Study On Primary Drug Resistance Mutations On Integrase Inhibitors Among Newly Diagnosed HIV-1 Infected Patients In Shenyang City

Objective:In order to achieve the UN’s 90-90-90 goals,the World Health Organization(WHO)in 2016 recommended that all HIV-infected people start antiretroviral treatment as soon as possible after diagnosis.Highly Active Antiroviral Therapy(HAART)is a method of combining three or more antiretroviral drugs to treat AIDS.It has significantly reduced the incidence of AIDS since it is widely used in HIV-infected patients.The death toll has also decreased accordingly.However,there are currently no drugs and methods to cure HIV infection,which means that patients must continue to receive antiviral therapy throughout their life.A meta-analysis of HIV / AIDS patients receiving antiretroviral drugs in different regions of China showed that for patients who have received antiretroviral therapy for a longer period of time,the risk of developing HIV resistance is relatively high.The development of resistance will increase the risk of virus rebound and opportunistic infection,and even lead to treatment failure.Therefore,early detection of drug resistance is of great significance in guiding clinical medication and avoiding treatment failure.Integrase inhibitors(InIs)is a new generation of antiretroviral drugs that play an antiviral role by blocking the integration of HIV-1’s double-stranded DNA into the host cell genome,as they often produce more complete virology suppressive effects are recommended as first-line antiviral drugs in US and European guidelines.Currently,the first-and second-line anti-HIV treatment programs in China do not include integrase inhibitors,and some HIV-infected patients use the drug at their own expense.Studies have reported that the genetic barrier to drug resistance in this class is low.One or two mutations can significantly reduce drug sensitivity,have cross-resistance,and drug resistance mutations have a certain relationship with viral genotypes.Therefore,early monitoring of the resistance of integrase inhibitors is of great significance in guiding clinical medication,timely changing treatment options,and improving survival rates.Studies in developed countries in Europe,the United States,the United Kingdom,and Canada show that resistance to integrase inhibitors is relatively rare at present,while there are few reports on the resistance of integrase inhibitors in China.This time,through the study of the resistance of untreated different genotypes of HIV-1 infected patients tointegrase inhibitors,to clarify the transmission of InIs resistant strains in newly diagnosed HIV-1 infected patients in Shenyang so as to provide a basis for clinical rational drug use.Methods : A retrospective collection of 80 newly diagnosed HIV-infected patients in Shenyang from June 2018 to March 2019,plasma samples were collected for HIV RNA extraction,and the integrase region 864bp(HXB2 4230-5096)was amplified using nested PCR The second round of amplification products were identified by agarose gel electrophoresis.The results of the gel imaging analysis system were used to observe the results.The second round of amplification products with positive fragments of interest were purified and sent to Beijing Nosay Genome Research Center Co.,Ltd.for Sanger sequencing.After the measured sequences are cleaned and spliced,genotype identification is performed.Construction of neighbor-Joining evolutionary tree and reorganization analysis.Conduct drug resistance mutation judgment and drug resistance related polymorphism judgment.Use SPSS20.0 software for statistical analysis.For continuous variables,mean description is used,and for categorical data,percentage is used for statistical description.X2 or Fisher test analysis was used to compare the frequency differences of amino acid natural polymorphisms at drug resistance-related sites of different subtypes.P <0.05 considered significant differences.Results:Among the 80 HIV-1 infected individuals,51,14 and 6 cases were genotyped as HIV CRF01＿AE,CRF07＿BC and subtype B,accounting for 63.8%,17.5% and 7.5%respectively.Nine cases(11.3%)were of classified as other HIV-1 recombinants.R263 K mutations were detected from two CRF01＿AE patients,and E138 A mutation was detected from a subtype B patient.The overal InIs drug resistance rate was 3.8%.CRF01＿AE infected individuals had amino acids polymorphisms at 50,74,119 and 153 on In Is resistance sites,with frequencies of 5.9%,2.0%,13.7% and 4.0%,respectively.The CRF07＿BC infected individuals had amino acids polymorphisms at 50,74 and 157 on InIs resistance sites,all with a frequency of 7.1%.Conclusion : The primary drug resistance rate of InIs among newly diagnosed HIV-infected people in Shenyang is still low.However,a small number of patients showed amino acid polymorphisms on In Is resistance sites.It is necessary to strengthenboth the monitoring of HIV In Is resistance and the researches on genotype and phenotype drug resistance study on non-B HIV-1 strains epidemic in China to better interpret the drug resistance mutations on InIs.