HIV病毒载量与HCV病毒载量间及与CD3,CD4和CD8细胞免疫功能的相关性研究

目的研究静脉吸毒人群HIV/HCV混合感染者病毒载量间的相关性及与CD3,CD4,CD8细胞计数的关系.方法采用荧光定量PCR技术和流式细胞技术分别检测HIV和HCV病毒载量及CD3,CD4,CD8细胞计数,并采用多元统计方法进行分析.结果综合分析显示,在HIV和HCV混合感染的静脉吸毒人群中,HIV病毒载量与CD3和CD4细胞计数存在有统计学负相关关系,HCV病毒载量与CD3和CD4细胞计数存在统计学正相关关系,两病毒载量均与CD8细胞计数和CD4/CD8比值无统计学关系,HIV病毒载量与HCV病毒载量间存在统计学负相关关系.进一步逐步回归分析表明,CD3和CD8细胞计数对HIV病毒载量影响较小,CD4细胞计数和CD4/CD8比值及HCV病毒载量对HIV病毒载量水平则产生决定性的影响.结论静脉吸毒人群HIV/HCV混合感染者病毒载量间存在一定程度的内在联系和相互干扰, CD3,CD4,CD8 T淋巴细胞免疫水平和作用机制有待于进一步研究.     

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。     

安徽省HIV／AIDS儿童的免疫学及病毒学现况调查

目的全面了解和掌握安徽省感染艾滋病病毒／艾滋病（HIV／AIDS）儿童的免疫学及病毒学状况。方法对2007年安徽省HIV／AIDS儿童进行病史调查,并检测CD4、CD8细胞计数和CD4／CD8比值以及病毒载量。结果安徽省HIV／AIDS儿童的传播途径以母婴传播为主,治疗组和未治疗组儿童病毒载量的对数值存在统计学差异（P〈0．01）,治疗组62．5％的儿童病毒载量低于最低检出限,未治疗组儿童病毒载量均高于最高检出限。母婴传播感染HIV／AIDS儿童的感染时间与CD4细胞计数和病毒载量水平呈反向相关关系（P〈0．05）,CD8细胞计数与CD4细胞计数呈正向回归关系（r=0．553）,病毒载量对数值与CD4细胞计数呈反向回归关系（r=0．273）。结论安徽省HIV／AIDS儿童以母婴传播为主,抗病毒药物能有效抑制HIV的增殖。     

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/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。     

静脉吸毒人群HIV感染者CD+3 CD+4 CD+8 T淋巴细胞定量研究与分析

目的　定量分析静脉吸毒人群艾滋病病毒 (HIV)感染者CD+ 3 、CD+ 4 、CD+ 8T淋巴细胞水平。方法　采用流式细胞技术 (FCM) ,对 76例无症状抗 HIV阳性的静脉吸毒者 ,16 5例抗 HIV阴性的静脉吸毒者及 6 1名正常对照 ,分别检测CD+ 3 、CD+ 4 、CD+ 8T淋巴细胞绝对计数和CD+ 4 /CD+ 8比值。结果　HIV感染组与静脉吸毒组及正常对照组各项指标间差异有非常显著的统计学意义 (F =10 5 0 2、15 9 13、2 2 0 0 8,P均 <0 0 1) ;CD+ 4 细胞计数和CD+ 4 /CD+ 8比值表现为HIV感染组 <静脉吸毒组 <正常对照组 (q =18 4、2 4 6、11 1,P均 <0 0 1) ,CD+ 3 细胞计数呈现为HIV感染组 >健康对照组 >静脉吸毒组 (q=19 8、6 5、10 8,P均 <0 0 1) ,CD+ 8细胞计数表现为HIV感染组 >静脉吸毒组 >健康对照组 (q=2 7 2、2 4 9,P均 <0 0 1;q =3 4 8,P均 <0 0 5 )。结论　HIV感染和 /或静脉吸毒均可不同程度的导致CD+ 4 和CD+ 8细胞水平的改变 ,有关静脉吸毒合并HIV感染对免疫细胞水平的影响尚需进一步深入研究。     

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.     

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。     

MSM HIV感染者外周血中ADCC反应水平与HIV-1感染早期病毒载量的关系

目的在艾滋病病毒（HIV）感染早期,观察HIV-1特异性抗体依赖的细胞毒性作用（ADCC）与病程进展的关系。方法利用HIV-1特异性多肽刺激和多色流式技术,对前期采集的、感染时间在1年以内的男男性行为人群（MSM）标本进行ADCC检测。结果共采集HIV-1感染者标本58份,CD4＋T淋病细胞计数与外周血病毒载量呈明显负相关（r=-0.281 6,P=0.032 3）。ADCC检测结果显示,病毒载量与HIV-1Pol特异性CD2＋IFN-γ＋细胞占CD3-细胞的比例呈显著的正相关（r=0.260 7,P=0.046 2）;而病毒载量与HIV-1Gp120特异性CD2＋CD107a＋细胞占CD3-[A1]细胞的比例呈显著负相关（r=-0.342 9,P=0.009 0）。结论在HIV-1感染早期,感染者体内即可产生针对Pol和Env蛋白的ADCC反应,其中针对Gp120蛋白的ADCC反应具有控制病程进展的作用。     

我国部分地区HIV感染者HCV协同感染状况的调查研究

目的 了解我国部分地区艾滋病病毒(HIV)感染者体内丙型肝炎病毒(HCV)的协同感染状况.方法 以我国北京、河南、广西部分地区的HIV感染者为研究对象,通过访谈了解病人的基本状况,采集病人的EDTA抗凝静脉血,对感染者的HIV感染状况、CD4细胞数、HIV病毒载量及HCV感染状况进行检测,分析我国部分地区HIV感染者中HCV的协同感染状况.结果 共收集到HIV感染者血液249份,其中有34.14%的感染者同时感染HCV.统计学分析显示,河南地区的HIV感染者同时感染HCV的比例显著高于北京和广西地区;经静脉吸毒和输血传播感染HIV的病人同时感染HCV的几率相近,但都明显高于性传播;感染了HCV的HIV感染者体内的病毒载量要显著高于未感染HCV的HIV感染者,但CD4细胞数没有显著差别.结论 HCV协同感染率在不同的HIV感染者人群中存在差异,而且这种协同感染会影响感染者HIV病毒载量,因此在观察HIV感染者疾病进程及考虑治疗措施时,应充分考虑HCV协同感染的影响.     

人类免疫缺陷病毒与重叠丙型肝炎病毒感染者免疫指标比较

目的 分析HIV/HCV重叠感染人群与HIV单独感染人群治疗前临床特征及免疫功能的差异,探讨其可能的影响因素.方法 以HIV/HCV重叠感染患者59例、HIV单独感染患者38例为研究对象,取患者治疗前外周血,检测其肝功能、血常规、外周血T细胞亚群(CD4+、CD8+)及HIV、HCV病毒载量,酶联免疫斑点法(ELISPOT)检测HIV特异性细胞毒性T淋巴细胞(CTL)的数量和功能.结果 HIV/HCV重叠感染率达60.8%.重叠感染组ALT、AST均明显高于HIV组(49.8 U/L比23.6 U/L,49.1 U/L比32.3 U/L,P值分别为0.000、0.013);重叠感染组PLT明显低于HIV组[(167.3±59.2)×109/L比(198.0±63.9)×109/L,P=0.040].外周血T细胞亚群检测结果两组间差异无统计学意义.重叠感染组HIV RNA定量为(4.046±0.541)lOglo拷贝/mL,低于HIV组的(4.394±0.507)log10拷贝/mL(P=0.018).重叠感染组对HIV-Gag全序列肽段的阳性孔斑点数(平均秩次30.85)较HIV组(平均秩次44.34)低,阳性孔数(4.60±5.52)低于HIV组(6.24±6.93),但两组比较差异无统计学意义.重叠感染组Alb与HCV病毒载量呈负相关(r=-0.540),CD4+与PLT呈正相关(P=0.000).结论 单采血浆感染HIV患者中,有较高的HIV/HCV重叠感染率和较低的细胞免疫功能.     

HCV recovery from peripheral blood mononuclear cell culture supernatants derived from HCV–HIV co-infected haemophilic patients with undetectable HCV viraemia

Hepatitis C viraemia, in 38 human immunodeficiency virus positive (HIV+)/hepatitis C virus positive (HCV+) patients, was determined in haemophilic patients during the 4 years since initiation of highly active antiretroviral therapy (HAART). Six of 38 patients had persistently HCV-negative viraemia for more than 2 years. No correlation between HCV-negative viraemia and CD4+ T-cell counts, HIV viral load, age, type or severity of haemophilia could be established. Reduced levels of HIV viral load and the immune reconstitution that follows the initiation of HAART were not enough to explain the disappearance of HCV from plasma. Individuals who cleared plasma HCV had significantly higher CD8+ T-cell counts (P=0.0013) (mean +/- SE: 1153 +/- 117.8 cells microL(-1)) than those with HCV-positive viraemia (819.1 +/- 40.72 cells microL(-1)). Because HCV could maintain a low replication level in peripheral blood mononuclear cells (PBMC), we cultured PBMC of five of six patients with undetectable HCV viraemia. We found four of five HCV RNA-positive cultures. The presence of HCV RNA in our cultures proved that these cells may be an important viral reservoir that could contribute to HCV recurrence in plasma even after long periods of negative viraemia. In summary, our results indicate that in spite of prolonged HCV-negative plasma viraemia, HCV patients that are co-infected with HIV may harbour replication-competent HCV in their PBMC. Therefore, true clearance of HCV infection is difficult to achieve in these patients.     

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。     

Antiviral CD8-mediated responses in chronic HCV carriers with HBV superinfection

Hepatitis B virus (HBV) superinfection in chronic hepatitis C represents a natural model to investigate whether or not hepatitis C virus (HCV) can influence priming and maturation of antiviral T cells; whether or not HBV superinfection, which is known to determine control of HCV replication, can restore HCV-specific T cell responsiveness; and whether or not cytokines stimulated by HBV infection can contribute to HCV control. To address these issues, the function of CD8 cells specific for HBV and HCV was studied longitudinally in two chronic HCV patients superinfected with HBV. Patients with acute hepatitis B were also examined. Frequency and function of HBV tetramer+ CD8 cells were comparable in patients acutely infected with HBV with or without chronic HCV infection. HBV-specific CD8 cell function was efficiently expressed irrespective of serum HCV-RNA levels. Moreover, fluctuations of HCV viremia at the time of HBV superinfection were not associated with evident changes of CD8 responsiveness to HCV. Finally, no correlation was found between serum levels of interferon alpha, interleukin (IL)-12, IL-10, or IL-18 and control of HCV replication. In conclusion, HCV did not affect the induction of primary and memory HBV-specific CD8 responses. HCV-specific CD8 responses were undetectable when HCV-RNA was negative, showing that inhibition of HCV replication in the setting of a HBV superinfection was not sufficient to induce a restoration of CD8 reactivity against HCV.     

Lopinavir/ritonavir treatment in HIV antiretroviral-experienced patients: evaluation of risk factors for liver enzyme elevation

OBJECTIVES: To evaluate the risk factors for lopinavir/ritonavir (LPV/r)-related liver enzyme elevation (LEE) in HIV antiretroviral-experienced patients. METHODS: An open prospective observational study was carried out to analyse the incidence and time of LEE development during LPV/r treatment, and to determine whether LEE development was correlated with epidemiological, clinical and biochemical data, immune and virological profiles, concomitant hepatic diseases, antiretroviral therapy, or histological and ultrasonography liver examination results. A diagnosis of LEE was considered when LEE symptoms occurred after LPV/r introduction and was confirmed by a second control within 2 weeks. RESULTS: A total of 782 HIV-positive outpatients have been enrolled in six different Infectious Diseases Departments in Northern Italy since August 2000. Of these patients, 71 (9.1%) developed LEE within 115+/-85 days (mean+/-standard deviation); 13 of these subjects discontinued LPV/r and four were hospitalized. Of the patients with LEE, 74.6% and 25.4% had grade 2 and > or =3 toxicity, respectively. No correlation between LEE and sex, baseline CD4 cell count, viral load, HIV stage, triglyceride values, histological and ultrasonography liver examination results, nevirapine use, or increase in CD4 cell count was observed. Higher baseline alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) values (P < 0.0001 and P=0.004, respectively), younger age (P=0.008), previous hepatitis B virus (HBV) infection (P=0.012), efavirenz use (P=0.04), and hepatitis C virus (HCV) and/or HBV coinfection (P < 0.0001, relative risk 4.78) were significantly related to LEE. No correlations between LEE and the same risk factors as investigated in the whole study population were found in subgroups of patients with HCV and/or HBV infection. CONCLUSIONS: HCV and HBV testing and measurement of baseline ALT values are essential for screening subjects at risk of LEE before starting LPV/r. Strict monitoring of clinical and biochemical parameters should be performed in these patients.     

用高效抗逆转录病毒治疗HIV/HCV重叠感染33例

目的研究HIV/HCV重叠感染者用高效抗逆转录病毒治疗(HAART)的疗效和药物的副作用以及HIV和HCV的相互影响.方法治疗前后定期采集33例HIV/HCV重叠感染者的外周血,分离血桨和单个核细胞,检测病毒载量、T淋巴细胞亚群以及HCVRNA和肝脏纤维化指标.结果治疗后患者血浆中HIVRNA含量全部<50copies/ml,CD4不同程度增多.结论施多宁、拉米夫定和赛瑞特联合治疗HIV/HCV重叠感染者可有效抑制HIV-1的复制,并部分改善机体免疫功能.     

The prognostic value of a single hepatitis C virus RNA load measurement taken early after human immunodeficiency virus seroconversion

Hepatitis C virus (HCV) RNA loads are measured sporadically in HCV-positive individuals. However, the prognostic value of these isolated measurements for predicting progression to acquired immune deficiency syndrome (AIDS) and all-cause mortality in coinfected individuals remains unclear. In this study, the prognostic value of a single HCV RNA load measurement taken early after human immunodeficiency virus (HIV) seroconversion was investigated in a cohort of 96 male patients with inherited bleeding disorders. Dates of HIV seroconversion had been estimated for all patients, and at least 4 HCV RNA load measurements per patient were done retrospectively after HIV seroconversion. HCV RNA load stabilized at 4 years after HIV seroconversion, and this point was used for analysis. There was a significant correlation between increased age and early HCV RNA load (r=0.25; P=.01). Adjusting for HIV RNA levels, CD4 cell counts, and the age effect, HCV RNA load >5.90 log(10) copies/mL was predictive of progression to AIDS and all-cause mortality over a period of at least 15 years.