| Background and PurposeWith the popularity of antiretroviral therapy(ART)and the prolongation of treatment time,the problem of drug resistance of human immunodeficiency virus(HIV)has become increasingly prominent.HIV transmission network research helps to discover the characteristics of HIV-1 transmission and high-risk groups.As one of the cities with severe AIDS epidemic in Guangxi,Qinzhou city still lacks of systematic studies on pretreatment drug resistance and transmission molecular network of HIV-1 infected individuals.In this study,ART-naive HIV-1 infected individuals in Qinzhou city were recruited to carry out the investigation of pretreatment drug resistance and the research about HIV transmission network.The aims of this study are to identify the situation of drug resistance and the characteristics of HIV-1 transmission,high-risk communicators,and key transmission clusters of ART-naive HIV-1 infected patients in Qinzhou City,and provide scientific evidence for Center for Disease Prevention and Control(CDC)workers and clinicians to carry out AIDS prevention activities,optimize treatment programs and precise interventions,and reduce the production of drug-resistant strains and the rate of new AIDS infections.MethodsFrom 2017 to 2018,we recruited 518 ART-naive people living with HIV-1/AIDS(PLWHA)from county-level or municipal CDC and hospitals in Qinzhou city by using convenient sampling methods.A questionnaire survey was conducted to collect demographic and behavioral information of the enrolled subjects.Meanwhile,peripheral venous blood was collected from PLWHA.Plasma and blood cells were separated,and stored at-80℃.HIV RNA was extracted from plasma,and nested reverse transcription polymerase chain reaction(RT-PCR)was used to amplify HIV-1 pol gene region which contains protease and reverse transcriptase regions.The successfully amplified products were sent to biotechnological company for sequencing.The HIV-1 pol sequences were uploaded to the Stanford University HIV drug resistance database(https://hivdb.stanford.edu/)for genotype resistance analysis,and a phylogenetic tree was constructed with MEGA software to determine the HIV-1subtype.HIV transmission network with sequences genetic distance(GD)less than 1.5% was constructed with Cytoscape software.Maxim HIV-1 Limiting Antigen Avidity EIA kit was used to detect whether the HIV-1 infected person is newly infected(infected with HIV-1 <6 months).Finally,Multivariate logistic regression was used to explore the influence factors of drug resistance,in-network(clustering),large clusters(sequence or node ≥10)and high connectivity(edge or degree ≥ 5)in the network.Results1.Demographic characteristics and HIV-1 subtypes: In this study,a total of 485 HIV-1 pol gene region sequences were obtained from ART-naive HIV-1-infected patients.The majority transmission route of the participants was heterosexual transmission(80.0%),followed by injection drug use(17.3%).The sampling sites include urban areas(53.0%),Lingshan County(36.3%)and Pubei County(10.7%).HIV-1 subtypes were mainly CRF01＿AE(53.0%),CRF08＿BC(33.4%),and CRF07＿BC(10.1%).In addition,there were a few URF,B subtype,C subtype and G subtype.2.Analysis of drug resistance: Among 485 ART-naive PLWHAs,the prevalence of pre-treatment drug resistance(PDR)was 9.9%,transmitted drug resistance(TDR)was 2.3%,and potential low-level resistance was 6.4%.All patients with PDR were one single drug resistance,including resistance to protease inhibitors(PIs),nucleoside reverse transcriptase inhibitors(NRTIs),non-nucleoside reverse transcriptase inhibitors(NNRTIs).The drug resistance rates of PIs,NRTIs,and NNRTIs were 2.1%,1.2%,and 6.6%,respectively.Among the patients with PDR,49.6%(19/48)were resistant to 2 or more drugs of the same type antiviral drug,while 60.4%(29/48)patients were resistant to only one drug.The proportion of low-level resistance accounted for 72.9%,intermediate-resistance for 18.8%,and high-level resistance for 8.3%.Of intermediate-and high-level resistance patients,69% were resistant to two or more antiretroviral drugs.Among the mutations that cause drug resistance,PIs mutations were dominated by Q58E(54.6%)and M46I/MI(27.3%),NRTIs mutations were dominated by V215(83.3%),NNRTIs mutations were dominated by V106(40.0%)and E138(28.6%).3.Analysis of high-risk communicator: There are 218 sequences have a GD less than 1.5% among 485 sequences.The rate of in-network was 44.9%,forming 52 molecular netwoks containing more two or more sequences.CRF01＿AE,CRF08＿BC,CRF07＿BC and URF clusters accounted for 59.6%,28.8%,7.7% and 3.8%,respectively.There were 56 patients with a connection degree ≥5,of which 14 were high-risk communicators.Those high-risk communicators were mainly characterized by age ≥50-year-old(64.3%),duration of diagnosis ≤1 year(64.3%),and sampling from urban of Qinzhou(78.6%).42.9%(6/14)of high-risk communicators had high-risk behaviors(including commercial/temporary sexual behaviors and sharing syringes).4.Analysis of active networks: 11.5% of the transmission networks are newly infected.There are 6 active propagation clusters,including 20 nodes..Among them,one network contained 7 newly infected persons,all of which were from urban areas and were ≥50 years old or older,and each of the remaining 5 networks has only one newly infected individual.In the active transmission cluster,the age were mainly ≥50 years old,accounting for 80.0%,and the sampling area were mainly from urban,accounting for 65.0%.In addition,25% and 15% of individuals have commercial and casual sex behavior in the past year,respectively.5.Analysis of dynamically expanding transmission network: There were 5 large clusters(nodes ≥10)and 1 active molecular network which were dynamically expanding clusters,that is progress clusters.Among them,the largest and oldest cluster individuals were characterized by younger than50-year-old(82.1%),derived from Lingshan(82.1%),male(96.4%),self-reported infected through injection drug use(IDU,67.9%),and diagnosed more than 4 years(57.1%);The characteristics of the other 5 networks’ members were aged ≥50 years(67.1%),came from urban(67.1%),male(65.7%),self-reported through heterosexual sex infection(92.9%)and diagnosis time ≤ 1 year(81.4%).6.Multivariate logistic regression: ART-naive PLWHA who were <50years old were more likely to produce PDR(OR=2.421,95%CI: 1.131～5.181);PDR patients were less likely to be in-network(OR=0.483,95%CI :0.245～0.951).However,patients with ≥50 years old were more likely to be in-network(OR=1.922,95%CI : 1.312～ 2.816).PLWHA who came from Lingshan were more likely to gather in large cluster(OR=1.864,95%CI:1.034～3.362);while HIV-1 infected individuals with a connection degree more than 5 in the transmission network were more likely from the urban area(OR=2.157,95%CI:1.083～4.295).Conclusion1.The subtypes of HIV-1 in Qinzhou city were mainly CRF01＿AE and CRF08＿BC,with unknown recombinant subtypes appearing.2.There was a low prevalence of transmission drug resistance(TDR)among HIV-1 infected persons in Qinzhou city;pretreatment drug resistance(PDR)was dominated by moderate prevalence,mainly in low-and single-drug resistance.And patients who with intermediate-and high-level resistance were mainly resistant to 2 or more drugs of the same type of antiviral drug.Furthermore,one risk factor of PDR was age <50 years.2.In recent years,although the proportion of individuals infected with HIV-1 by IDU has dropped significantly,the percentage of sexually transmitted infections has increased significantly.3.In terms of AIDS prevention and control,Qinzhou city could focus on people with high-risk behavior history,living in the urban area,older than 50 years old,newly reported,and off-farm occupations. |
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