Changes In Gene Subtypes And Clusters Of Major HIV Epidemic Strains And Drug Resistance Among 16-25 Year Old Heterosexually Transmitted Infections In China

Background and Objective:Heterosexual transmission?HET?accounted for 73.7%of the newly reported HIV-infected patients from January to October 2019.This route has become the main infection route for HIV-infected/AIDS patients in China.A national survey in 2015 showed that there are more than 20 HIV strains circulating in China,which is one of the countries with the most popular strains in the world.Among them,CRF01 AE?39.0%?,CRF07_BC?35.6%?and CRF08_BC?8.9%?The composition ratio of the three recombinant strains has exceeded 80%,so not only are there many types of HIV epidemic strains in our country,but also the countries with recombinant epidemic strains,so this is also a different feature of China's AIDS epidemic from other countries.One of the difficulties in controlling.Sexual behaviors of younger HIV-infected patients aged 16-25 years are believed to have occurred in recent years,and may be representative of the prevalence of newly infected HIV.Therefore,this study intends to study the HIV infection of 16-25 years old HET in China from 2008 to 2018 in 11 years,with a view to revealing the genetic changes and drug resistance characteristics of HIV strains in the HET population.Methods:1.Screen the pol gene region sequence of HIV-infected patients?self-reported as HET?of 16-25 year old HET from our laboratory's drug resistance monitoring data in 2008-2018,and use Neighbor-Joining to conduct systematic evolution Analysis,combined with the GTR model and Gamma model in Bayes to analyze the popular history of subtypes and subclusters.Use the HIV drug resistance database?https://hivdb.stanford.edu/?to refer to the 12 commonly used antiviral drugs recommended by the WHO drug resistance guidelines to determine the characteristics of drug resistance transmission.2.For the sequence of the pol gene region that cannot be clearly classified as a known subtype?cannot be clearly divided into subtypes?in the above study,conduct the following further research?1?to understand the pol gene of 16-25 years old in some areas of China in 2008-2018 The region cannot clearly distinguish the characteristics of HIV HET infected persons.?2?Select some representative samples for near full-length gene amplification?about 9000bp?.Use HIV database online tools?RIP and jpHMM?and SimPlot software to perform sequence recombination analysis to identify new HIV epidemic recombinant strains.Results:The first sectionA total of 1990 cases of HET infected persons aged 16-25 years were collected from 2008 to 2018.The main prevalent subtypes are:CRF01_AE?37.3%,742/1990?,CRF07_BC?33.2%,661/1990?,CRF08_BC?8.1%,162/1990?,B subtype?5.4%,107/1990?,CRF55₀1B?2.3%,46/1990?and new recombinant subtype?1.5%,29/1990?,and 11.4%cannot be clearly divided into subtypes?226 cases?;The main popular clusters are CRF01_AE-Cluster 1?13.4%,267/1990?,CRF01_AE-Cluster 4 clusters?11.7%,232/1990?,CRF01_AE-Cluster 5 clusters?3.0%,60/1990?,CRF07_BC-MSM Cluster?15.8%,314/1990?.In the past,CRF01_AE-Cluster 1 which was mainly popular among HET populations showed a downward trend?P=0.001?,while CRF01_AE-Cluster 5,CRF07_BC-MSM sub-clusters and CRF55₀1B subtypes derived from homosexual transmission groups showed an upward trend?P<0.01?.According to the gender stratification,the main subpopulations of the HET female population are CRF01_AE-Cluster 1?18.4%,179/973?and CRF07_BC-MSM,while the HET male population is CRF01_AE-Cluster 4?19.0%,188/990?and CRF07 BC-MSM;the change trend of the composition ratio of the above subtypes and subclusters is consistent with that before stratification.The time for CRF01_AE-Cluster 4 and CRF01_AE-Cluster 5 to enter China's HET was about 1996 and 2000,and the time for entering the MSM population was 1994 and 1995,respectively.The time period for rapid growth in both groups was 1997-2006;CRF07_BC-MSM and CRF55₀1B were in the same growth period as MSM in the HET population.The drug resistance rate of this study population was 2.8%?55/1990?,which was close to that of men having sex with men?MSM?in the 16-25 age group?drug resistance rate was 3.0%?,which was lower than that in 2015.The drug resistance rate of all age groups in a national survey?3.6%?.The drug resistance rate was basically the same at three time points,and there was no significant change?P=0.458?.The second section?1?The subtype strains that cannot be divided are mainly URF_C and URF_BC,which together account for 84.1%?190/226?of the total surveyed population.43.8%?99/226?of the strains that could not be clearly divided into subtypes found more than 2 subtype fragments in the pol gene region,and 1 case of URF_A1 and 5 cases of URF_G were identified.?2?According to further analysis of the pol gene region,this study selected samples with consistent recombination breakpoints,and newly identified two CRFs?CRF103₀1B and CRF106_cpx?by full-length sequence amplification.CRF103₀1B is formed by the recombination of 3 B fragments inserted into the CRF01_AE backbone;CRP106_cpx is formed by the recombination of 2 CRF01_AE fragments and 3 B fragments inserted into the C backbone.conclusion:In the 16-25 year-old age group,males with heterosexual HIV infection have more prevalent clusters of HIV strains than women,which is consistent with the prevalence of MSM populations.Combined with the analysis results of Bayesian epidemic history,the origin and epidemic rise time of each subcluster in HET are similar to MSM..In the past,CRF01_AE-Cluster 1 which was popular in heterosexual populations decreased in the proportion of 16-25 years old heterosexual populations,while CRF01_AE-Cluster 4,CRF01_AE-Cluster 5,CRF07_BC-MSM sub-clusters and CRF55₀1B subtypes derived from MSM populations were in rise.The spread of drug resistance among 16-25 year old heterosexual untreated infections in China is still at a low level.More than 10%of heterosexually transmitted HIV strains cannot be classified as known epidemic subtypes,and there are many potential new recombinant strains;the determination of new popular recombinant strains CRF103₀1B and CRF106_cpx not only explains the complexity of HIV subtypes in China,And can provide help for better subtype classification analysis in the future,and also provide data support for the development of diagnostic reagents,vaccines,and other drugs.