| Background and ObjectivesIn recent years,with the continuous spread of HIV/AIDS epidemic,the main mode of AIDS transmission in China has changed greatly.In some economically developed areas,MSM has become the main infected population.MSM in China is usually characterized by multiple partners and low condom use.The cross-transmission among infected individuals with different subtypes of virus increases the diversity of HIV-1 genes.Molecular epidemiological surveillance is helpful to get better understanding of the current situation of local HIV-1epidemic.Drug resistance monitoring,as a routine work in health departments,has played an important role in monitoring the spread of drug resistance sites,evaluating treatment effects and guiding treatment drug use.At the same time,drug resistance surveillance accumulated a lot of HIV-1 sequence data,which provided the support for molecular epidemiology surveillance.The HIV-1 molecular transmission network is being promoted as an effective transmission monitoring tool worldwide because of its effective identification of high-risk populations and the feasibility of conducting large-scale surveys.However,the molecular transmission network inferred transmission relationship does not represent a direct transmission association in reality,but only represents a genetic transmission association of HIV-1 in infected individuals,which still needs to be supported by traditional epidemiological investigation.In this study,the newly found HIV-1 infected patients in Jiangsu Province were used as research subjects.The aim of this study is to carry out HIV-1 molecular epidemiological investigation and study,combined with the advantages of molecular transmission network and social network,to fully understand the current situation of HIV-1 in Jiangsu Province,and to provide evidence for the accurate identification and intervention of high-risk population.Methods1.Chinese and English databases retrieved by computer include:China National Knowledge Infrustructure,Wanfang Data,Full-text Database of Chinese Scientific and Technological Journals,China Bio-medical Literature Database,Pub Med and Web of Science.The retrieval date was from the database establishment date to January 5,2021.Systematic review and meta-analysis were used to review the trends of HIV-1 subtypes in Chinese MSM population at different time and regions.2.All newly found HIV-1 positive patients in Jiangsu Province from May 2017 to December 2018 were selected as subjects.The molecular epidemiology of HIV-1 was studied by extracting HIV-1 nucleic acid and amplifying target genes（pol,env and gag）.Different gene fragments were used to identify HIV-1 subtypes in infected individuals.For those samples that could not identify subtypes,HIV-1 near-full-length genome amplification was used to explore the possible existence of new recombinant viruses in Jiangsu Province.Resistance analysis relies on the Stanford HIV Resistance Database and detects resistant mutation sites by uploading local pol sequences.Predictive analysis of receptor tropism using env sequence V3rings.Two on-line prediction tools（Web PSSM and Geno2pheno）were used to determine the prediction results together,so as to avoid overestimating a certain tropism due to different algorithms and to understand the general situation of newly discovered HIV-1 infection in Jiangsu Province from different perspectives.3.Investigating the molecular epidemiology of HIV-1 in untreated and newly discovered HIV-1 infected persons in Wuxi City from 2012 to 2018 with using the same research method as point 2.The trend analysis of multiyear continuous cross-sectional data was used to examine the variation of HIV-1 prevalence over time.In addition,a maximum likelihood（ML）tree was constructed using pol sequences of newly discovered infected individuals in Jiangsu Province as reference sequences.Bayesian phylogenetic inference was used to predict the future epidemic trend of some major epidemic subtypes.4.By constructing ML tree,determining transmission network parameters,extracting transmission clusters and visualizing the HIV-1 molecular transmission networks of newly infected individuals in Jiangsu Province,the rapid transmission networks with high transmission risk were identified.In order to explore the consistency of the two investigation results,we carried out in-depth interview with collecting companion network.Results1.Changes of major HIV-1 prevalence subtypes over time and region in Chinese MSM population:From 1999 to 2019,the main prevalent subtype of MSM in China was CRF01＿AE（51.37%,95%CI:48.90-53.84）,CRF07＿BC（26.51%,95%CI:24.23-28.86）and B（11.56%,95%CI:9.90-13.33）subtype.CRF01＿AE showed a slow increasing trend until 2013,but after that its proportion declined rapidly;CRF07＿BC showed a rapid upward trend during the study period,while subtype B was in a rapid downward trend,to nearly 3 years time the composition of B subtype has been less than 5%.The proportion of CRF07＿BC was the highest in the western region,In the northwest,Ningxia,Xinjiang and Gansu reached 68.70%,65.93%and60.71%,respectively.It is the most prevalent subtype in Northeast China.The proportion of subtype B is higher in the central and northern regions of China,but lower in the western regions.In addition,the study found increased genetic diversity of HIV-1 across the country,with the proportion of unique recombinant viruses（URFs）that cannot identify subtypes already exceeding 5%after 2017,Although the proportion of circulating recombinant viruses（CRFs）in the subtype composition is very low,most of them are in a fluctuating trend.2.Basic information of newly discovered HIV-1 infections in Jiangsu Province from 2017to 2018:4269 study subjects were mainly infected by sexual behavior in gay men（59.0%,2517/4269）,followed by heterosexual sexually transmitted infections（40.1%,1714/4269）.Differences in basic characteristics existed among different populations.Unmarried（78.6%,1340/1740）was much higher than that of the non-MSM（21.4%,364/1740）;The age distribution of different population showed a trend change,the younger the age,the higher the proportion of MSM,with the increase of age,non-MSM proportion gradually increased.MSM accounted for 93.2%（207/222）of those who self-reported as students.3.Molecular epidemiological characteristics of HIV-1 among newly found infected persons in Jiangsu Province:The target gene fragment（pol,env or gag）was successfully amplified in 3788 subjects.The main HIV-1 genotype in Jiangsu province was CRF01＿AE（36.0%,1367/3794）and CRF07＿BC（29.7%,1127/3794）.Other subtypes with composition ratios exceeding 1%were:CRF67＿01B（5.1%,194/3794）,CRF08＿BC（4.8%,181/3794）,subtype B（3.2%,120/3794）,CRF68＿01B（2.5%,94/3794）,and CRF55＿01B（2.4%,91/3794）.In addition,there was a higher proportion of URFs.The main recombinant type was CRF01＿AE/07＿BC（0107）（9.6%,365/3794）and CRF01＿AE/B/C（01BC）（2.6%,97/3794）.A total of 63 nearly full-length HIV-1 gene sequences were obtained,40 of which were 0107 with different recombinant forms.A cluster of 0107 with high similarity was found.All the infected persons were young MSM in Nanjing.The sequence was uploaded to Gene Bank sequence database.The query code was MT347589-MT3447597.The resistance rate of HIV-1 genotype in Jiangsu province was 5.9%.Baseline CD4,current address and HIV-1 subtype were related factors.A total of 427（17.8%）samples were predicted to be CXCR4-helper receptor tropism,Utilization of CXCR4 co-receptors was significantly higher in the MSM than in the non-MSM（21.1%vs.12.2%,χ2=29.868,P<0.001）。4.Trends of basic situation of untreated and newly found infected persons in Wuxi City from 2012 to 2018:A total of 1913 study samples were collected.The subjects were predominantly male（88.4%,1692/1913）,the main transmission route was MSM（63.9%,1222/1919）.The proportion of MSM increased year by year（P<0.001）,from 51.5%in 2012to 70.1%in 2018.The proportion of self-reported infected persons with STDs decreased year by year（P<0.001）,from 16.7%in 2012 to 9.2%in 2018.The proportion of those who were HIV-1 positive at the first test showed a decreasing trend（P<0.001）.5.Trends in HIV-1 subtypes in Wuxi.From 2012 to 2013 and 2014 to 2018 formed a completely different trend:（1）CRF01＿AE is in a state of fluctuation,no obvious increase or decrease trend.The proportion of CRF07＿BC gradually increased,and has surpassed CRF01＿AE in 2018,becoming the most prevalent subtype in Wuxi.The proportion of URFs was very small before 2013,but increased suddenly in 2014,and then decreased year by year.The proportion of CRF67＿01B and CRF68＿01B increased year by year after 2014,especially the CRF67＿01B.By 2018,it has become the third highest composition ratio subtype among decidable types,after CRF07＿BC and CRF01＿AE.The resistance rate of HIV-1 genotype in Wuxi was 5.30%（68/1273）.A total of 182（19.3%）samples were predicted to be CXCR4coreceptor tropism.No time-trend change was observed in the rates of resistance and the composition of receptor tropisms.6.Prediction of prevalence trends for different subtypes.CRF01＿AE in Jiangsu Province formed a total of seven small epidemic branches.The main population of epidemic branch 5was old male（85.9%,85/99）with heterosexual STI.The other 6 epidemic branches were young MSM.CRF07＿BC formed 5 epidemic branches,where the number of sequences contained in epidemic branch 1（57.1%,480/841）is more than all other popular branches combined and is the main popular branch of CRF07＿BC in Jiangsu Province.The evolutionary rate of CRF67＿01B in Jiangsu province is 3.45×10-3（95%HPD:2.91-3.98）.The Wuxi sequence accelerated the spread of CRF67＿01B in Jiangsu Province.The evolutionary rate of CRF68＿01B in Jiangsu province is 6.03×10-3（95%HPD:5.64-6.43）.The prevalence of CRF68＿01B in Wuxi was earlier than other cities in Jiangsu Province.7.Characteristics and influencing factors of HIV-1 molecular transmission networks in Jiangsu Province:A total of 1349 sequences formed 388 transmission networks,covering samples from all cities in Jiangsu Province.The MSM population formed a large scale of the propagation network,with 59.6%of the total nodes（804/1349）,is the main connecting object of all other populations.Nanjing accounted for the highest proportion in the transmission network（16.7%,225/1349）.It was followed by Suzhou（14.2%,192/1349）and Wuxi（13.0%,175/1349）.CRF07＿BC accounted for the highest proportion（36.6%,494/1349）in the transmission network,forming the largest spread network.Second,CRF01＿AE（32.1%,433/1349）,contrary to CRF07＿BC,mainly formed some small-scale transmission networks.Local residents,baseline CD4>200,those found in Voluntary Counselling Clinic（VCT）,and those infected with CRF07＿BC or CRF68＿01B are the factors that promote network formation.8.Characteristics and influencing factors of rapid propagation network in Jiangsu Province:A total of 21 fast propagation networks including 363 nodes were identified,accounting for26.9%（363/1349）of the total number of propagation networks.In this city,76.0%（276/1027）,64.7%（235/775）were infected with MSM.Gay sex（OR=2.431,95%CI:1.703-3.470）and bisexual（OR=5.225,95%CI:2.093-13.040）will accelerate the spread of HIV-1.9.Basic characteristics of social network survey subjects and their relationship to molecular transmission networks:A total of 83 infected individuals were interviewed in depth.The mode of transmission was mainly homosexual transmission（88.0%,73/83）,most had a clear idea of who they had been infected by（61.4%,51/83）.On average,each infected person had 1 fixed partner and 4 temporary partners.The main sites of HIV-1 transmission are parks,bathrooms and bars in different cities.The more clustered networks in molecular transmission networks and the results of the survey can reflect each other.Conclusions1.Major HIV-1 subtypes in MSM have changed dramatically over time and space.The increasing number of URFs suggests an increased diversity of HIV-1 subtypes in the MSM population,emphasizing the importance of regular epidemiological surveillance.2.MSM was the main group of newly found HIV-1 infection in Jiangsu Province,and the proportion of students infected with MSM was very high.It is suggested that we should strengthen the publicity and education of HIV-1 related knowledge in schools,actively mobilize the relevant behavior students to consult and test,strengthen their awareness of safe behavior,promote students to prevent HIV-1 transmission,prevent the further spread of highly effective epidemic situation.A large number of URFs were found in newly infected HIV-1 patients in Jiangsu Province.Some of the recombinant subtypes identified as 0107 have formed transmission clusters in Nanjing.It also spread rapidly among MSM population,suggesting that HIV-1 subtype diversity increased in Jiangsu Province,and targeted interventions should be taken in patients with multiple sexual partners.The drug-resistance rate of newly infected patients in Jiangsu Province is higher than the previous survey,suggesting that the frequency of HIV-1 molecular epidemiological surveillance should be increased.Baseline drug resistance monitoring should be carried out,and the prevalence and drug resistance levels of HIV-1subtypes should be grasped in time to prevent the further spread of drug resistant strains in the population.3.CRF67＿01B was first reported to be found in Jiangsu and Anhui provinces.At present,the proportion in Wuxi increased year by year,much higher than other provinces and cities in the country reported on this subtype,the main infected population is young MSM.Evolutionary analysis shows that CRF67＿01B sequence in Wuxi city increases the evolutionary rate of Jiangsu province,and the population size estimates show that this subtype may be in a stable growth trend for a long period of time.It is suggested that CRF67＿01B probably originated from Jiangsu Province or surrounding areas.CRF67＿01B in Wuxi played an important role in the wide spread of this subtype in Jiangsu.Effective therapeutic intervention on young MSM in Wuxi may inhibit the spread of CRF67＿01B in Jiangsu Province.4.There is a large cross-city HIV-1 molecular transmission network in Jiangsu Province.As the main connecting object of all other populations,the MSM population plays a role of"bridge population,"which promotes the spread of HIV-1.MSM generally has the characteristics of multiple sexual partners and bisexual behaviors,which accelerate the transmission of HIV-1.The dense molecular communication network and in-depth interview results can reflect each other,suggesting that it is feasible to carry out molecular communication networks in Jiangsu Province to accurately identify high-risk transmission populations.Customized and personalized interventions are supplemented with information from interviews and surveys to achieve precise interventions for high-risk groups. |
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