佳息患联合施多宁治疗艾滋病病毒1型感染的免疫反应效果

目的 观察非核苷类逆转录酶抑制剂施多宁与蛋白酶抑制剂佳息患联合用于治疗艾滋病病毒1型（HIV－1）后的机体免疫反应。方法 20例HIV－1慢性感染者，在治疗前后定期采集外周血，分离血浆及单个核细胞，检测病毒载量及T淋巴细胞亚群。结果 治疗后，病人血浆中HIV－1核糖核酸（RNA）含量降低，CD4^ T淋巴细胞数量增多，其免疫系统活化指标趋向于正常。结论 施多宁与佳息患联合治疗有效地抑制了HIV－1的复制，并提示机体免疫功能得以部分改善。     

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。     

人类免疫缺陷病毒合并结核菌感染的临床和治疗进展

人类免疫缺陷病毒 (HIV)是一种具有逆转录功能的 RNA病毒 ,主要侵犯破坏机体的细胞免疫系统 ,使机体的免疫处于崩溃状态 ,全身器官相继受累 ;而机体抵御结核杆菌 (TB)的主要力量靠细胞免疫 ,因而 HIV感染能促进结核病的恶化 ,并向其他非 HIV感染的人群传播。但 HIV侵犯 OKT4标志的 T淋巴细胞时 ,必要的条件就是前者已被激活并且增生活跃 ,TB感染是激活 T淋巴细胞并促使其增生活跃的病种之一 ,因此 TB感染是一种使 HIV感染加重的重要疾病 ,二者密切相关 ,互为因果 [1 ,2 ] ,造成疾病的复杂和治疗的极端困难。1.HIV合并 TB感染…     

对HIV感染、复活和抑制研究的一些新发现

1 HIV 感染机制的研究最近牛津大学的 Simmon 博士对 HIV 感染靶细胞的分子机制进行研究,发现 HIV 与树突状细胞(DC)上的 DC-Sign 受体结合后,不仅会提高机体免疫反应,还能促进病毒转运至局部的 T 淋巴细胞而     

去羟肌苷散、司他夫定和奈韦拉平联合治疗艾滋病患者6个月疗效观察

目的观察去羟肌苷散、司他夫定和奈韦拉平3药联合治疗艾滋病患者6个月时的疗效及不良反应。方法艾滋病患者8例，给予去羟肌苷散、司他夫定和奈韦拉平3药联合治疗，随访6个月。监测患者治疗前、治疗1个月、治疗3个月、治疗6个月时的血浆病毒载量及CD4^ T淋巴细胞计数，并评价药物不良反应。结果经过6个月治疗患者血浆中HIV RNA含量明显降低，CD4^ T淋巴细胞数量增加，药物不良反应轻微。结论去羟肌苷散、司他夫定和奈韦拉平3药联合治疗能有效抑制艾滋病病毒的复制，机体免疫功能亦有改善，并具有良好的耐受性。     

HIV合并HBV感染者T淋巴细胞亚群血浆病毒载量与肝脏功能的关系

目的 探讨HIV合并HBV感染者T淋巴细胞亚群、血浆病毒载量与肝脏功能的关系.方法 选取宁德师范学院附属宁德市医院2018年9月至2020年11月收治的103例HIV合并HBV感染者(研究组)及98例单纯HIV感染者(对照组)为研究对象,测定CD3+、CD4+、CD8+T淋巴细胞(简称CD3细胞、CD4细胞、CD8细胞...     

不同孕周高效抗反转录病毒治疗对HIV母婴阻断效果的比较

目的探讨不同孕周抗反转录病毒治疗对HIV母婴阻断的效果。方法选择2012-01~2014-01就诊HIV感染孕妇,以AZT+3TC+LPV/r方案进行HIV母婴阻断,孕14周组30例,孕28周组30例。检测孕妇治疗前及预产期前一个月的CD4+T淋巴细胞及病毒载量变化,观察婴儿出生情况及是否感染HIV(出生后18月龄进行HIV抗体检测)。结果孕14周组孕妇治疗前及预产期前一个月CD4+T淋巴细胞高于孕28周组,病毒载量低于孕28周组(P0.05)。两组婴儿18月龄时HIV抗体阳性率差异均无统计学意义(P0.05)。结论采用相同高效抗反转录病毒治疗方案对孕14周、孕28周的HIV孕妇进行母婴阻断,婴儿结局相似,但孕14周组应用高效抗反转录病毒治疗比孕28周组在抑制病毒复制,减少病毒负荷量,降低病毒传播性的效果更为显著。     

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.     

HIV感染者的免疫学功能变化及其与病程发展的关系

目的分析HIV感染者/AIDS病人体内病毒复制和免疫功能变化及其与病程发展的关系.方法应用定量RT-PCR、流式细胞计数和定量ELISA方法分析55例HIV感染者(n=42)和AIDS病人(n=13)外周血血浆病毒载量、T淋巴细胞亚群和细胞因子浓度。结果HIV感染者和AIDS病人CD4细胞和血浆IL-2浓度低于正常人群(P<0.001),血浆sIL-2R、TNF-a、NPT浓度高于正常人群(P<0.01),且随着CD4细胞水平降低呈明显上升趋势.CD4细胞、CD4/CD8比值和血浆IL-2水平随感染时间延长而不断下降,不同感染时间差异明显；机体感染HIV后CD4细胞年平均下降43/mm3,血浆sIL-2r、sTNFR-1、NFT年平均上升幅度分别为59.03pg/ml、38.69pg/ml、2.11ng/ml.各因素相关性分析显示CD4细胞、CD4/CD8比值与感染时间,CD3、CD4、CD8细胞变化分别与血浆病毒载量、sTNFR-I(P<0.005)\NPT(P<0.002)浓度变化间,以及IL-6与TNF-a(P<0.001)、NPT与IL-10(P<0.05)和sTNFR-I(P<0.001),血浆病毒载量与sTNFR-1(P<0.01)和NPT(P<0.002)之间则有明显的正直线相关性。结论本研究结果提示机体免疫活化、病毒复制和疾病进展间非常密切的关系,外周血CD4细胞、血浆IL-2水平的下降及血浆病毒载量、sII-2R、TNF-a、sTNFR-I、NPT浓度的明显上升量HIV感染者发展为AIDS的重要标志.     

病毒储存库优化方案治疗人类免疫缺陷病毒抑制患者2例

现报道2例在规律抗病毒治疗下人类免疫缺陷病毒(HIV)载量抑制成功而CD4+ T淋巴细胞增长并不理想的HIV抗体阳性患者。根据HIV病毒储存库(HIV DNA)信息对患者的抗病毒治疗方案进行优化后, 2例患者的CD4+ T淋巴细胞数量有所提升。通过总结患者的诊疗经过, 希望能给临床医师带来启发。     

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.     

Assessment of type 1 and type 2 cytokines in HIV type 1-infected individuals: impact of highly active antiretroviral therapy

Although the effect of highly active antiretroviral therapy (HAART) on HIV-1 replication has been established, the mechanisms involved in restoration of immune responses and reconstitution remain unknown. This study provides evidence of changes in expression of type 1 and type 2 cytokine-specific mRNA occurring during HIV-1 infection, before and after initiation of HAART. Unstimulated PBMCs from nine HIV-1-infected individuals obtained at different time intervals before and after the initiation of HAART were assessed for specific IFN-gamma, IL-2, IL-4, and IL-10 mRNA expression, using RT-PCR. Correlation with CD4+ T cell counts and viral load was also carried out. Before initiation of HAART, in all patients, little expression of specific IFN-gamma and IL-2 (type 1 cytokine) mRNA was noted. In contrast, expression of specific IL-4 and/or IL-10 (type 2) mRNA was readily detectable in the majority of patients. After initiation of HAART there was a continuous increase in IFN-gamma and IL-2 mRNA expression, although the latter occurred in lower amounts. This paralleled a dramatic reduction in viral load and increase in CD4+ T cell counts. Type 2 cytokine-specific mRNA expression fell to undetectable levels and in some cases reappeared later in the course of HAART. Predominant expression of type 2 cytokine mRNA, before initiation of HAART, concurs with previous findings of a dominant antiproliferative, type 2 cytokine profile during HIV-1 infection. Reversion of the cytokine profile, after HAART, to a strong type 1 profile suggests that in addition to suppressing virus replication directly the immune system may be given a chance to recover.     

Kinetics of the T-cell receptor CD4 and CD8 V beta repertoire in HIV-1 vertically infected infants early treated with HAART.

OBJECTIVES: To determine the kinetics and the relationship between the T-cell receptor V beta (TCRBV) complementary determining region 3 length, the CD4 T-cell count and HIV viral load changes in HIV-1 infected infants treated early with highly active antiretroviral therapy (HAART) during 1 year of follow-up. DESIGN: Two HIV-1 vertically infected infants, two HIV-1 vertically exposed uninfected and two healthy controls were analysed by spectratyping. Evaluation of viral load, CD4 naive and memory cell counts and a proliferation test were also carried out. METHODS: Twenty-six families and subfamilies of the TCR on CD4 and CD8 T cells were analyzed by spectratyping. Flow cytometric analysis on peripheral blood mononuclear cells for CD4CD45Ra, CD4CD45Ro, CD8CD38, proliferation tests and plasma viral load measurements were performed at baseline, 1, 6 and after 12 months of therapy. RESULTS: HAART induced a marked reduction of viral load in both HIV-1 infected infants and an increase to normal CD4 T-cell count in the symptomatic infant. At baseline the TCRBV family distribution in the majority of CD8 and a few of the CD4 T cells was highly perturbed, with several TCRBV families showing a monoclonal/oligoclonal distribution. During HAART a normalization of the TCR repertoire in both CD8 and CD4 subsets occurred. TCR repertoire normalization was associated with a good virological and immunological response. CONCLUSION: These results suggest that complete and early virus replication control as a result of early HAART leads to a marked reduction of T-cell oligoclonality and is an essential prerequisite to the development of a polyclonal immune response in HIV-1 infected infants.     

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。     

Immunological and virological impact of highly active antiretroviral therapy initiated during acute HIV-1 infection

The immunological and virological impact of short-term treatment initiated during acute human immunodeficiency virus type 1 (HIV-1) infection was assessed prospectively in 20 subjects, 12 of whom initiated highly active antiretroviral therapy (HAART) for 24 weeks and then terminated treatment. Treatment resulted in suppression of viremia, an increase in the CD4+ T cell count, enhanced differentiation of HIV-1-specific CD8(+) T cells from effector memory to effector cells at week 24 of HAART, and significantly higher virus-specific interferon- gamma+ CD8+ T cell responses after viral rebound (at week 48). However, despite these immunological changes, no differences in viremia or in the CD4+ T cell count were found 6 months after HAART was stopped, when treated subjects were compared with untreated subjects.     

Quantification of integrated and total HIV-1 DNA after long-term highly active antiretroviral therapy in HIV-1-infected patients.

OBJECTIVE: To assess the impact of long-term virus suppression on the peripheral blood CD4 T cells integrated and total HIV-1 DNA loads in patients receiving highly active antiretroviral therapy (HAART). METHODS: A total of 10 HIV-1-infected patients receiving a triple combination therapy (two nucleoside analogues and one protease inhibitor) were longitudinally studied to compare integrated and total HIV-1 DNA loads. HIV-1 DNA quantification was performed using a quantitative nested polymerase chain reaction (PCR) on genomic peripheral blood mononuclear cell (PBMC) DNA obtained at baseline and at 48 weeks of HAART. RESULTS: All the study patients showed an early and sustained decrease in plasma HIV-1 RNA to below the limit of detection (200 copies/ml). Concordant with the plasma viral decline, a significant increase in the CD4 T cell count was observed (P = 0.007). A statistically significant fivefold decrease in total HIV-1 DNA was detected after 48 weeks of HAART (P = 0.005). However, no statistically significant change was noted after the therapy when the integrated HIV-1 DNA copy number was compared (P = 0.333). Taken together, these results suggest that in the patients analysed the integrated HIV-1 DNA does not decay rapidly after HAART. CONCLUSION: Within the study cohort the total amount of PBMC HIV-1 DNA decreased drastically after 48 weeks of HAART. Nevertheless, the integrated HIV-1 DNA did not significantly decay during this period. Although the data presented here are limited by the number of patients analysed, our findings suggest that 48 weeks of HAART does not significantly reduce the integrated HIV-1 proviral DNA load in the latently infected CD4 T cell reservoir.     

Immunological and virological responses in HIV-1-infected adults at early stage of established infection treated with highly active antiretroviral therapy

OBJECTIVE: To evaluate the immunological and virological responses to highly active antiretroviral therapy (HAART) in blood and lymphoid compartments of HIV-1-infected patients at an early stage of infection. DESIGN: An open-label, observational, non-randomized, prospective trial of outpatients attending the Centre of Clinical Investigation in Infectious Diseases, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. SUBJECTS: Forty-one antiretroviral-naive HIV-1-infected adults with 400 CD4 T cells/microl or greater and 5000 plasma HIV-1-RNA copies/ml or greater were enrolled, and 32 finished the study. Forty-nine HIV-negative individuals were included as controls. All subjects gave written informed consent. INTERVENTIONS: All patients received abacavir 300 mg by mouth every 12 h and amprenavir 1200 mg by mouth every 12 h for 72 weeks. MAIN OUTCOME MEASURES: The extent of immune reconstitution in blood and lymph nodes after 72 weeks of HAART was evaluated, and compared with immunological measures of 49 HIV-negative subjects. RESULTS: Virus replication was effectively suppressed (-3.5 log10 at week 72). Substantial increments of CD4 T cell count in blood and percentage in lymph nodes were observed over time, and these measures were comparable to HIV-negative subjects by week 24 in blood and by week 48 in lymph nodes. The increase was equally distributed between naive and memory CD4 T cells. Recovery of HIV-specific CD4 responses occurred in 40% of patients. CONCLUSION: The initiation of HAART at an early stage of established HIV infection induces systemic quantitative normalization of CD4 T cells, a partial recovery of HIV-specific CD4 cell responses, and effective and durable suppression of virus replication.