Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level, to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level, to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level, From the Start:Optimizing First-Line Antiretroviral Therapy,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level, to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,#,Click to edit Master title style,#,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,按一下以編輯母片標題樣式,按一下以編輯母片,第二層,第三層,第四層,第五層,#,Click to edit Master title style,#,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,#,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,#,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,#,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,#,#,单击此处编辑母版标题样式,抗击hbv耐药hiv治疗和耐药的启示,抗击hbv耐药hiv治疗和耐药的启示,第1页,HIV,和,HBV,病毒学特点,HIV,HBV,单链,RNA,胞膜病毒,个别双链DNA胞膜病毒,依靠,逆转录酶,复制子代,RNA,依靠,逆转录酶,复制子代,DNA,蛋白激酶在病毒蛋白合成中饰演主要角色,主要感染淋巴细胞，也广泛存在其它组织中,主要感染肝细胞，也存在于其它组织中,病毒RNA逆转录成DNA整合到宿主CD4+T淋巴细胞基因组中长久存在,病毒DNA形成稳定cccDNA 甚至整合到宿主细胞DNA中长久存在,抗击hbv耐药hiv治疗和耐药的启示,第2页,HIV-1,复制周期,抗击hbv耐药hiv治疗和耐药的启示,第3页,HBsAg,被膜,个别双链,DNA,A(n),感染性,HBV,病毒颗粒,(-)-,DNA,感染性,HBV,病毒颗粒,mRNA,cccDNA,DNA,多聚酶,逆转录酶,被包裹前基因组,mRNA,Lai,et al.,J Med Virol,HBV,病毒复制周期,抗击hbv耐药hiv治疗和耐药的启示,第4页,HIV,和,HBV,在基因组结构,.,复制特征和感染有一定相同性,聚合酶,RT,区同源性高,尤其是与,dNTP,结合,7,个保守区域,(,包含,A-G,区,),同源性更高,二,.,具高复制能力,(HIV100,亿,/,天,HBV1000,亿,/,天,),1.,病毒多聚酶和单链,RNA,存在,多聚酶无校正功效,2.,高突变率（,10,5,碱基对,/,复制周期），所以以天天,10,10-12,病毒生成，每一个碱基对都有可能发生突变,一样,抗病毒治疗易产生耐药,3.,同一病人中病毒复杂基因型：准种,三,.,宿主免疫应答不良形成慢性感染,1.,相对平衡状态：高复制率和高去除率,2.HBV,和,HIV,连续保留在宿主细胞内：不能彻底去除或治愈,抗击hbv耐药hiv治疗和耐药的启示,第5页,抗,HIV,药品有各种类型，分别作用于不一样靶位点,NRTI,：核苷类逆转录酶抑制剂,(1987),PI,：蛋白激酶抑制剂,(1995),NNRTI,：非核苷类逆转录酶抑制剂,(1996),Entry inhibitor,：病毒黏附抑制剂,(),CCR5,受体阻断剂,整合酶抑制剂,抗击hbv耐药hiv治疗和耐药的启示,第6页,抗,HIV,药品作用靶位点及新同意药品,Maturevirus,Maraviroc,病毒黏附抑制剂,逆转录酶 抑制剂,Etravirine,整合酶抑制剂,Raltegravir,蛋白酶抑制剂,Darunavir Tipranavir,抗击hbv耐药hiv治疗和耐药的启示,第7页,87,91,92,94,95,96,97,98,99,00,88,89,90,01,02,03,93,05,04,06,ddC,3TC,NNRTI,NRTI,PI,Entry inhibitor,ddI,IDV,SQR,LPV/r,TDF,NVP,DRV,TPV,T-20,ZDV,d4T,ABC,DLV,EFV,FTC,RTV,NFV,ATV,FPV,07,MVC,当前共,23,种独特抗,HIV,药品被,FDA,同意上市,APV,抗击hbv耐药hiv治疗和耐药的启示,第8页,当前有抗,HIV,药品,Nucleoside Analogs,ddI,didanosine,VidexEC,ddC,zalcitabine,Hivid,AZT,zidovudine,Retrovir,d4T,stavudine,Zerit,3TC,lamivudine,Epivir,abacavir,Ziagen,FTC,emtricitabine,Emtriva,Nucleotide Analogs:,tenofovir,Viread,Non Nucleoside RT inhibitors,delavirdine,Rescriptor,nevirapine,Viramune,efavirenz,Sustiva,etravirine,Intelence,Protease Inhibitors,13.indinavir,Crixivan+/-r,14.saquinavir Invirase+r,15.ritonavir,Norvir,16.nelfinavir,Viracept,17.lopinavir+r,Kaletra,18.atazanavir,Reyataz+/-r,19.fos-amprenavir,Lexiva+/-r,20.tipranavir,Aptivus+r,21.darunavir,Prezista+r,Fusion Entry Inhibitors,22.enfuvirtide,Fuzeon,CCR5 Entry inhibitors,23.maraviroc,Selzentry,Integrase inhibitors,24.raltegravir,Isentress,抗击hbv耐药hiv治疗和耐药的启示,第9页,HIV,耐药,原发耐药：,ART,治疗前存在耐药株,1,.,ART,治疗前,其它治疗方案已选择出单药或多药耐药株,2.,耐药病毒株传输,因为抗,HIV,药品广泛使用，在发达国家已达,5%-20%,1-2,NRTI:5.5-12.4%,3,NNRTI:1.9-8.1%,3,PI:2.7-6.6%,3,继发耐药：治疗过程中因为药品选择性压力存在而筛选出来耐药。耐多药问题较常见。,Wheeler W,et al 14th conference on Retrovirueses and Opportunistic Infections Feb 25-28 Los Angeles,CA Abstract 648,SPREAD Programme,AIDS.;22(5):625-635,Martin S.et al Clinical Infectious Diseases,；,47:266-85,抗击hbv耐药hiv治疗和耐药的启示,第10页,Secondary versus Primary(Transmitted)Drug Resistance,Wild Type Virus,Drug Resistant Virus,Secondary,DR,Primary DR,Failing Therapy,WT,Rx,Rx,HIV+person not on treatment,抗击hbv耐药hiv治疗和耐药的启示,第11页,中国,HIV/AIDS,原发耐药,It,s as high as 15-27.8%among some high risk population,(FBD and IDU),抗击hbv耐药hiv治疗和耐药的启示,第12页,抗,HIV,药品治疗,起始,HIV,基因型耐药及药品敏感性分析,(,假如条件允许,),采取高效抗逆转录病毒,HAART,治疗,(,联合治疗,),联适用药方案,2 NRTIs,1 NNRTI,2 NRTIs,1 PI,1.Scott M.Hammer,et al JAMA Aug 6,Vol 300,No.5 555-570,抗击hbv耐药hiv治疗和耐药的启示,第13页,耐药检测方法,表型耐药（,Phenotyping,）,在不一样药品浓度下,(RT/PI),检测病毒复制能力。,基因耐药（,Genotyping,）,检测病毒,RT,和,PI,基因突变,抗击hbv耐药hiv治疗和耐药的启示,第14页,临床上耐药检测,Indications for use of resistance testing