2015—2019年南京市HIV-1 CRF07_BC毒株流行特征及分子进化分析

Epidemiological characteristics and molecular evolution analysis of HIV-1 CRF07_BC in Nanjing from 2015 to 2019

目的了解2015—2019年南京市HIV-1 CRF07_BC的流行史、进化模式和传播特征,为精准防控该毒株的传播提供科学依据。方法对南京市319例HIV-1 CRF07_BC患者的pol区基因序列扩增测序并构建最大似然树。使用MCMC(Markov Chain Monte Carlo)算法生成MCC树(Maximum Clade Credibility tree),使用BSP(Bayesian Skyline Plot)法重塑有效人口规模数变化趋势。采用成对基因距离法构建分子网络探究其传播特征。结果319名HIV-1 CRF07_BC感染者中,95.0%为男性,多性伴(2个及以上)比例达82.8%,仅4.4%病例自报一直使用安全套,男男同性性行为(MSM)为最主要的感染途径(77.4%)。进化树结果显示,HIV-1 CRF07_BC呈现两大流行簇:Cluster1和Cluster2,Cluster1以MSM感染病例为主,Cluster2以异性性行为感染病例为主。Cluster1和Cluster2的最近共同祖先时间分别为2002.47(1999.91,2005.43)年、1996.38(1992.55,1999.76)年,进化速率(95%highest posterior density,95%HPD)分别为1.73×10^(-3)(1.36×10^(-3)~2.16×10^(-3))substitutions·site^(-1)·year^(-1)、2.09×10^(-3)(1.50×10^(-3)~2.79×10^(-3))substitutions·site^(-1)·year^(-1),有效人口规模数分别在2002年、2003年之后趋于稳定。此外,Cluster1和Cluster2分别形成了11个、8个独特的分支,提示该基因型存在发散性流行的可能。分子传播网络中共形成35个传播簇,平均度数为4.3,92条南京分离序列分布在网络内。男性、MSM、多性伴有更大可能性入网,学生人群及年轻患者入网率较高。结论2015—2019年南京市HIV-1 CRF07_BC感染者存在低龄化现象,多性伴、无保护性行为及MSM突出。建议对学生、青年人群加以重点关注,对高危性行为制定更多有效的防控措施,并对CRF07_BC毒株进行持续的分子监测,为开展HIV CRF07_BC精准防控工作提供科学依据。

Objective To investigate the epidemiology,evolution and transmission characteristics of HIV-1 CRF07_BC in Nanjing between 2015 and 2019 to provide scientific basis for precise prevention and control of HIV-1 transmission.Methods Pol gene sequences of 319 patients with HIV-1 CRF07_BC infection in Nanjing were amplified and sequenced and a maximum likelihood phylogenetic tree was then constructed.Markov Chain Monte Carlo sampling method was used to generate Maximum Clade Credibility Tree.Bayesian Skyline Plot was used to reconstruct the changing trend of the effective population size.Pairwise gene distance method was used to construct molecular network to investigate the transmission features.Results Among the 319 patients,303(95.0%)were male;264(82.8%)had multiple sexual partners;only 14(4.4%)had been using condoms.Most of the infections were occurred in men who have sex with men(MSM),accounting for 77.4%.The maximum likelihood phylogenetic analysis of HIV-1 CRF07_BC revealed two clusters:Cluster1 and Cluster2.Cluster1 mainly contained the strains isolated from MSM and Cluster2 mainly consisted of the strains isolated from heterosexual patients.The most recent common ancestor was 2002.47(1999.91,2005.43)year for Cluster1 and 1996.38(1992.55,1999.76)year for Cluster2.The evolutionary rates(95%highest posterior density,95%HPD)of Cluster1 and Cluster2 were 1.73×10^(-3)(1.36×10^(-3)-2.16×10^(-3))substitutions·site^(-1)·year^(-1) and 2.09×10^(-3)(1.50×10^(-3)-2.79×10^(-3))substitutions·site^(-1)·year^(-1),respectively.The effective population sizes of Cluster1 and Cluster2 tended to be stable after 2002 and 2003,respectively.In addition,Cluster1 and Cluster2 formed eleven and eight unique branches,respectively,suggesting the possibility of divergent epidemics of this genotype.A total of 35 propagation clusters were formed in the molecular propagation network,including 92 Nanjing sequences with an average degree of 4.3.Males,MSM and people with multiple sexual partners were more likely to be connected to the network.Students and young patients were more likely to be connected to the network.Conclusions HIV-1 CRF07_BC infection was characterized by low age,multiple sexual partners,unprotected behaviors and transmission among MSM in Nanjing from 2015 to 2019.It was recommended to pay more attention to students and young people,to formulate more effective prevention and control measures for high-risk sexual behaviors,and to carry out continuous molecular monitoring of CRF07_BC strain,so as to provide scientific basis for the prevention and control of HIV CRF07_BC.