基于BALB/c裸小鼠构建SIV感染动物模型

目的构建可进行猴免疫缺陷病毒(SIV)复制的裸小鼠模型,为抗艾滋病病毒药物筛选的体内实验提供一种廉价、易于操作的艾滋病小动物模型。方法向BALB/c裸小鼠腹腔内接种已感染猴免疫缺陷病毒(SIVmac251)的TZM-b1细胞,构建SIV体内复制的裸小鼠动物模型,通过采集小鼠血浆,进行反转录实时荧光定量聚合酶链反应法(RT-PCR)检测血浆中SIVmac251病毒载量,并且通过HE染色法检测小鼠主要器官的组织学改变,通过高效联合抗反转录病毒疗法(HAART)对该模型进行药物干预,验证该模型的抗病毒药物评价效果。结果 1)BALB/c裸小鼠成功接种已感染SIVmac251的TZM-b1细胞。2)连续7周在BALB/c裸小鼠血浆里检测出SIVmac 251病毒载量。3)在小鼠主要器官出现了组织学改变。4)验证了HAART对小鼠体内SIVmac 251复制的抑制作用。结论构建了支持SIV复制的小动物模型,该模型能够支持SIVmac251的复制,并表现出组织学病理变化,为研究抗艾滋病药物体内抑制病毒复制提供了廉价、易于操作的小动物模型。     

杀微生物剂临床前安全性评价模型研究进展

近年来,性传播已经成为全球艾滋病病毒(HIV)传播的主要途径。在HIV疫苗研究暂时受挫的情况下,用于保护生殖道、直肠等局部粘膜部位免于HIV感染的杀微生物剂研究,受到越来越多的重视。而在进入临床前,对杀微生物剂进行全面可靠的安全性评价,是必不可少的重要步骤。该文对杀微生物剂安全性评价的各个阶段所采用的评价模型,包括细胞模型、组织模型和动物模型进行了介绍,对各种模型的优缺点及最新进展进行了阐述。指出从分子水平上建立一套合理、科学的检测指标和方法,是目前完善各种模型的当务之急。     

幽门螺杆菌感染动物模型的选择应用

人类疾病动物模型是研究疾病发生、发展、转归及防治的重要工具 ,好的动物模型是筛选药物 ,研制疫苗所不可缺少的关键环节。动物模型的缺乏一度成为该疾病研究的限制因素。近 10年来 ,幽门螺杆菌 (H .pylori)动物模型的建立及应用研究获得了突破性进展 ,先后在悉生小猪、普通小猪、小鼠、大鼠、豚鼠、沙鼠、恒河猴、日本猴、多乳房大鼠、裸鼠、无毛鼠及基因敲除小鼠中成功建立人工感染H .py lori动物模型 ,另外还发现了雪貂、猫等感染各种螺杆菌的自发性动物模型。广泛应用于观察H .pylori感染的致病过程 ;探讨致病机理 ;验证致病因子 ;研…     

艾滋病疫苗的研究进展

艾滋病是由艾滋病病毒引起的危害性极大的传染病,预防该疾病的重要手段是接种有效的疫苗。虽然艾滋病疫苗还未曾出世,但是近年来艾滋病疫苗的研究有了很多重大突破。目前艾滋病疫苗的种类主要包括传统疫苗(灭活疫苗和减毒活疫苗)和新型疫苗(病毒样颗粒、合成多肽疫苗、蛋白亚单位疫苗、脱氧核糖核酸疫苗、载体疫苗)。现如今多种艾滋病疫苗已进入临床试验。本文旨在对现阶段艾滋病疫苗研究进展进行综述。     

新疫苗可大幅降低猿类艾滋病病毒感染率

据英国《自然》杂志网站1月5日(北京时间)报道,美国科学家开发出的一种实验性猿类免疫缺陷病毒疫苗,可大幅降低恒河猴感染猿类艾滋病病毒的风险,让接触一次SIV的恒河猴感染病毒的概率减少80%。SIV是导致人类感染艾滋病的HIV的"远亲",因此,最新研究为人类研制出有效的HIV疫苗指明了新方向。     

巢式PCR检测猴免疫缺陷病毒基因

位于ＳＩＶ的ｇａｇ保守基因区内的特异巢式ＰＣＲ引物用于体外扩增ＳＩＶ病毒基因，其检出敏感性达到０．１ｆｇ水平，较常规ＰＣＲ敏感性高１００倍。巢式ＰＣＲ检测粗提ＳＩＶｍａｃ感染猴后期或经过药物治疗后的猴外周血淋巴细胞ＤＮＡ，证明９６．５％（２８／２９）的猴体内仍有ＳＩＶ病毒感染存在。巢式ＰＣＲ是一种敏感性极高，特异性强，操作简便易行的ＳＩＶ基因检测技术，它对确证ＳＩＶ病毒感染和正确评价药物和疫苗在猴艾滋病模型中的体内治疗效果提供了良好依据。     

AIDS潜伏期研究进展

艾滋病又称获得性免疫缺陷综合征(Acquired Immunodeficiency Syndrome，AIDS)，是目前严重危害人类健康和生命的传染病之一。作为一种还没有治愈方法和预防疫苗的疾病，对AIDS潜伏期的研究对于进一步了解该病自然史、评价治疗的效果、预测未来的发病情况、发现相关因素、延长艾滋病病毒(HIV)感染者的生存时间等方面都有重要的意义。     

爱滋病动物模型的研究

<正> 研制安全有效的疫苗及建立有效的药物治疗方法是今后几年爱滋病(AIDS)研究的方向,建立合适的AIDS动物模型有助于达到上述目的。根据感染动物的病毒及其诱导的疾病与AIDS病毒HIV及AIDS的相关性以及人类免疫缺陷病毒(HIV)感染动物的情况,目前可将AIDS动物模型的研究分为4类。即与HIV不相关病毒诱导的动物AIDS的研究,包括FeLV、LP-BM_5MuLV及D型逆转录病毒诱导的猫、鼠及猴AIDS的研究;与HIV相关的SIV诱导的猴AIDS的研究;与HIV相关但不诱导AIDS的有蹄动物慢病毒感染的研究及HIV感染黑猩猩的研究。     

行为干预是目前预防艾滋病的有效疫苗

“我们过分强调治疗而忽视预防.……我们习惯于依靠生物技术,并相信使用生物技术可以解决所有健康问题.然而,这并不是事实,这一信念越来越不符合客观实际.”——David Satcher美国联邦医务总督第13届世界艾滋病大会再一次警告人们,艾滋病病毒非常复杂,无论是治疗还是疫苗研究,远远比我们想象的要困难的多,复杂的多.最近的研究指出,采用目前的三联抗病毒药物治疗,可能需要68年才能彻底清除人体内的艾滋病病毒.然而,没有人可以忍受长期使用抗艾滋病病毒药物所产生的毒副作用.最近两年的疫苗研究进展表明,至少在近10年内,不太可能研制出有效的生物预防疫苗.因此,十三届艾滋病大会提出了“行为干预是目前预防艾滋病的有效疫苗”.     

HCV感染动物模型的研究进展

理想的HCV感染动物模型的建立,不仅有利于研究慢性丙型肝炎的致病机制(包括病毒-宿主相互作用、病毒变异性、宿主免疫应答规律),还为抗病毒药物的筛选和预防性疫苗的研发提供了更有效的技术途径。介绍了目前大家熟知的动物模型,包括黑猩猩模型、树鼩模型、小鼠模型等,并对各种模型的优势与缺陷进行了分析。近年来HCV感染小动物模型,尤其是转基因小鼠模型的建立,为HCV感染动物模型开创了新领域,是动物模型研究的热点和重点。     

Use of traditional herbal medicine by AIDS patients in Kabarole District, western Uganda

The objective of this cross-sectional study was to assess the use of traditional herbal medicine by AIDS patients in Kabarole District, western Uganda. Using systematic sampling, 137 AIDS patients were selected from outpatient departments of 3 hospitals and interviewed via questionnaire. The questions related to such areas as type and frequency of herbal medicine intake, concomitant herb-pharmaceutical drug use (including herb-antiretroviral drug cotherapy), and the perceived effectiveness of herbal medicine. Overall, 63.5% of AIDS patients had used herbal medicine after HIV diagnosis. Same-day herbal medicine and pharmaceutical drugs use was reported by 32.8% of AIDS patients. Patterns of traditional herbal medicine use were quite similar between those on antiretroviral therapy and those who received supportive therapy only. The primary conclusion is that AIDS outpatients commonly use herbal medicine for the treatment of HIV/AIDS. Pharmacological interactions between antiretroviral drugs and traditional herbal medicines need to be further examined.     

Efficacy and safety of traditional Chinese herbal medicine combined with HAART in the treatment of HIV/AIDS: A protocol for systematic review and meta-analysis

Background:Acquired immunodeficiency syndrome (AIDS) is one of the infectious diseases pandemic in the word. Traditional Chinese herbal medicine, as an alternative and complementary therapy of highly active antiretroviral therapy (HAART), has been put into the treatment of human immunodeficiency virus (HIV)/AIDS over 30 years due to its good therapeutic effects and high safety, while there is a lack of evidence-based medicine support. The purpose of this study is to explore the efficacy and safety of traditional Chinese herbal medicine combined with HAART for HIV/AIDS patients.Methods:We will search all randomized controlled trials of Chinese herbal medicine combined with HAART in the treatment of HIV/AIDS from electronic databases including PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, WanFang, China Science and Technology Journal Database and Chinese Biomedical Literature Database from inception to December 31, 2021. Literature screening will be conducted through EndNote software, and data extraction will be processed according to inclusion and exclusion criteria by two independent researchers. We will use Review Manager 5.4 and Stata 16 software for data analysis and publication bias test.Results:This systematic review and meta-analysis will provide a high-quality evidence for the efficacy and safety of traditional Chinese herbal medicine combined with HAART in the treatment of HIV/AIDS.Conclusion:The conclusion of this review will provide an objective assessment to evaluate whether Chinese herbal medicine integrated with HAART has the effect of improving the efficiency and depressing the toxicity.Registration number:INPLASY2021110082.     

Animal models used for the evaluation of antiretroviral therapies

Several animal models for the study of HIV/AIDS have been established and characterized and have been widely used to study the pathogenesis of HIV/AIDS as well as vaccine development. The purpose of this study was to review the literature and identify the animal models most frequently used for the evaluation of drugs, drug combinations, plant extracts and drug-plant combinations. Four of these animal models were evaluated namely the SIV model due to its similarities in pathogenesis of disease to humans, the FIV and the LP-BM5 model due to wide availability and the SCID murine model that combines components of both systems. The pathogenesis of disease in each model, application in the evaluation of drugs, drug combinations and plant extracts as well as the inherent advantages and disadvantages of each model are discussed. The LP-BM5 murine AIDS (MAIDS) model with its in vitro equivalent was identified as the animal model, although not identical to HIV/AIDS, most suitable for the rapid and cost effective initial screening of drugs, drug combinations, plant extracts and drug-plant combinations.     

中医药治疗艾滋病疗效评价指标体系构建的思考与实践

目的探索建立中医药治疗艾滋病临床疗效评价的指标体系,为全面客观评价中医药的临床疗效提供依据。方法以能够反映临床治疗效果的指标为切入点,通过对现有文献证据的分析、临床医生和典型患者的访谈,经过收集基础指标、指标分类、专家论证等研究过程,探索建立用于评价治疗效果的指标体系。结果形成了5个方面的评价指标,依次为患者自我感受的症状、生存质量、医生关注的症状与体征、终点指标、生物学指标。针对不同的治疗方案,各类指标间可以有机结合使用。结论全面客观的临床评价指标体系,为中医药治疗艾滋病疗效的判定提供了统一的标准和应用工具。     

The use of nonhuman primate models of HIV infection for the evaluation of antiviral strategies

Several nonhuman primate models are used in HIV/AIDS research. In contrast to natural host models, infection of macaques with virulent simian immunodeficiency virus (SIV) isolates results in a disease (simian AIDS) that closely resembles HIV infection and AIDS. Although there is no perfect animal model, and each of the available models has its limitations, a carefully designed study allows experimental approaches that are not feasible in humans, but that can provide better insights in disease pathogenesis and proof-of-concept of novel intervention strategies. In the early years of the HIV pandemic, nonhuman primate models played a minor role in the development of antiviral strategies. Since then, a better understanding of the disease and the development of better compounds and assays to monitor antiviral effects have increased the usefulness and relevance of these animal models in the preclinical development of HIV vaccines, microbicides, and antiretroviral drugs. Several strategies that were first discovered to have efficacy in nonhuman primate models are now increasingly used in humans. Recent trends include the use of nonhuman primate models to explore strategies that could reduce viral reservoirs and, ultimately, attempt to cure infection. Ongoing comparison of results obtained in nonhuman primate models with those observed in human studies will lead to further validation and improvement of these animal models so they can continue to advance our scientific knowledge and guide clinical trials.     

Knowledge,attitudes and perceptions of HIV/AIDS among traditional birth attendants and herbal practitioners in Lagos State,Nigeria

Recognising the widespread role of traditional birth attendants (TBAs) and herbal practitioners (HPs) in health care at community level in Nigeria, we set out to assess their knowledge, attitudes and practices in relation to HIV infection and prevention. Questionnaires were administered to a convenience sample of 189 participants in 20 local government areas of Lagos State. We found that knowledge of modes of transmission of HIV was less than adequate and included lack of knowledge of the existence of HIV/AIDS amongst some practitioners, claims for the ability to treat HIV/AIDS, failure to name major avenues of transmission and confusion of HIV/AIDS with other conditions. The use of measures to prevent infection of clients and themselves showed that normal standards of infection control are not adhered to. Considering that as many as 60% of children born in Nigeria are delivered by traditional birth attendants and that use of the services of herbal practitioners extends across the entire society in both rural and urban settings, this is seen as reason for concern. It is suggested that better incorporation of TBAs/HPs into the well-developed primary health care system offers not only a way of overcoming the risks of infection posed by traditional health practices but also offers an opportunity to extend the reach of voluntary counselling and testing and prevention of mother-to-child infection programmes. The research has shown the need for appropriate training of TBAs, to enable them to recognise the risk of HIV infection in their own practices and to encourage them to adopt universal precautions against spreading infection. We also recommend that they be more extensively integrated as primary health care workers in VCT and PMTCT programmes in Nigeria. We further suggest that referrals made between the traditional practitioners and professional health care providers can be an effective and successful element of HIV/AIDS prevention and control programmes.     

用CRISPR/Cas9系统消除潜伏的HIV前病毒基因组及其感染细胞的研究进展

艾滋病在全球采用联合抗逆转录病毒治疗后发病率及死亡率呈持续下降趋势,使之成为一种可管理的慢性传染病。但因受各种因素制约,艾滋病仍然是全球一个重要公共卫生问题。HIV/AIDS持续存在的主要原因是现有的治疗无法清除人体中存在的HIV潜伏库,由于这种库的存在,HIV/AIDS患者必须终生使用抗病毒药物来抑制病毒复制和反弹。成簇规律间隔短回文重复序列和相关核酸酶Cas9(CRISPR/Cas9)系统几年前以一种简单、快速及易操作的基因编辑技术问世,多项研究表明其在HIV感染的细胞和在动物模型实验中具有消除或破坏HIV储存库或HIV感染细胞的潜力,可能由此产生治愈HIV/AIDS的方法。本文分析了CRISPR/CAS9系统应用于消除潜伏HIV的结果,并对可能产生的问题和趋势进行了讨论。     

中药对807例HIV/AIDS病人CD4淋巴细胞计数的影响

目的观察中医药治疗艾滋病试点项目中,连续接受中药治疗36个月的807例艾滋病病毒（HIV）/艾滋病（AIDS）病人CD4淋巴细胞计数的变化情况,以探讨长期中药治疗对病人免疫功能的影响。方法用自身前后对照的方法 ,对807例HIV/AIDS病人经中医药治疗后7个时点（疗前、6、12、18、24、30、36个月）的CD4计数变化、分层分析（〈200个/mm3、200～350个/mm3、〉350个/mm3）、不同病期、不同干预手段、可能感染时间等方面进行分析,并对7个时点主要症状积分的变化进行观察。结果中药对CD4计数〈200个/mm3和200～350个/mm3之间的病人效果较好;可能感染时间集中在1990-1995年之间的病人,服用中药3年CD4的水平基本保持稳定;中西药合用的效果优于单纯使用中药。结论长期服用中药可以稳定病人的免疫功能,远期疗效较好。     

Popular Use of Traditional Chinese Medicine in HIV Patients in the HAART era

Seventy-six Chinese male HIV patients were interviewed on their use of traditional Chinese medicine (TCM). All except one had undetectable viral load, 28 had already progressed to AIDS. Forty-five (59.2%) had used TCM--11 infrequently and 33 commonly. No specific TCM recipe was preferentially used, while a variety of herbal tea and other over-the-counter health products of TCM in origin were reported. A minority (28.9%) have consulted a TCM practitioner in the preceding 6 months. Most patients admitted using TCM for the treatment of minor ailments (60.0%) and general health maintenance (57.8%), while western medicine was chosen for the therapy of major medical illnesses. TCM did not seem to have significant influence on the conventional HAART in this cohort. Many used TCM at a time interval from HAART in order not to affect the latter's effectiveness.     

艾滋病治疗的研究进展

艾滋病抗病毒治疗(ART),现已取得很大成效。该病原为致死性疾病,现已成为一种可治可管理的传染病,全球艾滋病病毒感染者/艾滋病(HIV/AIDS)的病例虽仍多达3 800万,但有一半以上已经抗病毒治疗。除了药物治疗外,目前一些新技术新方法如基因组编辑等也已介入艾滋病的治疗,并且在人源化动物试验中业已取得很好的效果。不容置疑,艾滋病终究会被人类控制消除。但随着艾滋病抗病毒治疗的不断发展,最根本的问题也就是HIV潜伏库的问题日益突出,不论是分子治疗、组合治疗都存在这样的问题。因此,不断寻找新的潜伏病毒细胞的标记,缩小病毒潜伏库,是当前艾滋病治疗必须解决的课题。此外,尽管艾滋病的防治取得了很大成绩,但目前全球每天仍有近6 000例HIV/AIDS感染的病例发生。因此,安全有效疫苗的研发,不论在预防领域、还是在临床治疗方面,都有其积极的意义。