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1、HIV的自然病史和ARV治疗的管理Caroline Teter，PA-C，MPHProject HOPE1Natural-History-of-HIV-and-Early-Indentification-(CH)解读简介正常免疫系统HIV的自然病史2Natural-History-of-HIV-and-Early-Indentification-(CH)解读正常免疫系统通过识别入侵细菌或病毒的抗原并对其产生反应而保护机体由淋巴器官和组织组成骨髓胸腺淋巴结脾扁桃腺Adenoids腺体阑尾血液淋巴管所有的组成部分对于淋巴细胞和白细胞的生成和发育是非常重要的3Natural-History-of-H
2、IV-and-Early-Indentification-(CH)解读B细胞和T细胞两者都来源于骨髓中的干细胞B-细胞在骨髓中成熟T-细胞离开骨髓，在胸腺中成熟4Natural-History-of-HIV-and-Early-Indentification-(CH)解读B细胞和T细胞(2)B-细胞可以识别特定的靶抗原并分泌特定的抗体来包被抗原，使他们更容易受到噬菌作用的影响或通过激发补体系统进行攻击T-细胞调节免疫系统并杀死具有特定靶抗原的细胞每个T-细胞都有一个表面标记物，如CD4，CD8和CD3以使其区别于其他细胞CD4细胞是辅助细胞，当存在特定的抗原时，它可以激活B-细胞，杀伤细胞(C
3、D8)和巨噬细胞5Natural-History-of-HIV-and-Early-Indentification-(CH)解读噬菌细胞噬菌细胞包括单核细胞和巨噬细胞大型的白细胞可以吞噬和消化携带特定微粒的细胞补体系统由25种蛋白构成，当它和抗体一起作用时，它能够产生一种炎性反应以促进噬菌作用或减弱细菌的细胞膜6Natural-History-of-HIV-and-Early-Indentification-(CH)解读HIV的自然病史7Natural-History-of-HIV-and-Early-Indentification-(CH)解读人类免疫缺陷病毒它是一种逆转录病毒利用它自身的R
4、NA 和宿主的DNA来合成病毒DNA它有比较长的潜伏期它由圆柱形的中心构成，外面包裹着球状的脂质包膜中心由两条单核糖核苷链（RNA）构成8Natural-History-of-HIV-and-Early-Indentification-(CH)解读HIV生命周期的五个阶段结合和进入逆转录复制发育成熟9Natural-History-of-HIV-and-Early-Indentification-(CH)解读人类免疫缺陷病毒引起免疫系统的严重损伤并最终摧毁整个免疫系统利用CD4淋巴细胞的DNA进行病毒复制在这个过程种，病毒将摧毁CD4淋巴细胞10Natural-History-of-HIV-a
5、nd-Early-Indentification-(CH)解读HIV生命周期感染HIV的宿主细胞只有很短的寿命HIV会不断地利用新的宿主细胞进行自身的病毒复制每天可以产生大约一千万个病毒11Natural-History-of-HIV-and-Early-Indentification-(CH)解读HIV的生命周期http:/www.hopkins-aids.edu/hiv_lifecycle/hivcycle_txt.htmlhttp:/www.roche- 病毒载量35Natural-History-of-HIV-and-Early-Indentification-(CH)解读后果1CD4
6、 = distance to the cliffCD4 =到悬崖到悬崖 距离距离病毒载量病毒载量 = speed of the truck病毒载量病毒载量= 车速HIV象一辆加速驶向悬崖的卡车象一辆加速驶向悬崖的卡车36Natural-History-of-HIV-and-Early-Indentification-(CH)解读CD4细胞计数是HIV疾病进展的主要的代表标记物正常值范围为350到1100/mm3如果不接受治疗，平均每年下降50-100/mm3在不同的患者或同一个患者长时间内变异比较大并发疾病可以短暂影响它的数目比较不同实验室的测定数据时必须非常谨慎用途确定是否需要进行抗i逆转录
7、病毒治疗，并进行监测确定发生机会性感染的风险和抗菌预防性用药的需求评估预后37Natural-History-of-HIV-and-Early-Indentification-(CH)解读HIV病毒载量测量技术通过PCR检测血浆中的病毒RNA枝状的(bDNA)技术较长时间内应使用相同的测定方法，因为PCR的结果可以高到bDNA结果的两倍超灵敏PCR测定方法的极差为100，000copies/ml高病毒载量与低CD4计数和临床疾病进展相关正常的变异范围为0.3对数值(3-5倍)并发疾病和免疫接种可以短期影响数值和CD4细胞计数一起使用以确定抗逆转录病毒治疗的需要和监测和对预后的评估38Natur
8、al-History-of-HIV-and-Early-Indentification-(CH)解读没有进行抗逆转录病毒治疗的情况下，HIV的自然病史CD4 + T 淋巴细胞淋巴细胞 计数计数 (细胞细胞/mmm3)CD4细胞数细胞数Source: Fauci， A.， Pantaleo， D.， Stanley S.， Weismann， D. Annals of Internal 药物药物 124: 6754-3， 1996周周年年CD4 + T 淋巴细胞淋巴细胞 计数计数 (细胞细胞/mmm3)0 3 6 9 121 2 3 4 5 6 7 8 9 10 1112001100100090
9、0800700600500400300200100039Natural-History-of-HIV-and-Early-Indentification-(CH)解读在每毫升血浆中在每毫升血浆中HIV/RNA拷贝数拷贝数血浆血浆HIV/RNA未用ART的HIV感染的自然病史Source: Fauci， A.， Pantaleo， D.， Stanley S.， Weismann， D. Annals of Internal 药物药物 124: 6754-3， 1996周周年年在每毫升血浆中在每毫升血浆中HIV/RNA拷贝数拷贝数1071061051041031020 3 6 9 121 2 3
10、 4 5 6 7 8 9 10 1140Natural-History-of-HIV-and-Early-Indentification-(CH)解读HIV自然病史Source: Fauci， A.， Pantaleo， D.， Stanley S.， Weismann， D. Annals of Internal 药物药物 124: 6754-3， 1996周周年年CD4+T淋巴细胞数淋巴细胞数(/mmm3)HIV/RNA拷贝数拷贝数/ml血浆血浆1071061051041031020 3 6 9 121 2 3 4 5 6 7 8 9 10 111200110010009008007006
11、005004003002001000原发感染原发感染急性急性HIV综合征综合征病毒播散病毒播散淋巴器官种植淋巴器官种植临床潜伏期临床潜伏期自身症状自身症状机会性感染机会性感染死亡死亡41Natural-History-of-HIV-and-Early-Indentification-(CH)解读未治疗的HIV感染的自然病史年年InfectionCD4Cells10008006004002000中期免疫建立症状中期免疫建立症状晚期机会性感染晚期机会性感染+1234567891011 1213 14早期免疫抑制早期免疫抑制AIDS42Natural-History-of-HIV-and-Early
12、-Indentification-(CH)解读机会性感染和时间的联系带状疱疹结核病口腔念珠菌感染PCP食道念珠菌感染黏膜皮肤疱疹弓形体脑病隐球菌病球孢子菌病MAC巨细胞病毒隐孢子球菌病多发性脑白质白斑病43Natural-History-of-HIV-and-Early-Indentification-(CH)解读HIV感染的分期记住在每个阶段，HIV都具有传染性!血清转化血清转化HIV感染抗体产生无症状期无症状期没有HIV的症状免疫系统控制病毒复制有症状期有症状期HIV感染的生理征兆感染的生理征兆一些免疫抑制的表现艾滋病期艾滋病期机会性感染终末期的疾病44Natural-History-of
13、-HIV-and-Early-Indentification-(CH)解读HIV皮疹癣牛皮癣脂溢性皮炎大疱性脓疱病细菌性毛囊炎花斑癣疣传染性软疣带状疱疹单纯疱疹获得性鱼鳞癣丘疹/毛囊性疹口腔念珠菌毛状黏膜白斑卡波氏肉瘤挪威疥疮机会性感染早期中期晚期45Natural-History-of-HIV-and-Early-Indentification-(CH)解读疾病进展的分期早期免疫损耗CD4细胞计数500/L在这个时期，血液中病毒的水平非常低HIV主要在淋巴结内复制通常持续5年或更长时间不伴有其他症状的持续性全身性淋巴结病值得重视通常没有症状，但是可以发生一些自体免疫的紊乱，如:先天性血小板减
14、少症(ITP)Guillain-Barre综合症46Natural-History-of-HIV-and-Early-Indentification-(CH)解读腋窝腹股沟颈部肿大淋巴结出现的三个部位47Natural-History-of-HIV-and-Early-Indentification-(CH)解读颈部淋巴结肿大48Natural-History-of-HIV-and-Early-Indentification-(CH)解读疾病进展的分期中期的免疫损耗CD4细胞计数在500和200/L之间免疫缺陷增加感染发生，持续或增加，因为CD4细胞计数下降开始ARV治疗和机会性感染的预防性用
15、药出现不是很严重的感染，尤其是皮肤病藓软疣contagiosum皮炎Seborrheicdermatitis细菌性毛囊炎疣齿龈炎开始出现其他感染在这个阶段的晚期出现口部念珠菌病可以发生带状疱疹和单纯疱疹再活化.在这个阶段的相当早的时候发生结核分枝杆菌感染慢性窦炎49Natural-History-of-HIV-and-Early-Indentification-(CH)解读HIV皮疹癣牛皮癣脂溢性皮炎大疱性脓疱病细菌性毛囊炎花斑癣疣传染性软疣带状疱疹单纯疱疹获得性鱼鳞癣丘疹/毛囊性疹口腔念珠菌毛状黏膜白斑卡波氏肉瘤挪威疥疮机会性感染早期中期晚期50Natural-History-of-HIV-
16、and-Early-Indentification-(CH)解读灰指甲Onychomycosis51Natural-History-of-HIV-and-Early-Indentification-(CH)解读灰指甲Onychomycosis52Natural-History-of-HIV-and-Early-Indentification-(CH)解读53Natural-History-of-HIV-and-Early-Indentification-(CH)解读54Natural-History-of-HIV-and-Early-Indentification-(CH)解读头癣Porrig
17、o55Natural-History-of-HIV-and-Early-Indentification-(CH)解读癣Tinea56Natural-History-of-HIV-and-Early-Indentification-(CH)解读花斑糠疹Pityriasisversicolor57Natural-History-of-HIV-and-Early-Indentification-(CH)解读癣Tinea58Natural-History-of-HIV-and-Early-Indentification-(CH)解读癣Tinea59Natural-History-of-HIV-and-
18、Early-Indentification-(CH)解读传染性软疣Molluscumcontagiosum60Natural-History-of-HIV-and-Early-Indentification-(CH)解读传染性软疣Molluscumcontagiosum61Natural-History-of-HIV-and-Early-Indentification-(CH)解读脂溢性皮炎Seborrhoeicdermatitis62Natural-History-of-HIV-and-Early-Indentification-(CH)解读脂溢性皮炎Seborrhoeicdermatiti
19、s63Natural-History-of-HIV-and-Early-Indentification-(CH)解读脂溢性皮炎Seborrhoeicdermatitis64Natural-History-of-HIV-and-Early-Indentification-(CH)解读银屑病Psoriasis65Natural-History-of-HIV-and-Early-Indentification-(CH)解读脓疱性银屑病Pustularpsoriasis66Natural-History-of-HIV-and-Early-Indentification-(CH)解读毛囊炎Follicu
20、litis67Natural-History-of-HIV-and-Early-Indentification-(CH)解读脂溢性皮炎Seborrhoeicdermatitis68Natural-History-of-HIV-and-Early-Indentification-(CH)解读毛囊炎Folliculitis69Natural-History-of-HIV-and-Early-Indentification-(CH)解读毛囊炎Folliculitis70Natural-History-of-HIV-and-Early-Indentification-(CH)解读疣Wart71Natu
21、ral-History-of-HIV-and-Early-Indentification-(CH)解读疣Wart72Natural-History-of-HIV-and-Early-Indentification-(CH)解读疣Wart73Natural-History-of-HIV-and-Early-Indentification-(CH)解读疣Wart74Natural-History-of-HIV-and-Early-Indentification-(CH)解读尖锐湿疣Pointcondyloma75Natural-History-of-HIV-and-Early-Indentific
22、ation-(CH)解读齿龈炎Gingivitis76Natural-History-of-HIV-and-Early-Indentification-(CH)解读齿龈炎Gingivitis77Natural-History-of-HIV-and-Early-Indentification-(CH)解读疱疹Herpes78Natural-History-of-HIV-and-Early-Indentification-(CH)解读疱疹Herpes79Natural-History-of-HIV-and-Early-Indentification-(CH)解读疱疹Herpes80Natural-
23、History-of-HIV-and-Early-Indentification-(CH)解读疱疹Herpes81Natural-History-of-HIV-and-Early-Indentification-(CH)解读带状疱疹Herpeszoster82Natural-History-of-HIV-and-Early-Indentification-(CH)解读带状疱疹Herpeszoster83Natural-History-of-HIV-and-Early-Indentification-(CH)解读带状疱疹Herpeszoster84Natural-History-of-HIV-a
24、nd-Early-Indentification-(CH)解读带状疱疹Herpeszoster85Natural-History-of-HIV-and-Early-Indentification-(CH)解读鹅口疮Thrush86Natural-History-of-HIV-and-Early-Indentification-(CH)解读鹅口疮Thrush87Natural-History-of-HIV-and-Early-Indentification-(CH)解读鹅口疮Thrush88Natural-History-of-HIV-and-Early-Indentification-(CH)
25、解读毛状白斑HairyLeukoplakia89Natural-History-of-HIV-and-Early-Indentification-(CH)解读毛状白斑HairyLeukoplakia90Natural-History-of-HIV-and-Early-Indentification-(CH)解读毛状白斑HairyLeukoplakia91Natural-History-of-HIV-and-Early-Indentification-(CH)解读肺结核PulmonaryTuberculosis92Natural-History-of-HIV-and-Early-Indentif
26、ication-(CH)解读肺结核PulmonaryTuberculosis93Natural-History-of-HIV-and-Early-Indentification-(CH)解读肺结核PulmonaryTuberculosis94Natural-History-of-HIV-and-Early-Indentification-(CH)解读疾病进展的分期晚期的免疫损耗CD4细胞计数200/L艾滋病诊断更多严重的机会性感染95Natural-History-of-HIV-and-Early-Indentification-(CH)解读HIV自然病史Source: Fauci， A.，
27、Pantaleo， D.， Stanley S.， Weismann， D. Annals of Internal 药物药物 124: 6754-3， 1996周周年年CD4+T淋巴细胞数淋巴细胞数(/mmm3)HIV/RNA拷贝数拷贝数/ml血浆血浆1071061051041031020 3 6 9 121 2 3 4 5 6 7 8 9 10 111200110010009008007006005004003002001000原发感染原发感染急性急性HIV综合征综合征病毒播散病毒播散淋巴器官种植淋巴器官种植临床潜伏期临床潜伏期自身症状自身症状机会性感染机会性感染死亡死亡96Natural-
28、History-of-HIV-and-Early-Indentification-(CH)解读AIDS-更多严重的机会性感染头头弓形体病(Toxo)Cryptococcal meningitis眼眼巨细胞病毒 (CMV)口腔和咽喉口腔和咽喉念珠菌病 (酵母菌)肺肺卡氏肺孢子虫肺炎 (PCP)结核 (TB)组织胞浆菌病内脏内脏巨细胞病毒 (CMV)Cryptosporidiosis禽分枝杆菌复合体 (MAC)皮肤皮肤单纯疱疹带状疱疹生殖器生殖器生殖器疱疹人乳头瘤病毒 (HPV)阴道念珠菌病(酵母菌)97Natural-History-of-HIV-and-Early-Indentificatio
29、n-(CH)解读98Natural-History-of-HIV-and-Early-Indentification-(CH)解读典型的弓形体脑炎表现为“环状增强”损害99Natural-History-of-HIV-and-Early-Indentification-(CH)解读100Natural-History-of-HIV-and-Early-Indentification-(CH)解读101Natural-History-of-HIV-and-Early-Indentification-(CH)解读0 01001001001002002002002003003003003004004
30、004004005005005005006006006006007007007007008008008008009009009009001000100010001000 0 1 2 3 4 5 1 2 3 4 5 6 7 8 9 10 11CD4+ 细胞细胞 计数计数无症状期无症状期无症状期无症状期带状疱疹病毒带状疱疹病毒口腔毛发样粘膜白斑口腔毛发样粘膜白斑口部念珠菌病口部念珠菌病PCPPCPCrypto. Crypto. 脑膜炎脑膜炎CMVCMV， MACMACTBTBTBTB月月年年急性急性 HIVHIV感染期感染期血浆中HIV-RNA的相对水平CD4+ T 细胞细胞VLHIV感染的自然病
31、史和常见的并发症及机会性感染卡波济肉瘤卡波济肉瘤弓形体病弓形体病血小板减少症血小板减少症淋巴结病淋巴结病102Natural-History-of-HIV-and-Early-Indentification-(CH)解读103Natural-History-of-HIV-and-Early-Indentification-(CH)解读病毒“定时”和进展为艾滋病的风险Ho DD， Science 1996；272:1124-5HIV不同“固定值” 5年发展到AIDS 百分比104Natural-History-of-HIV-and-Early-Indentification-(CH)解读在3年内
32、发展为艾滋病的可能性MMWR 1998；47(RR-5)0CD4细胞数、细胞数、HIV载量对预后影响载量对预后影响105Natural-History-of-HIV-and-Early-Indentification-(CH)解读改变自然病史106Natural-History-of-HIV-and-Early-Indentification-(CH)解读时间时间(年年)相关水平相关水平Relative LevelsVLCD4急性急性/早期早期急性急性/早期早期慢性慢性/无症状期无症状期晚期晚期/症状期有症状期有症状症状没有没有/有有HAART治疗对治疗对HIV感染的感染的病毒学和免疫学影响病
33、毒学和免疫学影响+ HAART+HAART107Natural-History-of-HIV-and-Early-Indentification-(CH)解读HIV感染自然病史总结HIV在CD4细胞复制并摧毁它们当CD4细胞计数降低和病毒载量增加时，免疫系统被削弱感染HIV的人们容易发生机会性感染HIV是一种目前还没有治愈方法的慢性疾病e不进行ARV治疗，HIV将进展为有症状的疾病和艾滋病108Natural-History-of-HIV-and-Early-Indentification-(CH)解读Xie Xie!109Natural-History-of-HIV-and-Early-Indentification-(CH)解读
