早期持续高容量血液滤过治疗重症急性胰腺炎的临床研究

 目的 研究早期持续高容量血液滤过（HVHF）对重症急性胰腺炎(SAP)患者的临床疗效。方法 以2005年1月至2011年7月南昌大学第一附属医院重症医学科收治的SAP患者60例为研究对象,随机分为血液滤过 (血滤) 组和对照组,血滤组在采用常规治疗方法的同时,使用HVHF进行早期干预,比较两组患者的腹部症状、生命体征、氧合指数、肝肾功能、急性生理与慢性健康（APACHEⅡ）评分变化。结果 与对照组相比,血滤组早期HVHF治疗后患者发热、心动过速、呼吸窘迫、腹痛、腹胀等症状明显缓解,APACHEⅡ评分［(13.3±1.0)分比(14.1±1.2)分］、血TBil［(20.4±11.3) μmol/L比 (28.1±10.9) μmol/L］、血肌酐［(178.7±71.8) μmol/L比 (215.6±51.3) μmol/L］、血尿素氮［(10.1±5.6) mmol/L比 (13.2±3.8) mmol/L］、血ALT［(51.3±13.2) U/L比(62.5±14.3) U/L］均显著下降(P值均<0.05),氧合指数(PaO₂/FiO₂)（197.3±32.4 比 178.3±31.7）有显著提高(P<0.05),且在血滤治疗过程中患者平均动脉压逐渐上升,心率逐渐下降,与对照组相比差异有统计学意义(P<0.05)。结论 早期持续性HVHF治疗SAP能早期缓解症状,改善病情,阻止全身炎症反应综合征发展为多器官功能障碍综合征;并能改善脏器功能,减少并发症,在SAP早期治疗中具有重要地位。     

男性HIV相关脂肪营养不良综合征患者骨矿含量DXA测量结果浅析

目的分析HIV相关脂肪营养不良综合征患者的骨矿量(BMC)及骨密度(BMD)变化特点。方法 2002年1月至2009年12月在北京协和医院接受抗逆转录病毒治疗(HAART)治疗并行双能X线骨密度测量(DXA)检查的成年男性HIV/AIDS患者41例,年龄20～71岁,平均年龄(43±11)岁。根据患者主诉和医师评估结果,将上述患者分为脂肪营养不良(LD)组与非LD组,分析2组患者骨矿量及骨密度的差异。结果 41例HIV/AIDS患者中,经调整年龄、身高、体重,BMC与脂肪量(FM)间呈正向线性回归关系;LD组患者全身和局部骨BMC均低于非LD组患者,2组患者腰椎BMC差异有统计学意义(P=0.038);LD组患者腰椎和右髋部BMD均低于非LD组患者,2组患者腰椎BMD差异有统计学意义(P=0.028)。结论 DXA对评估HIV-LD患者的骨矿量变化有重要意义,可为骨质疏松的综合预防提供客观依据。     

马利兰和氟达拉滨与马利兰和环磷酰胺预处理方案在急性髓性白血病异基因造血干细胞移植中的比较

 目的 比较马利兰（Bu）和氟达拉滨（Flu）组成的预处理方案（Bu/Flu）与Bu和环磷酰胺（Cy）组成的预处理方案（Bu/Cy）在急性髓性白血病第一次完全缓解（AML-CR1）患者异基因造血干细胞移植（allo-HSCT）中的移植相关毒性和疗效的差异。方法 32例接受allo-HSCT的AML-CR1患者按移植顺序交替分至Bu/Cy组（Bu 3.2 mg·kg^-1·d^-1,移植前第7~4天;Cy 60 mg·kg^-1·d^-1,移植前第3~2天）或Bu/Flu组（Bu 3.2 mg·kg^-1·d^-1,移植前第5～2天;Flu 30 mg·m^-2·d^-1,移植前第6～2天）。评价两组预处理相关毒性（RRT）、移植物抗宿主病（GVHD）发生率与严重程度、3年累积复发率、非复发死亡率（NRM）、3年无病生存（EFS）率和总生存（OS）率等方面的差异。结果 中位随访时间为617.5（6~1261）d。两组中性粒细胞和血小板中位重建时间无明显差异（P=0.121和P=0.171）,移植后30 d嵌合状态分析提示两组患者均达到完全植入。Bu/Cy组预处理后中性粒细胞持续<0.1×10⁹/L和血小板持续﹤20×10⁹/L中位时间明显长于Bu/Flu组［6（3~14）d比2.5（1~9）d,P=0.000;3（1~36）d比1（0~4）d,P=0.047］。Bu/Cy组与Bu/Flu组Ⅱ～Ⅳ度RRT发生率分别为68.8%和25.0%（P=0.032）;急性GVHD发生率分别为46.7%和75.0%（P=0.149）,慢性GVHD发生率分别为46.7%和80.0%（P=0.149）;NRM分别为25.0%和6.3%（P=0.333）;3年累积复发率分别为（17.9±11.7）%和（14.1±9.3）%（P=0.834）;3年EFS率分别为（65.5±12.7）%和（80.2±10.3）%（P=0.362）;3年OS率分别为（68.8±11.6）%和（87.5±8.3）%（P=0.111）。结论 Bu/Flu是一种清髓性预处理方案,与Bu/Cy方案比较具有低骨髓抑制毒性及RRT。Bu/Flu作为AML-CR1患者allo-HSCT预处理方案其疗效不低于Bu/Cy。     

和解通利法治疗结核性包裹性胸腔积液的临床研究

目的 探讨和解通利法治疗结核性包裹性胸腔积液的疗效。 方法 采用随机数字表法将120例结核性包裹性胸腔积液患者随机分为治疗组60例（2例退出,实际为58例）和对照组60例。观察两组治疗前后胸腔积液中肿瘤坏死因子α（TNF-α）浓度的变化情况,治疗后1个月末、3个月末、9个月末患者的胸膜厚度变化情况,以及治疗后3个月末、9个月末患者的综合疗效情况。 结果 胸腔积液中TNF-α浓度治疗组治疗后［（35.35±17.46）pg/L］及对照组治疗后［（47.16±18.89）pg/L］比较,差异有统计学意义（t=－3.114,P＜0.01）。治疗1、3、9个月末CT扫描显示的胸膜厚度治疗组［分别为（0.42±0.27）cm、（0.31±0.26）cm、（0.25±0.21）cm］小于对照组［分别为（0.54±0.30）cm、（0.42±0.32）cm、（0.37±0.28）cm］,差异均有统计学意义（F＝42.727,P=0.000）。两组综合疗效相比,治疗3个月末、9个月末治疗组显效率［分别为70.69%（41/58）、89.66%（52/58）］均优于对照组［分别为45.00%（27/60）、65.00%（39/60）］,差异均有统计学意义(Z=－2.856、－3.192,P值均＜0.05)。 结论 采用和解通利法用药联合抗结核西药治疗结核性包裹性胸腔积液与单纯应用西药抗结核治疗比较,显效率更高;可减少胸膜肥厚粘连;降低胸腔积液中TNF-α水平。     

γ干扰素和转化生长因子β水平与支气管结核治疗效果的关联性研究

目的 探讨血清和支气管灌洗液中γ干扰素(IFN-γ)和转化生长因子β(TGF-β)水平与支气管结核（EBTB）治疗效果之间的关联性。 方法 采用酶联免疫吸附（ELISA）方法测定78例EBTB患者支气管镜下介入治疗前后血清和支气管灌洗液中IFN-γ和TGF-β的水平,以及50名健康对照血清中IFN-γ和TGF-β的水平。EBTB患者被分成2组:一组治疗后表现为支气管狭窄,另一组治疗后未表现为支气管狭窄。 结果 研究显示：（1）与对照组相比,EBTB患者组支气管灌洗液中IFN-γ和TGF-β水平升高。（2）78例EBTB患者治疗后,27例患者显示有支气管的纤维狭窄,51例患者没有支气管狭窄。支气管狭窄组治疗前血清TGF-β水平［（783.21±478.67）pg/ml］比无支气管狭窄组［（1258.60±573.29）pg/ml］低（U=3.8905,P＜0.01）,而支气管灌洗液中TGF-β ［（1219.54±439.27）pg/ml］和IFN-γ ［（2152±1594.33）pg/ml］水平明显高于无狭窄组［（779.24±395.91）pg/ml,（1006.30±752.57）pg/ml］（U值分别为4.3553和3.5315,P值均＜0.01）。 结论 （1）EBTB患者支气管灌洗液中IFN-γ和TGF-β水平升高可能与支气管结核发病机制有关。（2）初始血清TGF-β低水平和支气管灌洗液IFN-γ和TGF-β高水平与治疗后支气管纤维狭窄有关。     

天津市高效抗逆转录病毒治疗艾滋病临床观察

目的评价天津市艾滋病（AIDS）初治患者,应用高效抗逆转录病毒治疗（HAART）的疗效、安全性和预后。方法将在天津市传染病医院就诊的62例AIDS患者,随机分成治疗组（45例）及对照组（17例）;治疗组应用一线HAART方案：AZT／D4T＋3TC＋NVP／EFV。观察两组患者的临床表现、免疫功能变化及预后。结果（1）HAART治疗组与对照组患者基线CD4 T细胞计数差异无统计学意义（P〉0．5）;治疗组的45例患者,HAART前CD4 T细胞计数均值为73／μl;HAART后3、6、12个月时分别为120／μl（39例）、139．5／μl（30例）和200／μl（22例）。（2）治疗组患者应用HAART后,机会性感染、肿瘤的发生率和病死率分别为40％和4．44％,均显著低于对照组的88．24％和47．06％（P〈0．01）。（3）初治患者一线HAART治疗的有效率为95．55%（43／45）,有17．78％（8／45）的患者因药物不良反应而调整HAART方案。结论天津市AIDS患者对一线HAART有较好的疗效,随着HAART疗程的延长,免疫功能得到恢复并改善了预后,存在药物不良反应和资源有限等问题。     

复苏促生长因子结构域及其突变体重组蛋白诱导小鼠免疫应答的研究

目的 评价复苏促生长因子结构域蛋白（Rpfd）及其突变体蛋白（Rpfd1、Rpfd2）等3种重组蛋白的免疫效能。 方法 2011年11月至2012年2月间,分别以本实验前期制备的重组蛋白Rpfd（A组）、Rpfd1（A1组）、Rpfd2（A2组）分别于0、2、4周免疫无特定病原体（SPF）级BALB/c小鼠,每组14只,并分别以BCG（B组）和生理盐水（C组）同期免疫同种小鼠各14只作为对照。第5周,每组取7只小鼠摘眼球取血,ELISA法检测血清特异性抗体、血清IFN-γ和IL-2表达水平;第8周,每组剩余7只小鼠用1×10⁵ CFU结核分枝杆菌标准株H37Rv感染小鼠,第9周检测感染后小鼠血清细胞因子IFN-γ和IL-2水平。 结果 （1）抗体水平：①Rpfd抗原包被。A1组刺激小鼠产生抗体A₄₅₀的检测值（0.990±0.272）高于B组（0.631±0.180）（t=4.635,P<0.05）;A2组（1.470±0.455）高于B组（t=6.634,P<0.05）。②Rpfd1抗原包被。A组刺激小鼠产生抗体A₄₅₀的检测值（1.030±0.304）高于B组（0.573±0.004）（t=5.276,P<0.05）;A1组（1.368±0.171）高于B组（t=17.20,P<0.05）;A2组（2.766±0.245）高于B组（t=31.643,P<0.05）;③Rpfd2抗原包被。A1组刺激小鼠产生抗体A₄₅₀的检测值（1.055±0.202）高于B组（0.538±0.100）（t=8.009,P<0.05）;A2组（1.605±0.544）高于B组（t=8.192,P<0.05）。（2） IFN-γ水平：①感染前。A组刺激小鼠产生IFN-γ水平［（553.47±132.00）pg/ml］高于B组［（385.28±129.07）pg/ml］（t=3.150,P<0.05）;②感染后。A1蛋白组刺激小鼠产生IFN-γ水平［（492.41±211.74）pg/ml］高于B组［（335.36±207.72）pg/ml］（t=2.874,P<0.05）;A2组［（543.09±223.07）pg/ml］高于B组（t=3.15,P<0.05）。（3）IL-2水平：①感染前。A组刺激小鼠产生IL-2水平［（1490.05±215.35）pg/ml］高于B组［（718.70±269.29）pg/ml］（t=7.763,P<0.05）;A1组［（1738.91±358.40）pg/ml］高于B组（t=7.903,P<0.05）;A2组［（2270.74±193.40）pg/ml］高于B组（t=16.308,P<0.05）;②感染后。A组刺激小鼠产生IL-2水平［（806.81±306.39）pg/ml］高于B组［（335.26±176.81）pg/ml］（t=4.627,P<0.05）;A1组［（1373.22±143.75）pg/ml］高于B组（t=15.90,P<0.05）。 结论 Rpfd、Rpfd1、Rpfd2蛋白具有启动宿主体液免疫功能及增强宿主细胞免疫功能的双重作用,可能成为预防及治疗Mtb感染的免疫新策略。     

CD4＋T淋巴细胞对肺结核患者血清白蛋白的影响

目的 探讨外周血CD4⁺ T淋巴细胞对肺结核患者血清白蛋白的影响。 方法 对119例初治肺结核患者进行淋巴细胞亚群和血清白蛋白测定,探讨细胞免疫功能与血清白蛋白相关性;同时,根据其CD4⁺ T淋巴细胞亚群水平,分为免疫低下组62例和正常组57例,探讨细胞免疫功能低下对低蛋白血症的影响。 结果 （1）所有纳入患者外周血CD4⁺ T淋巴细胞［（516.6±266.1）×10⁹/L］与CD3⁺ T淋巴细胞［（841.6±398.8）×10⁹/L］、CD8⁺ T淋巴细胞［（261.0±142.6）×10⁹/L］、CD4⁺/CD8⁺ T淋巴细胞比值（2.33±1.40）呈正相关（分别为r=0.883,P=0.000;r=0.579,P=0.000;r=0.365,P=0.000）。（2）外周血CD4⁺T淋巴细胞与血清白蛋白呈正相关（r=0.116,P=0.033）。（3）在免疫低下组中,肺部病灶范围达4个肺野以上者43例（占69.4%）,明显高于正常组的22例（占38.6%）,差异有统计学意义（χ²=11.335,P=0.001）;免疫低下组治疗前血清白蛋白［（33.9±5.5）g/L］明显低于正常组［（36.1±5.7）g/L］（t=2.187,P=0.031）。 结论 在肺结核患者中CD4⁺ T淋巴细胞与治疗前血清白蛋白水平呈正相关。CD4⁺ T淋巴细胞低下肺结核患者,其病灶范围较广,容易并发低蛋白血症。     

云南省245例AIDS患者死亡原因分析

目的　分析云南省245例AIDS患者的死亡原因及特点,为预防及干预策略提供参考。方法　收集云南省传染病医院2015年1月—2019年12月收治的245例AIDS死亡患者的病例资料,并进行回顾性分析。结果　245例AIDS死亡患者中CD4+ T淋巴细胞计数≤50个/μl 129例（52.65%）,86例行HIV RNA检测,病毒载量为（3.90±0.75）lg拷贝/ml;74例（30.20%）行高效抗反转录病毒治疗（highly active antiretroviral therapy, HAART）,平均生存时间为（1106.0±72.5）d;171例（69.80%）未行HAART,平均生存时间为（710.0±25.5）d,行HAART组生存时间长于未行HAART组,差异具有统计学意义（t=9.338,P=0.002）。245例AIDS患者中183例合并机会性感染（opportunistic infections, OIs）。死于HIV相关性原因192例（78.36%）,死于非HIV相关原因53例（21.64%）。在行HAART组与未行HAART组中死于HIV相关原因患者分别为70.27%、81.87%,两者相比,差异具有统计学意义（χ2=4.100,P=0.043）;HIV相关死亡原因中,感染性休克在行HAART组与未行HAART组中的占比分别为24.31%、41.52%,未行HAART组死于感染性休克发生率高于行HAART组,差异具有统计学意义（χ2=6.603,P=0.010）。结论　AIDS死亡患者普遍合并OIs,且确诊时间晚、HAART率低、CD4+ T淋巴细胞计数低、病毒载量高。OIs仍然是导致AIDS患者死亡的主要原因,早期有效的HAART可以延长AIDS患者的生存期,降低病死率。     

炎症性肠病患者外周血辅助性T细胞1和辅助性T细胞17水平及其临床意义

 目的 探讨炎症性肠病（IBD）患者外周血Th1和Th17细胞水平对IBD发病及活动度的意义。方法 收集2011年5月至2012年7月健康对照者40例和IBD患者81例［其中克罗恩病（CD）39例,溃疡性结肠炎（UC）42例］,采集外周血标本。分离外周血单个核细胞,经PMA及伊屋诺霉素联合刺激、培养后,利用流式细胞仪检测Th1和Th17细胞在外周血CD⁺₄T细胞中的百分比,并结合临床资料分析其临床意义。结果 （1）CD组及UC组Th1细胞百分比［(38.32±16.18)%和(34.23±11.60)%］均明显高于健康对照组［(24.58±10.02)%］（P值均<0.01）,而CD组及UC组的差异无统计学意义;CD及UC缓解期患者的Th1细胞百分比均低于活动期患者［(26.50±9.24)%比(48.46±13.83)%,P<0.01;(30.05±7.41)%比(37.68±13.35)%,P<0.05］。（2）CD组及UC组Th17细胞百分比［(2.51±1.59)%和(4.15±2.75)%］均高于健康对照组［(1.44±0.73)%］（P值均<0.01）,且UC组这一比例高于CD组（P<0.01）;CD及UC活动期患者的Th17细胞百分比明显高于缓解期患者［(3.39±1.56)%比(1.48±0.81)%,(5.77±2.77)%比(2.18±0.59)%,P值均<0.01］。（3）UC组外周血Th17/Th1比值（0.14±0.11）高于CD组（0.08±0.06）和健康对照组（0.07±0.06）,P值均<0.01。结论 IBD患者外周血中Th1、Th17细胞占CD⁺₄T细胞比例较健康人群明显升高,且与IBD活动度密切相关。Th1和Th17细胞在IBD发病中可能具有重要作用。     

Influenza-related mortality among adults aged 25-54 years with AIDS in South Africa and the United States of america

Background.?Data are limited on human immunodeficiency virus (HIV)-associated influenza burden in sub-Saharan Africa and the impact of highly active antiretroviral therapy (HAART). We compared influenza-related mortality in adults with AIDS in South Africa and the United States in the pre-HAART era and evaluated mortality trends after HAART introduction in the United States. Methods.?Monthly all-cause and pneumonia and influenza (P&I) mortality rates were compiled for adults with AIDS aged 25-54 years in South Africa (1998-2005) and the United States (pre-HAART era, 1987-1994; HAART era, 1997-2005). We estimated influenza-related deaths as excess mortality above a model baseline during influenza epidemic periods. Influenza-related mortality rates in adults with AIDS were compared with rates for age peers in the general population and adults ≥65 years old. Results.?In the United States before HAART, influenza-related mortality rates in adults with AIDS were 150 (95% confidence interval [CI], 49-460) and 208 (95% CI, 74-583) times greater than in the general population for all-cause and P&I deaths, respectively, and 2.5 (95% CI, 0.9-7.2) and 4.1 (95% CI, 1.4-13) times higher than in elderly adults. After HAART introduction , influenza-related mortality in adults with AIDS dropped 3-6-fold but remained elevated compared with the general population (all-cause relative risk [RR], 44 [95% CI, 16-121]); P&I RR, 73 [95% CI, 47-113]). Influenza-related mortality in South African adults with AIDS in recent years was similar to that in the United States in the pre-HAART era. Conclusions.?Adults with AIDS experience substantially elevated influenza-associated mortality, which declines with widespread HAART introduction but does not disappear. These data support increased access to HAART and influenza vaccination for HIV-infected adults.     

获得性免疫缺陷综合征患者胃黏膜组织人类免疫缺陷病毒感染分析

目的 探讨获得性免疫缺陷综合征(AIDS)患者胃黏膜组织中人类免疫缺陷病毒(HIV)感染的分布、数量及高效抗逆转录病毒治疗(HAART)前、后的变化.方法 选取伴有消化道症状的AIDS患者35例,对照组为HIV-1阴性者10例,均进行胃镜检查.PCR法制备地高辛标记HIV-1 LTR、gag基因的双链cDNA探针,对胃黏膜组织冰冻切片采取核酸原位杂交法观察HIV感染情况,并与外周血单个核细胞(PBMC)涂片对比.结果 ①AIDS患者胃镜下多表现为不同程度的慢性浅表性胃炎(CSG)和慢性萎缩性胃炎(CAG),AIDS患者临床消化道症状、胃镜下表现及病理结果未见明显特征性.②AIDS患者胃黏膜组织内HIV阳性显色多见于单个核细胞(MMC)中,胃黏膜上皮、腺上皮细胞和问质细胞中亦有阳性杂交信号.③胃窦黏膜组织与胃体黏膜组织HIV阳性率差异无统计学意义(P>0.05).④AIDS患者胃黏膜HIV阳性率为(1.97±3.25)%,AIDS未治疗组与HAART治疗组各组间胃窦和胃体部HIV阳性率差异均无统计学意义(P值均>0.05).PBMC中HIV总阳性细胞率为(12.38±9.17)%;AIDS未治疗组PBMC中HIV阳性细胞率为(19.37±9.23)%,AIDS治疗1～4年组为(4.25±3.47)%,两组间差异有统计学意义(P<0.05).结论 胃黏膜是HIV感染的靶部位之一,HAART治疗对AIDS患者胃黏膜感染收效甚微.     

艾滋病患者胃黏膜与外周血中人类免疫缺陷病毒感染和CD4~+T淋巴细胞数量的区室性差异的探讨

目的 探讨AIDS患者胃黏膜与外周血中HIV感染和CD4~+T淋巴细胞数量的区室性差异.方法 选取AIDS患者35例,对照组为HIV抗体阴性者10例,均进行胃镜检查并收集外周血.PCR法制备地高辛标记HIV-1长末端重复序列(LTR)、gag基因的双链cDNA探针,核酸原位杂交方法观察胃黏膜组织冰冻切片和外周血单个核细胞(PBMC)涂片H1V感染情况,免疫组织化学方法检测CD41T淋巴细胞,数据结果行t检验.结果 AIDS未治疗组胃黏膜中HIV阳性率为(1.67±1.48)%,PBMC中为(19.37±9.23)%.AIDS未治疗组与高效抗反转录病毒治疗(HAART)组各组间的胃黏膜HIV阳性率差异尤统计学意义(t=-0.996,t=-0.794,t=-0.461;P＞0.05).PBMC涂片中,治疗1～4年组HIV阳性率为(4.25±3.47)%,明显低于未治疗组的(19.37±9.23)%(t=3.000,P＜0.05).AIDS未治疗组胃黏膜单个核细胞(MMC)中CD4+T淋巴细胞阳性率为(12.53±8.14)%,PBMC中CD4+T淋巴细胞阳性率为(19.00±9.55)%,HAART1～4年组胃黏膜MMC中CD4~+T淋巴细胞计数为(37.44±18.00)%,仍低于对照组的(50.35±3.41)%(t=-4.620,P＜0.01),但PBMC中CD4+T淋巴细胞计数与对照组比较,差异无统计学意义(t=-2.094,P＞0.05).结论 胃黏膜与外周血中HIV感染和CD4~+T淋巴细胞数量存在区室性差异.     

Analysis of CCR5, CCR2, CX3CR1, and SDF1 polymorphisms in HIV-positive treated patients: impact on response to HAART and on peripheral T lymphocyte counts

Although polymorphisms of chemokine genes (SDF1, stromal cell-derived factor-1 and RANTES, regulated on activation, normal T cell expressed and secreted) and chemokine-receptor genes (CCR5, CCR2, CX(3)CR1) were shown to be associated with sensitivity to HIV infection and untreated HIV disease progression, their association with the response to highly active antiretroviral therapy (HAART) remains unclear. To explore the possible influence of such polymorphisms on the evolution of AIDS in treated patients, we have studied SDF1-3'A, CCR5Delta32, CCR2-64I, CX(3)CR1-249I, and CX(3)CR1-280M polymorphisms in HIV-infected patients under HAART (n = 169). We studied the evolution of plasma virus load and peripheral T lymphocyte counts in these patients up to 3 years after the initiation of HAART. We observed that some of the genetic polymorphisms studied had an impact on the evolution of these two parameters. After 1 year of HAART, patients with a virological response (undetectable plasma HIV-1 RNA) have a higher frequency of the homozygous SDF1-3'A genotype than other patients (p = 0.005). Similarly, patients with a CD4 increase of over 200/mm(3) from baseline after 1 year of HAART display higher frequencies of homozygous SDF1-3'A (p = 0.035) and homozygous CX(3)CR1-280M genotypes (p = 0.04) than other patients. Moreover, we showed that the CX(3)CR1- 280M allele was associated with higher peripheral CD4+ T cell counts not only in HIV+ patients but also in healthy controls (p = 0.003).     

Highly active antiretroviral-treated HIV-infected children show fat distribution changes even in absence of lipodystrophy.

BACKGROUND: Combined use of dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) allows a precise estimate of regional body composition and intra-abdominal adipose tissue (IAT). Data on body composition in HIV-infected children (HIV+) receiving highly active antiretroviral therapy (HAART) with (LD+) and without (LD-) lipodystrophy are lacking. METHODS: DXA scans were performed in 34 HIV+: six LD+, 28 LD- and 34 pair-matched (age, sex and body mass index) healthy controls (HC): six for LD+ (HC+) and 28 for LD- (HC-). MRI scans were performed in 16 HIV+: six LD+, 10 LD- and 16 pair-matched (age and sex) HC. Data were analysed by analysis of variance, post hoc Fisher test and Mann-Whitney test. RESULTS: LD+ and LD- were similar for: previous exposure to zidovudine/zidovudine + didanosine, months on HAART (stavudine + lamuvidine + one protease inhibitor), CD4+ cells, patients with HIV-RNA < 50 copies/ml. In HIV+ and HC, fat mass and distribution were significantly different, whereas lean mass was comparable. Thus, LD+ and LD- as compared to HC+ and HC- respectively showed: (1) reduced fat amount and percentage; (2) lower truncal fat mass; (3) markedly reduced limbs fat mass. Within the HIV+ group, (4) LD+ showed higher fat trunk/fat total (P = 0.04) and lower fat limbs/ fat total ratios (P = 0.009) than LD-; (5) LD+ showed larger IAT areas than LD- and HC (P < 0.0003). CONCLUSIONS: Increased central fat and peripheral lipoatrophy are distinctive features of all HAART-treated children. Changes in body fat composition are detectable by DXA even in the absence of signs of Lipodystrophy. Only LD+ show true central obesity.     

Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies

OBJECTIVE: To estimate the prognosis over 5 years of HIV-1-infected, treatment-naive patients starting HAART, taking into account the immunological and virological response to therapy. DESIGN: A collaborative analysis of data from 12 cohorts in Europe and North America on 20,379 adults who started HAART between 1995 and 2003. METHODS: Parametric survival models were used to predict the cumulative incidence at 5 years of a new AIDS-defining event or death, and death alone, first from the start of HAART and second from 6 months after the start of HAART. Data were analysed by intention-to-continue-treatment, ignoring treatment changes and interruptions. RESULTS: During 61 798 person-years of follow-up, 1005 patients died and an additional 1303 developed AIDS. A total of 10 046 (49%) patients started HAART either with a CD4 cell count of less than 200 cells/microl or with a diagnosis of AIDS. The 5-year risk of AIDS or death (death alone) from the start of HAART ranged from 5.6 to 77% (1.8-65%), depending on age, CD4 cell count, HIV-1-RNA level, clinical stage, and history of injection drug use. From 6 months the corresponding figures were 4.1-99% for AIDS or death and 1.3-96% for death alone. CONCLUSION: On the basis of data collected routinely in HIV care, prognostic models with high discriminatory power over 5 years were developed for patients starting HAART in industrialized countries. A risk calculator that produces estimates for progression rates at years 1 to 5 after starting HAART is available from www.art-cohort-collaboration.org.     

Increased fat accumulation in the liver in HIV-infected patients with antiretroviral therapy-associated lipodystrophy

OBJECTIVE: To determine liver fat content in patients with highly active antiretroviral therapy (HAART)-associated lipodystrophy. BACKGROUND: Lipodystrophy in several animal models is associated with fat accumulation in insulin-sensitive tissues, such as the liver. This causes hyperinsulinaemia, dyslipidaemia and other features of insulin resistance. DESIGN: A cross-sectional study. SUBJECTS AND METHODS: Three age- and weight-matched groups were compared: 25 HIV-positive men with HAART-associated lipodystrophy (HAART+LD+), nine HIV-positive men receiving HAART, but without lipodystrophy (HAART+LD-), and 35 HIV-negative healthy men (HIV-). Liver fat content was measured using proton spectroscopy. Intra-abdominal and subcutaneous fat were determined using magnetic resonance imaging. RESULTS: Liver fat content was significantly higher in the HAART+LD+ (8 +/- 10%) than the HIV- (5 +/- 7%; P < 0.05) or the HAART+LD- (3 +/- 5%; P < 0.01) group. Liver fat content correlated with serum fasting insulin in the HAART+LD+ (r = 0.47; P < 0.05) and HIV- groups (r = 0.65; < 0.001), but not with the amount of intra-abdominal fat. Within the HAART+LD+ group, serum insulin did not correlate with the amount of intra-abdominal fat. The HAART+LD+ group had a lower serum leptin concentration when compared to the two other groups. Features of insulin resistance, including hepatic fat accumulation, were not found in HAART+LD-group. CONCLUSIONS: The severity of the insulin resistance syndrome in patients with HAART-associated lipodystrophy is related to the extent of fat accumulation in the liver rather than in the intra-abdominal region. Fat accumulation in the liver may therefore play a causative role in the development of insulin resistance in these patients.