Study On Genotyping Drug-resistance Mutations In HIV/AIDS Patients With Antiviral Failure In Lincang City,Yunnan Province

Objective:To understand the main genetic mutation sites,the overall drug resistance and drug resistance trends of HIV/AIDS patients who failed antiviral therapy in Lincang city of Yunnan Province.At the same time,the main factors related to drug resistance in this area were analyzed,and the key areas and populations of HIV-1 drug resistance prevention and treatment were pointed out to provide a basis for guiding the implementation of local clinical anti-virus programs.Method:Using the In-House method,pol gene regions were amplified and sequenced in plasma samples of 1254 HIV/AIDS patients who failed antiviral therapy in Lincang area of Yunnan Province from 2011 to 2018.After the target sequence was determined and spliced by Contig Express,BioEdit and HIV BLAST software,it was submitted to the HIV resistance database(hivdb.stanford.edu)for online analysis.Statistical analysis was performed after determining the HIV-1 strain subtype,drug resistance mutation site and drug resistance levels of various drugs.Result:1.A total of 950 samples of HIV/AIDS patients with antiviral failure were successfully amplified in Lincang area from 2011 to 2018.Each year,45,66,77,89,112,157,198,206 samples were included in the test samples,of which the ratios of drug resistance were 24.4%,50.0%,48.1%,44.9%,65.2%,54.1%,57.1%,and 55.8%,respectively.The overall resistance rate in the eight years was 53.4%(507/950).2.The region is mainly young and middle-aged adults aged 30 to 50,accounting for64.8%(616/950)and males accounting for 57.3%(544/950).The ethnic group is dominated by the Han nationality,accounting for 63.6%(604/950).The main route of infection was sexually transmitted 77.3%(734/950).The anti-viral treatment program is dominated by the first-line program,accounting for 83.7%(795/950),and the main program is AZT+3TC+NVP/EFV,accounting for 51.4%.Antiviral treatment time is mostly 6 to 30 months,accounting for 43.5%(413/950).3.The drug resistance rate increased with age(?~2=28.452,P<0.001).The route of sexually transmitted infection is a risk factor for drug resistance(OR:0.64;95%CI:0.45-0.92).The highest rate of resistance was AZT+3TC+NVP accounting for 61.3%(152/248).The highest resistance rate for antiviral treatment for 42 months was 62.1%(87/140).And the drug resistance rate decreased with the increase of viral load(?~2=29.457,P<0.001).But,there were no significant differences in gender,ethnicity and gene subtype between drug resistance and non-resistance(P>0.05).4.The main HIV-1 drug-resistant drugs in each year are similar.The nucleosides mainly include 3TC,FTC and ABC,and the non-nucleoside drugs are mainly EFV and NVP.The resistance rate of non-nucleoside reverse transcriptase inhibitors(NNRTIs)was 49.9%(474/950),and the resistance rate of nucleoside reverse transcriptase inhibitors(NRTIs)was 32.0%(304/950).Protease inhibitors(PIs)have a lower resistance rate of 2.4%((23/950).The overall trend of drug resistance is mainly affected by NNRTIs-like drug resistance.The main mutation site for resistance to NNRTIs was K103N/S,accounting for 25.1%(238/950),followed by V179DTEF and E138AKGR,accounting for 20.3%(193/950)and 12.0%(114/950),respectively.The main resistance mutation site for NRTIs resistance was M184V,accounting for 29.3%(278/950),and there was a trend of increasing significantly year by year.The HIV-1 virus gene subtypes are mainly CRF08_BC,and the overall trend is relatively stable.Conclusion:The drug resistance of HIV/AIDS patients with antiviral failure in Lincang area of Yunnan Province is moderately prevalent.In recent years,the HIV-1 resistance rate in this area has been increasing year by year.Drug resistance occurs mainly in patients who receive first-line ART medication.Linxiang District and Gengma County are drug-resistant high-incidence counties(cities).Middle-aged and elderly patients were resistant to high-risk populations.In the case of limited medical resources,targeted publicity and education work should be carried out to actively monitor HIV-1 resistance in ART patients.At the same time,timely and rational adjustment of medication programs,standardize treatment and management,and prevent the spread of drug resistance.