Comprehensive Determination Of Recent HIV-1 Infection And Characteristics Of Recent HIV-1 Infection In Entry-exit Population In China

BackgroundThe prevention of recent HIV infections is a key link in the prevention and control of the spread of AIDS.Timely identification of recent infection and the adoption of intervention measures can effectively curb the second-generation transmission.The type and quantity of antibodies,immune status,and virus quantity produced in HIV-infected persons will continue to change with the time of infection.These changes can be reflected by immunological and virological indicators such as enzyme-linked immunosorbent assay results,western blot band pattern,CD4 cell count,viral load,etc.The timely detection of recent HIV infection through the results of routine testing methods is essential for monitori ng and evaluating the effectiveness of HIV prevention efforts.As one of the most effective laboratory methods for HIV-1 new infection detection,limiting antigen avidity enzyme immunoassay can preliminarily determine the infection status of HIV-1 infected persons.This method is affected by factors such as CD4 cell count and antiviral therapy.In order to minimize the impact on this method,the results of a variety of conventional testing methods can be combined with HIV-1 recent infection detections to form recent infection testing algorithms to make the results more realistic.Entry-exit population is highly mobile,among which the recent infection is the key population of high-risk transmission.There are about 143 countries in the world that do not restrict the entry of HIV infected people.In 2010,China cancelled the compulsory HIV testing for foreign tourists and Chinese returnees.With the accelerating process of globalization,the deepening of our country’s foreign exchanges may also increase the risk of HIV transmission and spread.There is no study of entry-exit people new infections,for the first time,for us to analyze the spread of HIV-1 dynamic monitoring,understand the exit and entry of recent infection in the crowd of major epidemic strains,drug resistance and regional transmission source,help master HIV epidemic,in order to discover recent HIV subtypes strains input as soon as possible,provide scientific basis for disease prevention and control.Objective1.Study the feasibility of immunological and virological indicators as prediction of recent HIV-1 infections,and provide scientific basis for timely and accurate determination of recent HIV-1 infections.2.Understand the HIV-1 virological characteristics of the entry-exit population and the source area of the virus strain,to provide reference for the preventionand control of HIV-1 among the entry-exit population.MethodsThe first sectionUsing cross-sectional survey,collecting antiviral treatment-naive confirmed positive samples of Beijing,Zhejiang,Yunnan form 2017 to 2019,at the same sampling time,CD4 cell count,viral load and limiting antigen avidity assay were performed.Through statistical analysis methods,explore the feasibility of routine test results to assist in judging recent infections;only use LAg-avidity assay,CD4 cell count combined with LAg-avidity assay,VL combined with LAg-avidity,CD4 cell count、VL simultaneously combined with LAg-avidity to form four RITAs,and the effects of four different testing algorithm in identifying recent infection are compared.The second sectionA cross-sectional survey was conducted to collect confirmed positive samples from seven customs departments in Jilin,Heilongjiang,Shaanxi,Shandong,Sichuan,Zhuhai and Guangxi during 2017-2019,and to detect recent infections with limitting antigen avidity at the same sampling time.The pol region sequences were obtained by nucleic acid extraction and nucleic acid amplification,and the phylogenetic tree was constructed to determine the subtypes.The sequences were uploaded to the HIV DB database to determine the drug resistance.Bayesian geographical analysis was used to study the regional transmission sources of HIV recent infection.ResultsThe first section1.Both 4444 HIV-infected samples had gp 160,but the positive rates of gp 120,p66,p55,p51,gp41,p31 and p17 of recent infection were lower than those of previously infected samples（P<0.05）,and the absence of p55 and p31 was the risk factor for recent infection.2.The results of multivariate binary logistic regression model showed that co-mpared with S/CO>30,S/CO≤20（aOR=1.822,95%CI:1.001～3.318）was more li-kely to be recent infection.Compared with CD4<200 cells/μl,CD4≥500 cells/μl（aOR=3.520,95%CI:2.318-5.346）,350/μl≤CD4≤499 cells/μl（aOR=2.921,95%CI:1.939～4.402）and 200 ≤CD4≤349 cells/μl（aOR=1.607,95%CI:1.078-2.396）were more likely to be recent infection,and CD4≥500 was the most likely to be recent infection.VL>100,000 copies/ml（aOR=2.646,95%CI:1.467-4.773）was mo-re likely to be recent infection than VL<1000 copies/ml.3.The area under the curve of S/CO combined with viral load and CD4 cell count was 0.674,and the sensitivity and specificity were 79.6%and 46.7%,respectively.4.The incidence of recent infections determined by RITA1 was 22.81%,RITA2 was 19.64%,RITA3 was 21.06%,RITA4 was 18.00%.The second section1.The proportion of new infection in entry-exit population was 24.76%by restriction antigen affinity method.2.This study found that CRF01_AE（75.00%）was the main HIV subtype in entry-exit population in China,followed by CRF07_BC（10.00%）,CRF08_BC（2.5%）,CRF55₀1B（5.00%）,others（5.00%）.3.Drug resistance was found in 5 of the 40 recent infection successfully amplified.Three samples had low resistance to RPV,one sample had high resistance to NFV,and one sample had multiple resistance to AZT and D4T.4.Bayesian geography analysis found that 23.33%came from abroad and 76.67%came from China.ConclusionThe first section1.When missing p55、p31 bands or S/CO≤30 or CD4 cells≥500/μl or VL>100,000 copies/ml,the samples were more likely to be recent infection.2.The combined prediction model of S/CO+CD4+VL was the best for the identification of recent infection.3.The recent infection testing algorithms combined with different indicators can provide more accurate classification of recent HIV-1 infection,thus providing information for targeted intervention measures.The second section1.The proportion of recent infection among the entry-exit population in China is high.It is necessary to strictly monitor the entry-exit population with large population mobility in order to reduce the transmission and spread of HIV.2.The types of HIV-1 subtypes of recent infection in China are complex,and drug-resistant strains to NNRTI,NRTI and PI drugs have emerged.The surveillance of entry-exit people should be strengthened to reduce the risk of transmission,and the drug resistance of infected people should be considered when implementing antiviral treatment.3.Cross-border transmission of recent infection with HIV-1 at entry and exit of customs requires effective monitoring,prevention and control measures based on HIV epidemic characteristics to effectively control cross-border transmission.