Minna Zheng, Hehe Zhao, Tielin Ning, Fangning Zhao, Hui Gong, Fan Lyu, Maohe Yu
Department of AIDS/STD Control and Prevention, Tianjin Centers for Disease Control and Prevention, Tianjin, 300011, China.
Tianjin Key Laboratory of Pathogenic Microbiology of Infectious Disease, Tianjin Centers for Disease Control and Prevention, Tianjin, 300011, China.
Virol J. 2025 May 8;22(1):137. doi: 10.1186/s12985-025-02704-y.
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.
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.
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⁻ vs. 1.48 × 10⁻ 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.
Subtype-specific strategies are critical: intensified resistance monitoring for CRF01_AE and cluster-focused interventions for CRF07_BC, particularly among young MSM.
作为中国北方的一个主要枢纽，天津面临着以CRF01_AE和CRF07_BC为主的HIV-1感染率上升的问题。本研究阐明了它们不同的传播模式和耐药动态，以指导针对性干预措施。
本研究纳入了2013年至2022年间通过各种方法鉴定为CRF01_AE和CRF07_BC亚型的样本。使用BEAST软件研究这些亚型在天津的时空传播模式。通过整合HIV-TRACE，我们构建了高风险传播集群，并根据斯坦福HIV耐药数据库确定耐药突变（DRM）。最后，采用出生-死亡天际线序列（BDSKY）模型动态评估两种亚型的有效繁殖数（Re），以预测未来传播动态。
CRF01_AE可能于1988年从河南和浙江传入，在天津形成多个小集群（<10个节点），并通过异性恋和男男性行为者（MSM）传播，而CRF07_BC于2004年来自重庆和贵州等地，经历了爆发性的本地传播，并在30岁以下的MSM中形成了一个170个节点的大集群（P<0.05）。系统发育分析表明，CRF01_AE的进化速率显著更高（2.08×10⁻与1.48×10⁻替换/位点/年，P<0.05），而CRF07_BC表现出更强的集群形成能力（56.6%对37.1%，P<0.05）。CRF01_AE的突变发生率更高（5.18%对2.49%，P<0.05），特别是与非核苷类逆转录酶抑制剂（NNRTI）相关的突变（如K101E）。虽然CRF07_BC的耐药负担较低，但K103E突变的出现表明需要警惕对新型NNRTIs敏感性的潜在降低。BDSKY模型显示，CRF01_AE的Re在2016年后降至1以下，而CRF07_BC的Re仍高于1，表明传播风险仍然存在。
亚型特异性策略至关重要：加强对CRF01_AE的耐药监测和对CRF07_BC的以集群为重点的干预措施，特别是在年轻MSM中。
