyang (Northeast China) and Shenzhen (South China) by constructing the CRF01_AE molecular network in China (n = 6140). Sub-subtyping was performed using an online HIV subtyping tool and phylogenetic analysis. A molecular network was constructed based on genetic distance, and viral dispersal in large clusters (size≥10) in the network was assessed using Bayesian inference.
01_C5 (46.7%), 01_C4 (37.2%), 01_C1 (8.1%), 01_C2 (2.3%), 01_C3 (0.3%), and 01_C8 (<0.1%) were detected, with 01_C5 (73.7%) dominating in Shenyang, and 01_C4 (53.0%) in Shenzhen. Molecular network analysis revealed 24 large clusters, including 12 01_C5 clusters (64.7%) and 10 01_C4 clusters (28.5%). Notably, 01_C5 accounted for 75.9% of the mixed large clusters containing sequences from both cities. Bayesian phylodynamic analysis indicated one-way transmission of 01_C5 from Shenyang to Shenzhen was driven by middle-aged MSM (30–49 years old).
Our findings provided a potential molecular epidemiological evidence for CRF01_AE transmission from Northeast China to South China, and highlighted the urgent need for targeted interventions focusing on middle-aged MSM to prevent cross-regional 01_C5 transmission. This study provided an example for applying traceability analysis based on the HIV molecular transmission network in guiding targeted public health interventions.