艾滋病免疫病理、艾滋病病理变化、抗HIV免疫反应与病毒感染过程、艾滋病临床表现与分期、诊断标准、常见机会性感染的诊治与预防


艾滋病免疫病理、艾滋病病理变化、抗HIV免疫反应与病毒感染过程、艾滋病临床表现与分期、诊断标准、常见机会性感染的诊治与预防

 
 
 
 
 

艾滋病免疫病理、艾滋病病理变化、抗HIV免疫反应与病毒感染过程、艾滋病临床表现与分期、诊断标准、常见机会性感染的诊治与预防

艾滋病是累及全身多器官系统的疾病。HIV感染引起的免疫系统病变、多系统机会性感染(包括原虫、病毒、细菌和真菌)和恶性肿瘤(包括卡波氏肉瘤、恶性淋巴瘤和子宫颈癌)构成了艾滋病复杂的临床病理变化。

  (一)常见的机会性感染和恶性肿瘤

  1.肺孢子虫病

  肺孢子虫病主要引起肺孢子虫肺炎。两肺显示弥漫性受累、实变、重量增加,含气显著减少。经福尔马林固定后,肺切面呈粗海绵状。肺泡腔内出现具有特征性的、泡沫状、红染、无细胞性渗出液,称为蜂窝状渗出液。肺泡上皮细胞增生为立方状。肺孢子虫包囊在肺泡腔内渗出液中,呈聚集分布。印片中,运用Gram 或 Giemsa染色时,滋养体可以显示清楚。运用Giemsa染色可清楚显示肺孢子虫包囊。

  2.弓形体病

  虽然播散性弓形体病也可累及眼、肺、心和胃肠道,但是多数患者发生弓形体性脑炎。脑病变可以是局限的或弥漫性。在大脑基底节和小脑皮质发生脓肿,并可进入蛛网膜下腔。弓形体脑脓肿在加强对比CT检查时具有特征性改变,病变呈单发或多发,位于灰质,呈环状包绕的囊状结构。局部脑组织发生凝固性出血性坏死,坏死区内少量弓形体。坏死区周围有一个淤血和血管内皮增生带,增生带内重度炎症浸润,并含有多量的弓形体分散的速殖子和含有缓殖子的假包囊。脑组织内的速殖子与其他组织内的不同,呈圆形或椭圆形,而不是呈新月形。在其他组织切片中,H&E染色即可清楚观察到2~3μm半月形速殖子和50μm包囊或假包囊。另外,血清抗体滴度升高对弓形体感染具有提示诊断的意义。

  3. 白念珠菌病

  艾滋病患者中,复发性白念珠菌病是最常见的机会性真菌感染。口腔白念珠菌病患者的舌表面由于渗出物覆盖,呈弥漫白色斑块,甚至形成厚厚的黑棕色覆盖物。口腔白念珠菌病指示疾病已进入艾滋病期。胃肠道的任何部位都可以受累。食管是胃肠道白念珠菌病最常累及的部位。粘膜表面可见灰色假膜,并有不规则形的溃疡。假膜由纤维素和坏死组织构成,其内可见网状的假菌丝。播散性白色念珠菌病常累及多个器官,如肾(约80%)、脑(约50%)和心(约58%),在受累的器官内形成多发性脓肿。组织学检查,白色念珠菌呈现出由酵母样孢子或芽生孢子(直径约3 到 4μm,呈圆形或卵圆形)与假菌丝(由串状的孢子构成)。

  4.分支杆菌病 

  艾滋病患者常出现分支杆菌病,包括结核病和鸟分支杆菌感染。

  结核病发生在艾滋病病程的早期和晚期。肺外结核常见,更具有侵袭性,易发生全身扩散。镜下,艾滋病患者的结核肉芽肿不典型,干酪样坏死显著、上皮样细胞和巨细胞较少。肺结核病常为渗出性病变,气腔实变,内有纤维素,中性粒细胞和组织细胞。经常可见广泛坏死和多量的抗酸结核杆菌。

  鸟分支杆菌感染可见于艾滋病病程的晚期,此时CD4+ T淋巴细胞数通常少于100/mm3,常引起播散性分支杆菌病。在脾、肝、淋巴结、心脏和肾的切面上有时可见粟粒性肉芽肿。镜下,局部结构都被组织细胞团所取代,组织细胞高度肿胀,条纹状或泡沫样,胞浆黄染或蓝染,核染色深,极少形成巨细胞,很少或没有坏死,无钙化和纤维化。抗酸染色显示巨噬细胞肿胀,充满大量的鸟分支杆菌。

  5. 巨细胞病毒感染

  艾滋病患者巨细胞病毒感染可以引起胃肠道溃疡,间质性肺炎,肾小球肾炎、视网膜炎。巨细胞病毒也可感染脑与脊髓的各个部位,包括脊神经根和颅神经。尸体解剖检查,肾上腺和呼吸系统最常受累。镜下,可见一些大细胞,核内与胞浆里有明显的、界清的包含体。在所有人类病毒中,巨细胞病毒包含体是最大的,感染细胞的胞核与胞浆内均可出现。巨细胞病毒包含体表现为:①核内双染性包含体,周围包绕一轮透明晕,宛如猫头鹰眼状;②胞浆双染性或嗜酸性包含体;③上皮细胞、内皮细胞、巨噬细胞和平滑肌细胞内均可见到包含体。免疫组织化学、DNA原位杂交和PCR有助于确诊。

  6. 卡波氏肉瘤

  卡波氏肉瘤是艾滋病患者最常见的肿瘤。流行型卡波氏肉瘤或艾滋病相关的卡波氏肉瘤与其他类型不同:①同性恋或双性恋的男性多见,也可见静脉吸毒者;②病变为多中心,侵袭力更强,不仅累及皮肤,而且累及内脏(约75%病例累及内脏),依次为肺、淋巴结、胃肠道、肝、泌尿生殖系统,甚至少数累及肾上腺、心和脾。皮肤卡波氏肉瘤呈红色或紫红色,早期为平坦的斑点;进而,发展为隆起的斑块;最终形成结节,并可发生糜烂、溃疡。肿瘤由梭形细胞构成,能够形成血管裂隙,其内可见红细胞,肿瘤细胞具有内皮细胞和平滑肌细胞的特点。人疱疹病毒8型与卡波氏肉瘤的发生有关。

  (二)免疫系统病理变化

  1.HIV相关性淋巴结病

  HIV相关性淋巴结病大致可以分为无滤泡破碎的滤泡增生、有滤泡破碎的滤泡增生、滤泡退化和滤泡耗竭四种类型。在艾滋病发生前,患者发生持续性全身淋巴结病,肿大的淋巴结一般不超过3cm,多数HIV感染者在艾滋病发生前淋巴结组织学改变为滤泡增生;艾滋病患者淋巴结体积小,淋巴结病变为滤泡退化或耗竭。

  2.脾的病理变化

  脾肿大是艾滋病患者常见的临床症状。成人患者脾重量超过400g时,常意味着脾内有机会性感染和恶性肿瘤发生。艾滋病脾的显著病变是淋巴细胞高度耗竭,仅有少量白髓,甚至白髓完全消失。

  儿童艾滋病脾的改变为显著的淋巴细胞耗竭和吞噬红细胞现象,约50%病例出现卡波氏样病变。

  3.胸腺病理变化

  成人艾滋病患者的胸腺无明显病理变化,可以出现B细胞滤泡增生。

  儿童艾滋病患者发生胸腺过早退化。HIV损伤胸腺上皮,引起淋巴组织发生萎缩和耗竭,可见浆细胞浸润和多核巨细胞形成。胸腺小体囊肿形成。

  4.骨髓的病理变化

  早期,3/4的病例表现为细胞增生,以粒细胞系和巨核细胞增生为主。晚期,患者衰竭时,骨髓细胞减少,可见不成熟的、发育不良的前体髓细胞、淋巴样细胞聚集、不典型巨核细胞、细网状硬化、轻度血管增生、组织细胞增生和含铁血黄素沉积。

艾滋病免疫病理


免疫病理

  1.CD4+ T淋巴细胞数量减少

  感染HIV后体内CD4+ T淋巴细胞数量不断减少,急性感染期以CD4+ T淋巴细胞数量短期内一过性迅速减少为特点,大多数感染者未经特殊治疗,CD4+ T淋巴细胞数可自行恢复至正常水平或接近正常水平;无症状感染期以CD4+ T淋巴细胞数量持续缓慢减少为特点,CD4+ T 淋巴细胞数多在800~350/mm3之间,此期持续时间变化较大(数月至十数年不等),平均持续约8年左右;进入有症状期后CD4+ T淋巴细胞再次较快速的减少,多数感染者CD4+ T淋巴细胞数在350/mm3以下,部分晚期病人CD4+ T淋巴细胞数甚至降至200/mm3以下,并快速减少。

  CD4+ T淋巴细胞数量的减少是多因素所致,可能由于CD4+ T淋巴细胞的破坏增加;CD4+ T淋巴细胞的产生减少;淋巴组织扣留外周血的CD4+ T淋巴细胞等。

  2.CD4+ T淋巴细胞功能障碍

  主要表现为T辅助细胞1(Th1)细胞被T辅助细胞2(Th2)细胞代替、抗原递呈细胞功能受损、白细胞介素-2产生减少和对抗原反应活化能力丧失,使HIV/AIDS病人易发生各种感染。

  3.异常免疫激活

  HIV感染后的另一免疫病理改变是免疫系统的异常激活,CD4+、CD8+ T淋巴细胞表达CD69、 CD38和HLA-DR等免疫激活标志物水平异常的升高,且与HIV血浆病毒载量有良好相关性,且随疾病进展,细胞激活水平也不断升高。因此,异常的免疫激活状况不仅可以衡量血浆病毒载量的变化,还可以预测CD4+ T淋巴细胞减少的速度。

  4.免疫重建

  业已证明HAART促使艾滋病病人的免疫功能重建,是近年来艾滋病研究领域的重大进展之一,对艾滋病的治疗与研究影响极大。艾滋病病人免疫功能重建的含义是指经抗病毒治疗后,上述HIV所引起的免疫异常改变能恢复至正常或接近正常水平,即:1)减少的CD4+ T 淋巴细胞恢复正常;2)CD4+ T淋巴细胞恢复对记忆抗原刺激的正常反应能力;3)病人体内异常的免疫激活恢复正常。当然,免疫重建更包括抗病毒治疗后,与艾滋病相关的各种机会性感染和肿瘤的发生率下降,艾滋病病人的死亡率和发病率减少。但HAART治疗对艾滋病免疫功能重建也有其局限性:1)HAART不能使所有艾滋病病人的免疫功能重建;2)HAART不能重建抗HIV的CD4+ T淋巴细胞特异性免疫反应,CD8+ T淋巴细胞特异性抗HIV的能力也下降,这意味着病人需长期维持用药。

抗HIV免疫反应


  抗HIV免疫反应包括特异性免疫和非特异性免疫反应,以特异性免疫反应为主。特异性体液免疫:HIV进入人体后2~12周,人体免疫系统即产生针对HIV蛋白的各种特异性抗体,其中仅中和性抗体具有抗病毒作用。特异性细胞免疫:主要有特异性CD4+ T淋巴细胞免疫反应和特异性细胞毒性T淋巴细胞反应(CTL)。

  CD4+ T淋巴细胞作为免疫系统的中枢细胞,在特异性免疫中起重要作用。通过分泌各种细胞因子,诱导B细胞产生抗HIV的抗体,促进抗HIV的特异性CTL的产生和成熟,活化巨噬细胞和NK细胞。CD8+ T淋巴细胞是特异性细胞免疫的效应细胞,通过直接或分泌各种细胞因子(如肿瘤坏死因子,干扰素等),抑制病毒复制。

病毒感染过程


  1.原发感染

  HIV需借助于易感细胞表面的受体进入细胞,包括第一受体和第二受体。HIV-1的外膜糖蛋白gp120首先与第一受体结合,然后gp120再与第二受体结合,gp120构象改变,与gp41分离,最终导致HIV与宿主细胞膜融合进入细胞。

  HIV进入人体后,在24—48小时内到达局部淋巴结,约5天左右在外周血中可以检测到病毒成份。继而产生病毒血症,导致急性感染。

  2.HIV在人体细胞内的感染过程

  吸附及穿入:HIV-1感染人体后,选择性的吸附于靶细胞的CD4受体上,在辅助受体的帮助下进入宿主细胞。

  环化及整合:病毒RNA在逆转录酶作用下,形成cDNA,在DNA聚合酶作用下形成双股DNA,在整合酶的作用下,新形成的非共价结合的双股DNA整合入宿主细胞染色体DNA中。这种整合的病毒双股DNA即前病毒。

  转录及翻译:前病毒被活化而进行自身转录时,病毒DNA转录形成RNA,一些RNA经加帽加尾成为病毒的子代基因组RNA;另一些RNA经拚接而成为病毒mRNA,在细胞核蛋白体上转译成病毒的结构蛋白和非结构蛋白,合成的病毒蛋白在内质网核糖体进行糖化和加工,在蛋白酶作用下裂解,产生子代病毒的蛋白和酶类。

  装配、成熟及出芽:Gag蛋白与病毒RNA结合装配成核壳体,通过芽生从胞浆膜释放时获得病毒体的包膜,形成成熟的病毒颗粒。

  3.HIV感染后的三种临床转归

  由于机体的免疫系统不能完全清除病毒,形成慢性感染,在临床上可表现为典型进展者、快速进展者和长期不进展者三种转归。影响HIV感染临床转归的主要因素有病毒、宿主免疫和遗传背景等。

艾滋病临床表现与分期

从初始感染HIV到终末期是一个较为漫长复杂的过程,在这一过程的不同阶段,与HIV相关的临床表现也是多种多样的。参照2001年制定的《HIV/AIDS诊断标准及处理原则》中华人民共和国国家标准(试行),将艾滋病的全过程分为急性期、无症状期和艾滋病期。

  (一)急性期

  通常发生在初次感染HIV后2-4周左右。部分感染者出现HIV病毒血症和免疫系统急性损伤所产生的临床症状。大多数病人临床症状轻微,持续1-3周后缓解。临床表现以发热最为常见,可伴有咽痛、盗汗、恶心、呕吐、腹泻、皮疹、关节痛、淋巴结肿大及神经系统症状。

  此期在血液中可检出HIV-RNA和P24抗原,而HIV抗体则在感染后数周才出现。CD4+ T淋巴细胞计数一过性减少,同时CD4/CD8比率亦可倒置。部分病人可有轻度白细胞和血小板减少或肝功能异常。

  (二)无症状期

  可从急性期进入此期,或无明显的急性期症状而直接进入此期。

  此期持续时间一般为6-8年。其时间长短与感染病毒的数量、型别,感染途径,机体免疫状况的个体差异,营养条件及生活习惯等因素有关。在无症状期,由于HIV在感染者体内不断复制,免疫系统受损,CD4+ T淋巴细胞计数逐渐下降,同时具有传染性。

  (三)艾滋病期

  为感染HIV后的最终阶段。病人CD4+ T淋巴细胞计数明显下降,多<200/mm3,HIV血浆病毒载量明显升高。此期主要临床表现为HIV相关症状、各种机会性感染及肿瘤。

  HIV相关症状:主要表现为持续一个月以上的发热、盗汗、腹泻;体重减轻10%以上。部分病人表现为神经精神症状,如记忆力减退、精神淡漠、性格改变、头痛、癫痫及痴呆等。另外还可出现持续性全身性淋巴结肿大,其特点为①.除腹股沟以外有两个或两个以上部位的淋巴结肿大;②.淋巴结直径≥1厘米,无压痛,无粘连;③.持续时间3个月以上。

  各系统常见的机会性感染及肿瘤如下(详见常见机会性感染诊断部分)。

  呼吸系统:卡氏肺孢子虫肺炎(PCP)、肺结核、复发性细菌、真菌性肺炎。

  中枢神经系统:隐球菌脑膜炎、结核性脑膜炎、弓形虫脑病、各种病毒性脑膜脑炎。

  消化系统:白色念珠菌食道炎,及巨细胞病毒性食道炎、肠炎;沙门氏菌、痢疾杆菌、空肠弯曲菌及隐孢子虫性肠炎。

  口腔:鹅口疮、舌毛状白斑、复发性口腔溃疡、牙龈炎等。

  皮肤:带状疱疹、传染性软疣、尖锐湿疣、真菌性皮炎和甲癣。

  眼部:巨细胞病毒性及弓形虫性视网膜炎。

  肿瘤:恶性淋巴瘤、卡波氏肉瘤等。

  需要注意的是,艾滋病期的临床表现呈多样化,并发症也不尽相同,所发疾病与当地流行现患率密切相关。

诊断原则:HIV/AIDS的诊断需结合流行病学史(包括不安全性生活史、静脉注射毒品史、输入未经抗HIV抗体检测的血液或血液制品、 HIV抗体阳性者所生子女或职业暴露史等)、临床表现和实验室检查等进行综合分析,慎重作出诊断。诊断HIV/AIDS必须是HIV抗体阳性(经确认试验证实),而HIV RNA和P24 抗原的检测有助于HIV/AIDS的诊断,尤其是能缩短抗体“窗口期”和帮助早期诊断新生儿的HIV感染。

  (一)急性期

  诊断标准:病人近期内有流行病学史和临床表现,结合实验室HIV抗体由阴性转为阳性即可诊断,或仅实验室检查HIV抗体由阴性转为阳性即可诊断。

  (二) 无症状期

  诊断标准:有流行病学史,结合HIV抗体阳性即可诊断,或仅实验室检查HIV抗体阳性即可诊断。

  (三)艾滋病期

  (1) 原因不明的持续不规则发热38℃以上,>1个月

  (2) 慢性腹泻次数多于3次/日,>1个月

  (3) 6个月之内体重下降10%以上

  (4) 反复发作的口腔白念珠菌感染

  (5) 反复发作的单纯疱疹病毒感染或带状疱疹病毒感染

  (6)肺孢子虫肺炎(PCP)

  (7) 反复发生的细菌性肺炎

  (8) 活动性结核或非结核分支杆菌病

  (9) 深部真菌感染

  (10)  中枢神经系统占位性病变

  (11)  中青年人出现痴呆

  (12)  活动性巨细胞病毒感染

  (13)  弓形虫脑病

  (14)  青霉菌感染

  (15)  反复发生的败血症

  (16)  皮肤粘膜或内脏的卡波氏肉瘤、淋巴瘤

  诊断标准:有流行病学史、实验室检查HIV抗体阳性,加上述各项中的任何一项,即可诊为艾滋病。或者HIV抗体阳性,而CD4+ T淋巴细胞数<200/mm3,也可诊断为艾滋病。

常见机会性感染的诊治与预防

(一)肺孢子虫肺炎

  1.诊断:

  (1)起病隐匿或亚急性,干咳,气短和活动后加重,可有发热、紫绀,严重者发生呼吸窘迫;(2)肺部阳性体征少,或可闻及少量散在的干湿啰音。体征与疾病症状的严重程度往往不成比例;(3)胸部X线检查 可见双肺从肺门开始的弥漫性网状结节样间质浸润,有时呈毛玻璃状阴影;(4)血气分析 低氧血症,严重病例动脉血氧分压(Pa02)明显降低,常在60mmHg以下;(5)血乳酸脱氢酶常升高;(5)确诊依靠病原学检查如痰液或支气管肺泡灌洗/肺组织活检等发现肺孢子虫的包囊或滋养体。

  2.治疗:

  (1)对症治疗:卧床休息,给予吸氧、改善通气功能,注意水和电解质平衡。如病人进行性呼吸困难明显,可人工辅助呼吸。中重度PCP病人(PaO2<70mmHg或肺泡—动脉血氧分压差>35mmHg,可用强的松40mg每日2次口服5天,改20mg每日2次口服5天,20mg每日1次口服至抗PCP结束;如静脉用甲基强的松龙,用量为上述强的松的75%。(2)病原治疗:首选复方新诺明9-12片/日(TMP每日15mg/kg,SMZ每日100mg/kg),口服,每日3-4次,疗程2-3周。复方新诺明针剂(剂量同上),每6-8h 1次,静滴。替代治疗:氨苯砜100mg,口服,每日1次;联合应用甲氧苄啶200—400mg,口服,每日2-3次,疗程2-3周。或克林霉素600-900mg,静注,每6h 1次,或450mg口服,每6h 1次;联合应用伯氨喹15-30mg,口服,每日1次, 疗程2-3周。或喷他脒,3-4mg/kg,每日1次,缓慢静滴(60分钟以上),疗程2-3周。

  3.预防:

  (1)预防指征: CD4+ T淋巴细胞计数<200/mm3的成人和青少年,包括孕妇及接受HAART治疗者。(2)药物选择:首选复方新诺明,体重≥60Kg者, 2片/日,体重<60Kg者,1片/日。若患者对该药不能耐受,替代药品有氨苯砜和TMP。患PCP病人经HAART治疗使CD4+ T淋巴细胞增加到>200/mm3并持续≥6个月时,可停止预防用药。如果CD4+ T淋巴细胞计数又降低到<200/mm3时,应重新开始预防用药。

  (二)结核病

  1.诊断

  临床证实有活动性结核。

  2. 治疗

  HIV阳性病人一旦并发结核病,其治疗原则与常规抗结核治疗方法相同,但疗程应适当延长。抗结核药物使用时应注意与抗病毒药物之间存在相互作用及配伍禁忌。

    治疗药物:异烟肼(H)、丁胺卡那(A)、利福平(R)、利福喷丁(L)、乙胺丁醇(E)、对氨基水杨酸钠(PAS)、吡嗪酰胺(Z)及链霉素(S)。

药物剂量、用法及主要毒副反应见下表

药名

每日疗法

间歇疗法

成人(g)

(周1-2次)

 

主要不良反应

成人(g)

儿童

Mg/kg

<50kg

≥50kg

<50kg

≥50kg

H

0.3 

0.3

10-15

0.5

0.6

肝毒性、末梢神经炎

S

0.75

0.75

20-30

0.75

0.75

听力障碍、肾功能障碍、过敏反应

R

0.45

0.6

10-20

0.6

0.6

肝毒性、胃肠反应、过敏反应

E

0.75

1.0

1.0-1.2

1.0-1.2

视力障碍、视野缩小

PAS

8.0

8.0

150-250

10

12

肝毒性、胃肠反应、过敏反应

Z

1.5

1.5

30-40

2.0

2.0

肝毒性、胃肠反应、痛风

L

 

 

 

0.6

0.6

同利福平


    化疗方案(列举2个初治常见化疗方案如下,更多治疗方案见国家结核病防治指南):

  ①2HRZE / 4HR:强化期:二个月、H、R、Z、E、每日一次;继续期:四个月,H、R每日一次。②2H3 R3 Z3 E3 / 4H3 R3:强化期:二个月、H、R、Z、E、隔日一次;继续期:四个月、H、R、隔日一次。

  3.预防

  指征:艾滋病病人不是必须对结核病进行化学药物预防,但临床医生可参考以下意见进行预防性化疗:病人的CD4+ T淋巴细胞计数〈200/mm3 时,可进行预防性化疗,其方案是:①异烟肼+利福喷丁,连续服用4-6个月(剂量见上表)。②异烟肼,连续服用12个月(剂量见上表)。

  (三)分支杆菌感染

  1.诊断

  分支杆菌感染的临床症状同活动性结核病相似,但全身播散性病变更为常见。确诊:血培养、痰培养、支气管肺组织活检、痰支气管冲洗物培养为非结核分枝杆菌。

  2.治疗

  其它分支杆菌治疗同结核病的治疗。

  鸟分支杆菌(MAC)治疗:首选治疗方案:克拉霉素500 mg /次,2次/日或(阿奇毒素600mg /日) +乙胺丁醇15 mg/kg /日(分次服),重症病人可同时联合应用利福布汀(300-600 mg /日)或阿米卡星(10 mg/kg/次肌肉注射,1次/日),疗程6个月。替代治疗方案:利福布汀(300-600 mg /日)+阿米卡星(10 mg/kg/次肌肉注射,1次/日)+环丙沙星(750 mg/次,2次/日),疗程6个月。

  3.预防

  艾滋病病人不是必须对非结核分枝杆菌病进行化学药物预防,医生根据临床可参考以下意见。艾滋病病人,当CD4+ T淋巴细胞<50/mm3者,可预防性治疗,以减少发生播散性MAC的机率。方案是克拉霉素500mg/次,2次/日;或阿齐霉素,1200mg/周。如病人经HAART治疗使CD4+ T淋巴细胞增加到>100/mm3并持续≥6个月时,可停止预防用药。

  (四)巨细胞病毒视网膜脉络膜炎

  1.诊断

  临床常见的表现为快速视力下降,确诊有赖于眼底镜检查。

  2.治疗

  (1)更昔洛韦 5mg/kg/日,分为2次静滴,2-3周后改为5mg/kg/日,每日1次,静滴,终身维持。可引起白细胞减少,血小板减少和肾功能不全。病情危重或单一药物治疗无效时可联用膦甲酸钠 90mg/kg 静滴,每日2次。若为视网膜炎亦可球后注射更昔洛韦。

  (2)膦甲酸钠 90mg/kg 静滴,每日2次 ,应用2-3周后改为长期90mg/kg 静滴,每日1次,可导致肾功能不全,恶心及电解质紊乱,若肌酐清除率异常,则需调整剂量。

  3.预防

  对于CD4+T淋巴细胞计数<200/mm3的AIDS的病人,应定期检查眼底。一旦出现CMV病,应积极治疗,在疾病控制之后需终身服药以预防复发。对于CD4+ T淋巴细胞计数<50/mm3的AIDS的病人应常规给予预防服药(更昔洛韦口服),在经HAART治疗有效的病人若其CD4+ T淋巴细胞计数>100/mm3且持续6月以上时可以考虑停止预防给药。

  (五)弓形虫脑病

  1.诊断

  弓形虫脑病常发生在CD4+ T淋巴细胞计数<100/ mm3的患者。表现为局灶性或弥漫性中枢神经系统损害,有头痛、低热、嗜睡、躁动和昏睡,局灶症状包括癫痫和中风,。其它症状包括:复视、偏盲、失明、步态不稳、肌阵挛、颤动、人格改变、幻觉和晕厥。脑膜炎不常见。头颅CT为一个或多个低密度病灶,增强扫描呈环状或结节样增强。头颅MRI较CT更敏感,典型的MRI表现为颅内多发长T1和长T2信号。确诊依靠脑活检。

  2.治疗

  首选治疗:乙胺嘧啶(负荷量100mg,口服,2次/日,此后50-75mg/日维持)+磺胺嘧啶(1-1.5g,口服,4次/日),疗程一般为3周,重症患者和临床、影像学改善不满意患者疗程可延长至6周以上。不能耐受者和磺胺过敏者可以选用克林霉素600mg/次,静脉给药,每6小时给药一次,联合乙胺嘧啶。为减少血液系统不良反应,合用甲酰四氢叶酸10-20mg/日。

  3.预防

  对无弓形虫脑病病史但CD4+ T细胞计数<100/mm3且弓型体抗体IgG阳性的病人应常规用复方新诺明2片/日预防,对既往患过弓形虫脑病的病人要长期用乙胺嘧啶(25-50mg/日)+联合磺胺嘧啶(2-4g/日)预防。病人经HAART治疗使CD4+ T细胞增加到>200/mm3并持续≥3-6个月时,可停止预防用药。对弓形虫抗体阴性且CD4+ T细胞计数<100/mm3的病人应避免弓形虫感染。具体措施包括:肉类食物应在-20℃冷藏;肉类食物要煮熟(至少60℃以上)以杀灭组织中的包囊;蔬菜水果要清洗干净;不养宠物。

  (六)真菌感染

  1.诊断

  临床诊断为真菌感染,常见的是念珠菌感染和新型隐球菌感染。

  2.治疗

  (1)念珠菌感染

  口腔念珠菌感染的首选治疗是制霉菌素局部涂抹加碳酸氢钠漱口水漱口,如果对上述治疗无反应,可以给予如下治疗:氟康唑:50mg-100mg/次,口服,1次/日,疗程1-2周。食道念珠菌感染:氟康唑首剂200mg/日,后改为100mg /次,1次/日, 应用1-2周;重症病人氟康唑可增加剂量和延长疗程。对复发性念珠菌感染建议氟康唑100mg/日,长期服用。

  (2)新型隐球菌脑膜炎

  1)降颅压治疗:首选甘露醇,重症者可行侧脑室外引流。

  2)抗真菌治疗:首选两性霉素B,先从每天1mg,加入5%的葡萄糖水中500ml缓慢静点(不宜用生理盐水,需避光),滴注时间不少于6-8小时。第二天和第三天各为2 mg和5 mg,加入500ml的葡萄糖水中滴注。若无反应第四天可以增量至10mg。若无严重反应,则以后按5mg/日增加,一般达30-40 mg(最高剂量50mg/日)。疗程需要3个月以上,两性霉素B的总剂量为2-4g。两性霉素B不良反应较大,需严密观察。二性霉素B与5-氟胞嘧啶(5FC)合用具有协同作用。5FC为100mg/kg/日(1.5g-2.0g,3/日),二者共同使用至少8-12周。二性霉素B也可与氟康唑联合使用,用法为氟康唑200mg/日,口服或静滴,疗程8-12周。

  3)必要时可由脑室引流管注射两性霉素B 0.5-1mg/次,隔日一次。

  4)病情稳定后可改用氟康唑维持,200mg/次,1次/日,长期维持,以预防复发。

AIDS immune pathology, the pathological changes of AIDS, anti-HIV immune response and the course of HIV infection, AIDS Clinical manifestations and staging, the diagnostic criteria, common diagnosis and treatment of opportunistic infections and prevention

AIDS is a multi-organ system involvement of systemic diseases. HIV infection of immune system disease, multiple system opportunistic infections (including parasites, viruses, bacteria and fungi) and malignant (including Kaposi's sarcoma, malignant lymphoma and cervical cancer) AIDS poses a complex clinical pathological changes.

(A) the common opportunistic infections and malignancies

1. Lung disease spores

The main disease caused by pneumocystis carinii pneumonia lung.两肺showed diffuse involvement, it is changed, the weight increase in a significant reduction in gas. By the formalin-fixed, the pulmonary cavernous rough cut surface. Alveolar cavity with characteristic appears, the bubble-shaped, red dye, no effusion cell, known as the honeycomb-like exudate. Alveolar epithelial cell hyperplasia cubic-shaped. Pneumocystis carinii cysts in the alveolar cavity effusions, showed aggregated distribution. Indian film, the use of Gram or Giemsa staining, the trophozoites can be displayed clearly. The use of Giemsa staining clearly shows that Pneumocystis carinii cyst.

2. Toxoplasmosis

Although disseminated toxoplasmosis may also be involved eyes, lungs, heart and gastrointestinal tract, but the majority of patients with Toxoplasma encephalitis. Brain lesions can be limited or diffuse. Basal ganglia in the brain cortex and cerebellar abscess occurred, and into the subarachnoid space. Toxoplasma brain abscess in the CT examination to enhance contrast with the characteristic changes in one or more lesions were made, is located in gray matter, showing the cystic structure enveloping the ring. Regional cerebral hemorrhage coagulative tissue necrosis, necrosis of a small number of Toxoplasma region. There is a necrotic area around the congestion zone and vascular endothelial hyperplasia, hyperplasia with severe inflammation with infiltration and contains scattered多量of Toxoplasma tachyzoites and the ease with sub-yield false cyst. Within the brain tissue of tachyzoites with other organizations of the different, were round or oval-shaped, rather than positive crescent. In other tissues, H & E staining can be clearly observed that the half-moon 2 ~ 3μm and 50μm tachyzoites cyst cyst or false. In addition, serum antibody titers to Toxoplasma gondii infection increased with the significance of prompt diagnosis.

3. White candidiasis

AIDS patients, patients with recurrent Candida albicans is the most common opportunistic fungal infection. Candida albicans in patients with oral tongue surface coverage as a result of exudation, was filled with white patches, or even form a thick cover of dark brown. Candida albicans mouth disease indicative of AIDS disease has entered a period. Any part of the gastrointestinal tract can be affected.道白gastrointestinal esophageal candidiasis is the most commonly involved site. Gray pseudome mucosal surface can be seen, as well as irregular-shaped ulcers. Pseudome from cellulose and tissue necrosis, which can be seen in the pseudohyphal mesh. Candida albicans disseminated disease often involving multiple organs, such as the kidney (about 80%), brain (about 50%) and heart (about 58%), in the involvement of multiple organs with abscess formation. Histological examination showed Candida albicans from yeast-like spores or blastospore (diameter of about 3 to 4μm, were round or oval) and pseudohyphal (by the string-like spores pose).

4. Mycobacterial disease

AIDS patients often Mycobacterium, including Mycobacterium tuberculosis and infected birds.

AIDS, tuberculosis occurred in the early and late course of disease. Common extra-pulmonary TB, more invasive, the body prone to proliferation. Microscope, AIDS patients are not typical of tuberculosis granuloma, caseous necrosis significantly, epithelioid cells and giant cell less. TB often exudative lesions, gas chamber is changed, there are cellulose, neutrophils and tissue cells. Extensive necrosis can be seen frequently and the acid-fast Mycobacterium tuberculosis多量.

Mycobacterium infection in birds can be found in advanced HIV disease, when the number of CD4 + T lymphocytes is usually less than 100/mm3, often caused by disseminated mycobacterial disease. In the spleen, liver, lymph nodes, heart and kidney can be seen sometimes cut miliary granuloma. Microscope, the local structure of cell mass organizations have been replaced by a high degree of tissue swelling, striped or bubble-like, cytoplasmic staining yellow or blue staining, nuclear staining of deep, minimal formation of giant cells, with little or no necrosis, no calcification and fibrosis. Acid-fast staining showed that macrophages swelling, a large number of birds with Mycobacterium.

5. Cytomegalovirus infection

AIDS patients with cytomegalovirus infection can cause gastrointestinal ulcers, interstitial pneumonitis, glomerular nephritis, retinitis. CMV can also be infected with brain and spinal cord of all parts, including spinal nerve roots and cranial nerves. Autopsy examination, adrenal gland and the most commonly involved the respiratory system. Microscope, we can see some large cell, the nucleus and cytoplasm, there are obvious, the inclusion body clearance sector. In all human viruses, cytomegalovirus inclusion bodies is the largest of the infected cells within the nucleus and the cytoplasm may occur. Cytomegalovirus inclusion bodies expressed as: ① double staining of nuclear inclusion body surrounded by a transparent halo enveloping, like owl-like eyes; ② double staining of the cytoplasm or eosinophilic inclusion bodies; ③ epithelial cells, endothelial cells, giant macrophage and smooth muscle cells can be seen in inclusion body. Immunohistochemistry, DNA in situ hybridization and PCR confirmed contribute.

6. Kaposi's sarcoma

Kaposi's sarcoma in AIDS patients is the most common tumor. Epidemic Kaposi's sarcoma or AIDS-related Kaposi's sarcoma and other types of different: ① homosexual or bisexual men mostly, but also shows that intravenous drug users; ② lesions for the multi-center, more invasive, involving not only the skin and visceral involvement (about 75% of cases involving internal organs), followed by lung, lymph nodes, gastrointestinal tract, liver, urogenital system, and even a small number of affected adrenal gland, heart and spleen. Kaposi's sarcoma skin red or purple-red, flat spots early to; then, the development of the plaque for the uplift; ultimately the formation of nodules, and erosion occurred, ulcers. Posed by the spindle cell tumors, blood vessels can form cracks, which can be seen inside the red blood cells, tumor cells with endothelial cells and smooth muscle cell characteristics. Human herpesvirus 8 with Kaposi's sarcoma related to the occurrence of.

(B) pathological changes in the immune system

Lymphadenopathy associated 1.HIV

HIV-related lymphadenopathy can generally be broken into non-follicular follicular hyperplasia, follicular broken follicular hyperplasia, follicular follicular degradation and depletion of four types. Prior to the occurrence of AIDS, patients with persistent generalized lymphadenopathy, enlarged lymph nodes are generally not more than 3cm, the majority of HIV-infected persons prior to the occurrence of lymph node in AIDS histological changes for follicular hyperplasia; AIDS patients small lymph nodes, follicular lymph node disease degradation or depletion.

2. Splenic pathologic changes

Splenomegaly is common in patients with clinical AIDS symptoms. Adult patients weighing more than 400g of spleen, the spleen often means that there are opportunistic infections and malignant tumors occur. AIDS significant splenic lesions is a high degree of depletion of lymphocytes, only a small amount of white pulp, white pulp or even completely disappear.

AIDS children for significant changes in spleen lymphocyte depletion and the red blood cell phagocytosis phenomenon, about 50% of cases of Kaposi's lesions appear.

3. Thymic pathological changes

Adult AIDS patients with no significant pathological changes in thymus, B cells can occur follicular hyperplasia.

Thymus of children with AIDS premature degradation occurred. HIV thymic epithelial injury, caused by lymphoid tissue atrophy and depletion, showing plasma cell infiltration and formation of multinucleated giant cells. The formation of thymic cyst body.

4. The pathological changes in bone marrow

Early, 3 / 4 cases showed cells to granulocyte and megakaryocyte cell line-based cell proliferation. Late failure in patients with bone marrow cells decreased, showing immature and dysplastic myeloid precursors, lymphoid cells, atypical megakaryocytes, fine mesh sclerosis, mild vascular proliferation, tissue hyperplasia and hemosiderosis Huang Su-deposition.

AIDS immunopathological


Immunopathological

1.CD4 + T lymphocytes reduce the number of

After HIV infection in vivo number of CD4 + T lymphocytes in the steady decline in acute infection period in the number of CD4 + T lymphocytes in a short period of transient is characterized by a rapid decline in the majority of infected persons without special treatment, CD4 + T lymphocytes can be restored to normal on its own the level of or close to normal levels; asymptomatic infection to the number of CD4 + T lymphocytes characterized by the continued slow decrease, CD4 + T lymphocytes in a number of more than 800 ~ 350/mm3 in between the duration of this period of change in the larger (a few months to more than a dozen years), average duration of about 8 years; symptoms after entering the CD4 + T lymphocytes to a faster reduction in the majority of infected CD4 + T lymphocyte number below 350/mm3, some terminally ill people the number of CD4 + T lymphocytes even fell below 200/mm3, and rapid reduction.

CD4 + T lymphocytes is to reduce the number of factors, may be due to CD4 + T lymphocytes increased the damage; CD4 + T lymphocytes have reduced; detained peripheral lymphoid tissue of CD4 + T lymphocytes and so on.

2.CD4 + T lymphocyte dysfunction

Is mainly expressed in T helper cell 1 (Th1) cells are T helper cell 2 (Th2) cells instead of, antigen-presenting cell function is impaired, Interleukin-reduction and -2 have a response to antigen activation of incapacity, so that HIV / AIDS patients prone to various infections.

3. Abnormal immune activation

Another HIV infected immune changes in the abnormal activation of the immune system, CD4 +, CD8 + T lymphocyte expression of CD69, CD38 and HLA-DR immune activation markers such as abnormal levels rise, and with HIV plasma viral load have a good relevance, and with disease progression, cell activation levels are rising. Therefore, the abnormal state of immune activation can be measured not only in plasma viral load changes, but also can predict the CD4 + T lymphocytes reduce the speed.

4. Immune reconstitution

HAART has proven to immune function in AIDS patients the reconstruction field of AIDS research in recent years, significant progress in the one of the Treatment and Research AIDS impact. Immune function in AIDS patients is the meaning of the reconstruction by the anti-viral treatment, the above-mentioned HIV caused by abnormal immune changes can return to normal or near normal levels, namely: 1) reduction of the CD4 + T lymphocytes returned to normal; 2) CD4 + T lymphocyte antigen to stimulate the resumption of the memory capacity of a normal reaction; 3) patients with abnormal immune activation in vivo back to normal. Of course, also include immune reconstitution after antiretroviral therapy, a variety of AIDS-related opportunistic infections and decrease the incidence of tumors, AIDS patients to reduce mortality and morbidity. However, HAART therapy on immune reconstitution of AIDS also has its limitations: 1) HAART can not all AIDS patients the reconstruction of the immune function; 2) HAART can not be re-anti-HIV-specific CD4 + T lymphocyte immune response, CD8 + T lymphocytes the ability of specific anti-HIV has declined, which means that patients will be long-term maintenance medication.

Anti-HIV immune response


Anti-HIV immune responses, including specific immune and non-specific immune response to specific immune response to the main. Specific humoral immunity: HIV enters the body 2 to 12 weeks, the body's immune system protein that is produced for a variety of HIV-specific antibodies, and only one with antiviral antibody. Specific cell-mediated immunity: the main-specific CD4 + T lymphocyte immune response and specific cytotoxic T lymphocyte response (CTL).

CD4 + T lymphocytes in the immune system as a central cell in specific immunity plays an important role. Through the secretion of various cytokines to induce B cells to produce anti-HIV antibodies, and promote anti-HIV-specific CTL in the generation and maturation, activation of macrophages and NK cells. CD8 + T lymphocytes is a specific cell-mediated immune effector cell, directly or through the secretion of various cytokines (such as tumor necrosis factor, interferon, etc.), inhibit viral replication.

The course of HIV infection


1. Primary infection

Need to help HIV-susceptible cell surface receptor to enter cells, including the first and second receptor receptor. HIV-1 glycoprotein gp120 of the outer membrane with the first receptor-binding first, and then again with the second gp120 receptor binding, gp120 conformation change, separation and gp41, which eventually led to integration of HIV with host cell membranes to enter cells.

After HIV enters the human body in 24-48 hours to reach the local lymph nodes, about 5 days in the peripheral blood can detect the virus components. Then produce viremia, leading to acute infection.

2.HIV in human cells infected with the process of

Adsorption and penetration: HIV-1 infection in the human body, the selective adsorption of target cells in the CD4 receptor, in the help of co-receptor to enter host cells.

Central and integration: viral RNA in the role of reverse transcriptase to form cDNA, in the role of DNA polymerase to form double-stranded DNA, the role of the integrase, the newly formed non-covalent binding of double-stranded DNA into host cells DNA in chromosomes. This integration of double-stranded DNA virus that is, before the virus.

Transcription and translation: the former virus was carried out in self-activation of transcription, the virus DNA transcription, the formation of RNA, some RNA cap increases by the end of Canada to become the progeny virus genome RNA; other RNA virus by splicing into mRNA, protein in the cell body turn to the virus structural proteins and non-structural protein, viral protein synthesis, including ribosomal endoplasmic reticulum for glycosylation and processing, in the role of protease cleavage, resulting in progeny virus proteins and enzymes.

Assembly, and budding maturity: Gag virus RNA binding protein and assembly into the nuclear shell, through the budded from the cytoplasmic membrane when the virus body to release the capsule, the formation of mature virus particles.

After infection 3.HIV three clinical outcome

As the body's immune system can not be completely clear the virus, chronic infection can be clinically manifested as typical progressors, rapid progressors and long-term non-progressors three vesting. The impact of HIV infection of the main factors vesting virus, host immune and genetic backgrounds.

Clinical manifestations and stages of AIDS

From the initial to the end-stage HIV infection is a long complex process, in the process at different stages of HIV associated with a wide range of clinical manifestations. Established in 2001 with reference to "HIV / AIDS diagnostic criteria and treatment of the principle of" People's Republic of China national standard (for trial implementation), the whole process of AIDS is divided into the acute stage, asymptomatic period and the AIDS period.

(A) acute phase

Usually occurs in HIV infection after the initial 2-4 weeks. Part of the emergence of HIV infection viremia and immune system damage produced by acute clinical symptoms. A slight majority of patients with clinical symptoms, sustained remission after 1-3 weeks. Clinical manifestations to the most common fever can be accompanied by pharyngodynia, sweating, nausea, vomiting, diarrhea, rash, joint pain, swollen lymph nodes and nervous system symptoms.

This period could be detected in blood HIV-RNA and the P24 antigen, and HIV antibody in a few weeks after infection only. CD4 + T lymphocyte count had a reduction, at the same time can also be inverted CD4/CD8 ratio. Some patients may have mild reduction in white blood cell and platelet or liver dysfunction.

(B) asymptomatic period

From the acute phase in this period, with or without obvious symptoms of the acute phase and direct access to this period.

The duration of this period is generally 6-8 years. Its duration and the number of infected, type, infection, immune status of the individual differences, nutrition and other lifestyle conditions and factors. In the asymptomatic period in HIV-infected persons as a result of continuous replication in vivo, impaired immune system, CD4 + T lymphocyte count decreased, while infectious.

(C) a view of AIDS

For HIV infection in the final stage after. Patients with CD4 + T lymphocyte count decreased more <200/mm3, HIV plasma viral load increased significantly. The main clinical manifestations of this period for HIV-related symptoms, a variety of opportunistic infections and tumors.

HIV-related symptoms: mainly for the more than one month of continuous fever, sweating, diarrhea; more than 10% weight loss. Some patients showed neuropsychiatric symptoms such as memory, mental apathy, personality changes, headache, such as epilepsy and dementia. In addition there may also be persistent systemic lymph nodes, which is characterized by ①. The exception than the groin two or more parts of the lymph nodes; ②. Lymph node diameter ≥ 1 cm, no tenderness, no adhesions; ③. Continued time for more than 3 months.

Systems common opportunistic infections and tumors is as follows (see diagnosis of opportunistic infections common part).

Respiratory: Pneumocystis carinii pneumonia (PCP), tuberculosis, recurrent bacterial, fungal pneumonia.

Central nervous system: cryptococcal meningitis, tuberculous meningitis, toxoplasma encephalopathy, a variety of viral meningoencephalitis.

Digestive system: Candida albicans esophagitis and cytomegalovirus esophagitis, enteritis; Salmonella, Shigella, Campylobacter jejuni, and Cryptosporidium enteritis.

Oral: thrush, tongue, hairy leukoplakia, recurrent oral ulcers, gingivitis and other.

Skin: herpes zoster, molluscum contagiosum, condyloma, fungi and甲癣dermatitis.

Eye: Cytomegalovirus retinitis and Toxoplasma gondii.

Tumor: malignant lymphoma, such as Kaposi's sarcoma.

Note that AIDS was a view to the diversification of the clinical manifestations, complications are not the same, the local prevalence of diseases and is closely related to the prevalence rate.

Principles of diagnosis: HIV / AIDS diagnosis to be combined with epidemiological history (including the life history of unsafe sex, intravenous drug use history, type of anti-HIV antibody testing without blood or blood products, HIV-positive children born to or occupational exposure History, etc.), clinical manifestations and laboratory tests such as comprehensive analysis, careful to make the diagnosis. Diagnosis of HIV / AIDS must be HIV-positive (confirmed by the confirmatory test), and P24 antigen and HIV RNA detection help HIV / AIDS diagnosis, in particular antibodies can shorten the "window period" and to help the early diagnosis of neonatal HIV infection.

(A) acute phase

Diagnostic criteria: patient history of the near future epidemiological and clinical performance, combined with laboratory HIV antibodies can be from negative to positive diagnosis, or only by laboratory tests negative for antibodies to HIV-positive diagnosis can be.

(B) asymptomatic period

Diagnostic criteria: There are epidemiological history, can be combined with HIV-positive diagnosis, or laboratory tests to diagnose HIV-positive.

(C) a view of AIDS

(1) unexplained persistent irregular fever above 38 ℃,> 1 month

(2) the number of chronic diarrhea more than 3 times / day,> 1 month

(3) 6 months more than 10% weight loss

(4) recurrent oral Candida albicans infection

(5), recurrent herpes simplex virus infection or herpes zoster virus infection

(6) Pneumocystis carinii pneumonia (PCP)

(7) recurrent bacterial pneumonia

(8) active tuberculosis or Mycobacterium tuberculosis disease

(9) deep fungal infection

(10) central nervous system lesions

(11) dementia occur in young people

(12) of active cytomegalovirus infection

(13) Toxoplasma encephalopathy

(14) marneffei infection

(15) recurring sepsis

(16) mucocutaneous or visceral Kaposi's sarcoma, lymphoma

Diagnostic criteria: A History of epidemiology, laboratory tests HIV-positive, the above plus any one can be diagnosed as AIDS. Or HIV-positive, while the number of CD4 + T lymphocytes <200/mm3, can also be diagnosed as AIDS.

Common diagnosis and treatment of opportunistic infections and prevention

(A) Pneumocystis carinii pneumonia

1. Diagnosis:

(1) occult or subacute onset, dry cough, shortness of breath and after the increase, may have fever, cyanosis, respiratory distress occurred in severe cases; (2) the lungs less positive signs, or could be heard and a small amount of wet and dry bulk in La Music . Signs and symptoms of disease are often out of proportion to the severity of; (3) chest X-ray examination shows that the beginning of lungs from the hilar diffuse reticular nodular interstitial infiltration, and sometimes ground-glass-like shadow was; (4) hypoxia, blood gas analysis hyperlipidemia, serious cases of arterial partial pressure of oxygen (Pa02) significantly reduced, often below 60mmHg; (5) often increase in blood lactate dehydrogenase; (5) Inspection diagnosis rely on the etiology, such as sputum or bronchoalveolar lavage / found in lung tissue biopsy, such as Pneumocystis carinii cysts or trophozoites of.

2. Treatment:

(1) symptomatic treatment: bed rest, give oxygen and improve the ventilation function, attention to water and electrolyte balance. Such as dyspnea patients obviously, can be artificial ventilators. PCP in patients with severe (PaO2 <70mmHg or alveolar - arterial oxygen difference> 35mmHg, available 40mg prednisone orally 2 times a day 5 days, 2 to 20mg daily oral 5 days, 20mg daily oral 1 to the end of anti-PCP; such as intravenous methylprednisolone, prednisone dosage for 75% of the above. (2) Pathogen treatment: 9-12 of choice cotrimoxazole tablet / day (TMP daily 15mg/kg, SMZ daily 100mg/kg), oral, 3-4 times daily, 2-3 week course of treatment. cotrimoxazole injection (dose ibid.), each at 6-8h 1, intravenous infusion. replacement therapy: dapsone 100mg, oral, 1 day; trimethoprim combined with 200-400mg, oral, 2-3 times daily, 2-3 week course of treatment. or clindamycin 600-900mg, iv, every 6h 1 times, or 450mg orally every 6h 1 times; primaquine combined with 15-30mg, oral, 1 day, 2-3 week course of treatment. or Pentamidine ,3-4mg / kg, day 1, slow intravenous infusion ( more than 60 minutes), course of 2-3 weeks.

3. Prevention:

(1) prevention indications: CD4 + T lymphocyte count <200/mm3 and young adults, including pregnant women and acceptance of HAART treatment. (2) Drug choices: first choice cotrimoxazole, weight ≥ 60Kg, and 2 / day, body weight <60Kg, the one / day. If patients can not tolerate the drug, alternative drugs are dapsone and TMP. Patients suffering from PCP by HAART therapy increased CD4 + T lymphocytes> 200/mm3 and sustained ≥ 6 months, to stop drug use prevention. If the CD4 + T lymphocyte count has decreased to <200/mm3 should be re-started the prevention of drug use.

(B) TB

1. Diagnosis

Confirmed that the activities of clinical tuberculosis.

2. Treatment

Once the concurrent HIV-positive TB patients, the treatment with conventional anti-TB treatment, but treatment should be extended. Should pay attention to the use of anti-tuberculosis drugs and anti-viral drugs and the interaction between the incompatibility.

Drugs: isoniazid (H), amikacin (A), rifampicin (R), rifapentine (L), ethambutol (E), sodium p-aminosalicylic acid (PAS) , pyrazinamide (Z) and streptomycin (S).

Drug dosage, usage, and the major toxicity in the table below

The name of the drug
  Daily therapy
  Intermittent therapy

Adults (g)

(Week 1-2 times)

 
  The main adverse reactions
 
Adults (g)
  Children

Mg / kg
 
<50kg
  ≥ 50kg
  <50kg
  ≥ 50kg
 
H
  0.3
  0.3
  10-15
  0.5
  0.6
  Liver toxicity, peripheral neuritis
 
S
  0.75
  0.75
  20-30
  0.75
  0.75
  Hearing impairment, renal dysfunction, allergic reactions
 
R
  0.45
  0.6
  10-20
  0.6
  0.6
  Liver toxicity, gastrointestinal reactions, allergic reactions
 
E
  0.75
  1.0
  --
  1.0-1.2
  1.0-1.2
  Visual impairment, narrow field of vision
 
PAS
  8.0
  8.0
  150-250
  10
  12
  Liver toxicity, gastrointestinal reactions, allergic reactions
 
Z
  1.5
  1.5
  30-40
  2.0
  2.0
  Liver toxicity, gastrointestinal reactions, gout
 
L
  
  
  
  0.6
  0.6
  With rifampin
 


     Chemotherapy program (listed in the beginning of two common chemotherapy administration are as follows, more treatment options, see the national tuberculosis control guidelines):

① 2HRZE / 4HR: strengthening period: twelve months, H, R, Z, E, once a day; continue Duration: four months, H, R once a day. ② 2H3 R3 Z3 E3 / 4H3 R3: strengthen the period: two months, H, R, Z, E, the next day once; continue Duration: four months, H, R, the first day.

3. Prevention

Indications: AIDS patients with tuberculosis is not necessary to the prevention of chemical drugs, but clinicians can refer to the following advice for preventive chemotherapy: patients with CD4 + T lymphocyte count <200/mm3, they can carry out preventive chemotherapy, and its programs are: ① rifapentine + isoniazid, take 4-6 consecutive months (dosage see table above). ② Isoniazid, continuous use of 12 months (dosage see table above).

(C) infected with Mycobacterium

1. Diagnosis

Mycobacterium infection in clinical symptoms similar to those with active disease, but systemic change for the common sexually transmitted diseases spread. Diagnosis: blood culture, sputum culture, lung biopsy, bronchial washing sputum of non-material culture of Mycobacterium tuberculosis.

2. Treatment

Other treatment with Mycobacterium tuberculosis.

Mycobacterium Bird (MAC) therapy: treatment of choice: clarithromycin 500 mg / time, 2 times / day or (azithromycin toxin 600mg / day) + ethambutol 15 mg / kg / day (sub-sub-services), critically ill patients can be combined with Rifabutin (300-600 mg / day) or amikacin (10 mg / kg / times by intramuscular injection, 1 times / day), treatment for 6 months. Replacement therapy program: Rifabutin (300-600 mg / day) + amikacin (10 mg / kg / times by intramuscular injection, 1 times / day) + ciprofloxacin (750 mg / time, 2 times / days), treatment for 6 months.

3. Prevention

AIDS patients are not to be of non-tuberculous mycobacterial disease prevention for chemical drugs, doctors can refer to the following based on clinical opinion. AIDS patients, when the CD4 + T lymphocytes <50/mm3 may prophylactic treatment in order to minimize the chance of disseminated MAC. Is clarithromycin 500mg / times, 2 times / day; or Azithromycin, 1200mg / week. If a patient is treated by HAART so that increased CD4 + T lymphocytes> 100/mm3 and sustained ≥ 6 months, to stop drug use prevention.

(D) cytomegalovirus retinal choroiditis

1. Diagnosis

The performance of clinical common vision for the rapid decline in fundus diagnosis depends on microscopic examination.

2. Treatment

(1) Ganciclovir 5mg/kg / day, divided into 2 intravenous ,2-3 weeks later renamed 5mg/kg / day, day 1, intravenous infusion, to maintain life. Can cause neutropenia, thrombocytopenia and renal insufficiency. In a critical condition or a single drug therapy may be combined with intravenous infusion of foscarnet 90mg/kg, 2 times daily. If retinitis also retrobulbar injection of ganciclovir.

(2) intravenous infusion of foscarnet 90mg/kg, 2 times daily, 2-3 weeks after the application changed to long-term intravenous infusion of 90mg/kg per day 1 times, can lead to renal failure, nausea, and electrolyte imbalance, if the creatinine clearance rate of abnormal, then adjust the dose.

3. Prevention

For CD4 + T lymphocyte count <200/mm3 of AIDS patients should have regular eye checks. If CMV disease, should be actively treated disease control in the after life-long medication required to prevent recurrence. For CD4 + T lymphocyte count <50/mm3 of AIDS patients should be given to the prevention of conventional medication (oral ganciclovir), effective in the treatment of patients with HAART if their CD4 + T lymphocyte count> 100/mm3 continued in June and more than can be given to stopping the prevention of drug delivery.

(E) toxoplasma encephalopathy

1. Diagnosis

Toxoplasma encephalopathy often occurred in CD4 + T lymphocyte count <100 / mm3 patients. Manifested as focal or diffuse central nervous system impairment, headache, low fever, drowsiness, restlessness and drowsiness, focal symptoms, including epilepsy and stroke. Other symptoms include: double vision,偏盲, blindness, ataxia, myoclonus, fibrillation, personality changes, hallucinations and syncope. Meningitis is not common. Head CT for one or more low-density lesions, CT-like ring or nodular enhancement. Head MRI is more sensitive than CT, MRI showed the typical multiple intracranial long T1 and long T2 signal. Diagnosis relies on brain biopsy.

2. Treatment

Preferred treatment: pyrimethamine (loading dose 100mg, orally, 2 times / day, then 50-75mg / day to maintain) + sulfadiazine (1-1.5g, orally, 4 times / day), the general course of treatment for three weeks, with severe patients and the clinical, imaging to improve the patients are not satisfied with the treatment could be extended to more than six weeks. Can not be tolerated and will be able to choose sulfa allergy clindamycin 600mg / time, intravenous administration, every administration of the first six hours, the Joint pyrimethamine. Blood system in order to reduce adverse reactions, co-folinic acid 10-20mg / day.

3. Prevention

History of non-Toxoplasma encephalopathy but CD4 + T cell count <100/mm3 and gondii IgG antibody-positive patients should be routine use of cotrimoxazole 2 / day to prevent, for the past suffered from Toxoplasma encephalopathy patients to long-term with pyrimethamine (25-50mg / day) + sulfadiazine joint (2-4g / day) to prevent. HAART treatment of patients with CD4 + T cells make to> 200/mm3 and sustained ≥ 3-6 months, to stop drug use prevention. Antibodies to Toxoplasma gondii negative and CD4 + T cell count <100/mm3 should be avoided in patients infected with Toxoplasma gondii. Specific measures include: meat food should be frozen in -20 ℃; meat cooked food (at least more than 60 ℃) in order to kill tissue cysts; to wash fruits and vegetables; do not a Pet.

(F) fungal infections

1. Diagnosis

Clinical diagnosis of fungal infection, Candida infection is common and cryptococcal infection.

2. Treatment

(1) Candida infection

Oral candidiasis is the first choice for the treatment of partial smear plus nystatin mouthwash mouthwash of sodium bicarbonate, if no response to the above treatment, the treatment can be given as follows: fluconazole: 50mg-100mg / times, oral, 1 times / day , course of 1-2 weeks. Esophageal candidiasis: the first dose of fluconazole 200mg / day, later changed to 100mg / time, 1 times / day, applied 1-2 weeks; increase the dose of fluconazole in critically ill patients and prolong the course of treatment. Candida infection of the proposed recurrent Fluconazole 100mg / day, long-term use.

(2), cryptococcal meningitis

1) The intracranial pressure lowering treatment: the first choice of mannitol, severe lateral drainage are feasible.

2) anti-fungal treatment: the first choice of amphotericin B, first day 1mg, 5% glucose 500ml water slowly static points (should not use normal saline, to be dark), no less than 6-8 hours of infusion. For the second and third days of the 2 mg and 5 mg, by adding glucose 500ml water drip. The fourth day of the absence of reaction can increase to 10mg. If there are no serious response, then later by 5mg / day increase in general up to 30-40 mg (maximum dose 50mg / day). Treatment needs of more than 3 months, the total amphotericin B dose of 2-4g. Adverse effects of amphotericin B greater need close observation. Amphotericin B and 5 - fluorocytosine (5FC) combined with synergy. 5FC to 100mg/kg / day (1.5g-2.0g, 3 / day), the two shared at least 8-12 weeks. Amphotericin B and fluconazole may also be joint use, use for fluconazole 200mg / day, oral or intravenous infusion, 8-12 week course of treatment.

3) if necessary, by the intraventricular injection tube amphotericin B 0.5-1mg / times a day.

4) can be used in stable condition after the maintenance fluconazole, 200mg / time, 1 times / day, the long-term maintenance to prevent recurrence.
 

 
 
 
 
 

[ 作者:佚名    转贴自:本站原创    点击数:196    更新时间:2009-8-13    文章录入:nnb ]

 

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