HIV/AIDS抗病毒治疗前CD4+T淋巴细胞计数自然变化与治疗后免疫恢复及死亡率的相关性

目的 探讨云南省玉溪市艾滋病病毒感染者/艾滋病病人（human immunodeficiency virus/acquired immunodeficiency syndrome,HIV/AIDS）获得抗病毒治疗（antiretroviral therapy,ART）前CD4+T淋巴细胞（简称CD4）自然变化与ART后免疫恢复及死亡率的相关性。方法 将HIV/AIDS获得ART前CD4自然变化分为四组,描述不同组间ART后免疫恢复情况,应用非条件Logistic回归进行单因素和多因素分析HIV/AIDS病例ART后免疫无应答（immune non-responses,INRs）的相关因素,采用Kaplan-Meier法绘制不同组间ART后生存曲线。结果 777例HIV/AIDS中ART前快速上升组、平缓上升组ART后CD4月均上升速率慢于ART前快速下降组,差异均具有统计学意义（均有P<0.05）。多因素Logistic回归分析发现:ART前CD4自然变化为上升（OR=2.416,95%CI:1.264~4.616,P=0.008;OR=1.997,95%CI:1.067~3.737,P=0.031）、基线CD4值>500 cell/μL（OR=6.550,95%CI:3.315~12.941,P<0.001）、ART时年龄≥ 50岁（OR=4.276,95%CI:1.761~10.3865,P=0.001）的病例ART后更容易出现INRs。ART前平缓上升组ART后累计生存率低于ART前平缓下降组和快速下降组（χ2=8.979,P=0.003;χ2=4.158,P=0.041）,在基线CD4值<200 cell/μl层,ART前平缓上升组在ART后累计生存率低于ART前平缓下降组和ART前快速下降组,差异均有统计学意义（均有P<0.05）。结论 HIV/AIDS患者ART前CD4自然变化与ART后免疫恢复、INRs及死亡率存在一定关联。     

广西壮族自治区2005-2021年抗病毒治疗男男性行为人群HIV感染者免疫重建及影响因素分析

目的 分析广西壮族自治区（广西）抗病毒治疗（ART）的MSM中HIV感染者（MSM感染者）实现免疫重建的比例及影响因素。方法 资料来源于中国疾病预防控制信息系统,研究对象为2005-2021年广西首次接受ART≥24周MSM感染者,并维持24个月内HIV RNA低于检测限。计算其接受ART后免疫重建的比例,采用Cox比例风险回归模型分析其免疫重建的影响因素。采用SPSS 24.0软件进行统计学分析。结果 在3 200例MSM感染者中,免疫重建不良、中等免疫重建和完全免疫重建的比例分别为15.56%（498/3 200）、14.78%（473/3 200）和69.66%（2 229/3 200）。免疫重建的ART时间M（Q₁,Q₃）为12（5,27）个月。多因素Cox比例风险回归模型分析结果显示,相比于开始ART年龄≥30岁、WHO临床分期为Ⅲ期/Ⅳ期、基线BMI<18.50 kg/m²和基线CD4⁺T淋巴细胞（CD4）计数<200个/µl者,开始ART年龄<30岁、WHO临床分期为Ⅰ期/Ⅱ期、基线BMI≥24.00 kg/m²和基线CD4计数≥200个/µl者更容易实现完全免疫重建。结论 2005-2021年广西ART的MSM感染者存在一定比例的免疫重建不良者,应针对年龄较大者和基线CD4计数较低者等重点人群调整和优化ART方案及监测。     

2013年江西省新报告HIV-1感染者新发感染检测状况及其免疫印迹条带特征分析

摘要:目的　分析2013年江西省新报告HIV-1感染者新发感染检测状况及其免疫印迹条带特征。方法　应用BED-CEIA法对2013年新报告HIV-1感染者中符合新发感染检测要求的样本进行检测。结果　符合新发感染检测要求的852名HIV-1感染者,检出新发感染者206名,长期感染者646名,BED-CEIA新发感染检测判定为长期感染和新发感染的HIV-1感染者在婚姻、文化程度和感染途径上差异有统计学意义（P＜0.05）。新发感染者WB检测条带中p66、p55、p51、gp41、p39和p31的阳性检出率显著低于长期感染者（P＜0.05）。结论　WB检测结果缺失p51和gp41时应高度怀疑其为HIV-1新发感染。     

二联方案对HIV感染者免疫活化的影响

抗逆转录病毒治疗（ART）虽然能有效抑制HIV复制,降低AIDS的发病率和死亡率,但HIV感染者体内仍存在慢性免疫活化。近年来,随着ART方案的不断优化,指南推荐使用的二联方案能否与三联方案一样有效降低免疫活化的水平,是现阶段抗病毒治疗领域热点问题之一。本文总结分析了二联方案免疫活化的相关研究,并通过与三联方案的比较,...     

高效抗逆转录病毒治疗后HIV/AIDS免疫无应答者研究进展

高效抗逆转录病毒治疗（HARRT）可显著降低病毒复制,重建HIV/AIDS患者的免疫功能。但仍有15%～30%的HIV-1感染者在病毒抑制到较低水平的情况下不能取得良好的免疫重建,我们称之为免疫无应答者。文章对其定义及发生因素进行综述,为攻克艾滋病免疫无应答梳理思路。     

德宏傣族景颇族自治州2017年HIV-1感染者抗病毒治疗前耐药和病毒基因亚型研究

目的 了解德宏傣族景颇族自治州（德宏州）抗病毒治疗（ART）前的HIV-1感染者基因型和耐药株的流行水平。方法 2017年1-6月在德宏州收集初始ART的HIV-1感染者170例,扩增pol基因,进行HIV-1基因分型和基因型耐药分析。结果 147份样品获得了pol基因,通过进化分析,发现12种HIV-1基因型,居于前3位包括C亚型（29.9%,44/147）、独特型重组形式（URFs）（27.2%,40/147）和CRF01_AE（19.7%,29/147）,还检测到了近年该地区新鉴定出的流行重组形式（CRFs）,包括CRF62_BC、CRF64_BC、CRF86_BC和CRF96_cpx。基因型在异性性传播和注射吸毒传播人群中的分布差异有统计学意义。发现耐药突变的比例为8.8%（13/147）。注射吸毒的HIV-1感染者中耐药株的比例（25.0%,8/32）,高于异性性传播的HIV-1感染者（4.6%,5/109）（χ²=10.166,P=0.002）。结论 2017年德宏州初始ART的HIV-1感染者中病毒基因型高度复杂,HIV-1耐药株的流行达中度水平。     

抗逆转录病毒治疗与免疫重建炎性综合征 FREE

抗逆转录病毒治疗（antiretroviral therapy, ART）在人免疫缺陷病毒/获得性免疫缺陷综合征（HIV/AIDS）患者中的应用极大地降低了HIV病毒载量,随之使CD4+细胞上升,免疫功能恢复。这些免疫学的改变对患者是有利的,减少了机会性感染的发生,可延长生命。但经ART后不久,部分患者却由于对病原特异性免疫反应的失控而引起病情加重［1-2］,这被称为免疫重建炎性综合征（immune reconstitution inflammatory syndrone, IRIS）、免疫重建综合征或免疫重建疾病（immune reconstitution disease, IRD）。IRIS绝大多数在ART后3个月内发生。IRIS在一些非HIV相关的快速恢复免疫功能的病例中亦有描述,如免疫抑制治疗撤退或癌症患者停止化疗后可发生。     

台州市2016-2018年新报告HIV/AIDS抗病毒治疗前HIV-1耐药及亚型流行特征分析

目的 了解台州市新报告HIV/AIDS抗病毒治疗（ART）前HIV-1耐药情况及亚型流行特点。方法 于2016年1月至2018年12月在台州市开展新报告HIV/AIDS在ART前HIV-1耐药的横断面调查,RT-PCR扩增获得HIV-1 pol基因片段并测序,提交序列至斯坦福大学耐药数据库,根据2014年WHO耐药监测指南的推荐标准,确定耐药突变位点以及HIV-1毒株对抗病毒药物的敏感性。结果 2016-2018年台州市新报告HIV/AIDS中成功获得HIV-1 pol基因区序列的研究对象806例,ART前HIV-1耐药率为2.9%（23/806）,其中,非核苷类反转录酶抑制剂（NNRTIs）、核苷类反转录酶抑制剂（NRTIs）和蛋白酶抑制剂（PIs）耐药率分别为1.9%（15/806）、0.6%（5/806）和0.0%。2016-2018年新报告HIV/AIDS在ART前HIV-1耐药率依次分别为1.6%、1.8%和4.8%。NNRTIs和NRTIs耐药突变位点以K103 N（0.7%）和M184I/V（0.5%）为主。HIV-1亚型以CRF01_AE（42.7%,344/806）、CRF07_BC（28.9%,233/806）和CRF08_BC（11.2%,90/806）为主。同性性传播者HIV-1亚型以CRF01_AE（53.3%,136/255）和CRF07_BC（32.2%,82/255）为主;异性性传播者HIV-1亚型以CRF01_AE（37.7%,203/539）、CRF07_BC（27.5%,148/539）和CRF08_BC（16.1%,87/539）为主。结论 2016-2018年台州市新报告HIV/AIDS在ART前HIV-1耐药率处于低流行状态,但存在上升趋势,需加强对HIV-1耐药型毒株的监测工作。     

不同亚型HIV感染者免疫恢复研究将助力精细化抗病毒治疗

正据2018年我国分子流行病学调查结果显示,HIV-1 CRF01_AE和CRF07_BC分别占当年报告感染者人群的36.2%和40.8%,其已成为我国艾滋病主要流行毒株。现今,有关艾滋病治疗后免疫恢复的研究大多数针对是欧美地区的HIV-1 B亚型患者,而对于感染CRF01_AE和CRF07_BC亚型人群研究较少,因此有必要深入探究不同亚型患者的免疫恢复进展情况及其与宿主免疫之间相互作用的差异,这对于制订更加精细化的HIV治疗方案至关重要。     

脑肠肽ghrelin在胃肠功能中的研究进展

脑肠肽激素ghrelin是一种引起生长激素释放的多肽,是迄今发现的唯一生长激素释放激素受体(GHSR)的内源性配体。循环中的生长激素释放肽主要由胃黏膜产生。Ghrelin可促进胃肠运动、调节能量代谢和影响心血管功能等。有很多研究发现,ghrelin与胃肠功能关系密切,以下就这些方面研究进展作一综述。     

Influence of carbohydrate delivery on the immune response during exercise and recovery from exercise

Acute, sustained, moderate- to high-intensity exercise has been shown to induce significant alterations in the distribution and function of leukocytes during recovery. In many instances, these changes have been found to reflect a transient impairment of immune function in vitro during recovery from such exercise. Carbohydrate supplementation during exercise has been associated with an attenuation of cortisol production. Because cortisol has been linked to immunosuppression, a growing body of research has examined the influence of carbohydrate supplementation on immune function in response to exercise. New areas along this line of inquiry involve examination of the cytokine response to exercise and the role that carbohydrate may play in regulating the production of proinflammatory cytokines. Inter-relations among the immune response, production of specific cytokines, and cortisol are also examined. The clinical significance of an attenuated immune response when exercising as a result of the administration of supplemental carbohydrate is yet to be determined.     

先天性运动型眼球震颤的分子遗传学研究进展

先天性运动型眼球震颤(Congenital motor nystagmus,CMN)是一种常见的眼科遗传病,在新生儿中发生率较高,具有较高的遗传异质性,其遗传方式包括常染色体显性、常染色体隐性和X连锁等。近年来随着分子生物学技术的发展和在遗传病研究中的应用,CMN的遗传学研究取得了较多进展。目前X连锁遗传的CMN致病基因FRMD7已经被定位在Xq26-q27,但对FRMD7基因的功能和致病机制仍需进一步研究。本文对CMN的分子遗传学研究进展进行综述。     

Predictors of immune recovery and the association with late mortality while on antiretroviral treatment in Cambodia

The objectives of this study were to examine the association of the on-treatment CD4 cell count with late mortality (after >6 months of antiretroviral treatment [ART]) and to identify the determinants of the long-term CD4 cell count evolution after treatment initiation. We conducted a retrospective analysis including all antiretroviral (ARV)-naïve adults initiating ART in a tertiary hospital in Phnom Penh, Cambodia from 2003-2010. We used Cox proportional hazards modelling (mortality analysis), including time-updated CD4 counts, and mixed-effects modelling (CD4 response over time). Overall, 2840 patients were included (47% male, median age: 34 years, median baseline CD4 count: 78 cells/μL). The median time on ART was 2.5 years (IQR 1.1-4.3); 71 patients died after >6 months of ART. The baseline CD4 count was the main determinant of the on-treatment CD4 cell count. Time-updated CD4 cell counts was the strongest determinant of late mortality with a HR of 0.32 (95% CI 0.16-0.63) and 0.29 (95% CI 0.11-0.71) for CD4 values of 200-350 cells/μL and 350-500 cells/μL respectively. We conclude that baseline CD4 counts strongly determine the long-term immune recovery, which critically affects late mortality. This calls for increased efforts for early ART initiation and availability of CD4 count testing in low-income countries.     

Controlled trial of zinc supplementation during recovery from malnutrition: effects on growth and immune function

To evaluate the effect of zinc on growth and immune function, 32 marasmic infants were selected on admission to the nutrition recovery center; 16 received 2 mg/kg daily of elemental zinc supplement as acetate and the remaining received a placebo. Immunity was assessed by skin-test response, T-cell blastic proliferation immunoglobulins, and infectious morbidity. Weight-for-length gain for initial 60 days in Zn-supplemented group was 9% of standard vs 3% for placebo (p less than 0.05). Energy intake was similar in both groups. Incidence of infections, especially pyoderma, was significantly higher in placebo group: 10 of 16 vs 3 of 16 in the supplemented group (p less than 0.025). Plasma Zn was correlated with number of febrile days in the prospective month (r = -0.66, p less than 0.05). The percent anergic infants decreased and serum IgA increased significantly only in Zn-supplemented group. Zinc supplementation has significant effects on weight gain and host defense mechanisms despite normal plasma levels. Zinc supplementation is recommended for optimal recovery from marasmus.     

阿尔茨海默病的危险因素研究进展

阿尔茨海默病(alzheimer disease,AD)是一种严重危害老年人健康的慢性退行性疾病,随着人口老龄化的加剧,其发(患)病率有增无减.患病率高、预后差、病因复杂、临床疗效不理想是人们对该病的共同感受,因此消除和减少危险因素已成为研究AD的重要命题.近些年来,人们对AD的病因除了从分子生物学角度进行大量探索,并取得一定成果外,还涉及到社会人口学特征、生物遗传、个人特质与经历、体内某些宏、微量元素含量与分布等因素,并且在该病的预防中越来越被人们关注.本文就目前AD相关的主要危险因素(分子生物学探索除外)研究情况作一概括.     

Antibody response to hepatitis B re-vaccination in HIV-infected children with immune recovery on highly active antiretroviral therapy

Despite a history of hepatitis B virus (HBV) vaccination prior to highly active antiretroviral therapy (HAART), most of HIV-infected children do not have protective antibody to HBV infection. The efficacy of an additional booster dose in children with immune recovery on HAART remains unknown. This study was conducted to determine the response rate of HBV antibody after re-vaccination in HIV-infected children with immune recovery on HAART. Sixty-three successfully HAART-treated HIV-infected children with history of prior HBV vaccination received 10microg doses of recombinant HBV vaccine (Government Pharmaceutical Organization-Merieux Biological Product, Bangkok, Thailand) intramuscularly at 0, 2 and 6 months. The vaccine response rates were 17.4, 82.5, and 92.1% at 2, 6 and 7 months after the first dose of vaccine, respectively. Plasma HIV RNA level below the limit of detection at the time of re-vaccination was associated with successful vaccine response. HIV-infected children with immune recovery after HAART are likely to benefit from three-dose HBV re-vaccination.     

登革病毒包膜蛋白E第三结构域的研究进展

登革病毒是目前人类最重要的虫媒病毒之一,登革病毒包膜蛋白E的第三结构域是研究登革病毒亚单位疫苗及病毒入侵宿主细胞的重要靶点。     

Japanese encephalitis vaccination in HIV-infected children with immune recovery after highly active antiretroviral therapy

HIV-infected children are vulnerable to infections by vaccine preventable pathogens. However, they have poorer responses to childhood immunization than healthy children. The objectives of this study are to determine the prevalence of Japanese encephalitis (JE) protective antibody in HIV-infected children with immune recovery after highly active antiretroviral therapy (HAART) and evaluate response to JE revaccination. JE neutralizing antibody titer of plasma was determined by a plaque reduction neutralization assay. An antibody titer of more than 1:10 was defined as protective antibody. Children who did not have protective antibody to JE were enrolled to receive a two-dose JE revaccination during the study. There were 96 children with mean age of 9.7 years (S.D. 2.6) and mean CD4 percentage of 25 (S.D. 5) who participated in the study. Forty-four children (46%) had protective antibody to JE. A two-dose JE revaccination was administered to 50 children who did not have JE antibody. At 1 month after revaccination, 44 children (88%) developed protective antibody. This study demonstrated that there is a low prevalence of JE protective antibody in HIV-infected children despite history of JE primary childhood vaccination. However, the majority of HIV-infected children with immune recovery after HAART can develop protective antibody after JE revaccination.