| BackgroundBy inhibiting viral replication,antiviral therapy can reduce death from people infected with HIV and effectively reduce HIV transmission.Since the launch of our free antiretroviral treatment programme in 2003,HIV-1-related morbidity and mortality have declined significantly nationwide.Fuyang is located in the northwest of Anhui Province,adjacent to Henan Province,with a permanent population of 7.823 million,of which about2.8 million are migrant workers.In the 1990’s,infections were mainly triggered by illegal plasma collection and were a key area for HIV-1 epidemics in Anhui Province.In recent years,after the implementation of the standardized management policy of blood banks,the transmission route has changed from blood transmission of sexual transmission.The HIV-1 epidemic strain has become more complex and diverse than before.In Fuyang City,HIV/AIDS infection is still dominated by young adults,but the number of reports on the 15-24 and≥50 age groups have increased to recent years Trends.The drug resistance situation in Fuyang City is not encouraging,and previous studies have shown that the pre-treatment drug resistance rate in the elderly in Fuyang City in 2019 has reached moderate epidemic levels.Molecular transmission network analysis reveals HIV transmission relationships and transmission patterns from the molecular dimension.It has unique advantages in real-time monitoring of network expansion dynamics,identification of new and fast-spreading networks and high-risk groups,which can make up for the shortcomings of social communication networks and accurately locate and quickly intervene in key groups.Object1.Understand the subtype distribution and molecular network transmission relationship of all newly reported infected persons in Fuyang City from 2020 to 2021 and their influencing factors,identify high-risk groups and rapid transmission networks,and obtain the epidemiological characteristics and influencing factors of this population.2.To master the degree of drug resistance of pre-treatment drug-resistant infected persons and acquired drug-resistant infected persons during 2020-2021 and 2019-2020 in Fuyang City,identify drug-resistant mutations and analyze drug-resistant sites,construct drug-resistant molecular clusters,provide scientific basis of formulating reasonable and effective treatment plans,and supplement data onto HIV-1 drug resistance monitoring in Fuyang City.3.Understand the effect of antiviral therapy in Fuyang City in reducing HIV transmission and identify active drug-resistant transmission clusters through molecular transmission networks.MethodsThe first sectionNewly reported HIV infection patients in Fuyang City,Anhui Province in 2020-2021and patients who failed viral suppression with antiviral therapy in 2019-2020 as the research object,blood sample collection and epidemiological investigation were carried out on site,viral RNA was extracted,and the fragment of the pol gene region was amplified and sequenced by nested PCR.A phylogenetic tree of adjacency method was constructed,subtypes were determined and their epidemic characteristics analyzed.A gene distance from 0.5%was selected as the threshold to construct and visualize the molecular propagation network.The sequence of patients that failed HIV antiviral therapy in 2019-2020 in Fuyang City was combined with the sequence of newly reported HIV infected patients in 2020-2021,and the effect of antiviral therapy was analyzed by connection.Logistic regression is used to analyze the influencing factors of network entry and connection.The second sectionPre-treatment drug-resistant infections and acquired drug-resistant infections from2020-2021 and 2019-2020 in Fuyang City,Anhui Province were investigated and blood samples were collected.Viral RNA and pol gene regions were extracted and amplified and sequenced.The sequences were submitted to the drug resistance database of Stanford University in the United States,HIVDB system was used to judge the degree of drug resistance of drug-related mutations and combinations,and the relationship between genotype resistance mutations and ART drugs was analyzed online,and drug resistance transmission clusters were constructed.Molecular transmission network method was used to identify HIV resistant transmission clusters in Fuyang City and the network association with acquired and pre-treatment drug-resistant infections.The influencing factors of drug resistance were analyzed by logistic regression.ResultsThe first section1.From 2020 to 2021,there were 1049 newly reported HIV infections in Fuyang City,a total of 601 blood samples were collected,the sampling coverage rate was 57.3%,and a total of 589 pol gene region sequences were successfully amplified.The newly reported infections were mainly over 50 years old(40.7%,240/589),males(78.6%,463/589),primary school and illiterate education level(40.4%,238/589),married(47.5%,280/589),and heterosexual transmission(53.7%,316/589).The main subtypes were CRF07＿BC(205,34.8%),B(179,30.4%)and CRF01＿AE(132,22.4%).2.The molecular propagation networks of subtype B,CRF01＿AE and CRF07＿BC were constructed and visualized with 0.5%as the gene distance threshold.Among the516 sequences,a total of 172 sequences were networked,with a total network access rate of 33.3%(172/516).The network access rate was 41.3%(74/179)for subtype B from the highest to lowest,34.6%(71/205)for subtype CRF07＿BC and 20.5%(27/132)for CRF01＿AE subtype.The largest cluster of transmission of subtype B consisted of 16infected persons with a mean age of(67.3±8.2)years.The largest cluster of transmission of the CRF07＿BC subtype consisted of 15 infected persons with a mean age of(66.5±10.7)years,predominantly divorced,widowed,or single(60.0%).Among the clusters of 3 or more nodes in the CRF01＿AE subtype,MSM accounted for 54.5%.Among them,the transmission cluster formed by 4 single MSMs,the average age were(21.3±6.7)years,and all of them had high school education and above.In multivariate logistic regression analysis,the results showed that the age>50 years(compared with<30 years,a OR=2.419,95%CI:1.189～4.921),CRF07＿BC(compared with CRF01＿AE,a OR=1.875,95%CI:1.085～3.242),Subtype B(compared with CRF01＿AE,a OR=1.954,95%CI:1.086～3.513)and CD4~+cell count at 200～500 cells/μL(compared with<200/μL,a OR=2.155,95%CI:1.296～3.582),drug resistance(compared with non-resistant,a OR=5.142,95%CI:2.383～11.095)is easier to enter the network.3.500 patients that failed HIV antiviral therapy in Fuyang City were combined with589 newly reported HIV infections,shared in the molecular transmission network Fifty-five failed antiviral therapy were directly or indirectly linked to 83 newly reported infections.Multivariate logistic regression models.Results showed that married(compared to unmarried,a OR=0.265,95%CI:0.100～0.702),unmarried infected people are more likely to have a connection with newly reported infections.CRF07＿BC(compared with CRF01＿AE,a OR=24.478,95%CI:2.914～202.046),Subtype B(compared with CRF01＿AE,a OR=24.264,95%CI:2.542～154.793)and others subtype(compared with CRF01＿AE,a OR=15.797,95%CI:1.975～126.338),Discontinuation(compared with treatment,a OR=4.227,95%CI:1.904～9.385)is easier to connect with newly reported infected people.The second section1.In Fuyang City,Anhui Province,the pre-treatment drugs resistance rate of newly reported HIV infection was 8.7%(51/589)in 2020-2021.It was mainly subtype B,and the drug resistance rate was 3.6%(21/589).Secondly,CRF07＿BC drugs resistance rate was 3.1%(18/589).Drug resistance rates to NNRTI,PI and NRTI were 5.3%,3.1%and1.0%,respectively.The highest drug resistance rate of non-nucleoside drugs(NNRTIs)was NVP(4.2%),followed by EFV(4.0%),and the proportion of high drug resistance to EFV and NVP was higher.The multivariate logistic regression analysis showed that subtype B(compared to CRF01＿AE,a OR=3.910,95%CI:1.348～11.344)is more likely to develop drug resistance.The 13 drug resistance sequences in the B subtype network participated in 6 transmission clusters,of which 3 sequences with K20T formed a cluster,and 6 sequences with K103N were clustered in pairs.The 12 drug resistance sequences in the CRF07＿BC network participated in 5 transmission clusters,of which 1 was formed by 5 sequences,and the drug resistance mutations were all Q58E.2.In Fuyang City,Anhui Province,the acquired drug resistance rate of HIV antiviral therapy losers was 43.2%(216/500)during 2019-2020.It was mainly subtype B,and the drug resistance rate was 29.6%(146/500).Drug resistance rates to NNRTI,NRTI and PI were 41.2%,22.8%and 2.0%,respectively.The drug with the highest resistance rate of NNRTI was NVP(40.2%),followed by EFV(39.8%),EFV and NVP had higher rates of high drug resistance,the most common drug resistance mutations was K103N/KN/S(133,26.6%).The multivariate logistic regression analysis showed that mother-to-child transmission(compared with MSM,a OR=4.876,95%CI:1.133～20.974)is more likely to develop drug resistance,while CD4~+cell counts is 200～500/μL(compared with<200/μL,a OR=0.657,95%CI:0.441～0.979)is not easy to develop drug resistance.A total of 500 patients that failed to receive HIV antiviral therapy in Fuyang City were combined with 589 newly reported HIV infected persons.In the constructed molecular transmission network,there were 6 cases of HIV acquired drug-resistant infection and 4cases of HIV pre-treatment drug-resistant infection with direct or indirect transmission relationship.All were CRF07＿BC subtype and drug resistance mutations were K103N/KN.Conclusion1.In Fuyang City,Anhui Province,the newly reported HIV infection population is mainly older men over 50 years old with low education level,transmitted through heterosexual contact.The main subtypes were CRF07＿BC(205,34.8%),B(179,30.4%),and CRF01＿AE(132,22.4%).2.The PDR among newly reported infections in Fuyang City was 8.7%,a significant increase in 2019.The ADR was 43.2%in the losers of antiviral therapy.All were highly resistant to EFV and NVP,and the drug resistance mutations were mainly K103KN/N/NS in NNRTI.3.By constructing a molecular transmission network,the transmission characteristics of the main subtypes of HIV-1 were revealed from the population level,and the elderly population of low education level in local rural areas was effectively identified as key intervention objects.4.The construction of molecular transmission networks connecting losers of antiviral therapy with newly reported infected persons further confirmed that standardized antiviral therapy can reduce the risk of virus transmission and identify active drug-resistant transmission clusters. |
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