CD+8 T细胞激活分子CD38、HLA-DR与HIV-1载量的相关性研究

目的研究HIV/AIDS患者CD8^＋ T细胞表达激活分子CD38、HLA-DR水平与血浆病毒载量（VL）的相关性,以及用CD8CD38、CD8HLA-DR比例替代VL检测的可行性.方法用流式细胞术分析103例接受12个月高效抗逆转录病毒治疗（HAART）患者的CD＋8 T细胞表达CD38和HLA-DR水平;用分支DNA扩增技术检测血浆VL.用敏感性、特异性、准确性等参数分析能有效预测VL＜50拷贝/ml、VL＜500拷贝/ml、VL＞1000拷贝/ml和VL＞10 000拷贝/ml时CD8CD38和CD8HLA-DR的检测范围.结果103例艾滋病患者CD38、HLA-DR和VL在12个月治疗中均呈下降趋势;CD38和VL在HAART治疗前及治疗第1、3、6、9、12个月6个检测点的总相关系数为0.483（P＜0.001）、HLA-DR和VL的总相关系数为0.477（P＜0.001）.用CD8CD38和CD8HLA-DR的水平预测VL值有显著诊断价值：当CD38＜68.5%和＜72.5%时预测VL＜50拷贝/ml和＜500拷贝/ml有较高的灵敏度和特异性;当HLA-DR在＞39.5%和＞46.5%时预测VL＞1000拷贝/ml和＞10 000拷贝/ml有较高的灵敏度和特异性.结论在条件匮乏的艾滋病高发区,可以用CD8CD38和CD8HLA-DR激活亚群的结果来预测血浆VL,作为监测HIV疾病进展和评价抗病毒疗效的参考.     

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.     

中国HIV/AIDS患者CD+4 CD+8T淋巴细胞与外周血各组份间关系的研究

目的研究艾滋病病毒/艾滋病(HIV/AIDS)患者CD+4、CD+8T淋巴细胞数与外周血各组份间白细胞(WBC)、血小板(PLT)、血红蛋白(HGB)、粒细胞百分数(GR%)、淋巴细胞百分数(LY%)、LY的相关性,为临床治疗提供参考依据.方法 HIV/AIDS患者抗凝外周血513份,在6小时之内检测其血细胞分类和CD+4、CD+8T淋巴细胞计数,比较CD+4、CD+8T淋巴细胞计数与WBC、HGB、PLT、LY%、GR%和LY的相关性.结果 CD4/CD8全部倒置,其中CD4/CD8＜1者达94.7%;CD+4细胞数＜500/mm3与HGB(r＝0.160,P＜0.01)、PLT(r＝-0.014,P＜0.01)、GR%(r＝-0.281,P＜0.01)、LY%(r＝0.321,P＜0.01)、LY((r＝0.494,P＜0.01)相关均有非常显著的统计学意义;CD+8细胞数与WBC数(r＝0.112,P＜0.05)、HGB(r＝0.131,P＜0.01)、GR%(r＝-0.526,P＜0.01)、LY%(r＝0.569,P＜0.01)、LY(r＝0.904,P＜0.01)相关均有显著性;200/mm3＜CD+4细胞数＜500/mm3与LY(r＝0.279,P＜0.01)、PLT(r＝0.192,P＜0.01)相关有显著性,CD+4细胞数＜200/mm3与LY(r＝0.262,P＜0.01)、LY%(r＝0.279,P＜0.01)、GR%(r＝-0.294,P＜0.01)相关有显著性.结论 HIV/AIDS患者CD+4、CD+8T淋巴细胞数与外周血中HGB、LY%、LY呈正相关,与GR%呈负相关.CD4/CD8与HGB、PLA、LY相关无显著性.     

成人HIV／AIDS CD^4＋细胞数与病毒载量之间关系分析

目的分析成人HIV/AIDS患者CD4~+细胞数与病毒载量(VL)之间的关系。方法对1990年—2001年在本院就诊的200例HIV/AIDS患者进行跟踪分析。结果 CD4~+≥200/μl时,血浆VL(log10)为4.17±0.79;CD4~+<200/μl时,血浆VL(log10)为5.01±0.72,VL水平明显高于CD~+≥200/μl组(P<0.01)。其中CD4~+>350/μl时,血浆VL(log10)为3.95±0.82;CD4~+200～350/μl时.血浆VL(log10)为4.43±0.63;CD4~+100～200/μl时,血浆VL(log10)为4.85±0.68;CD4~+<100/μl时,血浆VL(log10)为5.16±0.68。结论 HIV/AIDS患者CD4~+细胞数与病毒复制有非常密切的关系,外周血CD4~+细胞数与血浆VL的变化呈负相关关系。当血浆VL(log10)>5.01±0.72时,应考虑患者已进入艾滋病期。     

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     

外周血非编码微小RNA与HIV-1感染者病情进展的关系研究

目的 检测HIV-1感染者外周血微小RNA-155(miR-155)水平,并研究其与疾病进展的关系.方法 收集121例接受抗病毒治疗(HAART) HIV-1感染者和43例未接受HAART的感染者,实时荧光定量PCR法测定miR-155表达水平,流式细胞术检测CD3+CD4+和CD3+CD8+T细胞数及其活化细胞的比例(CD4+CD38+％和CD8+CD38+％). 结果 HIV-1感染者特别是治疗无效组外周血单核细胞(PBMC),CD4+和CD8+T细胞中的miR-155水平显著升高(F=11.317,P＜0.01).治疗无效者和未HAART治疗者CD38+的CD4+和CD8+T细胞比例高于正常对照和治疗有效组(F=5.813,P＜0.05),miR-155表达水平与T细胞免疫活化正相关(r=0.581,P=0.037;r=0.732,P=0.001).结论 本研究提示HIV-1感染者外周血miR-155表达水平显著升高,并与T细胞免疫活化正相关,可以作为HIV-1免疫应答的指标之一.     

正常T细胞分泌激活因子基因多态性与HIV-1感染者病毒载量、CD+4细胞计数和CD+4/CD+8比值的关系

目的分析正常T细胞分泌激活因子(RANTES)启动子和内含子等位基因,对艾滋病病毒1型(HIV-1)感染者外周血CD+4细胞计数、CD+4/CD+8比值和病毒载量的关系,以期探讨RANTES单核苷酸多态性(SNP)和艾滋病(AIDS)发病的关系.方法用流式细胞仪和real time法对40例汉族HIV-1感染者测定外周血CD+4、CD+8细胞计数和病毒载量,应用PCR-RFLP法进行基因分型.结果对RANTES-403、-28和In1.1三个位点等位基因与外周血CD+4T淋巴细胞计数、CD+4/CD+8+比值和病毒载量的关系的分析表明,具有RANTESIn1.1 C/C和T/C基因型的感染者,与较高的病毒载量、较低的C+4T细胞计数和C+4/CD+8比值有关.In1.1 T/T与T/C、C/C基因型的log10病毒载量的差异有非常显著的统计学意义(P＜0.01),但是不同基因型之间CD+4T淋巴细胞计数和CD+4/CD+8细胞比值则无显著性差异.log10病毒载量和CD+4T淋巴细胞计数(r=-0.447,P＜0.01)、CD+4/CD+8比值(r=-0.369,P＜0.05)有显著的负相关关系.结论所研究人群中,具有RANTES In1.1C的基因型者,与较高的病毒载量、较低的CD+4T细胞计数和CD+4/CD8+比值有关,它们是反映AIDS进程的主要指标,可能加速AIDS发病进程;而RANTES-403和-28等位基因的影响则处于相对次要的作用.     

支气管哮喘患者外周血中的CD+4 CD+25 T淋巴细胞的测定

目的阐明支气管哮喘(简称哮喘)患者外周血中是否存訡D+4 CD+25 T调节性淋巴细胞,并探讨CD+4 CD+25细胞的免疫抑制活性.方法应用流式细胞仪检测29例过敏性哮喘患者[急性发作期患者(急性发作期)15例、缓解期患者(缓解期)14例和16名非过敏性健康志愿者(正常对照组)外周血中CD+4 CD+25 细胞数量变化.应用免疫磁珠法分离提纯CD+4 CD+25 细胞,将纯化的CD+4 CD+25细胞和(或)CD+4 CD-25细胞在体外培养,观察CD+4 CD-25细胞的增殖反应,将收集培养的上清液用酶联免疫吸附测定(ELISA)法检测Th1类细胞因子γ干扰素(IFN-γ)和Th2类细胞因子白细胞介素4(IL-4)和IL-13.结果急性发作期患者外周血中CD+4 CD+25细胞比值为(14.9±1.8)%,缓解期患者为(11.8±0.7)%,正常对照组为(11.2±0.8)%,发作期与缓解期患者比较差异有统计学意义(P<0.01);缓解期患者与正常对照组比较差异无统计学意义(P>0.05).哮喘组CD+4 CD-25细胞增殖反应为(74±9)%,正常对照组为(72±8)%,两组比较差异无统计学意义(P>0.05).此外,哮喘组和正常对照组的CD+4 CD+25 细胞均能抑制CD+4 CD-25细胞产生IFN-γ、IL-4和IL-13,而且两组的抑制能力也无明显区别.结论急性发作期哮喘患者外周血CD+4 CD+25 细胞数明显高于缓解期患者和正常对照组.哮喘患者的CD+4 CD+25 细胞的抑制活性和正常对照组比较差异无统计学意义.谮     

CD+4 CD+25调节性T细胞抑制持续性丙型肝炎病毒感染患者CD+4T细胞反应

目的探讨CD+4 CD+25调节性T细胞(CD+4 CD+25Treg细胞)在持续性HCV感染患者CD+4 T细胞下调中的意义.方法流式细胞术检测慢性丙型肝炎患者外周血中CD+4 CD+25Treg细胞的数量以及细胞内因子的合成;与正常人或患者CD+4 CD-25 T细胞共同培养,检测其抑制功能;RT-PCR检测Foxp3的mRNA表达.结果 CD+4 CD+25Treg细胞约占慢性丙型肝炎患者外周血中CD+4 T细胞的(13.5±1.8)%,高于正常对照(5.3±0.8)% (P=0.004);主要合成IL-10,高表达Foxp3;CD+4 CD+25Treg细胞显著抑制CD+4 T细胞的增殖,以及合成IFNγ,并且抑制活性较正常人增高(P=0.034),这种作用不依赖IL-10和转化生长因子β.结论持续性HCV感染患者CD+4 CD+25Treg细胞表达增加,抑制活性增强,特异性抑制Th1反应.     

系统性红斑狼疮患者外周血CD4+ CD8+和CD22+淋巴细胞活化分子CD69的表达

目的探讨系统性红斑狼疮(SLE)患者外周血淋巴细胞(PBL) T细胞(CD4+、CD8+)和B细胞(CD22+)活化分子CD69的表达.方法应用双染色流式细胞术检测CD4、CD8、和CD22细胞亚群CD69分子;在植物凝集素(PHA)刺激后20 h淋巴细胞亚群CD69分子的表达.结果①SLE患者PBMC的CD69分子活动期高于静止期(P＜0.001)和正常对照组(P＜0.01)的表达,SLE静止期患者与正常对照组CD69表达差异无显著性(P＞0.05).②进一步分析CD4+、CD8+和CD22+淋巴细胞亚群的CD69的表达,其中,SLE活动期患者CD4+细胞的CD69表达显著高于静止期(P＜0.001)和正常对照组(P＜0.01)的表达,SLE静止期患者与正常对照组CD69表达差异无显著性(P＞0.05);CD8+细胞活动期高于静止期患者(P＜0.05),其余组间差异无显著性(P＞0.05);CD22+B细胞各组间差异无显著性.③PHA刺激20 h后,CD4+、CD22+B细胞的CD69表达,活动期显著高于静止期患者和正常对照组(P＜0.01).结论 SLE患者外周血CD4+T细胞和CD22+B细胞存在着异常的活化,这种淋巴细胞的异常活化是SLE重要的发病机制之一.     

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.     

Higher risk of AIDS or death in patients with lower CD4 cell counts after virally suppressive HAART

Background The clinical implications of a failure to achieve high CD4 cell counts while receiving virally suppressive highly active antiretroviral therapy (HAART) are uncertain.
Methods We analysed data from HIV-infected men participating in the Multicenter AIDS Cohort Study (MACS) to elucidate associations between CD4 cell counts achieved during virally suppressive HAART and risks of AIDS or death. Inclusion criteria were: CD4 cell count <200 cells/μL before HAART initiation; ≥2 viral load (VL) determinations after HAART initiation; and sustained viral suppression, defined as all VL <50 HIV-1 RNA copies/mL, but allowing a single VL of 50–1000 copies/mL.
Results One hundred and twenty-one men were included; median age was 42 years. After first VL <50 copies/mL, six participants had a new AIDS diagnosis and seven died. The median CD4 cell count change/year (cells/μL) after first VL <50 copies/mL was zero among patients who either developed AIDS or died vs . 39 among those who did not meet either endpoint ( P =0.119). After controlling for time from HAART initiation to first VL <50 copies/mL, age at first VL <50 copies/mL, history of AIDS and antiretroviral therapy (ART) experience before HAART, the hazard ratio for AIDS or death at CD4 cell count of ≤200 vs . >350 cells/μL was 10.7 ( P =0.013), and at CD4 cell count of 201–350 vs . >350 cells/μL was 8.54 ( P =0.014).
Conclusion In this cohort, lower CD4 cell count at the time of viral suppression was associated with increased risk of AIDS or death.     

The potential for CD4 cell increases in HIV-positive individuals who control viraemia with highly active antiretroviral therapy

OBJECTIVES: To study the long-term CD4 cell responses to highly active antiretroviral therapy (HAART) in treatment-naive patients whose viral loads remained below 500 copies/ml for prolonged periods. DESIGN: A total of 237 patients whose viral loads remained below 500 copies/ml for one year or more. Median follow-up was 1.9 years. METHODS: CD4 cell counts were analysed to investigate long-term immunological response using mixed-effects models with the slope allowed to change after 1, 12 and 24 months of HAART. RESULTS: The median baseline CD4 cell count was 175 cells/mm3. After an initial rapid increase in the first month after HAART (97.2 cells/mm3 a month), increases in CD4 cell counts continued less rapidly (11.6 cells/mm3 a month). This increase slowed by 2.4 cells/mm3 a month after one year. CD4 cell counts continued increasing after 2 years, but the rate of increase again slowed (estimated slope at 2 years 5.4 cells/mm3 a month; decrease in slope from year 2 compared with years 1-2 3.7 cell/mm3 a month). A total of 198 out of 211 patients (94%) with measurements at baseline and one year experienced an increase in CD4 cell counts in this interval; 81 and 67% had an increasing slope between 1 and 2 and 2 and 3 years, respectively. By the end of follow-up, CD4 cell counts had increased by 319 cells/mm3, and were more than 500 cells/mm3 in 40% of patients. CONCLUSION: Although the rate of immune recovery slowed after 2 years, CD4 cell counts rose in most and began to return to levels seen in HIV-negative individuals.     

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。     

CD8+ cell noncytotoxic anti-HIV response: restoration by HAART in the late stage of infection

Highly active antiretroviral therapy (HAART) is currently the best HIV infection management strategy. However, its effects on the CD8+ T cell noncytotoxic anti-HIV response (CNAR) are not well known. We investigated if HAART has different effects on CNAR in patients at the intermediate and late stages of HIV infection. Untreated healthy HIV-infected subjects with a mean CD4+ T cell count of 606 cells/microl were examined as a reference group. Plasma viral load, CD4+ T cell count, and CNAR activity were measured at baseline and regular intervals for at least 48 weeks following initiation of HAART. Baseline CNAR activity in all subjects correlated inversely with viral load and directly with CD4 T+ cell counts. The level of CNAR in the latestage group was significantly lower than in the intermediate-stage and the healthy reference group (p < 0.01). Following initiation of HAART, substantial increases in CD4+ T cell counts and decreases in viral loads were observed in both groups, indicating treatment success. CNAR activity was found to be increased significantly during HAART, but only in the late-stage group (p < 0.01). This increase in CD8+ cell function was seen within 4 weeks of treatment initiation and resulted in levels of CNAR activity almost equal to those observed in the healthy reference subjects. Our findings suggest a beneficial effect on CNAR in those individuals with reduced activity, typically in late-stage infection.     

Prolonged CD4+ cell/virus load discordance during treatment with protease inhibitor-based highly active antiretroviral therapy: immune response and viral control

Mechanisms that underly discordant CD4+ cell/virus load (VL) responses in patients who receive highly active antiretroviral therapy (HAART) were studied in 30 human immunodeficiency virus (HIV)-positive patients, in 3 groups. Discordant responders maintained CD4+ cell levels >200/mm(3) with stable or increasing trend, despite sustained VLs of 500-5000 copies/mL, for >2 years. Treatment-success patients had CD4+ cell counts >200/mm(3) with stable or increasing trend and VLs <50 copies/mL, for >2 years. Treatment-failure patients initially responded to HAART, followed by decreasing CD4+ cell counts and increasing VLs. Interferon-gamma production to gag and noncytolytic CD8+ cell suppressive activity were greater in discordant responders. Cellular activation was greatest in patients with treatment failure. All discordant responders had non-syncytium-inducing (CCR5-tropic) viruses. Viruses from discordant responders and from patients with treatment failure had extensive resistance mutations; discordant responders had significantly lower viral replication capacities. These findings suggest that discordant responses may be related to enhanced HIV-directed immune responses, diminished cellular activation, decreased viral replication capacity, and preservation of non-syncytium-inducing virus strains.     

Sustained CD4+ T cell response after virologic failure of protease inhibitor-based regimens in patients with human immunodeficiency virus infection

The relationship between plasma human immunodeficiency virus (HIV) RNA levels and peripheral CD4+ T cell counts was examined in 380 HIV-infected adults receiving long-term protease inhibitor therapy. Patients experiencing virologic failure (persistent HIV RNA >500 copies RNA/mL) generally had CD4+ T cell counts that remained greater than pretherapy baseline levels, at least through 96 weeks of follow-up. The CD4+ T cell response was directly and independently related to degree of viral suppression below the pretreatment baseline. For any given HIV RNA level measured 12 weeks after virologic failure, subsequent CD4+ T cell decline was slower in patients receiving a protease inhibitor-based regimen than in a historical control group of untreated patients. These observations suggest that transient or partial declines in plasma HIV RNA levels can have sustained effects on CD4+ T cell levels.     

HCV coinfection does not alter the frequency of regulatory T cells or CD8+ T cell immune activation in chronically infected HIV+ Chinese subjects

Regulatory T cell (Treg) is a subset of CD4(+) T cells that play a critical role in regulating the immune responses. Human immunodeficiency virus (HIV) infection is associated with T cell abnormalities and alters effector T cell function. There are a large number of patients coinfected with HIV and hepatitis C virus (HCV). Here, we evaluated the proportion of CD4(+) Treg cells expressing CD25 and FOXP3, and the status of immune activation of CD8(+) T cells in 60 Chinese patients chronically infected with HIV and/or HCV. Furthermore, we investigated the influence of highly active antiretroviral therapy (HAART) on the level of Treg cells and immune activated CD8(+) T cells. We observed that the Treg level was upregulated in HIV infection and HCV infection could not enhance this kind of upregulation significantly. The level of Treg cells was negatively correlated with CD4(+) T cell counts and positively correlated with HIV viral loads. We observed considerably elevated CD38 and HLA-DR expression in CD8(+) T cells in HIV-infected subjects but not in HCV-infected patients in comparison to that in healthy controls. There is no significant difference concerning the proportion of CD8(+) T cells expressing CD38 or HLA-DR between HIV-1-monoinfected and HIV/HCV-coinfected patients. After 12-week HAART, the proportion of Treg cells dropped, but still more than the level in healthy controls. HAART could reverse the abnormal immune activation of CD8(+) T cells. The decrease of Tregs did not alter the downregulation of HIV-1-specific CTL responses in these HIV-infected patients after HAART therapy. The level of HIV virus might be the key point for the decline of CTL responses.     

Structured antiretroviral treatment interruptions in chronically HIV-1-infected subjects

The risks and benefits of structured treatment interruption (STI) in HIV-1-infected subjects are not fully understood. A pilot study was performed to compare STI with continuous highly active antiretroviral therapy (HAART) in chronic HIV-1-infected subjects with HIV-1 plasma RNA levels (VL) <400 copies per ml and CD4(+) T cells >400 per microl. CD4(+) T cells, VL, HIV-1-specific neutralizing antibodies, and IFN-gamma-producing HIV-1-specific CD8(+) and CD4(+) T cells were measured in all subjects. STIs of 1-month duration separated by 1 month of HAART, before a final 3-month STI, resulted in augmented CD8(+) T cell responses in all eight STI subjects (P = 0.003), maintained while on HAART up to 22 weeks after STI, and augmented neutralization titers to autologous HIV-1 isolate in one of eight subjects. However, significant decline of CD4(+) T cell count from pre-STI level, and VL rebound to pre-HAART baseline, occurred during STI (P = 0.001 and 0.34, respectively). CD4(+) T cell counts were regained on return to HAART. Control subjects (n = 4) maintained VL <400 copies per ml and stable CD4(+) T cell counts, and showed no enhancement of antiviral CD8(+) T cell responses. Despite increases in antiviral immunity, no control of VL was observed. Future studies of STI should proceed with caution.