CXCR5~+CD8~+ T细胞在HIV感染中的免疫特征及其与疾病进展关系的研究

目的探讨HIV感染者外周血CXCR5~+CD8~+T细胞的频率、功能变化及其与病情进展的相关性。方法收集40例HIV感染者和15例健康对照者,采用流式细胞分析术检测其外周血CXCR5~+CD8~+T细胞频率及IFN-γ和IL-10表达,并分析其与血浆HIV载量和外周血CD4~+T细胞计数的相关性。结果与健康对照组相比,HIV感染组外周血CXCR5~+CD8~+T细胞频率上调(P0.05),且与外周血CD4~+T细胞计数呈弱正相关(r=0.349,P=0.027),与血浆HIV载量呈弱负相关(r=-0.377,P=0.040);HIV感染者外周血CXCR5~+CD8~+T细胞IFN-γ表达与血浆HIV载量呈负相关(r=-0.514,P=0.002);而CXCR5~+CD8~+T细胞IL-10的表达在HIV感染者中明显上调(P0.05),与外周血CD4~+T细胞计数呈弱负相关(r=-0.317,P=0.046),与血浆HIV载量呈正相关(r=0.670,P=0.002)。结论 HIV感染者外周血CXCR5~+CD8~+T细胞频率功能变化与疾病进展密切相关。     

HIV/HCV混合感染患者肿瘤坏死因子相关凋亡诱导配体水平分析

目的探讨肿瘤坏死因子相关凋亡诱导配体(TRAIL)及其受体在艾滋病病毒(HIV)/丙型肝炎病毒(HCV)混合感染者发病机制中的作用。方法用流式细胞术检测DR4~+CD4~+T淋巴细胞(CD4~+T淋巴细胞简称CD4细胞)、DR5~+CD4~+T细胞、TRAIL~+CD4~+T细胞的比例,CD4细胞计数;用酶联免疫吸附试验检测血浆可溶性TRAIL(s TRAIL)浓度;用荧光定量聚合酶链反应(PCR)测定血浆HIV、HCV核糖核酸载量。结果混合感染者DR5~+CD4~+T细胞比例高于HCV单纯感染者(P=0.03),与HIV单纯感染者相比无统计学差异(P 0.05)。未接受高效抗反转录病毒治疗(HAART)的HIV单纯感染者的sTRAIL浓度高于接受HAART的HIV单纯感染者(P 0.01)。sTRAIL浓度与HIV病毒量呈正相关(r=0.631,P 0.01);DR5~+CD4~+T细胞比例与CD4细胞计数呈正相关(r=0.377,P 0.01)。结论在HIV感染状态下,CD4细胞可能对TRAIL诱导的凋亡更加敏感,而混合感染HCV后对CD4细胞凋亡的进一步影响或许并不涉及TRAIL及其受体。     

HIV和HCV重迭感染者病毒载量间及与T淋巴细胞计数的相关性研究

目的探讨艾滋病病毒(HIV)和丙型肝炎病毒(HCV)重迭感染者两病毒载量间及其与T淋巴细胞计数的相关性。方法采用流式细胞技术和荧光定量PCR技术，对15例HIV和FICV重迭感染者进行了CD3^ 、CD4^ 、CD8^ 淋巴细胞计数和病毒核酸载量测定，并选用多种数学模型进行相关性分析。结果单因素相关回归分析显示：HIV病毒载量与CD3^ 和CD4^ 细胞计数分别呈现良好的负相关关系(r=-0．6013，P=0．0177；r=-0．8828，P=0．0000)，HCV病毒载量与CD3^ 和CD4^ 细胞计数分别呈现良好的正相关关系(r=0．5931，P=0．0198；r=0．8627，P=0．0000)，HIV和HCV病毒载量间存在统计学负相关关系(r=-0．8954，P=0．0000)。多因素线性相关回归分析表明：CD3^ 和CD4^ 细胞计数及HCV病毒载量与HIV病毒载量间均呈现良好的统计学负相关关系(r=-0．6051，P=0．0169；r=-0．8828，P=0．0000；r=-0．8954，P=0．0000)。逐步回归分析显示：CD4^ 细胞计数和CD4^ ／CD8^ 比值及HCV病毒载量与HIV病毒载量间分别存在统计学负相关关系。结论HIV／HCV重迭感染时．两病毒间表现出竞争性抑制或干扰现象．导致CD4^ 细胞计数多样化改变并呈现出下降趋势。     

滤泡调节性T细胞与HIV感染疾病进展关系的研究

目的　探索滤泡调节性T细胞（follicular regulatory T cell, TFR）与HIV感染疾病进展的关系。方法　以2015—2019年于首都医科大学附属北京佑安医院门诊就诊及随访的47例HIV感染者（包括未治疗HIV感染者，抗病毒治疗免疫重建成功和免疫重建失败患者）及9例健康体检者作为研究对象。将CD3+CD4+CXCR5+Foxp3+的细胞定义为TFR，分析HIV感染者TFR数量与CD4+ T细胞计数及病毒载量的关系，并对比分析不同疾病阶段患者TFR数量的差异。结果　TFR数量与CD4+ T细胞计数呈正相关（r=0.567，P=0.002），与HIV载量呈负相关（r=-0.394，P=0.042）；HIV感染者的TFR数量明显低于健康体检者，免疫重建成功的患者TFR数量明显高于免疫重建失败的患者。结论　随着HIV感染疾病的进展，TFR数量逐渐降低。     

人类免疫缺陷病毒和丙型肝炎病毒重叠感染者的临床及免疫特征

目的 观察人类免疫缺陷病毒(HIV)和HCV重叠感染者与慢性丙型肝炎患者临床特征及HCV特异性细胞毒性T淋巴细胞(CTL)的数量及功能,探讨两组患者免疫功能的差异及其可能的影响因素.方法 以HIV和HCV重叠感染患者59例、慢性丙型肝炎患者36例为研究对象,取治疗前外周血检测肝脏生物化学指标、血常规、外周血T淋巴细胞亚群(CD4+T、CD8+T淋巴细胞计数)及HIV、HCV病毒载量,以酶联免疫斑点法检测HCV特异性CTL的数量和功能,统计学分析两组问免疫功能的差异及与上述检测指标的相关性. 结果 中国河南省有偿献血、单采血浆人群HIV感染者中HIV和HCV重叠感染率达60.8%.ALT、AST值在重叠感染组与HCV组间差异无统计学意义;球蛋白在重叠感染组为(40.3±5.8)g/L,HCV组为(32.8±6.3)g/L,差异有统计学意义(P＜0.01).重叠感染组外周血CD4+T淋巴细胞数明显低于HCV组(P＜0.01),而CD8+T淋巴细胞数高于HCV组(P＜0.01).重叠感染组HCV RNA定量高于HCV组(P＜0.01).重叠感染组对HCV-NS3区肽段的反应强度(每106个外周血单个核淋巴细胞中斑点形成细胞的个数)较HCV组弱,649.34±685.90对比1233.70±1085.16,差异有统计学意义(P＜0.05).重叠感染组白蛋白与HCV病毒载量呈现负相关(r=0.540);重叠感染组对HCV-NS3区肽段反应强度与HIV病毒载量负相关(r=0.356);重叠感染患者CD4+T淋巴细胞数与血小板正相关(P＜0.05).但未见重叠感染组HCV RNA与CD4+T淋巴细胞数量及HIVRNA水平有相关关系.结论 重叠HIV感染有利于HCV的复制,而HIV载量可影响针对HCV的特异性免疫反应,HIV载量高则不利于HCV的清除.慢性丙型肝炎患者重叠HIV感染时,病情易慢性化,预后更差.     

人类免疫缺陷病毒感染者重叠输血传播病毒感染的临床研究

目的 了解中国地区人类免疫缺陷病毒（HIV-1）感染者重叠输血传播病毒（TTV）感染的流行情况,并探讨重叠感染TTV对CD4^＋T淋巴细胞计数及HIVRNA病毒载量的影响。方法收集55例HIV-1感染者的血浆标本,采用荧光定量PCR法检测TTVDNA,流式细胞法检测T淋巴细胞亚群,bDNA方法检测HIVRNA。结果HIV感染者中TTVDNA检出率及TTVDNA滴度明显高于健康对照组（P〈0．05）。HIV／TTV重叠感染者CD4^＋T淋巴细胞计数低于单纯HIV感染者。HIVRNA病毒载量高于单纯HIV感染者,两组比较差异有统计学意义（P〈0．05）。结论中国地区HIV感染者易重叠感染TTV,且滴度较高。重叠感染TTV可能导致细胞免疫功能进一步下降,加快病毒复制,促进HIV病程的进展。     

T淋巴细胞激活亚群在HIV感染中的变化及其临床意义

目的：研究HIV／AIDS患者T淋巴细胞激活亚群的变化，探讨其临床意义。方法：用流式细胞仪检测59例HIV／AIDS患者和51例健康献血员的T淋巴细胞，对其中40例患者的所有健康献血员进一步分析T淋巴细胞激活亚群（HLA－DR^ CD4^ 、HLA-DR^ CD8^ 和CD38^ CD8^ ）；用bDNA病毒定量检测仪检测59例HIV／AIDS患者的血浆HIV病毒载量。结果：与正常人组相比，HIV组和AIDS组的T淋巴细胞各激活亚群的百分比均显著升高，所有激活亚群均与T4细胞计数成反比，而与病毒载量成正比。其中，CD38^ CD8^ 亚群的百分比与T4细胞计数和病毒载量的相关性最为密切，相关系数分别为r=-0.603和r=0.523，（P＜0．01）。结论；HIV／AIDS患者的T淋巴细胞发生持续和异常的免疫激活，细胞激活程度与疾病进展高度相关，测定这些激活的T细胞亚群变化不仅有助于评价HIV／AIDS患者的免疫状况、判断病毒复制的活跃程度，而且对预示疾病进展和临床疗效评价方面均具有重要价值。     

HIV-1慢性感染者CD39~+PD-1~+CD4~+T淋巴细胞特点与抗病毒治疗疗效的关系

目的通过分析1型艾滋病病毒(HIV-1)感染者不同疾病阶段CD39~+PD-1~+CD4~+T淋巴细胞(简称CD39~+PD-1~+CD4细胞)的特点及其与潜伏病毒库形成的关系,探讨CD39~+PD-1~+CD4细胞的临床意义。方法通过流式细胞术检测CD4细胞上CD39及PD-1的表达情况,分析CD39~+PD-1~+CD4细胞与CD4细胞计数、病毒载量及CD4细胞内病毒指标的相关性。通过实时荧光定量聚合酶链反应(PCR)检测免疫重建成功患者(CRs)和免疫重建失败患者(INRs)的HIV库,分析CD39~+PD-1~+CD4细胞与HIV库的关系。结果入组11例健康对照(HCs)和69例HIV-1感染者,其中包括38例未抗病毒治疗(ART)者(TNs)、21例CRs、10例INRs。1)与HCs相比,TNs组患者CD39~+PD-1~+CD4细胞亚群占比显著升高(平均值0.99%vs. 2.50%);与TNs组相比,ART后,CRs组患者的CD39~+PD-1~+CD4细胞亚群占比显著降低(平均值2.50%vs. 0.86%);而INRs组患者该细胞亚群占比显著高于CRs组(平均值2.74%vs. 0.86%);2)在TNs组患者中CD39~+PD-1~+CD4细胞亚群占比与CD4细胞计数呈负相关(r=-0.359 6, P=0.026 6),与病毒载量呈正相关(r=0.451 1, P=0.004 5);3)ART两年以上患者CD39~+PD-1~+CD4细胞亚群占比与HIV脱氧核糖核酸(HIV DNA)正相关(r=0.565 9,P=0.047 3),与细胞相关的未剪接HIV核糖核酸(HIV us RNA)正相关(r=0.675 8,P=0.013 7)。结论 CD39~+PD-1~+CD4细胞与ART后免疫重建失败相关,其机制可能是CD39~+PD-1~+CD4细胞促进HIV建立潜伏病毒库。     

HIV急性期/早期感染者合并HBV感染的临床特征

目的探讨艾滋病病毒(HIV)急性期/早期感染者合并感染乙型肝炎病毒(HBV)的临床特点及实验室特征,进一步明确影响HIV/HBV重叠感染疾病进展的关键因素。方法采用回顾性分析的方法,了解单独HIV急性期/早期感染者(单独HIV感染组)和合并HBV的HIV急性期/早期感染者(HIV/HBV重叠感染组)的初始CD+4T淋巴细胞(简称CD4细胞)计数和病毒载量调定点,以及两组病人感染HIV一年内CD4细胞计数和HIV病毒载量的动态变化,和HIV急性期/早期合并HBV感染的临床特征。结果 20例HIV/HBV重叠感染组的初始CD4细胞计数平均值为(443.55±197.00)个/μL(213~985个/μL),病毒载量调定点(4.34±0.99)Log10拷贝/mL(1.82~5.47Log10拷贝/mL)。30例单独HIV感染组病人的初始CD4细胞计数平均值为(497.37±121.29)个/μL(196~792个/μL),病毒载量调定点(3.87±0.62)Log10拷贝/mL(2.77~5.19Log10拷贝/mL)。HIV/HBV重叠感染组的初始CD4细胞计数明显低于单独HIV感染组,两组比较差异有统计学意义(P0.05)。HIV/HBV重叠感染组的病毒载量调定点明显高于单独HIV感染组,两组间差异有统计学意义(P0.05)。结论在我国HIV急性期/早期感染者中,HIV/HBV重叠感染者与单独HIV感染者比较,初始CD4细胞计数明显降低,病毒载量调定点明显升高,HIV病毒复制更为活跃。     

HIV／AIDS患者血浆病毒载量及外周血T淋巴细胞亚群的变化

目的：观察国内HIV／AIDS患者血浆病毒载量和外周血CD4^ 、CD8^ T淋巴细胞的变化，探讨这些变化的临床意义。方法：选择未经抗病毒治疗的HIV／AIDS患者124例，用bDNA法检测血浆病毒载量，并用流式细胞仪检测外周血CD4^ 、CD8^ T淋巴细胞。结果：AIDS患者的血浆病毒载量明显高于HIV感染者，血浆病毒载量与CD4^ 细胞计数呈显著负相关，但其最高峰位于CD4^ 细胞计数100／μl处，然后随着CD4^ 细胞计数的下降而减少。CD4^ T细胞计数为AIDS组＜HIV组＜正常对照组：HIV感染者的CD8^ T细胞计数显著高于正常组和AIDS组，而AIDS患者CD8^ T细胞数则随着CD4^ T细胞减少而下降。结论：血浆病毒载量随着疾病进展而显著升高，但在疾病晚期则有所降低。外周血CD4^ T细胞计数随着疾病的进展而进行性减少；CD8^ T细胞计数在感染早期显著升高，进入晚期则减少。在评价HIV感染者和AIDS患者病情时，应结合病毒载量、CD4^ 、CD8^ T细胞计数综合分析。     

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.     

HIV感染者外周浅表淋巴结中CD4~+T淋巴细胞计数与胶原沉积的关系研究

目的通过对不同感染阶段HIV感染者外周浅表淋巴结中CD4+T淋巴细胞、胶原蛋白、白细胞介素(interleukin,IL)-7的检测,以及CD4+T淋巴细胞计数与胶原沉积的相关性分析,探讨HIV感染后胶原沉积对CD4+T淋巴细胞的影响。方法选择HIV感染者43例,分为HIV感染无症状组和AIDS组,留取外周浅表淋巴结活体组织检查(活检)组织;另外选择非HIV感染者12名为健康对照组,同样留取其外周浅表淋巴结活检组织。利用免疫组织化学方法检测研究对象淋巴结中CD4+T淋巴细胞、Ⅰ型胶原蛋白和IL-7定量及分布情况。结果 1随着病程进展,HIV感染者外周浅表淋巴结中胶原沉积逐渐增加,AIDS组高于无症状组,无症状组高于健康对照组,差异均有统计学意义(P均0.05);2HIV感染无症状组外周浅表淋巴结中CD4+T淋巴细胞计数与健康对照组相比差异无统计学意义(P0.05),而AIDS组则显著减少(P0.01);3HIV感染者外周浅表淋巴结中CD4+T淋巴细胞计数与胶原沉积量呈负相关(R2=0.724,P=0.000),与外周血中CD4+T淋巴细胞计数呈正相关(R2=0.702,P=0.000);43组IL-7的表达水平差异无统计学意义(P0.05),而AIDS组部分患者淋巴结中IL-7呈局部聚集性分泌。结论 HIV感染后外周浅表淋巴结中胶原沉积逐渐增加导致结构破坏,可能是CD4+T淋巴细胞进行性减少的一个重要原因,虽然IL-7有随病程进展而分泌增加的趋势,但仍不足以弥补淋巴结结构破坏对CD4+T淋巴细胞的影响。     

HIV感染者CD4+调节性T细胞与HIV DNA呈正相关

目的分析CD4+调节性T细胞与艾滋病病毒(HIV)脱氧核糖核酸(DNA)之间的关系。方法随机选择门诊病人50例,采用流式细胞仪细胞内染色技术检测CD4+CD2+5Foxp3+调节性T细胞的水平,并用实时定量聚合酶链反应(PCR)检测外周血单个核细胞中的DNA水平,分析CD4+调节性T细胞与CD4计数、病毒载量及HIV-1DNA之间的相关性。结果在HIV感染病人CD4+调节性T细胞与HIV DNA呈正相关,与CD4计数呈正相关,与病毒载量呈负相关。结论未进行治疗的HIV病人,其CD4+调节性T细胞与HIV DNA呈正相关,说明CD4+调节性T细胞越多,HIV-1DNA越多,CD4+调节性T细胞可能对机体发挥不利的作用。     

Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART

Recent evidence indicates that regulatory T cells (T(regs)) play an important role in HIV infection. However, although the gastrointestinal mucosa is a key compartment in HIV disease, no data on mucosal T(regs) in HIV infection are available. In this study, we compared the frequency of T(regs) in duodenal mucosa and peripheral blood (PB) of 13 treatment-naive and 13 suppressively treated HIV-infected patients with that of 6 patients with norovirus infection and 12 healthy controls. T(regs) were quantified by immunohistochemistry (CD3/FOXP3) and further characterized (CD25, CTLA-4, GITR) by immunohistochemistry, immunofluorescence, and fluorescence-activated cell sorting (FACS). Both the frequency and the absolute count of mucosal T(regs) were highly increased in untreated HIV patients but were normal in treated HIV patients. In contrast, in peripheral blood of HIV patients, the absolute number of T(regs) was not increased, and their frequency was only slightly elevated. In norovirus infection, frequency of mucosal T(regs) in the CD4+ T-cell subset was not elevated. The high increase in count and frequency of mucosal T(regs) seems to be a characteristic feature of untreated HIV infection, suggesting a significant contribution of T(regs) to the pathogenesis of HIV disease. Their role may be 2-edged: attenuating HIV-induced immune hyperactivation while suppressing the immune response to HIV and mucosal pathogens.     

HIV persistence in the gut mucosa of HIV-infected subjects undergoing antiretroviral therapy correlates with immune activation and increased levels of LPS

We investigated the relationship between viral persistence in the gut, microbial translocation, and T cell activation during chronic HIV infection. Plasma levels of LPS, fraction of circulating CD8+CD38+ T cells, and levels of HIV-DNA in rectosigmoid biopsies and peripheral blood mononuclear cells were determined in 22 HIV-infected individuals and 10 healthy controls. We found that in untreated HIV-infected individuals, HIV-DNA load was higher in the gut mucosa than in the blood. Also, ART-treated patients exhibited lower levels of LPS and CD8+CD38+ T cells than untreated patients, but higher levels than controls. In ART-treated individuals, the level of HIV-DNA in the gut correlated with levels of LPS and fraction of CD8+CD38+ T cells. We concluded that in ART-treated individuals, higher levels of gut-associated HIV-DNA are associated with persistent immune activation and microbial translocation.     

Lymphoid organs function as major reservoirs for human immunodeficiency virus.

The total number of human immunodeficiency virus type 1 (HIV-1)-infected circulating CD4+ T lymphocytes is considered to be a reflection of the HIV burden at any given time during the course of HIV infection. However, the low frequency of HIV-infected circulating CD4+ T lymphocytes and the low level or absence of plasma viremia in the early stages of infection do not correlate with the progressive immune dysfunction characteristic of HIV infection. In this study, we have determined whether HIV-infected circulating CD4+ T lymphocytes are a correct reflection of the total pool of HIV-infected CD4+ T cells (i.e., HIV burden). To this end, HIV burden has been comparatively analyzed in peripheral blood and lymphoid tissues (lymph nodes, adenoids, and tonsils) from the same patients. The presence of HIV-1 DNA in mononuclear cells isolated simultaneously from peripheral blood and lymphoid tissues of the same patients was determined by polymerase chain reaction amplification. We found that the frequency of HIV-1-infected cells in unfractionated or sorted CD4+ cell populations isolated from lymphoid tissues was significantly higher (0.5-1 log10 unit) than the frequency in peripheral blood. Comparable results were obtained in five HIV seropositive patients in the early stages of disease and in one patient with AIDS. These results demonstrate that a heavy viral load does reside in the lymphoid organs, indicating that they may function as major reservoirs for HIV. In addition, the finding of a heavy viral load in the lymphoid organs of patients in the early stages of disease may explain the progressive depletion of CD4+ T lymphocytes and the immune dysfunction associated with the early stages of HIV infection.     

Immune activation in the female genital tract during HIV infection predicts mucosal CD4 depletion and HIV shedding

Plasma viral load predicts genital tract human immunodeficiency virus (HIV) shedding in HIV-infected women. We investigated whether local mucosal T-cell activation (HLA-DR, CD38, CCR5, and Ki67) contributed to HIV shedding in the genital tracts of HIV-infected women. We showed that cervical cytobrush-derived T cells expressed higher frequencies of T-cell activation markers (CD38+ and HLA-DR+) than blood-derived T cells. Expression was significantly higher in HIV-infected women than in uninfected women. We found that the frequency of activated proliferating cervical T cells (Ki67+; Ki67+CCR5+) broadly predicted HIV shedding in the genital tract in HIV-infected women, independently of plasma viral loads. Furthermore, activated cervical T cells (HLA-DR+CD38+ and HLA-DR+CCR5+) and local HIV shedding were independently associated with CD4 depletion in the genital tract. These data suggest that the presence of high frequencies of activated T cells in the female genital mucosa during HIV infection facilitates both local HIV shedding and CD4 T-cell depletion.     

不同形式的HIV DNA与疾病进展的相关性分析

目的研究不同形式的HIV DNA与疾病进展之间的关系。方法采用实时定量PCR法来检测48例具有明确感染时间的患者总的、整合的及2个长末端重复序列(long terminal repeat,LTR)的环状HIV DNA。分析随着时间的变化,不同形式HIV DNA的动力学变化特点及其与疾病进展的关系。结果随着疾病的进展,总的及整合的HIV DNA增加。总的HIV DNA与病毒载量呈正相关。总的及整合的HIV DNA与CD4+T淋巴细胞计数呈负相关。2个LTR的环状HIV DNA与病毒载量及CD4+T淋巴细胞计数无相关性。结论总的及整合的HIV DNA与疾病进展密切相关,2个LTR的环状HIV DNA与疾病进展无相关性。     

Characterization of intestinal disease associated with human immunodeficiency virus infection and response to antiretroviral therapy

Combination antiretroviral therapies suppress human immunodeficiency virus (HIV) in peripheral blood, but the effect in gastrointestinal mucosa is uncertain. The occurrence of pathogen-negative diarrhea led to speculation that local HIV infection is etiologic. Mucosal cellular reservoirs for HIV were documented by use of several techniques. Correlations were found among gastrointestinal symptoms, histopathologic findings, cytokine expression, lymphoid apoptosis, and HIV RNA and protein expression in rectal mucosa. Disproportionate depletion of mucosal CD4+ lymphocytes also was found. The short-term effects of antiretroviral therapies were examined to test the hypothesis that these changes are directly related to mucosal HIV infection. Therapy was associated with decreased symptoms, with comparable drops in peripheral blood and mucosal HIV RNA contents, and by increases in blood and mucosal CD4+ lymphocyte contents. In addition, the number of apoptotic cells also declined during therapy. These results suggest that HIV plays a direct role in producing intestinal dysfunction.