| High-efficiency antiviral reverse transcription therapy(HAART)has been widely used clinically to significantly reduce the infection rate,morbidity and mortality of HIV-1.However,under the pressure of long-term drug selection,genetic mutations in the site of action of HIV-1 drugs have led to drug resistance,which has brought great challenges to the effective treatment of HIV-1.In recent years,the global population of HIV-1 drug resistance has been increasing year by year,and the WHO has called for global attention to HIV-1 drug resistance.Yunnan is located in the southwestern border of my country,adjacent to Southeast Asian countries,and has a border of 4,060 kilometers.Since the first discovery of HIV-1 in Dehong in 1989,Yunnan Province has been endangered by HIV-1.At present,the number of HIV-1 infections in my country is relatively high.One of the earliest provinces where AIDS patients were treated by HAART.Based on the special geographical location of Yunnan,with the trade exchanges and frequent population movements between Yunnan and Southeast Asian countries,the HIV-1 epidemic in Yunnan has shown rapid mutation speed,complex and diverse genotypes and recombination types.However,what is the proportion of pre-existing drug resistance among untreated HIV-1 patients in Yunnan in recent years? What is the correlation between the characteristics of drug resistance gene mutations and genotypes and recombination types? Lack of systematic and large sample research reports.Based on this,this paper aims at 1411 AIDS patients who have not been treated with HAART between 2017 and 2020,and studies the relationship between HIV-1 pre-existing drug resistance in this population and the relationship between drug resistance gene mutations and genotypes and recombination types.First,we randomly screened the blood samples of 1,411 untreated AIDS patients during the four years from 2017 to 2020.Nested PCR technology was used to amplify the PR and RT resistant areas of HIV-1.Among them,1319 cases were successfully amplified and sequenced,with a success rate of 93.5%.The proportion of pre-existing highly resistant mutations in this population was 2.34%(32 cases),and the resistance gene mutations were K103 N and G190 A.The corresponding drug resistance was the non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine,which produced high resistance.medicine.In addition,the proportion of non-highly resistant-related mutations was 19.1%,the related gene mutations were V179D/T/E,E138A/G and V106 I,and the corresponding drug resistance was the low-level effect of non-nucleoside reverse transcriptase inhibitor ripavirin.The above HIV-1pre-existing drug resistance ratio showed relatively stable and low prevalence characteristics during 2017-2020.Secondly,in order to further study the correlation between resistance mutations and genotypes,we analyzed the prevalence of HIV-1 genotypes and recombinant types in Yunnan from 2017 to 2020.The study found that CRF08＿BC accounted for40.3%,CRF01＿AE(21.7%),CRF07＿BC(12.3%),B(2.6%),C(1.4%),CRF55＿01B(0.45%),CRF62＿BC(0.15%)among 1319 HIV-1 infected persons.And URF(21%).URF is mainly based on the recombination of B and C subtypes(20.5%).From the analysis of annual changes,the proportion of CRF07＿BC showed a decrease from 41%to 20.5% year by year,CRF08＿BC increased from 20.9% to 35.7%,and URF increased from 14.9% to 44.9%.Further analysis of the characteristics of drug resistance mutations and the correlation between genotype and recombination showed that the proportion of pre-existing drug resistance in CRF08＿BC was 2.83%,and its drug resistance mutation gene was mainly K103N(1.32%),and the corresponding drug resistance was nevirapine.The drug resistance rate was 1.86%;CRF01＿AE had a pre-existing drug resistance rate of 2.81%,and its resistance mutation genes were mainly K103N(1.75%),and the corresponding drug resistance was nevirapine 2.81%and efavirenz 2.46%;CRF07＿BC was pre-existed The drug resistance rate was 1.86%,and its drug resistance mutation gene was mainly Y181C(1.24%),and the corresponding drug resistance was nevirapine 1.86%.Finally,based on the above-mentioned HIV-1 genotype and recombination studies in Yunnan,we found three groups of potential HIV-1 new epidemic recombination types(CRF).In order to further verify that these three sets of sequences are new CRFs.We performed phylogenetic tree analysis of HIV-1full-length sequence homology relationship,gene recombination pattern analysis,gene recombination site analysis,and subgene phylogenetic tree analysis based on recombined gene fragments on these samples.After the above analysis,these three groups of HIV-1 genomes conform to the naming rules of HIV-1 new recombinant types,and we named them CRF110＿BC,CRF118＿BC and a group of recombination patterns with C as the backbone inserting B fragments to be named.In order to further study the pre-existing drug resistance characteristics of these three new recombinant strains,we used Sanger sequencing to explore their pre-existing drug resistance.The results of the study found that CRF110＿BC has four mutations: M184V(34%)/N(66%),K103N(62%)/S(38%),G190A(71%),and P225H(98%).Mivudine,nevirapine and efavirenz are highly resistant.There are three resistance-related mutation sites in CRF118＿BC: M184 V,V106A,and V179 D.The mutations at these sites can affect emtricitabine(FTC),lamivudine(3TC),nevirapine(NVP)and efavirenz(EFV).)These four drugs are highly resistant.In the unnamed CRF,low-frequency pre-existing drug resistance gene mutations at E138A(6%)and S147G(6%)were detected by NGS,and the drug resistance was low-resistance to rilpivirin.In summary,this paper summarizes the pre-existing drug resistance rate of HIV-1 in Yunnan from 2017 to 2020,the characteristics of drug resistance gene mutations,and the correlation analysis of drug resistance,drug resistance gene mutations and genotypes and recombination types.In addition,we also discovered and named three new HIV-1 recombinant forms.This study provides important scientific data for the precise clinical treatment of AIDS patients in Yunnan,and has important scientific significance for my country’s AIDS treatment to reach the goal of "three 90%". |
PDF Full Text Request