HIV感染者的阴性配偶对杀微生物剂的可接受性研究

目的研究艾滋病病毒（HIV）感染者的阴性配偶,对杀微生物剂的可接受性及相关影响因素。方法采用横断面设计,于2009年5-7月,在云南省德宏州潞西市和盈江县,采用便利抽样选取301名HIV感染者的阴性配偶进行调查。结果共有278名调查对象符合研究标准,47.5%的调查对象表示将来愿意购买并使用杀微生物剂。影响调查对象购买并使用杀微生物剂的因素有：调查对象的阳性配偶近半年是否有外出打工经历,是否参加过HIV相关防治和调查项目,是否愿意使用安全套。具有以下特点的杀微生物剂易被调查对象接受：（1）能安全有效地预防HIV感染;（2）一次使用的价格在5元以下;（3）非处方药;（4）剂型为栓剂。结论调查对象对杀微生物剂的使用态度较积极,但购买需求较低。     

杀微生物剂的可接受性与影响因素及其在中国的应用前景

全球范围内艾滋病疫情日益严重.近10年来,女性HIV感染率不断上升,成为艾滋病流行的一个明显趋势.杀微生物剂将成为女性能自主控制的预防HIV感染的新方法.国外在杀微生物剂的可接受性与影响因素的研究方面,已取得了很多成绩.在中国,近年来经性途径感染艾滋病的比例有所上升,女性感染者比例有较大幅度增加,因此杀微生物剂今后也是中国低避孕套使用率群体中,可以选择的预防HIV感染的一种方法.     

新的HIV预防技术——杀微生物剂

杀微生物剂作为一项可能的艾滋病病毒(HIV)预防技术,是目前国际上艾滋病研究领域的一个热点。通过应用于阴道和直肠能够预防HIV经性传播,具有使用便利、女性能够自己控制等优点。目前有多个产品处于临床研发阶段,预计2007年将有产品完成临床试验,并将投放市场,为艾滋病防治增添新的有力的预防工具。该文从杀微生物剂的定义、公共卫生意义、当前研究进展和前景展望等4个方面进行了综述,为我国开展针对杀微生物剂的研究以及制定相关防治政策提供参考。     

预防性传播疾病的新药：杀微生物剂的研究进展及应用前景

艾滋病（AIDS）在全世界的传播,严重威胁着人类健康与社会发展,而大约80%的艾滋病病毒（HIV）感染者是通过性传播感染的。杀微生物剂由于能够阻止HIV及其他性传播疾病（STD）病原体经生殖道和直肠黏膜感染人体,具有使用便利、女性能够自己控制等优点,已经成为目前国际上艾滋病研究领域的一个热点。该文介绍了正在进行临床研究的几类杀微生物剂及其应用前景。     

一种新的安全有效的抗HIV阴道凝胶问世

新的研究表明，妇女每天使用一种含有抗艾滋病病毒（HIV）药物Tenofovir的阴道凝胶是安全的。这一研究在2008年2月25日于印度新德里举行的国际杀微生物剂2008年会上公布。     

《艾滋病生物医学预防性临床试验伦理指南》介绍

近年来,人们对艾滋病病毒(HIV)生物医学预防的许多策略都进行了探索,包括阴道杀微生物剂、疫苗、单纯疱疹病毒-2(HSV-2)的治疗/控制、源头同伴治疗、暴露前抗病毒预防、母婴传播预防和静脉吸毒者的药物替代/维持治疗.     

防制按蚊的微生物

防制传病媒介的化学杀虫剂的应用,由于费用的增涨,昆虫抗药性的产生,杀虫剂对环境的污染及对其他非攻击对象虫种的影响等原因受到了干拢,从而引起了在综合防制措施中应用生物剂的重视。本文简要叙述了将来防制疟疾可能有防制媒介作用的微生物和寄生虫,以及目前研究的进展情况。一、微生物剂在综合防制措施中的运用昆虫成虫对病原体是不易感的,而病原体对幼虫和蛹有一定程度的攻击作用,所以病原体可作为杀蚴剂而不作为杀成虫剂。生物杀蚴剂的发展可补充现有的化学杀蚴剂,     

实时相对定量反转录PCR检测小鼠阴道黏膜炎症因子的表达

目的建立实时相对定量反转录聚合酶链反应(real-time RQ RT-PCR)方法,能快速准确地检测各种炎症因子在阴道黏膜的转录表达情况,从而评价包括杀微生物剂在内的生殖道或直肠黏膜用候选药物的刺激毒性。方法以Eppendorf Mastercycler ep realplex实时荧光定量PCR仪为检测平台,选择小鼠β-actin基因为内参,建立基于SYBR GreenⅠ荧光染料的real-time PCR检测方法,对白介素2(Interleukin 2,IL-2)、IL-4、IL-6、IL-10、IL-17A、肿瘤坏死因子α(Tumor necrosis factorα,TNF-α)、γ干扰素(Interferonγ,IFN-γ)等炎症因子在生殖道黏膜的mRNA转录水平,同时进行检测,并用2-⊿⊿Ct方法计算实验组小鼠目的基因相对于空白组小鼠的表达差异情况。用微量样本多指标流式蛋白定量技术(Cytometric Bead Array,CBA)对结果进行验证。结果使用real-time RQRT-PCR能对小鼠阴道黏膜炎症因子的表达情况进行快速检测,结果与CBA检测结果相吻合。结论该方法快速、灵敏、特异性强、价格低廉、高通量。可用于杀微生物剂等生殖道或直肠黏膜用候选药物的临床前安全性评价工作。     

植物杀螺剂的研究概况

药物灭螺在防治血吸虫病感染及流行中有着极其重要的意义。化学杀螺剂价格昂贵、有毒性、污染环境 ,而且螺蛳可能会对有限的几种化学杀螺剂产生耐药性。研究植物杀螺剂是增加有效杀螺药多样化的有效途径 ,植物杀螺剂的筛选方法仍然按照 WHO专家委员会于 1 96 5年公布的“杀螺剂的筛选及评估”的具体标准进行 ,对理想的植物杀螺剂的要求是高效、低廉、对非靶生物无害。1　植物杀螺剂的有效成分自 1 933年 Balanitaceae科的 Balanites aegyptiace果实用于控制血吸虫病 ,开创植物杀螺剂以来 ,已测试了1 0 0 0多种植物的杀螺作用 ,并进行了有…     

杀微生物剂与性传播疾病的预防

杀微生物剂（Microbicides）是指性生活前应用于阴道和宫颈或者直肠内,能够杀灭或中和HIV-1等病毒和细菌类病原体的、人工合成的或天然的物质。使用剂型可以是凝胶、乳膏、栓剂或薄膜等。杀微生物剂特别适用于不想或不能使用安全套的人。与安全套不同,它的使用无需性伴侣的主动协同或知晓。1 社会迫切需要杀微生物剂 性传播疾病（sexually transmitted disease,STD）是全球性的生殖健康和卫生防疫的难题。仅以美国为例,在前10位常见疾病中,STD就有5种。每年的新病例有1200万,仅1994年的预防开支即达到170亿美元左右,由此可见它的危害。在其它国家,特别是发展中国家（包括中国）,STD引起的危害和     

New biomedical strategies for HIV-1 prevention in women

Novel HIV-1 prevention strategies continue to be urgently needed. This article reviews the current state of biomedical prevention against HIV-1, focusing on recently completed and ongoing clinical trials of new prevention interventions, particularly those relevant to prevention of HIV-1 in women. Male circumcision, cervical barrier devices, suppressive therapy against herpes simplex virus type 2, treatment of vaginal infections and other vaginal health interventions, pre-exposure antiretroviral prophylaxis, and topical vaginal microbicides are discussed.     

Prioritizing prevention of HIV and sexually transmitted infections: first-generation vaginal microbicides

PURPOSE OF REVIEW: As the HIV/AIDS pandemic continues unabated, novel control measures for the spread of HIV and other sexually transmitted infections are urgently needed. Topical microbicides are designed to prevent transmission of sexually transmitted infections when applied vaginally. The microbicides discussed in this review may provide a new opportunity for decreasing the spread of HIV and other sexually transmitted infections. RECENT FINDINGS: Epidemiological studies suggest a synergistic relationship between HIV and sexually transmitted infections, particularly between HIV and genital herpes infection. Compounds have been developed to block transmission of HIV-1 and herpes simplex virus, as well as Neisseria gonorrhoea and Chlamydia trachomatis. Several of these compounds have advanced to clinical trials as candidate microbicides. Candidate compounds fall into the following categories: detergents or surfactants that inactivate viral particles, anionic polymers that block attachment of virus to target cells, vaginal acid-buffering agents that maintain a protective vaginal pH, and antiretroviral drugs specific for HIV. Evaluation of the safety of topical microbicides remains problematic. Clinical experiences indicate that current models to assess safety in vitro and in vivo may be insufficient to assess the safety of vaginal microbicides. A critical direction of future studies is to identify which assay(s) provide surrogate laboratory markers of safety that correlate with clinical outcomes. SUMMARY: The spread of HIV, and its increasing burden of disease in women, necessitates the development of novel prophylactic strategies. Topical microbicides offer women an empowering preventative option but require vigorous testing for safety and effectiveness.     

Non-specific microbicide product development: then and now

Despite the identification of HIV-1 as the etiological agent responsible for AIDS nearly 30 years ago, a sterilizing vaccine capable of preventing transmission of the virus remains elusive. In response to struggles on the vaccine development front, significant effort has been devoted to preventing the transmission of HIV with alternative products, technologies, and strategies. One of the early alternative HIV prevention strategies was microbicides, which are topical products that can be used to prevent sexual transmission of HIV either vaginally or rectally. First generation microbicide products were designed to be simple gel formulations comprised of readily available active agents that were inexpensive and broadly active (i.e., non-specific). Unfortunately, despite the clinical investigation of multiple product concepts satisfying these requirements, none were shown to be efficacious in pivotal trials. More recently, microbicide and oral prevention strategies involving highly specific and potent anti-retroviral (ARV) drugs have shown to be efficacious in trials. Although building on these successes continues, these products have a number of issues including potential toxicity with long term use, selection of HIV resistance, and cost. Further, all of the original justifications for non-specific microbicide products remain valid. This review provides a brief history of non-specific microbicide development, outlines the evolution to, and limitations of, ARV based microbicides, and summarizes the current activity on non-specific microbicide product development.     

The last decade of microbicide clinical trials in Africa: from hypothesis to facts

Microbicide clinical trials have dominated biomedical HIV prevention research in the past decade. Two generations of microbicides have gone through large-scale human clinical trials. Candidate microbicides assessed in clinical trials in Africa have fallen into the categories of surfactants, polyanionic entry inhibitors, or vaginal milieu protectors. These include compounds such as nonoxynol-9, SAVVY, cellulose sulphate, Carraguard, PRO 2000, and BufferGel. Disappointingly, none of the products have shown efficacy against HIV. Each successive trial has benefited from the lessons learned in preceding trials. The trials have provided important lessons in basic, clinical, social, and behavioural science. More importantly, we have learned that the concept of a vaginally inserted product for HIV prevention is acceptable by women. We have now reached an end of an era of clinical testing with non-HIV-specific microbicides and move forward to testing novel strategies of antiretroviral therapeutic products such as preexposure prophylaxis (PrEP) for HIV prevention. PrEP for vaginal administration in various formulations is being tested to continue our commitment to providing more HIV prevention options to millions of women worldwide.     

Use of frozen-thawed cervical tissues in the organ culture system to measure anti-HIV activities of candidate microbicides

Cervical tissue-based organ culture system has been used to test the cytotoxicity and antiviral activity of microbicides. One of the problems of using current organ culture methods for routine microbicide testing is the need to continually obtain fresh tissue, which can be limited in access and supply. Use of frozen tissue, stored when available and thawed when needed, would alleviate the need for constant access to new tissue. This study was designed to explore the possibility of using frozen-thawed cervical tissue to test microbicides for their anti-HIV activity. We provided biochemical, histological, and quantitative immunohistochemical data to demonstrate the integrity of the frozen-thawed organ culture system. Significant levels of HIV-1 mucosal transmission were noted with both fresh and frozen-thawed tissue, regardless of the coreceptor usage of the virus isolate. Furthermore, candidate microbicides UC781, beta-cyclodextrin, and octylglycerol inhibited HIV-1 transmission across the mucosa of frozen-thawed tissues with a level of efficiency similar to that of fresh tissues. Therefore, frozen-thawed cervical tissue in the organ culture system provides a practical and convenient model to screen topical microbicides for their ability to block sexual transmission of HIV-1, and reduces the problems associated with procurement of the numerous tissues required for evaluation and comparison of microbicide candidates among different laboratories.     

Microbicides to prevent HIV transmission: overcoming obstacles to chemical barrier protection

BACKGROUND: Microbicides are topical compounds that could prevent sexually transmitted infections. Several compounds have demonstrated activity both in vitro and in animal models, but none has been approved for use in humans. METHODS: A review of >100 recent publications from MEDLINE (through October 2005) and abstracts presented at recent conferences was undertaken to describe the current status of microbicide research and to delineate why microbicides are not yet available. RESULTS: More than 15 candidate microbicides are currently being studied in clinical trials. Their mechanisms of action include disruption of the viral membrane by surfactants, maintenance of an acidic vaginal pH, binding to the viral envelope to block receptor binding, and blocking of receptors; they may also be combined with antiretroviral drugs. The development of safe and effective microbicides has been delayed by limitations in understanding the biological processes of human immunodeficiency virus (HIV) transmission, difficulties in extrapolation from animal models, lack of established correlates of protection, and the need to enroll and follow large cohorts of high-risk participants for several years in order to demonstrate efficacy. CONCLUSIONS: Safe and effective topical microbicides are biologically plausible. Several trials that are under way may demonstrate the ability of microbicides to protect against transmission of HIV, but multiple challenges remain.     

The molecular basis of nonoxynol-9-induced vaginal inflammation and its possible relevance to human immunodeficiency virus type 1 transmission

Topical microbicides are being sought to prevent sexually transmitted diseases by inactivating pathogens while preserving or enhancing the natural mucosal barrier. Serious public health concerns were raised by a recent phase 3 clinical trial that showed that nonoxynol-9 (N-9), a leading microbicide candidate widely used as an over-the-counter spermicide, may actually increase human immunodeficiency virus type 1 (HIV-1) transmission. The present study links N-9-induced vaginal inflammation to increased risk of HIV-1 infection. Analysis of molecular and cellular components in cervicovaginal secretions, as well as results from in vitro activation of cervicovaginal epithelial cells and U1/HIV promonocytic cells, showed that multiple N-9 use can promote HIV-1 transmission through interleukin-1-mediated NF-kappaB activation, which leads to chemokine-induced recruitment of HIV-1 host cells and increased HIV-1 replication in infected cells. Furthermore, this study identifies in vitro and in vivo model systems for monitoring undesirable proinflammatory effects of microbicides and other vaginal products.     

Microbicides to prevent heterosexual transmission of HIV: ten years down the road

The development of topical microbicides for HIV prevention originated in response to the unabated spread of HIV despite the availability of an effective HIV prevention tool (condoms), as well as the lack of an effective HIV vaccine. Initially, hopes were pinned on existing over-the-counter spermicides containing nonoxynol-9. Concern about the toxicity of nonoxynol-9 with frequent use, and its small or nonexistent protective effect against HIV and other sexually transmitted infections (STIs), has spurred the development of new microbicides with a number of novel mechanisms of action. Significant progress has been made in the last decade. The microbicides pipeline currently contains approximately 34 products in preclinical development, 15 in Phase I safety trials, four in Phase II expanded safety and preliminary effectiveness trials, and three in Phase II/III or Phase III effectiveness trials. Laboratory and clinical research has been complemented by a growing body of research and literature on microbicide acceptability, harm reduction and dual protection strategies, and potential markets. However, many challenges remain, including the need for a significant increase in investment to accelerate product development and complementary research, and to plan for availability and access once effective microbicides are available.