Comparison Of Naturally Occurring Antiviral Drug Resistance And Virological Characteristics In HIV Patients Who Are Mono-infected Or Co-infected With HBV Or HCV

Backgroud:An estimated 33 million people are infected with human immunodeficiency virus(HIV)worldwide.Since hepatitis B virus(HBV),hepatitis C virus(HCV)and HIV share the routes of transmission,5-20%and 4.5-25%of HIV-infected patients are co-infected with HBV and HCV,respectively.These diseases have become severe public health problems with serious disease burdens.Several studies have revealed that HIV patients co-infected with HBV or HCV have increased the risks of liver cirrhosis and hepatocellular carcinoma.Therefore,effective antiviral therapies are important for HIV mono-or co-infections with HBV or HCV.Drug resistance mutations(DRMs)occur in treatment-naive HBV,HCV and HIV mono-infected patients,however,the data on naturally occurring,pre-existing DRMs among co-infected patients are limited.In China,HBV and HCV infection prevalence is high.Accordingly,HIV/HBV and HIV/HCV co-infections are common;however,naturally occurring DRMs in HIV,HBV and HCV in co-infected patients have yet to be fully defined.Furthermore,DRMs may yield important information for clinician to choose antiviral drugs.HBV and HCV exists in the form as quasispecies within the host,at present,limited studies were focused on the change of HBV or HCV quasispecies diversity in HIV/HBV or HIV/HCV co-infected patients.Moreover,for HBV infected patients,the mutations of HBV BCP/preC gene are important factor related to the end stage liver diseases,however,the conclusion of HBV BCP mutations in HIV/HBV co-infected patients was vary drastically according to the literatures,so further studies are needed.AIM:1.To investigate DRMs prevalence in HIVmono-,HBV and HCV co-infected patients in China.2.To compare the HBV or HCV quasispecies diversity between HIV/HBV or HIV/HCV co-infected patients and HBV or HCV mono-infected patients;and to study the difference of HBV BCP/PC mutations in HIV/HBV co-infected and HBV mono-infected patients.Method:1.A total of 570 patients were recruited,487 patients whose potential DRMs regions were successfully amplified were included in four cohorts.(1)The HBV cohort comprised treatment-naive HIV/HBV co-infected and HBV mono-infected patients for HBV sequencing;(2)The HCV cohort comprised treatment-naive HIV/HCV co-infected and HCV mono-infected patients for HCV sequencing;and(3)The HIV cohort comprised treatment-naive HIV/HCV co-infected,HIV/HBV co-infected and HIV mono-infected patients for HIV sequencing.(4)HIV/HBV/HCV tri-infected cohort.Samples from the HBV and HCV cohorts were collected from 2012 to 2016,and samples from the HIV cohort were collected in 2017.2.Analyze and compare the HBV or HCV quasispecies diversity between HIV/HBV or HIV/HCV co-infected and HBV or HCV mono-infected patients.HBV S and preC/C and HCV NS5A gene were analyzed in this study.3.Compare the HBV BCP/preC gene mutations in HIV/HBV co-infeted and HBV mono-infected patinets.4.Investigate the orgin of HCV 3b in HIV/HCV co-infeted and HCV moon-infected patients in Guangdong province using Bayesian-MCMC Method.5.Analyze the HIV-1 URF AlC nearly full length genome which was found in a HIV/HBV/HCV tri-infected patient in this study.Results:1.HBV DRMs prevalence was significantly higher in patients co-infected with HIV/HBV than in those only infected with HBV.HCV DRMs did not significantly differ between HIV/HCV co-infected and HCV mono-infected patients with different genotypes.HIV DRMs did not significantly differ between HIV/HBV,HIV/HCV co-infected and HIV mono-infected patients.2.HBV preC/C and HCV NS5A quasispecies diversity were significantly lower in HIV/HBV or HIV/HCV co-infected than HBV or HCV mono-infected patients.3.The prevalence of HBV BCP/PC mutations was significantly lower in HIV/HBV co-infected than HBV mono-infected patients within the HBV C genotype and HBeAg(-)group.4.HCV 3b genotype in HIV/HCV co-infeted and HCV mono-infected patients in Guangdong province was originated from Yunnan province,China,moreover,a part of HCV 3b genotype in HIV/HCV co-infeted paitnets were originated from HCV mono-infected patients in Guangdong province.5.HIV-1 URF A1C was found in 1 case of HIV/HBV/HCV tri-infected patient,and we confirmed the existence of HIV-1 URF A1C in Guangdong province.Conlusion:1.The prevalence of HBV DRMs was significantly higher in HIV/HBV co-infected than HBV mono-infected patients,however,the prevalence of HCV and HIV DRMs did not differ between co-infected and mono-infected patients.2.HBV or HCV quasispecies diversity and the prevalence of HBV BCP mutations were lower in the patients who are co-infected with HIV.3.HCV 3b genotype in HIV/HCV co-infeted patients of Guangdong province was orginated from Yunnan province and HCV mono-infected patients in Guangdong province.4.HIV-1 URF A1C was found within a HIV/HBV/HCV tri-infected patient in Guangdong province.