HIV感染者和AIDS患者淋巴细胞免疫功能的研究

我们观察了HIV感染者和AIDS患者外周血中淋巴细胞亚群的数量，以探讨机体在HIV感染后细胞免疫所发生的变化。     

高效抗逆转录病毒治疗对中国HIV/AIDS患者淋巴细胞活化及第二受体表达的影响

目的　了解高效抗逆转录病毒治疗后中国HIV/ AIDS患者淋巴细胞活化及CCR5、CXCR4表达的变化,探讨HIV感染者对于抗病毒治疗的免疫应答。方法　10例HIV /AIDS患者给予高效抗逆转录病毒治疗(HAART),用流式细胞仪检测治疗前和治疗第3、6 个月T淋巴细胞活化(HLA DR、CD38表达)及第二受体CCR5、CXCR4表达情况,比较HIV/ AIDS患者治疗前后淋巴细胞活化、第二受体表达的变化。结果　治疗前,10例HIV /AIDS患者CD4+、CD8+ T淋巴细胞活化水平均明显高于健康对照,CD8+ T淋巴细胞表面CCR5的表达明显高于健康对照,CXCR4 的表达明显低于健康对照(P<0.05);HAART治疗后,患者淋巴细胞活化水平随治疗时间明显下降(P<0.05),CD8+ T淋巴细胞表面CCR5表达水平显著降低(P< 0. 01), CXCR4 的表达升高;治疗6 个月时, CD38 CD4、HLA DRCD38 CD4、CCR5 CD8、CXCR4 CD8表达水平恢复至健康人水平;HIV AIDS淋巴细胞活化水平及第二受体CCR5的表达降低与HAART治疗后CD4+T淋巴细胞数量的升高具有显著的相关性。结论HAART能够降低中国HIV /AIDS患者淋巴细胞活化水平,使第二受体表达水平趋于正常,促进免疫功能的恢复。     

210例HIV/AIDS患者淋巴细胞计数与机会性感染相关分析

目的分析HIV/AIDS患者总淋巴细胞计数（TLC）与机会性感染的关系,为HIV/AIDS患者机会性感染的治疗及一级、二级预防提供参考依据。方法对2009年6月至2011年5月210例HIV/AIDS患者的淋巴细胞及出现的机会性感染进行分析。将患者分为TLC〉1300个/μl组（G1组）和TLC≤1300个/μl组（G2组）,比较两组患者机会性感染发生率的差异。结果 210例HIV/AIDS患者机会性感染的总感染率为86.7%,主要的机会性感染为口腔念珠菌感染（56.2%）、细菌性肺炎（46.7%）、肺结核（42.4%）、败血症（21.4%）、感染性腹泻（20.5%）。G2组患者机会性感染的发生率为93.6%,高于G1组患者（55.3%）,差异有统计学意义（P〈0.05）;随着TLC的下降,患者发生机会性感染的机率增高。结论 HIV/AIDS患者机会性感染的发生率高,TLC是HIV/AIDS患者发生机会性感染的独立危险因素。因此,应定期监测HIV/AIDS患者TLC,加强患者机会性感染的一级和二级预防。     

HAART和HIV感染的免疫重建

人免疫缺陷病毒(HIV)感染可以引起以细胞免疫缺陷为主的免疫缺损。高效抗逆转录病毒治疗(HAART)降低HIV的复制,使T淋巴细胞亚群发生数量和功能的改善,抑制异常免疫激活,改变了HIV感染的进程,改善了患者的生活质量和预后。但HAART在多大程度能恢复患者的免疫功能,以及HAART恢复免疫重建的长期效果还有待于进一步研究,本文拟就有关内容作一综述。     

人类白细胞抗原与HIV/AIDS相关的研究进展

HIV引起的AIDS严重威胁着人类的健康。近年来的研究表明,HLA抗原尤其是I类抗原的多态性与HIV/AIDS患者病情进展的状况有着明显的关联作用。在对AIDS的病原体HIV病毒的研究过程中,HLA分子与病毒的相互作用似乎是一个非常关键的要素。本文对目前HLA抗原与HIV相关的一些研究进展进行综合性的回顾,以期进一步加深人们对HIV病毒和人体自身免疫系统的了解,并促进人们更行而有效地对抗HIV/AIDS。     

HIV感染的免疫异常与HAART介导的免疫重建

HIV感染造成CD4^＋T细胞数量的下降和功能的改变及机体的异常免疫激活。有效的HAART治疗除抑制HIV病毒复制外,还可以部分地恢复CD4^＋T细胞的数量和功能,起到免疫重建的作用。但HAART治疗免疫重建的机制及机体免疫力恢复的程度等一系列问题尚需进一步研究。本文就HAART治疗对HIV感染引起诸方面的免疫异常的重建作用作一综述。     

抗逆转录病毒与HIV患者颈动脉粥样硬化相关

西班牙巴塞罗那del Mar医院的Juan Pedro-Botet医生及其同事在3月的《卒中》（Stroke，2006；37：812-817）杂志上报告，联合使用抗逆转录病毒治疗是HIV患者发生亚临床颈动脉粥样硬化的强独立风险因素。研究者观察到，虽然常规心血管风险因素在颈动脉粥样硬化风险中起一定作用，但是抗逆转录病毒治疗起主要作用。他们总结说，应使用不同的、心血管毒性较小的抗逆转录病毒药。     

经血感染HIV/AIDS患者pDCs与艾滋病疾病进展关系的研究

目的 了解中国HIV/AIDS患者外周血中类浆细胞样树突状细胞（plasmacytoid dendritic cells，pDC）绝对值的变化，分析其与HIV感染及疾病进展的关系。方法采集56例未经治疗的H1VIMDS患者及34例健康人抗凝静脉血，采用流式细胞仪单平台检测技术，分析计算三色荧光抗体标记的全血中pDC（Lin1^＋／HLA-DR^＋／CD123^＋）绝对值。结果MDS组pDC绝对值为3．31个／μl（0．31～6．46个/μl），显著低于正常对照组、HIV慢性感染组及HIV感染疾病长期不进展（long term non-progressors，LTNP）组（P〈0．01）。HIV慢性感染组pDC绝对值为5．27个/μl（2．25～9．80个/μl），显著低于正常对照组及LTNP组（P〈0．01）。LTNP组pDC绝对值为9．95个／μl（6．16～20．88个／μl），显著高于正常对照组（7．84个/μl，3．45～13．97个／μl，P〈0．01）。56例HIV/AIDS患者pDC绝对值与CD4^＋T淋巴细胞绝对值及百分率呈显著正相关（r=0．422，P〈0．01；r=0．488，P〈0．01），与病毒载量呈显著负相关（r=-0．444，P〈0．05）。结论HIV／AIDS患者pDC数量减少，并且随疾病进展逐渐下降；HIV感染LTNP的血pDC数量显著高于HIV慢悱感染者及MDS患者，甚至高于正常对照。提示外周血pDC在控制HIV感染方面有重要作用，与艾滋病疾病进展明显相关。     

团体心理干预对HIV感染者/AIDS患者的影响效果研究

目的以建立HIV感染者/AIDS患者心理支持小组的形式,探讨团体心理干预对HIV感染者/AIDS患者的影响效果。方法实施地点为湖南省某地区的疾病预防控制中心,自愿参加小组心理辅导和干预的HIV/AIDS患者19人组成2个小组,对小组成员进行为期4次,每次3小时的团体心理干预,采用激惹、抑郁和焦虑自评量表（IDA）、社会支持评定量表（SSS）及特质应对方式问卷（TCSQ）对干预效果进行评估。结果干预后小组成员的焦虑、抑郁情绪及由外部环境引起的易激惹状态有所改善;在寻求社会支持和应对问题的方式方面也有显著变化。结论团体心理干预对改善HIV感染者/AIDS患者的心理问题、提高其社会支持和同伴支持、改善应对策略有一定效果,值得应用和进一步的推广。     

HIV/AIDS患者特异性细胞毒性T细胞功能的研究

目的 了解中国HIV／AIDS患者HIV特异性细胞毒性T细胞(CTL)功能。方法 将覆盖HIV-1 P15、P17和P24 Gag全长的94个重叠多肽作为抗原，用IFN-γ ELISPOT方法检测HIV／AIDS患者HIV-1特异性CTL功能。结果 HIV-1抗原多肽P17-15、P17-16、P24-7、P17-8，P24-28最易被HIV／AIDS患者特异性CTL识别。HIV感染者识别HIV-1多肽的数量和强度均高于AIDS患者。结论 我国HTV／AIDS患者体内存在识别不同HIV-1 Gag多肽的特异性CTL，且HIV特异性CTL功能与疾病进展相关。     

HIV感染者/AIDS病人生存质量现状及相关因素研究

目的了解HIV感染者/AIDS病人生存质量的现状并分析其相关因素。方法应用世界卫生组织生存质量量表（WHOQOL-BREFF）中文版评价HIV感染者及AIDS病人的生存质量,同时调查可能影响生存质量的人口学特征、HIV感染有关情况和社会支持等。采用t检验、方差分析进行单因素分析,多元线性回归模型分析生理、心理、社会关系及环境4大领域的影响因素。结果 112例HIV感染者/AIDS病人生存质量4大领域平均得分分别为：生理领域（60.5±16.2）分、心理领域（51.8±17.5）分、社会关系领域（58.1±19.3）分,环境领域（47.5±15.6）分。各维度得分均低于全国常模,差异有统计学意义（P〈0.05）。主观支持得分越高,HIV感染者/AIDS病人生存质量4个领域得分就越高;静脉吸毒途径感染的HIV感染者/AIDS病人生理领域总分低于性途径感染者;有工作/学习的HIV感染者/AIDS病人生理和心理领域得分高于无业者;对支持利用度高者,其心理领域得分也高;在环境领域得分中,患者文化程度越高,其得分越高。结论应加强失业、文化程度低、抗病毒治疗患者、静脉注射感染者以及社会支持差者的心理健康辅导,以提高其生存质量。     

高效抗病毒治疗促使艾滋病患者免疫功能重建

艾滋病的特征是ＨＩＶ 1感染人体后 ,造成ＣＤ4 +Ｔ淋巴细胞数量进行性减少、细胞免疫功能损害 ,最后导致艾滋病 (ＡＩＤＳ)。先前的研究表明这种免疫功能的丧失是不可逆转的 ,抗ＨＩＶ病毒治疗仅能控制或减缓其进展。近年来 ,由于强效联合抗病毒治疗 (ＨＡＡＲＴ)的应用 ,艾滋病的发病率和死亡率均较前明显下降 (指西方国家 )。说明ＨＡＡＲＴ不仅能有效的控制ＨＩＶ 1的复制 ,并能使艾滋病病人的免疫功能得到恢复。这种ＨＡＡＲＴ使艾滋病病人免疫功能重建的假说最近被一组法国研究人员证实 ,艾滋病的免疫重建规律是 :(1)治疗早期ＣＤ4 +…     

An update on the neuropathology of HIV in the HAART era

This review compares the neuropathology of highly active antiretroviral therapy (HAART)-treated HIV+ individuals with the reported central nervous system (CNS) findings from the pre-HAART era. HAART has had considerable success in combating HIV-related immune collapse and has prevented many of the former end-stage complications of AIDS. However, with increased survival times the prevalence of minor HIV-associated cognitive impairment appears to be rising among treated patients and this may be a particular risk for older individuals. HIV encephalitis (HIVE) is still prevalent in treated patients although attenuated forms of HIVE and CNS opportunistic disorders are also observed. Some subjects show very significant CNS lymphocytic infiltrates in the context of HAART-induced immune reconstitution. HIV-associated cognitive impairment correlates best with the increased presence of activated, though not necessarily infected, microglia and CNS macrophages. This suggests that indirect mechanisms of neuronal injury and loss occur in HIV/AIDS as a basis for dementia since neurones are not themselves productively infected. Research to elucidate the mechanisms of neuronal injury in HIV/AIDS may contribute to the understanding of CNS function not only in HAART-treated subjects but also in other neurodegenerative disorders.     

Intensification of a suppressive HAART regimen increases CD4 counts and decreases CD8+ T-cell activation

A significant proportion of HIV-1-infected individuals on suppressive HAART regimens do not reconstitute CD4 counts well. If viral reservoirs persist and impact on CD4 reconstitution in a percentage of cases then addition of another antiretroviral agent could further suppress these reservoirs resulting in enhanced CD4 recovery. To evaluate this possibility, we studied the effect of adding abacavir to a chronically suppressive NNRTI containing HAART regimen for 8 patients on their CD4 count and expression of activation markers. Over the first 24 weeks of intensification, CD4 counts increased significantly (p=0.028). This increase continued after a year in follow-up with a significant rate of change in CD4 T-cells of 0.959+/-1.27 per week. In addition, during intensification changes in the percentage of CD38+CD8+ T-cells over time were significantly negatively correlated with changes in CD4 cell number over time above increases predicted without intensification (r(2)=0.716, p=0.008). These data support the possibility that in certain cases where suboptimal CD4 reconstitution occurs that intensification of the regimen can impact immunologic parameters.     

艾滋病HAART治疗免疫重建炎性综合征的免疫机制初步研究

目的 为探讨我国艾滋病病人(AIDS)启动高效抗反转录病毒治疗(HAART)后,发生免疫重建炎性综合征(IRIS)的免疫学发病机制,在前瞻性研究队列中对启动HAART的AIDS病人部分淋巴细胞亚群、调节性T细胞和部分Th1和Th2细胞因子等进行追踪分析.方法 将接受HAART初始治疗的238例AIDS病人建立前瞻性研究队列,分为在24周内发生IRIS的47例病人(IRIS组)和未发生IRIS的191例病人(非IRIS组).在HAART的0周、12周和24周采集两组血标本,对47例IRIS病例及随机选择的50例非IRIS病例进行免疫机制的研究分析,检测HIV病毒载量和CD4+细胞计数;使用流式细胞术检测部分淋巴细胞亚群和调节性T细胞(CD4+CD25+Foxp3+).在HAART的0周、4周、12周、24周及发生IRIS时分别采集全部238例患者的血标本,使用ELISA法测定血浆细胞因子IL-2、IFN-γ、IL-4、IL-10以及IL-7水平.结果 两组感染者的CD4+、CD8+纯真细胞和记忆细胞比例在0周、12周、24周及发生IRIS时比较差异均无统计学意义,但CD4+记忆细胞和CD8+记忆细胞比例在启动HAART后均明显上升.两组感染者CD4+CD38+活化细胞和CD8+CD38+活化细胞比例在基线时均较正常值明显升高,治疗后均有下降趋势.在0周、12周、24周及发生IRIS时CD4+CD25+Foxp3+调节性T细胞在IRIS组中均较非IRIS组要低.两组IL-2及IFN-γ在HAART后均呈上升趋势,且IRIS组在4周及发生IRIS时更明显高于非IRIS组;两组IL-4及IL-10在HAART后均呈下降趋势,IRIS组中IL-10在4周及发生IRIS时更明显低于非IRIS组.IL-7在两组中基线时均较正常值升高,并随HAART进程逐渐降低,其中IRIS组在各随访点IL-7均要高于非IRIS组.结论 接受HAART治疗者早期即出现记忆T细胞快速上升,在IRIS炎症反应中可能起重要作用.IL-2、IL-10和IFN-γ在发生IRIS时的水平差别,提示IRIS的发生与炎性细胞因子大量增加,炎性抑制因子相对不足有一定关系.IL-7也可能参与到IRIS的发病机制中.

Abstract：

Objective To investigate the immunological pathogenesis of immune reconstitution inflammatory syndrome (IRIS) during highly active antiretroviral therapy( HAART), in this prospective cohort study we analyzed the lymphocyte subsets, lymphocyte activation, changes in regulatory T cells, and levels of Th1 and Th2 cytokines in both IRIS and non-IRIS groups. Methods Two hundred and thirty-eight AIDS patients received HAART and participated prospective research cohort for 24 weeks follow-up. Forty-seven IRIS cases and 191 non-IRIS cases were enrolled in the IRIS group or non-IRIS group respectively. Blood samples were collected in both groups at pre- and post-HAART 12 weeks, 24 weeks. Using flow cytometer to detect the immunophenotypes of lymphocyte subsets (CD4 + CD45RA+ CD62L+, CD8+ CD45RA+ CD62L+naive T cells; CD4+ CD45RO+, CD8+ CD45RO+ memory T cells), activated T lymphocytes (CD4+CD38 +, CD8 + CD38 + cells), and regulatory T cell ( CD4 + CD25 + Foxp3 + ). Blood samples collected at pre-and post-HAART4 weeks, 12 weeks, 24 weeks and used ELISA to detect IL-2, IFN-γ, IL-4, IL-10and IL-7 cytokine serum levels. Results The percentages of CD4 + and CD8 + naive T cells and mlemory T cells exhibited no significant differences at the baseline, 12 weeks, 24 weeks of HAART initiation between both groups, but CD4 + and CD8 + memory T cells were demonstrated a trend towards to increase while compared to baseline during HAART. The percentages of CD4 + and CD8 + activated T cells are significantly higher at the baseline while compared to normal control and demonstrated a downward trend, but between both groups showed no significant difference. The percentages of CD4 + regulatory T cell was lower in IRIS group than non-IRIS group at the baseline, 12 weeks, 24 weeks and the onset of IRIS. Th1 cytokines, IL-2 and IFN-γshowed an upward trend during HAART at the levels of IRIS group had significantly increased at 4 weeks and the onset of IRIS. Th2 cytokines, IL-4 and IL-10 showed a downward trend during HAART,and the levels of IL-10 in IRIS group had significantly decreased at 4 weeks and the onset of IRIS. IL-7 was higher than normal control at the baseline in two groups and showed a downward trend during HAART. The level of IL-7 was higher than non-IRIS group at all follow-up points. Conclusion Memory T cells appear rapid increase in the early stage of HAART and may play a significant role in the inflammatory response of IRIS. CD4 + and CD8 + naive T cells, memory T cells and activated T cells showed no significant difference between IRIS and non-IRIS group within 24 weeks after HAART started. There was a significant reduction in the frequency of regulatory T cells in IRIS group without obvious upward trend during HAART, suggesting that the immune suppression function of regulatory T cells in IRIS was impaired. IL-2 and IFN-γ significantly increased while IL-10 significantly decreased at 4 weeks post-HAART initiation and onset of IRIS in IRISgroup than non-IRIS group, suggested that IRIS was related to cytokines environment disorder. That is, a significant increase in inflammatory cytokines, while the relative lack of non-inflammatory cytokines. The level of IL-7 decreased gradually after HAART started, and it was higher in IRIS group when compared to non-IRIS group in the first 24 weeks after HAART started. Also IL-7 may play a role in the pathogenesis of IRIS.     

A non-specific biomarker of disease activity in HIV/AIDS patients from resource-limited environments

Background

A general non-specific marker of disease activity that could alert the clinician and prompt further investigation would be of value in patients with HIV/AIDS, especially in resource limited environments.

Objective

To investigate the potential of neopterin as non-specific biomarker in patients with advanced HIV/AIDS.

Methods

Cross-sectional study in 105 HIV positive patients (75 on highly active antiretroviral treatment (HAART). Neopterin was assessed by enzyme linked immune-absorbent assay and cytokines by flow cytometry.

Results

Neopterin levels were significantly higher (p<0.001) for the total patient than for the control group. Significant correlations between neopterin and plasma indicators of inflammation showed neopterin to be a good indicator of active inflammatory status and of the effect of HAART on the immune system. Neopterin was superior to C-reactive protein and to individual cytokines as indicator of immune deficiency. Increased neopterin levels were associated with a decline in albumin, haemoglobin and the albumin/globulin ratio, and with increases in red cell distribution width.

Conclusions

Plasma neopterin is a good non-specific biomarker of disease activity in HIV/AIDS patients. It is a good indicator of inflammatory activity, perpetuation of inflammation-associated co-morbidities, degree of immune deficiency and has predictive value for underlying disease, and for monitoring the HAART response.     

The relationship between genotypic sensitivity score and treatment outcomes in late stage HIV disease after supervised HAART

This study investigated the effect of resistance testing quantified through a genotypic sensitivity score (GSS) on virologic, immunologic, and clinical responses among patients with late stage HIV‐1 disease receiving supervised highly active antiretroviral therapy (HAART). Newly admitted patients received drug resistance testing (n = 198) and then HAART supervised by residential health‐care facilities nurses. After initiating a resistance testing‐informed HAART regimen, patients were followed for HIV‐1 RNA suppression (<50 copies/ml), mean change in CD4⁺ T‐cells, new AIDS defining category C opportunistic conditions and death. GSS was constructed using the HAART regimen prescribed after resistance testing and data derived from IAS‐USA consensus mutations table with modification. Regressions with generalized estimating equations for robust estimation of standard errors and Cox proportional hazards regression estimated independent associations between GSS and treatment responses. After adjusting for adherence, initial log₁₀ HIV‐1 RNA levels, and other covariates, patients with a GSS ≥3 had significantly greater HIV‐1 RNA suppression (adjusted odds ratio (AOR) 2.32; 95% CI 1.14, 4.75). HIV‐1 RNA levels were lower among patients with ≥95% adherence, but the effect of GSS on viral suppression was not modified by adherence. Self‐rated health status, and baseline CD4⁺ T‐cell counts independently predicted HIV‐1 RNA suppression. GSS did not predict mean change in CD4⁺ cells/mm³ (236 vs. 233, P = 0.92), occurrence of new AIDS defining category C conditions or death. These data support resistance testing‐guided therapy as an independent predictive factor to improve virologic responses in treatment‐experienced patients. J. Med. Virol. 81:1323–1335, 2009. © 2009 Wiley‐Liss, Inc.