Yang Yue, Zhao Xiu-Ping, Zou Hua-Chun, Chu Min-Jie, Zhong Ping, Li Xiao-Shan, Li Xiao-Yan, Yu Yu-Hui, Zhu Ke-Xin, Chen Yu-Jia, Xia Fei, Zhu Bo-Wen, Ruan Luan-Qi, Bao Yi-Ning, Zhuang Xun
Department of Epidemiology and Health Statistics, School of Public Health, Nantong University, Nantong Department of Infection Management Office, the First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Nanjing, Jiangsu Province Department of AIDS and STD, Shanghai Municipal Center for Disease Control and Prevention; Shanghai Municipal Institute for Preventive Medicine, Shanghai Department of AIDS and STD, Suzhou Center for Disease Prevention and Control, Suzhou, Jiangsu Province School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong Province, China Kirby Institute, University of New South Wales, Sydney, Australia Teaching and Research Office of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, Jiangsu Province Ningbo Medical Center Lihuili Eastern Hospital; Taipei Medical University Ningbo Medical Center, Ningbo, Zhejiang Province, China.
Medicine (Baltimore). 2018 Feb;97(6):e9826. doi: 10.1097/MD.0000000000009826.
The prevalence and incidence of human immunodeficiency virus type 1 (HIV-1) among men who have sex with men (MSM) are on the rise throughout China. With a large population of MSM, Jiangsu Province is facing an escalating HIV-1 epidemic.The aim of this study was to explore the phylogenetic and temporal dynamics of HIV-1 CRF01_AE and CRF07_BC among antiretroviral therapy (ART)-naïve MSM recently infected with HIV-1 in Jiangsu Province.We recruited MSM in Jiangsu Province (Suzhou, Wuxi, Nantong, Taizhou and Yancheng) 2012 to 2015. We collected information on demographics and sexual behaviors and a blood sample for HIV genome RNA extraction, RT-PCR amplification, and DNA sequencing. Multiple alignments were made using Gene Cutter, with the selected reference sequences of various subtypes/recombinants from the Los Alamos HIV-1 database. Phylogenetic and Bayesian evolutionary analysis was performed by MEGA version 6.0, Fasttree v2.1.7. and BEAST v1.6.2. Categorical variables were analyzed using χ test (or Fisher exact test where necessary). χ test with trend was used to assess the evolution of HIV-1 subtype distribution over time. All data were analyzed using SPSS20.0 software package (IBM Company, New York, NY).HIV-1 phylogenetic analysis revealed a broad viral diversity including CRF01_AE (60.06%), CRF07_BC (22.29%), subtype B (5.88%), CRF67_01B (5.26%), CRF68_01B (2.79%), CRF55_01B (1.55%), CRF59_01B (0.93%), and CRF08_BC (0.62%). Two unique recombination forms (URFs) (0.62%) were also detected. Four epidemic clusters and 1 major cluster in CRF01_AE and CRF07_BC were identified. The introduction of CRF01_AE strain (2001) was earlier than CRF07_BC strain (2004) into MSM resided in Jiangsu based on the time of the most recent common ancestor.Our study demonstrated HIV-1 subtype diversity among ART-naïve MSM recently infected with HIV-1 in Jiangsu. We first depicted the spatiotemporal dynamics, traced the dates of origin for the HIV-1 CRF01_AE/07_BC strains and made inference for the effective population size among newly infected ART-naïve MSM in Jiangsu from 2012 to 2015. A real-time surveillance of HIV-1 viral diversity and phylodynamics of epidemic cluster would be of great value to the monitoring of the epidemic and control of transmission, improvement of antiretroviral therapy strategies, and design of vaccines.
在全中国，男男性行为者（MSM）中1型人类免疫缺陷病毒（HIV-1）的流行率和发病率都在上升。江苏省有大量男男性行为者，正面临着不断升级的HIV-1疫情。本研究的目的是探讨江苏省近期感染HIV-1且未接受抗逆转录病毒治疗（ART）的男男性行为者中HIV-1 CRF01_AE和CRF07_BC的系统发育和时间动态。
我们于2012年至2015年在江苏省（苏州、无锡、南通、泰州和盐城）招募男男性行为者。我们收集了人口统计学和性行为信息，并采集血样用于HIV基因组RNA提取、逆转录-聚合酶链反应（RT-PCR）扩增及DNA测序。使用Gene Cutter进行多重比对，并选用来自洛斯阿拉莫斯HIV-1数据库中各种亚型/重组体的参考序列。通过MEGA 6.0版、Fasttree v2.1.7和BEAST v1.6.2进行系统发育和贝叶斯进化分析。分类变量采用χ检验（必要时采用Fisher精确检验）。采用趋势χ检验评估HIV-1亚型分布随时间的演变。所有数据均使用SPSS20.0软件包（IBM公司，纽约州纽约市）进行分析。
HIV-1系统发育分析显示出广泛的病毒多样性，包括CRF01_AE（60.06%）、CRF07_BC（22.29%）、B亚型（５.88%）、CRF67_01B（5.26%）、CRF68_01B（2.79%）、CRF55_01B（1.55%）、CRF59_01B（0.93%）和CRF08_BC（0.62%）。还检测到两种独特的重组形式（URF）（0.62%）。在CRF01_AE和CRF07_BC中鉴定出四个流行簇和一个主要簇。根据最近共同祖先的时间，CRF01_AE毒株（2001年）比CRF07_BC毒株（2004年）更早传入居住在江苏的男男性行为者中。
我们的研究表明江苏省近期感染HIV-1且未接受抗逆转录病毒治疗的男男性行为者中存在HIV-1亚型多样性。我们首次描绘了时空动态，追溯了HIV-1 CRF01_AE/07_BC毒株的起源日期，并对2012年至2015年江苏省新感染且未接受抗逆转录病毒治疗的男男性行为者中的有效种群大小进行了推断。对HIV-1病毒多样性和流行簇的系统发育动态进行实时监测，对于疫情监测和传播控制、抗逆转录病毒治疗策略的改进以及疫苗设计具有重要价值。
