Analysis On The Pretreatment Drug Resistance And Transmission Characteristics Of Newly Reported HIV Infected Individuals In City A And City B Of Guangxi

Background and objective:The widespread use of antiretroviral therapy(ART)has made acquired immune deficiency syndrome(AIDS)a treatable and manageable chronic disease,but the resulting problem of HIV drug resistance puts the antiretroviral drugs at risk of failure,and even the development of HIV drug-resistant strains.Pretreatment drug resistance(PDR),recommended by the World Health Organization(WHO),has great value in guiding the targeted ART regimen.In this study,the characteristics,network connectivity,trends and related transmission factors of PDR and drug resistance mutations(DRMs)for HIV strains prevalent in City A and City B,which were located along the border or coastal areas with high incidence of HIV/AIDS,and mainly involved in injecting drug abuse in the early stage of the epidemic,were analyzed based on molecular network,aiming to provide ideas for local targeted HIV interventions.Methods:Cross-sectional molecular epidemiological investigations were conducted in City A and City B of Guangxi to recruit newly reported HIV infected individuals during 2018 to 2019.Demographic and behavioral information of the subjects were obtained through questionnaire survey.Peripheral venous blood samples were collected for viral RNA extraction,amplification of reverse transcriptase region and protease region(PR-RT)of HIV gene sequence.The positive amplified samples were sent for sequencing.Also,pol sequences of newly reported HIV infected individuals from January 1,2015 to August 31,2018 were selected from the laboratory HIV sequence database and included in this study.The obtained pol sequences were subtyped and screened for drug resistance,and characteristics such as the prevalence and trends of PDR and DRMs were analyzed.The transmission characteristics of PDR and DRMs were analyzed based on molecular networks.Logistic regression model was used to investigate the related factors of clustering,transmission of shared DRMs and PDR.Results:1.Source and basic characteristics of the research subjectsA total of 1025 HIV infected individuals were recruited and HIV gene pol sequences were obtained one by one,of which 603 sequences were obtained from investigation and 422 sequences were selected from the laboratory HIV sequence database.Among the participants,674 were from City A and 351 were from City B,with an average age of(46±14)years old,and were mainly male,Han ethnicity,married,with junior high school education level or below,farmers,infected through heterosexual transmission.2.Characteristics of the subtype distributionThere were 10 HIV subtypes prevalent in City A and City B of Guangxi,and CRF08＿BC(45.0%)and CRF01＿AE(40.9%)subtypes were the main subtypes.CRF01＿AE subtype was prevalent in City A while CRF08＿BC subtype was prevalent in City B(P=0.006).Statistically differences of HIV subtype distribution were found in sampling city,sampling year,age,gender,marital status,educational level,infection route and CD4+ cell count(P<0.05).3.Prevalence of DRMs and PDRThe prevalence of DRMs among newly reported HIV infected individuals in Guangxi was 21.1%,which was dominated by NNRTIs related.NRTIs and PIsrelated mutations showed a downward trend(P for trend<0.05).The prevalence of PDR was 8.3%,which was at a moderate level and also dominated by NNRTIs related.The overall PDR prevalence and PIs related resistance showed a downward trend(P for trend<0.05).CRF08＿BC was associated with higher prevalence of DRMs(P<0.001)and PDR(P=0.044).4.Characteristics of the molecular networkThe optimal genetic distance threshold of the molecular network was 1.5%.543 infected individuals were included within the network and formed 111 molecular transmission clusters consisting of 2 to 143 individuals,with a clustering prevalence of 53.0%.The elderly individuals aged >50 years old were associated with clustering(P=0.001),and they were at the central of the molecular network(P<0.05).HIV Infected individuals aged 31-40 years old,farmer,injecting drug use,CRF08＿BC and CRF07＿BC subtypes were more likely to form large transmission clusters(P<0.05).Those infected by injection drug use were more connected within the network(P<0.05).5.Characteristics of PDR and shared DRM within the molecular network The prevalence of PDR and shared DRM within the network were 6.8% and9.8%,respectively.Shared DRM was most common in V179E/D and V106 I.The overall PDR prevalence showed a downward trend within the network(P for trend=0.005),while the prevalence of shared DRM showed an increasing trend(P for trend=0.027).CRF08＿BC subtype was more prone to PDR(P=0.007)and shared DRMs(P<0.001)within the molecular network.6.PDR and DRMs transmission within networks of three major subtypes The optimal genetic distance thresholds of CRF01＿AE,CRF08＿BC and CRF07＿BC subtype molecular networks were 1.6%,1.2% and 1.4%,respectively,with clustering prevalence of 57.8%,43.6% and 40.7%,respectively.The infection routes were all mainly heterosexual transmission.The prevalence of PDR and shared DRM were 2.5%,11.4%,2.7% and 3.7%,15.9%,0% for CRF01＿AE,CRF08＿BC and CRF07＿BC subtype,respectively.CRF08＿BC subtype was associated with higher prevalence of PDR and shared DRM,resulting in more frequent and larger shared DRM related clusters.Conclusions:1.There are subtype diversity among newly reported HIV infected individuals in City A and City B.The elderly infected individuals >50 years old are more likely to cluster and occupy important positions within network,resulting in a higher risk of HIV transmission.Therefore,the surveillance of HIV and intervention in the elderly population in this area should be strengthened.2.The prevalence of PDR in City A and City B is at a moderate level,and shows a downward trend.However,the prevalence of shared DRM is increasing with time.The independent clusters of drug-resistant individuals in the network should be intervened as soon as possible to optimize and adjust the ART regimen,and to prevent the spread of HIV drug-resistant strains.3.CRF08＿BC subtype has a higher risk of PDR and shared DRM transmission,resulting in more frequent and larger shared DRM related clusters.Therefore,routine PDR surveillance of CRF08＿BC subtype should be strengthened.