Divergent transmission dynamics and drug resistance evolution of HIV-1 CRF01_AE and CRF07_BC in Tianjin, China (2013-2022)

中国天津市HIV-1 CRF01_AE和CRF07_BC的传播动力学和耐药性演变差异(2013-2022年)

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Abstract

BACKGROUND: Tianjin, a major hub in northern China, faces rising HIV-1 infections dominated by CRF01_AE and CRF07_BC. This study elucidated their divergent transmission patterns and drug resistance dynamics to guide targeted interventions. METHODS: This study included samples identified as CRF01_AE and CRF07_BC subtypes through various methods between 2013 and 2022. BEAST software was used to examine the spatiotemporal transmission patterns of these subtypes in Tianjin. By integrating HIV-TRACE, we constructed high-risk transmission clusters and identified drug resistance mutations (DRMs) based on the Stanford HIV Drug Resistance Database. Finally, the birth-death skyline serial (BDSKY) model was employed to dynamically assess the effective reproductive number (Re) of both subtypes to predict future transmission dynamics. RESULTS: CRF01_AE might be introduced in 1988 from Henan and Zhejiang, forming multiple small clusters (< 10 nodes) and spreading through both heterosexual and men who have sex with men (MSM) in Tianjin, while CRF07_BC from Chongqing and Guizhou, et al. in 2004, experiencing explosive local transmission and forming a large cluster of 170 nodes primarily among MSM under 30 years old (P < 0.05). Phylogenetic analysis indicated that CRF01_AE has a significantly higher evolutionary rate (2.08 × 10⁻(3) vs. 1.48 × 10⁻(3) substitutions/site/year, P < 0.05), while CRF07_BC demonstrates a greater cluster formation capacity (56.6% vs. 37.1%, P < 0.05). CRF01_AE showed a higher mutation occurrence rate (5.18% vs. 2.49%, P < 0.05), particularly with non-nucleoside reverse transcriptase inhibitor (NNRTI) associated mutations (e.g., K101E). Although CRF07_BC had a lower resistance burden, the emergence of K103E mutations suggests a need for vigilance regarding potential decreases in sensitivity to newer NNRTIs. BDSKY modeling revealed that the Re for CRF01_AE dropped below 1 after 2016, whereas CRF07_BC's Re remains above 1, indicating that the risk of transmission still exists. CONCLUSION: Subtype-specific strategies are critical: intensified resistance monitoring for CRF01_AE and cluster-focused interventions for CRF07_BC, particularly among young MSM.

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