人类免疫缺陷病毒感染者及艾滋病患者外周血总淋巴细胞数和CD4+T细胞计数的相关性研究

目的探讨人类免疫缺陷病毒(HIV)感染者和获得性免疫缺陷综合征(AIDS,艾滋病)患者(HIV/AIDS)外周血总淋巴细胞数(TLC)和CD4 T细胞计数的相关性,明确将TLC作为HIV/AIDS疾病进展监测指标的可行性。方法分析2000年1月至2006年5月在北京协和医院艾滋病诊疗中心诊治的未经抗病毒治疗的317例HIV/AIDS患者TLC和CD4 T细胞计数之间的相关性,判断TLC代替CD4 T计数<100×106/L,<200×106/L和<350×106/L的准确度和最佳临界值,计算各临界值的敏感度、特异度、阳性预测值和阴性预测值。结果317例HIV/AIDS患者外周血TLC和CD4 T细胞计数[中位数(25%分位数,75%分位数),单位为×106/L]分别为1300(1754,932)和242(384,86),二者呈显著正相关性(r=0.722,P<0.01)。以TLC预测CD4 T细胞计数<100×106/L,<200×106/L和<350×106/L具有较高准确度,其ROC曲线下面积分别达到0.866、0.853和0.863(P均<0.01)。随着TLC临界值取值的降低,敏感度逐渐减低,特异度则逐渐增大。结论该研究结果为应用TLC作为监测HIV/AIDS初诊、初治患者疾病进展和确定抗病毒治疗时机的替代指标提供了试验依据。     

Focal tuberculosis of the liver with local hemorrhage in a patient with acquired immunodeficiency syndrome

Abstract: Tuberculosis of the liver is common in patients with acquired immunodeficiency syndrome (AIDS). Tuberculous liver granulomas in such patients are usually atypical. The liver granulomas may be even totally absent, but liver tissue usually reveals numerous acid-fast bacilli. Focal tuberculosis of the liver is a less common form of liver tuberculous infection. We present a 33-year old white homosexual man infected with the human immunodeficiency virus. He had three tumour-like lesions in the left liver lobe, which were subsequently diagnosed as focal hepatic tuberculosis with local hemorrhage. This unusual presentation of liver tuberculosis indicates the necessity of an aggressive diagnostic approach for the evaluation of focal liver lesions in patients with AIDS.     

艾滋病功能性治愈研究新进展

抗反转录病毒治疗(antiretroviral therapy, ART)虽然能有效抑制HIV 1型(HIV-1),但不能根治AIDS。AIDS功能性治愈须为停止ART后患者体内HIV-1 RNA长期低于检测下限,CD4~+T淋巴细胞数量和机体免疫功能保持正常,这一直是全球研究热点和难点。近年来,AIDS功能性治愈研究在HIV-1储存库激活和清除、免疫治疗、干细胞移植、基因编辑等方面取得了长足进步,本文就此进行综述,为进一步研究提供理论指导。     

Immune dysregulation in human immunodeficiency virus infection: know it,fix it,prevent it?

Infection of humans by the human immunodeficiency virus (HIV) causes a progressive, multifactorial impairment of the immune system eventually leading to the acquired immunodeficiency syndrome (AIDS). No cure or vaccine exists yet against HIV infection. More worrisome is the fact that despite having identified HIV as the cause of the AIDS, we still do not understand what pathogenic mechanisms lead to the debacle of the immune system. In this review we consider the extent and the limits of our knowledge of HIV pathogenesis, and how this knowledge may be used to design preventive and therapeutic approaches.     

Human immunodeficiency virus (HIV) associated non-Hodgkin's lymphomas in Denmark: report of three cases

High grade malignant non-Hodgkin's lymphoma (NHL) was the presenting manifestation of the acquired immunodeficiency syndrome (AIDS) in 3/81 reported cases of AIDS in Denmark (by April 2, 1986). Asymptomatic HIV infection, 1 and 5 yr prior to the onset of lymphoma, was documented in 2 cases. 1 patient became infected by Factor VIII treatment, 2 were male homosexuals. 2 patients had an uncommon tumour presentation in the oral cavity, 1 patient presented with an abdominal mass. The histologic subtypes were immunoblastic (2), and small noncleaved cell, Burkitt's (1). Helper/suppressor T-cell ratio was decreased at onset of lymphoma in 2 cases. All 3 patients have died, 4, 6, and 24 months after diagnosis of NHL. Only 1 patient died of NHL, 1 died of an unclassified pneumonia and the third developed progressing supranuclear HIV-associated polyneuropathy without evidence of CNS lymphoma. Thus, high grade malignant B-cell NHL is a regular initial manifestation of AIDS, and may develop after years of asymptomatic HIV infection.     

MR imaging features of acquired immunodeficiency syndrome patients complicated with intracranial tuberculosis and its relationship with CD4 + T cell count

目的 探讨获得性免疫缺陷综合征(AIDS)并发颅内结核的磁共振成像(MRI)特征及与CD4 ⁺T淋巴细胞计数的关系。 方法 回顾性分析2014年1月至2017年12月首都医科大学附属北京地坛医院收治的46例AIDS并发颅内结核患者的临床资料,总结其MRI特点。采用Mann-Whitney检验脑实质结核与脑膜结核患者CD4 ⁺T淋巴细胞计数的差异;采用χ ²检验比较CD4 ⁺T淋巴细胞计数≥100个/μl和<100个/μl患者间MRI特征的差异,包括病灶部位、范围、大小、形态、强化方式,以及并发其他脏器结核情况等,并统计CD4 ⁺T淋巴细胞计数与病变大小和强化方式之间的关系。 结果 46例AIDS并发颅内结核患者中,脑实质型结核患者的CD4 ⁺T淋巴细胞计数[47(20.5,131.5)个/μl]低于脑膜型结核[153(130.5,228.5)个/μl](Z=-2.37,P=0.018)。CD4 ⁺T淋巴细胞计数≥100个/μl的患者脑膜型结核(19.6%,9/46)、累及基底池(17.4%,8/46)、外侧裂池(13.0%,6/46)和脑沟(13.6%,6/46)较<100个/μl[分别为4.3%(2/46),2.2%(1/46), 2.2%(1/46), 2.2%(1/46)]更常见(χ ²=7.62,P=0.006; Fisher精确概率检验,P值分别为0.001、0.008和0.008),而分布于大脑皮层下(19.6%,9/46)较<100个/μl(47.8%,22/46)更少见(Fisher精确概率检验,P=0.037)。病变直径3~5mm(136个病灶,47.1%)者呈点状强化,>5mm(89个病灶,30.8%)者呈环形强化,差异有统计学意义(χ ²=105.36,P<0.001)。脑实质结核组病变多位于大脑皮层下,增强扫描呈点状或环形强化(88.6%,31/35);脑膜结核以基底池脑膜增厚强化为主(81.8%,9/11);且脑实质[17.4%(8/46)]及脑膜结核灶[21.7%(10/46)]均易呈簇集状分布,差异有统计学意义(χ ²=4.13,P=0.042)。 结论 AIDS并发颅内结核的MRI表现与患者的CD4 ⁺T淋巴细胞计数密切相关。当AIDS患者CD4 ⁺T淋巴细胞计数<100个/μl时,颅内结核以脑实质型为主,病灶多分布于大脑皮层下;当CD4 ⁺T淋巴细胞计数≥100个/μl时,以脑膜结核为主,病变易累及基底池、外侧裂池和脑沟;颅内病灶直径<5mm时以点状强化为主,≥5mm时以环形强化为主。     

CD4:CD8 ratio in children with perinatally acquired HIV‐1 infection

Objectives

In adults with horizontally acquired HIV infection, an inverted CD4:CD8 ratio is associated with persistent immune activation, size of HIV reservoir and predicts an increased risk of non‐AIDS‐defining adverse events. Normalization of this ratio with antiretroviral therapy (ART) is suboptimal in adults, despite viral suppression, and is less well described in paediatric populations. We investigated rates of CD4:CD8 ratio recovery in children with perinatally acquired HIV infection (PaHIV) on ART.

Methods

A cross‐sectional, retrospective analysis of routine clinical data in children with PaHIV (5–18 years old) attending a single UK centre was carried out.

Results

CD4:CD8 normalization was seen in 62% of children on suppressive ART. A negative correlation was found between current CD4:CD8 ratio and age at start of ART. Positive correlations were found between current CD4:CD8 ratio and total time with suppressed HIV viral load and nadir CD4 counts. Multiple linear regression analysis showed that age at start of ART was significantly associated with current CD4:CD8 ratio (standardized β = ?0.680; P < 0.001). Patient sex, ethnicity and antiretroviral regimen did not affect ratio recovery.

Conclusions

We found higher rates of CD4:CD8 ratio normalization compared with previous adult studies. Children who started ART at a younger age were more likely to recover a normal ratio. The current policy of universal treatment for all HIV‐positive adults and children will enhance immunological normalization.

     

110例人类免疫缺陷病毒感染及获得性免疫缺陷综合征患者合并血小板减少症临床分析

目的:了解人类免疫缺陷病毒感染或获得性免疫缺陷综合征(HIV/AIDS)患者合并血小板减少症的临床特点。方法:回顾性分析2009年8月至2012年12月上海市公共卫生临床中心收治的110例HIV/AIDS合并血小板减少症患者的临床资料,分析血小板减少的病因、治疗及转归。结果:110例患者中机会性感染49例(44.5%),乙型肝炎病毒和(或)丙型肝炎病毒(HBV/HCV)感染26例(23.6%),HIV相关免疫性血小板减少性紫癜(HIV-ITP)20例(18.2%),药物相关骨髓抑制7例(6.4%),AIDS相关肿瘤及其他疾病8例(7.3%)。以血小板减少为HIV/AIDS首发临床表现者10例。82.7%(91/110)的患者同时合并其他血液学异常,包括贫血(68.2%)或白细胞减少(58.2%)。81.3%的HIV-ITP患者对激素及静脉注射免疫球蛋白治疗敏感,治疗无效或复发者长期抗病毒治疗后血小板缓慢上升。结论:HIV/AIDS患者血小板减少常见病因有机会性感染、合并HBV/HCV感染、HIV-ITP、药物相关骨髓抑制等。HIV-ITP可为HIV/AIDS患者首要临床表现,其根本治疗措施为抗病毒治疗。血小板减少患者常同时合并贫血和(或)白细胞减少,多重血液学异常预示病情严重,需要积极处理原发病。     

The development of AIDS or AIDS-related conditions in a cohort of HIV antibody-positive homosexual men during a 3-year follow-up period

One hundred and thirty-three homosexual men seropositive for the antibody against human immunodeficiency virus (HIV) were enrolled in a prospective study in 1984-85. The 3-year cumulative incidences of the acquired immunodeficiency syndrome (AIDS) and AIDS-related conditions, by life-table analyses, were 18% and 34%. The cumulative incidence of immune deficiency defined as CD4 lymphocytes less than 0.5 x 10(9) l-1 was 70% at 3 years. Absence of antibodies to p24 antigen, HIV antigenaemia, CD4 lymphocytes less than 0.3 x 10 l-1 and elevated serum level of IgA were significantly associated with the development of AIDS. There was no association between disease progression and persistent generalized lymphadenopathy. When adjusted to the probable year of infection, these results are in accordance with previous cohort studies. It is concluded that most, or all, subjects seropositive for HIV will develop progressive loss of CD4 lymphocytes followed by clinical signs of immune deficiency, and that differences among previous cohorts with respect to disease progression are probably due to differences in the duration of infection.     

广东地区762例住院人类免疫缺陷病毒感染患者机会性感染分析

目的 探讨广东地区HIV/AIDS患者机会性感染的特点及其与外周血CD4+T淋巴细胞计数(CD4+)之间的关系.方法 对762例HIV/AIDS住院患者机会性感染发生情况及其外周血CD4+进行分析.结果 762例患者中,704例(92.39%)发生机会性感染,共发生感染1428例次,其中真菌、细菌、病毒感染分别占38.38%、36.20%和7.77%.以肺部、口腔、皮肤、消化道感染、败血症及其他全身播散性疾病为主,分别占33.05%、26.89%、10.29%、8.96%、6.58%和9.94%.CD4+≥2001μ1的患者机会性感染率为75.74%(103/136),而CD4+<200/μ1的患者则为96.01%(601/626),两组比较差异有统计学意义(P<0.01).所有的AIDS指征性机会性感染均发生在CD4+<200/μ1患者,其中81.97%的耶氏肺孢子茵肺炎(PCP)、71.43%的巨细胞病毒(CMV)视网膜炎及所有的隐球菌脑膜炎、播散性隐球菌病、播散性组织胞浆病、播散性鸟型分枝杆菌病(MAC)、播散性青霉病及弓形虫脑病均发生在CD4+<50/μ1的患者.结论 广东地区HIV/AIDS患者机会性感染主要病原为真菌、细菌、病毒等,以肺部、口腔、皮肤、胃肠道和全身播散性感染为主.CD4+水平越低,机会性感染特别是指征性机会性感染越常见,CD4+对机会性感染发生的预测、预防和早期诊断与治疗有重要的指导意义.     

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。     

A simple clinical staging system that predicts progression to AIDS using CD4 count,oral thrush,and night sweats

Objective: To develop a simple clinical staging system based on CD4 count and clinical variables that predicts progression to AIDS in HIV-infected non-AIDS patients. Design: Retrospective cohort study. Setting: A primary care outpatient clinic for HIV-infected patients at a VA Medical Center. Patients: One hundred seventy-six HIV-infected non-AIDS patients seen at the Houston VA Special Medicine Clinic between January 1986 and December 1990 and followed for a mean of 22 months. Fifty-four patients (31%) progressed to AIDS during follow-up. Measurements: The medical records were reviewed, and data corresponding to the initial (baseline) clinic visit and subsequent sixmonth visits were extracted. Main results: “Predictive” baseline variables (i.e., those associated with progression to AIDS) were first identified and then examined in Cox proportional hazards modeling. In the final model, CD4 category, oral thrush, and night sweats made significant independent contributions. A three-stage prognostic system was constructed by assigning points to the three variables: CD4>500 cells/mm³=0; 500≥CD4≥200=1; CD4<200=2; presence of oral thrush=1; presence of night sweats=1. Stages were assigned as follows: stage I=0 points, stage II=1−2 points, and stage III=3−4 points. The proportions of patients who progressed to AIDS were: stage I, 6/39 (15%); stage II, 31/106 (29%); and stage III, 17/31 (55%). Conclusion: These results demonstrate that simple, clinically sensible prognostic staging systems that predict progression to AIDS can be constructed using CD4 count and clinical variables. Supported in part by grants from the University of Texas School of Public Health Biomedical Research Group, the Veterans Affairs Health Services Research and Development Houston Field Program, and the Houston VA Research Center for AIDS and HIV Infection (RCAHI).     

HIV/HCV重叠感染患者病情进展的相关因素研究

探讨HIV/HCV重叠感染患者病情进展的原因和影响预后的相关因素.选择HIV/HCV重叠感染患者这一特定人群,按照疾病进展分成艾滋病组(AIDS)和HIV感染组(free of AIDS),回顾性分析两组间免疫功能、HIV病毒载量、肝脏功能的差异,探讨可能影响病情进展的相关因素.艾滋病组与HIV感染组比较:艾滋病组患者的细胞免疫功能(CD 4T、CD 8T)均低于HIV感染组,差异非常显著(P＜0.001;P=0.003);HIV病毒载量在艾滋病组明显高于HIV感染组,差异显著(P=0.005);艾滋病组的肝脏功能(ALT、AST)明显高于HIV感染组(P值分别为0.043、0.002);蛋白合成指标(TP、ALB)艾滋病组较HIV感染组低下,差异非常显著(P＜0.001).以Logistic回归分析,CD 4T、感染时间和ALB是预测疾病进展的独立危险因素(P＜0.001).回归方程预测准确率为97.0%.HIV/HCV重叠感染可加快病情进展,ALB与CD 4T细胞数及感染时间是预测艾滋病病程进展的独立危险因素.     

HIV感染者外周浅表淋巴结中CD4~+T淋巴细胞计数与胶原沉积的关系研究

目的通过对不同感染阶段HIV感染者外周浅表淋巴结中CD4+T淋巴细胞、胶原蛋白、白细胞介素(interleukin,IL)-7的检测,以及CD4+T淋巴细胞计数与胶原沉积的相关性分析,探讨HIV感染后胶原沉积对CD4+T淋巴细胞的影响。方法选择HIV感染者43例,分为HIV感染无症状组和AIDS组,留取外周浅表淋巴结活体组织检查(活检)组织;另外选择非HIV感染者12名为健康对照组,同样留取其外周浅表淋巴结活检组织。利用免疫组织化学方法检测研究对象淋巴结中CD4+T淋巴细胞、Ⅰ型胶原蛋白和IL-7定量及分布情况。结果 1随着病程进展,HIV感染者外周浅表淋巴结中胶原沉积逐渐增加,AIDS组高于无症状组,无症状组高于健康对照组,差异均有统计学意义(P均0.05);2HIV感染无症状组外周浅表淋巴结中CD4+T淋巴细胞计数与健康对照组相比差异无统计学意义(P0.05),而AIDS组则显著减少(P0.01);3HIV感染者外周浅表淋巴结中CD4+T淋巴细胞计数与胶原沉积量呈负相关(R2=0.724,P=0.000),与外周血中CD4+T淋巴细胞计数呈正相关(R2=0.702,P=0.000);43组IL-7的表达水平差异无统计学意义(P0.05),而AIDS组部分患者淋巴结中IL-7呈局部聚集性分泌。结论 HIV感染后外周浅表淋巴结中胶原沉积逐渐增加导致结构破坏,可能是CD4+T淋巴细胞进行性减少的一个重要原因,虽然IL-7有随病程进展而分泌增加的趋势,但仍不足以弥补淋巴结结构破坏对CD4+T淋巴细胞的影响。     

Thrombotic thrombocytopenic purpura in patients with human immunodeficiency virus infection: a report of three cases and review of the literature.

Three cases of thrombotic thrombocytopenic purpura (TTP) and coexistent human immunodeficiency virus (HIV) infection are presented with a review of 15 cases reported in the literature. Of the 18 total patients, one-half presented with no symptoms of HIV infection while nine patients presented with symptomatic HIV disease before or simultaneous to the diagnosis. The presenting symptoms were similar to those with classic TTP and included fever in 75% and 40% with neurologic symptoms. Laboratory parameters reflected the microangiopathic hemolytic anemia typically seen in patients with TTP. The median hematocrit was 19.4%, while the median platelet count was 16,000/mm3. As with classic TTP, patients with HIV-related TTP only had mild renal dysfunction (median creatinine of 1.2 mg/dl, range 0.8-4.8 mg/dl). Plasma exchange produced clinical remission in a majority of the patients. Importantly, approximately one-third of the patients died prior to the initiation of therapy. We conclude that TTP is a rare but treatable condition in patients with HIV infection. A TTP diagnosis should be considered in patients with HIV infection who present with severe anemia and thrombocytopenia. Plasma exchange should be considered as initial therapy. The role of both antiplatelet therapy and aspirin is unknown.     

Cardiac involvement in acquired immunodeficiency syndrome—a review to push action

As more effective therapies have produced longer survival times for human immunodeficiency virus (HIV)-infected patients, new complications of late-stage HIV infection including HIV-related heart disease have emerged. Almost any agent that can cause disseminated infection in patients with acquired immunodeficiency syndrome (AIDS) may involve myocardium, but clinical evidence of cardiac disease is usually overshadowed by manifestations in other organs, primarily the brain and lungs. Cardiac abnormalities are found at autopsy in two-thirds of patients with AIDS, and more than 150 reports of cardiac complications have been published. Cardiac involvement in HIV disease includes pericardial effusion, myocarditis, dilated cardiomyopathy, and/or endocardial involvement at any stage of the disease. This review deals with all the cardiac manifestations of AIDS and serves to highlight two problems and one indication. First of all, there are very few clinical studies. Current knowledge is based almost exclusively on echocardiography and autopsy studies. Observational or clinical trials would be useful. Second, there exists very poor information on the impact of treatment; and epidemiologic and clinicopathologic studies are mandatory for obtaining detailed data concerning the mechanisms of myocardial damage in AIDS. Finally, because cardiac complications are often clinically inapparent or subtle in the initial stages, periodic screening of HIV-positive patients by electrocardiogram and echocardiogram is probably indicated. in addition, AIDS may also provide the opportunity to gain insights into the pathogenesis of little understood cardiac diseases such as lymphocytic myocarditis and dilated cardiomyopathy.     

Medical management of benign oesophageal disease in patients with human immunodeficiency virus infection

Oesophageal diseases are common in human immunodeficiency virus infection, and Candida is the most frequent cause. Empiric therapy with oral antifungal therapy is cost-effective in most patients presenting with oesophageal symptoms. The "gold standard" of diagnosis, endoscopy with brushings and biopsies, is reserved for non-responders within 2 weeks. Since the use of empiric antifungal drugs, the percentage of viral and idiopathic ulcers has increased. The latter frequently recur after treatment, and have been associated with the development of oesophageal strictures. More information is needed on the role of maintenance therapy particularly for viral infections.     

Absolute lymphocyte count as a surrogate marker for CD4+ cell count in monitoring of antiretroviral therapy,Northwest Ethiopia: retrospective evaluation

Objective

To determine the use of total lymphocyte count as a surrogate marker for CD4+ cell count among HIV infected patients at the University of Gondar Hospital.

Methods

A retrospective cross sectional study was conducted at the University of Gondar Hospital antiretroviral therapy laboratory from December 2011 to May 2012. Data on CD4+ cell count, total lymphocyte count, sex, and age were collected from 2964 HIV infected patients and analyzed using SPSS version 16 computer software.

Results

Total lymphocyte count was significantly correlated with CD4+ cell count (P<0.001; r²=0.434). The sensitivity, specificity, positive predictive value, negative predictive value of total lymphocyte count<1 200 cells/mm³ to predict CD4+ cell count <200 cells/mm³ was 57.8%, 86.4%%, 34.1%, 86.39%, respectively. A total lymphocyte count<1 000cells/mm³ was found to have suboptimal sensitivity (69.0%), and specificity (85.0%) for predicting a CD4+ cell count <200 cells/mm³.

Conclusions

Total lymphocyte count and CD4+ cell count was positively correlated. Hence, lymphocyte count less than or equal to 1 000/mm³ can be used as a cutoff value in place where there is no CD4+ cell counting machine.     

Multicenter trial of octreotide in patients with refractory acquired immunodeficiency syndrome-associated diarrhea

Diarrhea is a significant problem in patients with acquired immunodeficiency syndrome (AIDS). The aim of this study was to determine octreotide effectiveness in refractory AIDS-associated diarrhea. In a 3-week protocol, 129 patients with a stool weight of >500 g/day despite standard antidiarrheal therapy were randomized to receive octreotide or placebo (3:2 ratio). Octreotide dose was increased 100 μg weekly to a maximum of 300 μg three times a day based on weekly 72-hour stool collections. Subsequently, patients received open-label octreotide at doses of up to 500 μg three times a day. A 30% decrease in stool weight defined response. After 3 weeks, 48% of octreotide- and 39% of placebo-treated patients had responded (P = 0.43). At 300 μg three times a day, 50% of octreotide- and 30.1% of placebo-treated patients responded (P = 0.12). At a baseline stool weight of 1000–2000 g/day, 57% of octreotide- and 25% of placebo-treated patients responded (P = 0.06). Response rates based on CD4 counts, diarrhea duration, body weight, human immunodeficiency virus risk factor, and presence or absence of pathogens showed no benefit of octreotide. Adverse events were more frequent in the octreotide-treated group. In the doses studied, octreotide was not more effective than placebo in patients with refractory AIDS-associated diarrhea. This lack of effectiveness may be attributable to inadequate sample size, doses, and duration of study treatment.