人类免疫缺陷病毒感染者及艾滋病患者CD8+ CD38+ CD8+ HLA-DR+比IV载量的相关性研究

目的 研究人类免疫缺陷病毒(HIV)感染者和获得性免疫缺陷综合征(AIDS,艾滋病)患者CD8+ T细胞激活分子CD38、人类白细胞Ⅱ类抗原(HLA-DR)与血浆HIV载量的相关性,分析用CD8+ CD38+、CD8+ HLA-DR+的比例替代HIV载量的可行性.方法 采集1998-2006年期间在北京协和医院初诊的HIV感染者或AIDS患者236例和56名同期健康献血员的抗凝静脉血,用流式细胞术分析CD8+ T细胞分别表达CD38和HLA-DR的比例,用分支DNA技术(bDNA)检测血浆病毒载量(VL).用受试者工作特征曲线(ROC)分别预测VL＞1×103拷贝/mL、＞1×104拷贝/mL和＞1×105拷贝/mL时CD8+ CD38+、CD8+ HLA-DR+比例的临界值范围.结果 236例患者的CD4+ T细胞计数138(16,262)×106/L,显著低于对照组(P＜0.01);CD8+ T细胞计数618(353,879),显著高于对照组(P＜0.05);CD8+ CD38+、CD8+ HLA-DR+的比例分别为85.4%(72.5%,92.2%)和40.3%(17.5%,59.7%),显著高于对照组(P＜0.01),与HIV载量的相关性分别为0.429(P＜0.01)和0.282(P＜0.01).用CD8+ CD38+＞80.4%预测VL＞1×103拷贝/mL的敏感度和特异度为80.6%和75.0%;用CD8+ HLA-DR+预测VL＞1×105拷贝/mL的敏感度和特异度为78.7%和81.4%.结论 对HIV感染或AIDS初诊的患者可以尝试用CD38和HLA-DR激活亚群来预测血浆HIV载量,这种替代检测方法具有一定的可行性.     

人类免疫缺陷病毒感染者及艾滋病患者CD8~ CD38~ CD8~ HLA-DR 比例与HIV载量的相关性研究

目的研究人类免疫缺陷病毒(HIV)感染者和获得性免疫缺陷综合征(AIDS,艾滋病)患者CD8 T细胞激活分子CD38、人类白细胞Ⅱ类抗原(HLA-DR)与血浆HIV载量的相关性,分析用CD8 CD38 、CD8 HLA-DR 的比例替代HIV载量的可行性。方法采集1998—2006年期间在北京协和医院初诊的HIV感染者或AIDS患者236例和56名同期健康献血员的抗凝静脉血,用流式细胞术分析CD8 T细胞分别表达CD38和HLA-DR的比例,用分支DNA技术(bDNA)检测血浆病毒载量(VL)。用受试者工作特征曲线(ROC)分别预测VL>1×103拷贝/mL、>1×104拷贝/mL和>1×105拷贝/mL时CD8 CD38 、CD8 HLA-DR 比例的临界值范围。结果236例患者的CD4 T细胞计数138(16,262)×106/L,显著低于对照组(P<0.01);CD8 T细胞计数618(353,879),显著高于对照组(P<0.05);CD8 CD38 、CD8 HLA-DR 的比例分别为85.4%(72.5%,92.2%)和40.3%(17.5%,59.7%),显著高于对照组(P<0.01),与HIV载量的相关性分别为0.429(P<0.01)和0.282(P<0.01)。用CD8 CD38 >80.4%预测VL>1×103拷贝/mL的敏感度和特异度为80.6%和75.0%;用CD8 HLA-DR 预测VL>1×105拷贝/mL的敏感度和特异度为78.7%和81.4%。结论对HIV感染或AIDS初诊的患者可以尝试用CD38和HLA-DR激活亚群来预测血浆HIV载量,这种替代检测方法具有一定的可行性。     

AIDS患者高效抗逆转录病毒联合治疗后外周血CD+8 CD+38T细胞与病毒载量同步变化

目的了解艾滋病(AIDS)患者高效抗逆转录病毒联合治疗(HAART)前后外周血CD+38抗原在CD+8T淋巴细胞上的表达情况.方法应用流式细胞仪采用双色荧光抗体检测技术检测CD+8 CD+38 T细胞;用罗式核酸扩增荧光定量聚合酶链反应(PCR)法检测血浆病毒载量(VL).结果 HAART后2周内CD+8 CD+38 T细胞数与VL开始同步下降,12周后83%AIDS患者的VL降至＜500拷贝/ml,同时CD+8 CD+38 T细胞计数与治疗前相比非常明显地降低(P＜0.001).而且63%的AIDS患者在血浆VL低于检测水平时,其CD+8 CD+38 T细胞数仍继续下降(与VL开始达到检测水平以下时相比,P＜0.001).结论 AIDS患者在HAART开始后,CD+8 CD+38 T细胞数与VL快速下降,在24周左右降至正常水平;并且CD+8 CD+38 T细胞数在VL达到检测不到时仍继续下降,提示在血浆VL低于检测水平时,CD+8 CD+38 T细胞数能够作为判断病毒是否复制的标记.     

HIV感染者检测病毒载量和CD4淋巴细胞计数的关系

目的 探讨HIV感染者抗逆转录病毒治疗前血液标本HIV病毒载量(VL)及CD4淋巴细胞计数的关系.方法 采用RT-PCR法和流式细胞分析系统,对重庆地区部分HIV病毒感染者169份血液标本的VL和CD4平行检测结果进行分析.结果 169份标本中VL能被定量的有160份(94.7%),其结果6.0×103~2.80×107拷贝/ml之间,CD4细胞计数3~836个/μl.经相关性分析,CD4细胞值与VL对数值呈负相关(r=-0.43,P<0.01).结论平行检测VL和CD4细胞数可帮助了解疾病进展状况,选择开始治疗的时机.     

佳息患联合施多宁治疗HIV感染者/AIDS患者6个月效果及耐药性初步观察

目的探讨规范化应用蛋白酶抑制剂茚地那韦(Indinavir,佳息患)联合非核苷类逆转录酶抑制剂依非韦仑(Efavirenz,施多宁)治疗艾滋病病毒(HIV)感染者/AIDS患者的疗效和耐药情况。方法用施多宁联合佳息患对10例HIV感染者/AIDS患者进行为期6个月的治疗,于治疗前,治疗第1、3、6个月随访,监测病毒学和免疫学参数[病毒载量(VL)、CD4+细胞绝对计数、CD4+和CD8+免疫活化标志HLA-DR、CD3+8],药物毒副作用,基因型耐药变异情况,临床表现和依从性。结果10例HIV感染者/AIDS患者治疗前平均VL为5.17log拷贝/ml(3.58×105拷贝/ml),治疗6个月后平均下降3.25log拷贝/ml(P<0.001),其中9例达到检测不出的水平(<400拷贝/ml)。CD4+T细胞绝对计数平均上升178个/μl(P<0.001)。CD3+8HLA-DR+CD4+细胞平均百分比和CD3+8HLA-DR+CD8+细胞平均百分比分别降低了14.9%(P<0.01)和22.9%(P<0.001)。病人临床症状缓解且耐受性良好,无严重不良反应发生。10例患者在治疗前和治疗6个月后均未出现原发耐药变异。结论佳息患联合施多宁规范化治疗不同感染阶段的中国HIV感染者/AIDS患者6个月,可有效抑制HIV-1复制,促进机体免疫重建,改善临床症状,提高生活质量,副作用在可接受范围内,无原发耐药变异发生。     

北京市50例HIV/AIDS病人CCR5 CXCR4 HLA-DR和CD38表达与疾病进展关系

目的了解艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人(HIV/AIDS病人)淋巴细胞表面CCR5、CX-CR4、HLA-DR和CD38表达,分析其与疾病进展的关系,探讨HIV感染的免疫学基础。方法收集50例HIV/AIDS病人及14例健康对照的抗凝全血,用流式细胞仪检测CCR5、CXCR4、HLA-DR和CD38表达,并分析其与疾病进展情况的相关性。结果艾滋病组、HIV感染者和正常对照CCR5/CD4,CXCR4/CD4,CD38/CD4,CCR5/CD8,CD38/CD8和HLA-Dr/CD8表达有显著性差异,CXCR4/CD4和CD38/CD4与疾病进程呈明显正相关,CCR5/CD8和CD38/CD8与疾病进程呈明显负相关。结论 HIV/AIDS病人淋巴细胞表面CCR5、CXCR4和CD38表达与疾病进展密切相关。     

高效抗逆转录病毒治疗12个月后艾滋病患者的免疫重建观察

目的探讨高效抗逆转录病毒治疗（HAART）对AIDS患者的疗效及毒副作用。方法45例未经治疗的AIDS病人按基线CD4^＋T细胞计数分为两组,予12个月HAART,分别在基线及治疗1、3、6、9、12个月末随访血浆病毒载量（VL）、T细胞亚群和临床症状。结果抗病毒治疗12个月后45例病人血浆VL平均下降2．8lg拷贝／ml;CD4^＋细胞平均增长187个／μl,其中记忆表型增长119个／μl,纯真表型增长68个／μl,CD4^＋CD28^＋细胞比例显著升高;CD8^＋T激活亚群比例显著降低。基线CD4^＋T细胞计数〉100个／μl的14例病人治疗12个月后有10例血浆VL〈50拷贝／ml,而〈100个／μl的31例病人治疗后仅有11例血浆VL〈50拷贝／ml（P〈0．05）。出现血浆波动的病例数在两组也有统计学差异（分别为2例和14例,P〈0．05）。CD4^＋T细胞计数呈双相增长过程,其增量与血浆VL减少量呈显著正相关。常见的药物副作用有消化道反应、外周神经炎、肝功能损害等。结论HAART方案对AIDS病人有较好的疗效,能够实现免疫重建,但也存在较多毒副作用。     

经治HIV-1感染者CD8细胞免疫紊乱与CXCL9/10/11的相关性分析

目的 分析经治HIV-1感染者CD8细胞分化及激活特征,探索其与趋化因子CXCL9/10/11及CD4/CD8细胞比值的关系。方法 入组33例ART时间大于2年且血浆VL小于20拷贝/mL的HIV-1感染者以及15例健康对照,通过流式细胞术检测CD8细胞分化和激活水平,利用酶联免疫吸附法检测血浆CXCL9/10/11水平,随后分析CD8细胞分化、激活水平和血浆CXCL9/10/11水平以及CD4/CD8细胞比值的相关性。结果 与健康对照相比,经治HIV-1感染者幼稚CD8细胞占比（中位数9.6%vs. 28.6%,P=0.004）显著降低,而效应记忆CD8细胞占比（中位数36.9%vs.7.0%,P<0.000 1）及HLA-DR+CD38+CD8细胞占比（中位数7.4%vs. 3.3%,P<0.000 1）显著升高。在经治HIV-1感染者中,HLA-DR+CD38+CD8细胞占比与CXCL9(r=0.477,P=0.005)和CXCL11(r=0.402 9,P=0.020 1)水平显著正相关,效应CD8细胞占比与CXCL9(r=0.581 9,P=0.000 4)、CX...     

HIV抗体阳性者短期内发展至AIDS的危险

为了探明影响艾滋病病毒 (HIV)抗体阳性者的病情发展到艾滋病 (AIDS)的因素 ,英国学者利用未开展高效抗逆转录病毒联合治疗 (HAART)之前的数据 ,对 32 2 6名HIV感染者发展至AIDS的危险进行评估。在病毒载量 (VL)和CD4细胞计数已知的情况下 ,1年间随访 5 12 6人 ,已发现有 2 19人发展至AIDS。本研究提出CD4细胞计数、VL和 3～ 6个月患者发展至AIDS存在相关关系如下 :CD4 细胞计数 VL(拷贝 /ml)3～ 6个月发展至AIDS的危险 (% )<2 0 0 / μl1 <1 0 0 0 0 4 92 1 0 0 0～ 2 99991 2 73 30 0 0 0～ 99990 1 7 74 ≥ 1 0 0 …     

重庆市HIV/AIDS病人首次病毒载量和CD4^＋T淋巴细胞检测结果及相关性

目的探讨重庆市艾滋病病毒（HIV）感染者/艾滋病（AIDS）病人（简称HIV/AIDS病人）外周血病毒载量（VL）和CD4^＋T淋巴细胞（简称CD4细胞）计数相关性。方法采用BD流式细胞仪和LightCycler PCR仪检测585例HIV/AIDS病人同期外周血CD4细胞及VL,分析其相关性。结果 48例VL低于试剂盒检测下限,537例能被定量检测。VL与CD4细胞总体呈显著负相关（r=-0.57,P〈0.01）,不同CD4细胞区间VL值有显著性差异（χ2=134.29,P〈0.01）,在CD4细胞≤200区间VL与CD4细胞呈显著负相关（r=-0.34,P〈0.01）,CD4细胞在201-400区间二者无相关（r=-0.16,P=0.09）,CD4细胞〉400区间二者呈负相关（r=-0.28,P=0.04）。结论 HIV/AIDS病人CD4细胞与VL在CD4细胞不同区间相关性表现各异,同时检测CD4细胞及VL有助于掌控病人病情变化和调整救治措施。     

Parallel decline of CD8+/CD38++ T cells and viraemia in response to quadruple highly active antiretroviral therapy in primary HIV infection

OBJECTIVES: To monitor changes in the numbers of CD8 lymphocytes expressing the activated CD38++ phenotype in peripheral blood samples from patients with primary HIV infection (PHI) treated with highly active antiretroviral therapy (HAART). METHODS: Zidovudine, lamivudine, abacavir and amprenavir were initiated during PHI as part of the Quest study. Absolute numbers of CD8+/CD38++ T cells were determined using three-colour flow cytometry, and plasma viral load (VL) was measured using the Roche Amplicor method. RESULTS: The median, pre-therapy CD8+/CD38++ T cell count was 461/mm(3)(interquartile range 216, 974) in 131 patients compared with normal control values of less than 20 cells/mm(3). Levels fell markedly in parallel with VL within the first 2 weeks of HAART initiation, to a median of 47 cells/mm(3) at 28 weeks (median 436 cell decline; P < 0.001). At that time, 80% of patients had a VL less than 50 copies/ml, and 16.3% of all patients had less than 20 CD8+/CD38++ T cells/mm(3). A continued decrease in CD8+/CD38++ T cell count occurred in 67.2% of patients whose VL was maintained below 50 copies/ml (median change from first to last value -18 cells/mm(3); P < 0.001). CONCLUSION: After the initiation of HAART in PHI, CD8+/CD38++ lymphocytes declined rapidly in parallel with VL, and allowed for a normalization of CD8+/CD38++ T cell numbers in a subset of patients at week 28. Cell numbers continued to decline in patients who maintained VL below 50 copies/ml, indicating that the CD8+/CD38++ T cell count may represent a marker of residual viral replication when VL falls below detectable levels after HAART intervention.     

HIV感染者/AIDS患者外周血CD38 HLA-DR分子在CD4+ CD8+T淋巴细胞上的表达

目的　观察国内艾滋病病毒 (HIV)感染者 /艾滋病 (AIDS)患者外周血CD38、HLA DR分子在CD+4 、CD+8T淋巴细胞上表达的变化 ,并探讨这些变化的临床意义。方法　用流式细胞仪检测 5 1例正常对照、14例HIV感染者和 3 6例AIDS患者的外周血CD+4 、CD+8T淋巴细胞表面的CD38、HLA DR分子的表达 ,用分枝DNA(bDNA)法检测 11例HIV感染者和 18例AIDS患者的血浆病毒载量。结果　CD+4 HLA DR+细胞百分比显示 ,AIDS组显著高于正常组及HIV组 ;CD+8HLA DR+T细胞百分比显示HIV组与AIDS组间无差异 ,而它们均显著高于正常组。CD+8、CD38+细胞百分比则是AIDS组 >HIV组 >正常组 ,CD+8CD38+、CD+8HLA DR+、CD+4 HLA DR+细胞百分比与病毒载量显著正相关。结论　在HIV感染过程中 ,HLA -DR+、CD38+在CD+4 、CD+8T淋巴细胞上的表达均显著增加 ,反映T淋巴细胞异常激活 ;尤其是CD+8CD38+细胞百分比随着疾病进展逐渐升高 ,预示疾病进展程度。在评价HIV感染者和AIDS患者的免疫状况时 ,不仅要考虑免疫细胞数量和功能的变化 ,还应考虑免疫细胞的激活水平     

Immunological changes after highly active antiretroviral therapy with lopinavir-ritonavir in heavily pretreated HIV-infected children

We evaluated the effect of salvage antiretroviral therapy with lopinavir/ritonavir (LPV/r) on the immune system of heavily antiretroviral pretreated HIV-infected children. We carried out a longitudinal study in 20 antiretroviral experienced HIV-infected children to determine the changes in several immunological parameters (T cell subsets, thymic function) every 3 months during 18 months of follow-up on salvage therapy with LPV/r. Statistical analyses were performed with the Wilcoxon test, taking as a reference the basal value at the entry in the study. HIV-infected children showed an increase of CD4+ T cells, a decrease in CD8+ T cells, and an increase in T cell rearrangement excision circle (TRECs) levels. The percentage of HIV children with undetectable viral load (VL < or = 400 copies/ml) increased significantly (p = 0.007) and the percentage with SI viral phenotype decreased significantly (p = 0.002) at the end of the study. Thus, the viral phenotype changed to NSI/R5 after salvage therapy with LPV/r. Interestingly, we observed a significant decrease of memory (CD4+ CD45RO+) and a moderate decrease of activated (CD4+ HLA-DR+, CD4+ HLA-DR+CD38, CD4+, CD45RO+HLA-DR+) CD4+ T cells during the follow-up. On the other hand, memory (CD8+ CD45RO+ and CD8+ CD45RO+CD38+), activated (CD8+ HLA-DR+CD38+, CD8+ HLA-DR+, CD8+ CD38+), and effector (CD8+ CD57+, CD8+ CD28(-)CD57+) CD8+ T cells had a very significant decrease during follow-up. Our data indicate an immune system reconstitution in heavily pretreated HIV-infected children in response to salvage therapy with LPV/r as a consequence of a decrease in immune system activation and an increase in thymic function.     

Persistent low viral load on antiretroviral therapy is associated with T cell-mediated control of HIV replication

BACKGROUND: It is unclear how stable low-level viral replication and CD4 cell numbers can be maintained under highly active antiretroviral therapy (HAART). This study was designed to analyse whether HIV-specific responses in stable partially controlled patients during antiretroviral therapy (ART) differ from those observed in complete HAART failure and whether they contribute to the control of viral load (VL). METHODS: Three groups of patients were selected according to plasma HIV RNA levels during 18 months of ART: persistently low VL (LoVL; HIV RNA <10,000 copies/ml; n = 28), undetectable VL (UnVL; HIV RNA <200 copies/ml; n = 29) and high VL (HiVL; HIV RNA >10,000 copies/ml; n = 14). T-cell responses were studied using lymphoproliferative and interferon (IFN)-gamma-ELISpot assays against HIV-p24, -gp160, recall antigens, and 15 pools of HIV-(Gag + RT) peptides. RESULTS: Frequencies of IFN-gamma-producing CD4 T cells against HIV-p24 were higher in LoVL than in UnVL or HiVL groups [median, 131, 47 and 23 spot-forming cells (SFC)/1 x 10 peripheral blood mononuclear cells (PBMC), respectively; P = 0.012 and P = 0.047]. Lymphoproliferative responses to HIV-p24 and recall antigens were similar in LoVL and UnVL groups but lower in HiVL (P = 0.004). Frequencies of HIV-specific CD8 T cells were higher in LoVL than in UnVL (1340 versus 410 SFC/1 x 10 PBMC; P = 0.001). They correlated negatively with VL in the LoVL and HiVL (r, -0.393, P = 0.039 and r, -0.643, P = 0.024, respectively) and positively correlated with anti-HIV CD4 cell frequencies in the LoVL group only (r, 0.420; P = 0.026). CONCLUSION: Persistently low viral replication (<10,000 copies/ml) during ART stimulates high frequencies of HIV-specific CD4 and CD8 T cells compared to full virus suppression or complete ART failure. The association of high anti-HIV activity with large numbers of HIV-specific CD8 T cells contribute to the control of viral replication.     

Immune activation in patients infected with HIV type 1 and maintaining suppression of viral replication by highly active antiretroviral therapy

Immune activation associated with HIV infection declines after highly active antiretroviral therapy (HAART), but may persist or recur in some patients. It is not clear whether this reflects a resurgence of HIV replication or another cause of immune activation, such as inflammatory reactions to opportunistic pathogens (immune restoration disease [IRD]). Here, we studied plasma and cellular immune activation markers in adult HIV-1 patients who had received HAART for >12 months and maintained plasma HIV RNA levels of <400 copies/ml for >6 months. Plasma interleukin 1 receptor antagonist and tumor necrosis factor receptor I levels were similar in patients and HIV-negative control subjects, but the highest levels occurred mainly in patients with a history of IRD. In contrast, expression of HLA-DR and CD38 on monocytes and of HLA-DR on CD8(+) T cells was higher in patients than in control subjects. Thus, cellular markers of immune activation are abnormal in some patients with a good virological response to HAART, and abnormalities of plasma immune activation markers correlate with a history of IRD.     

Low-level viremia and proviral DNA impede immune reconstitution in HIV-1-infected patients receiving highly active antiretroviral therapy

BACKGROUND: Immunological and virological consequences of low-level viremia in human immunodeficiency virus (HIV) type 1-infected patients receiving highly active antiretroviral therapy (HAART) remain to be determined. METHODS: For 24 months, 101 HAART-treated, HIV-1-infected patients with HIV RNA levels 20 copies/mL at >/=1 visit (dVL patients) (median increase, 81 copies/mL [interquartile range, 37-480 copies/mL]). dVL patients had higher concentrations of CD8 cells, activated and memory T cells, and proviral DNA, compared with uVL patients (P<.05). A higher HIV RNA level was independently associated with reduced CD4 gain (P<.001). A higher HIV RNA level also was associated with increases in activated CD8(+)CD38(+) and CD8(+)HLA-DR(+) cells (P<.05), and a higher level of activated CD8(+)CD38(+) cells was independently associated with reduced CD4 gain (P<.05). A higher proviral DNA level was associated with increases in CD4(+)CD45RA(-)CD28(-) effector cells and reductions in naive CD4(+)CD45RA(+)CD62L(+) and CD8(+)CD45RA(+)CD62L(+) cells (P<.05). Higher levels of activated CD4(+)HLA-DR(+) and early differentiated CD4(+)CD45RA(-)CD28(+) cells predicted increased risk of subsequent detectable viremia in patients with undetectable HIV RNA (P<.05). CONCLUSION: These findings indicate that low-level viremia and proviral DNA are intimately associated with the immunological and virological equilibrium in patients receiving HAART.     

300例艾滋病患者高效抗逆转录病毒治疗后免疫重建规律探讨

目的探讨高效抗逆转录病毒治疗（HAART）对中国南部地区艾滋病患者的免疫重建规律。方法收集近3年来300例患者的完整资料,按基线CD4^＋T细胞数分为A、B、C三组,观察基线及治疗1、3、6、12月末CD4^＋T淋巴细胞数、12月末血浆病毒载量（VL）、临床症状和毒副作用。结果抗病毒治疗12月末300例患者CD4^＋T淋巴细胞计数平均上升127个／1,以治疗3月后增长明显,3、12月末与基线CD4^＋T淋巴细胞计数比较差异有显著性（P〈0．05）;12月末273例（91％）患者血浆病毒载量（VL）〈5copies/ml,27例（9％）患者病毒载量（VL）〉50copies/ml,高病毒载量A组16例,C组4例;A组与C组比较差异有显著性（P〈0．05）;药物不良反应主要是外周神经炎（35．4％）、骨髓抑制（18．2％）、皮疹（15．2％）、肝功能损害（12．1％）、乳酸酸中毒（12．1％）和肾结石（6．1％）。结论HAART治疗对中国南部地区的艾滋病患者有效,能够实现免疫重建,但存在较多毒副作用。