| BackgroundAntiviral therapy(ART),as an effective intervention,can significantly reduce the death and transmission of HIV infection.With the comprehensive development of ART in China,the HIV drug resistance(HIVDR)rate gradually increases in the treated and untreated patients,which has become an important factor affecting the effectiveness of antiviral treatment.Liangshan Prefecture is an important drug trafficking corridor in western China.The local AIDS epidemic caused by injecting drug use,and then HIV transmitted and spread through sexual.In recent years,the monitoring results of Liangshan Prefecture in Sichuan province show the severe AIDS epidemic situation.There are a large number of migrant workers in Liangshan,and the floating population has become one of the important factors affecting the AIDS epidemic.However,the regional transmission source of newly diagnosed HIV infections is still unclear in Liangshan.The drug resistance rate of untreated population in Liangshan was at a medium epidemic level,and the rate of virologic failure and stopping ART was high,but the level of HIVDR was still unknown.The application of molecular epidemiology methods,such as molecular transmission networks,can help to understand the HIV epidemic better and guide prevention interventions.Through the integration of field epidemiological data and gene sequence data,molecular transmission network and Bayesian genetic system dynamics analysis in these new technologies and methods can be used to characterize HIV transmission,analyze and calculate the effect of community antiviral treatment on the reduction of HIV transmission and the second-generation transmission of HIV-infected persons.Object1.To analyze the distribution of regional transmission sources of newly diagnosed cases of HIV in Liangshan between 2018 and 2019,and to analyze the factors of infected HIV outside Liangshan.2.To describe the drug resistance of newly diagnosed cases of HIV,patients in virological failure and stopped ART in Liangshan,and analyze the factors associated with drugresistance.3.To identify the active transmission clusters and drug-resistant related transmission clusters that need precise intervention,to guide the precise prevention intervention in Liangshan.To evaluate the efficacy of treatment as an intervention to reduce second-generation transmission in Liangshan.MethodsThe first sectionA cross-sectional survey was conducted to collect samples and socio-demographic information of newly diagnosed cases of HIV between 2018 and 2019 in Liangshan.The sequence of HIV pol gene region was obtained by nucleic acid extraction and amplification sequencing.Bayesian analysis was performed on the sequence of newly diagnosed HIV infections between 2018 and 2019,and the MCC(Maximum clade credibility)tree was constructed to infer the regional transmission sources.Logistic regression was used to analyze the factors of regional transmission sources.The second sectionA cross-sectional survey was conducted to collect samples and socio-demographic information of patients in virological failure and stopped ART in Liangshan in 2018.The sequence of HIV pol gene region was obtained by nucleic acid extraction and amplification sequencing.The HIVDR of the three groups was detected through the Stanford Drug Resistance Database.Logistic regression was used to analyze the factors of drug resistance.The third sectionMolecular transmission network analysis was performed on newly diagnosed HIV infected persons between 2014 and 2019,to identify active transmission clusters and drug-resistant transmission clusters,and to analyze the factors of clustering in transmission network.In addition,transmission network analysis was carried out on newly diagnosed HIV infections between 2014 and 2019,patients in virological failure and stopped ART,and the effect of treatment on reducing second-generation transmission was evaluated.Based on the Bayesian analysis,the R0 of different subtypes and transmission clusters were calculated to evaluate the epidemic trend in Liangshan.ResultsThe first sectionOf 1325 cases newly diagnosed in Liangshan between 2018 and 2019,32 cases may got infected outside Liangshan,accounting for 2.4%.The transmission source regions outside Liangshan mainly included East China(9 cases),North China(9 cases)and South China(5 cases).In addition,3 cases came from Sichuan province(excluding Liangshan),Southwest China(excluding Sichuan province)and Northwest China,respectively.No HIV infection has been infected in Central China and Northeast China.The factors for infected outside Liangshan were 18～29 years old(OR=9.53,95%CI:1.09～83.27),senior high school or above(AOR=7.01,95%CI:1.81～27.1),Xichang city(AOR=3.41,95%CI:1.06～20.32),CRF08_BC(AOR=8.45,95%CI:2.45～29.0)and CRF 01_AE(AOR=5.74,95%CI:1.62～20.32).The second sectionThe drug resistance rate of newly diagnosed HIV infections in liangshan between 2014 and 2019 was 9.1%(225/2470).The drug resistance rate increased from 7.2%in 2014 to 10.8%in 2019,and showed an increasing trend with time(r=0.71,P<0.05).The multivariate logistic regression model showed that the factors significantly correlated with drug resistance were injection drug user(AOR=1.55,95%CI:1.14-2.10),CRF 08_BC(AOR=5.51,95%CI:3.00-10.13),Xichang city(AOR=2.55,95%CI:1.59-4.09),and diagnosed in 2018-2019(AOR=1.87,95%CI:1.08～3.25).The drug resistance rate was 37.5%(374/997)of patients in virological failure in ART.The multivariate logistic regression model showed that the factors significantly correlated with drug resistance were CD4<200/μl before treatment(AOR=2.45,95%CI:1.69-3.54)and treatment duration longer than 72 months(AOR=2.28,95%CI:1.62-3.20).Of the 256 patients stopping ART and viral load was detected,140(54.7%)had a viral load>1000 copies/ml.The proportion of viral load≥1000 copies/ml increased with the extension of discontinuation time(χ2=19.134,P=0.001).The drug resistance rate was 16.0%(33/206)in 206 patients who obtained the pol region sequence.The multivariate logistic regression model showed that the factors significantly correlated with drug resistance were unmarried(AOR=2.95,95%CI:1.16-7.52),the duration was shorter than 24 months after stopped ART(AOR=3.33,95%CI:1.43-7.69),and Zhaojue county(AOR=3.13,95%CI:1.31-7.50).The third sectionIn the molecular transmission network of newly diagnosed HIV infected persons between 2014 and 2019,55.4%of the clusters were spread across regions,and 71.0%were spread among people with different transmission routes.A total of 7 active transmission clusters and 6 drug-resistant related transmission clusters were identified.The factors significantly correlated with the internet access rate were male(AOR=1.22,95%CI:1.02～1.45),illiterate(AOR=2.13,95%CI:1.06～4.27),primary and junior high school education(AOR=2.42:95%CI:1..20-4.88),and HIV drug intolerance(AOR=1.88,95%CI:1.33～2.59).ART significantly reduced second-generation transmission by 42.0%(95%CI:2～66%)compared with untreated infected persons.At the same time,drug discontinuation and high viral load can weaken the effectiveness of treatment in reducing second-generation transmission.Undertreat with viral load<1000 copies/ml could reduce HIV transmission by 52%(95%CI:12-74%);There were no statistically significant differences between drug withdrawal,loss of follow-up,unknown,or undertreat with viral load≥1000 copies/ml with untreated patients in molecular network.R0 of CRF 07_BC,CRF 08_BC,CRF 01_AE,0708,01BC and BC subtypes in Liangshan between 2014 and 2019 were 2.17,1.83,1.81,1.56,2.10 and 1.21,respectively.In the CRF 07_BC,the R0 of heterosexual transmission population was 2.01,and R0 of injecting drug users was 1.96;In the CRF 08_BC subtype,R0 of heterosexual transmission population was 1.80,R0 of injecting drug users was 1.25;R0 of heterosexual transmission population in CRF 01_AE was 1.72.ConclusionIn 2018 and 2019,the transmission sources of newly diagnosed HIV infections were mainly in Liangshan.The groups with a high proportion from outside Liangshan were mainly in the young age group(18-29 years old),high educational level(senior high school or above),CRF 01_AE,CRF 08_BC and new diagnosed HIV infections in Xichang.The drug resistance rate of newly diagnosed HIV infections in Liangshan between 2014 and 2019 was 9.1%,and the drug resistance rate was increasing year by year.The drug resistance rate of patients in virological failure in 2018 was 37.5%,and the drug resistance rate of stopping ART in 2018 in Liangshan was 16.0%The molecular transmission network shows that the boundary between the transmission area and the population of HIV in Liangshan is blurring,and there are drug-resistant related transmission clusters and rapidly growing active transmission clusters that need close attention.Antiviral treatment in Liangshan reduced second-generation transmission by 42%.The R0 of HIV regeneration in Liangshan is greater than 1,indicating that the HIV epidemic in liangshan prefecture is still on the rise.The R0 of heterosexual transmission population was higher than injecting drug users. |
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