艾滋病治疗药物的研究进展

作者全面系统地阐述了近年来抗艾滋病新药的研发策略和研究进展,并根据药物作用靶点分别介绍了新上市的抗艾滋病药物的作用机制和结构特点,如第二代HIV-1逆转录酶抑制剂和HIV-1蛋白酶抑制剂,以及全新作用机制的HIV-1进入抑制剂和HIV-1整合酶抑制剂,并对今后抗艾滋病药物的发展方向进行了展望。     

抗耐药性逆转录病毒药物研究的新进展

最近1种抗HIV-1感染疫苗的失败提示了抗逆转录病毒疗法对治疗HIV-1感染患者的重要性。迄今为止,2种病毒蛋白酶（逆转录酶和蛋白酶）的抑制剂对于HIV-1感染患者的存活有着显著影响。由于当前使用的抗逆转录病毒药物耐药性的发展,迫切需要新的能作用于病毒复制不同环节的抑制剂。本文综述了最近抗逆转录病毒药物的发现进展,并着重探讨了病毒进入、病毒DNA与宿主细胞基因组整合和病毒颗粒成熟等病毒复制阶段新抑制剂的发展。     

HIV-1蛋白酶抑制剂的研究新进展

HIV-1蛋白酶抑制剂（PI）是一类重要的抗HIV/AIDS药物。近年来，药物化学家们从大量化合物中筛选出一些具有抑制HIV-1蛋白酶活性的非核苷的拟肽类化合物。尤其是近2-3年，FDA陆续批准了多种HIV-1 PI进入临床后，艾滋病治疗出现了很大进燕尾服。HIV-1 PI与HIV-1逆转录酶抑制剂的联合应用，大大降低了病毒在体内的复制水平，提高了抗病毒效能。HIV-1 PI多为拟肽类化合物。本文就HIV-1 PI的研究进展作一综述。     

针对艾滋病毒复制周期新靶点的药物研究进展

目前,抗逆转录病毒的治疗虽然已经有了显著进展,但寻找价格低廉、活性更强、不易耐药的抗HIV药物研发工作仍在继续。目前国内外针对HIV复制周期进入、融合、整合以及成熟过程中新靶点的研究成为热点。文中对药物进入/融合抑制剂（包括病毒吸附抑制剂、病毒辅助受体抑制剂、病毒融合抑制剂）、整合酶抑制剂和成熟抑制剂的作用机制和特点进行了综述,并且,介绍了2008年新上市的非核苷类逆转录酶抑制剂intelence（etravirine）的特点。     

HIV-1对核苷类逆转录酶抑制剂产生耐药性的分子机制研究进展

从核苷类逆转录酶抑制剂的作用机制、HIV-1对其产生耐药性的分子机制、导致耐药性产生的HIV-1逆转录酶基因突变以及HIV-1产生耐药性的分子水平检测方法等诸方面。概述近年来有关HIV-1对核苷类逆转录酶抑制剂的耐药性在分子水平上的研究进展。核苷类逆转录酶抑制剂是一类重要的抗HIV-1药物，其耐药性病毒株的产生是导致抗HIV-1治疗失败的主要原因。对HIV-1耐药性的分子机制研究必将有助于对耐药性HIV-1有效的新型抗HIV-1药物的研究与开发。     

HIV化学治疗的最新进展

分两部分介绍了抗HIV的化学治疗药物的新进展,一是作用于现有病毒靶位的属于逆转录酶抑制剂和蛋白酶抑制剂的新化合物,另一部分是作用于病毒新靶位的化合物如HIV整合酶抑制剂、核糖核酸酶-H抑制剂以及病毒进入抑制剂。主要从化学结构、对耐药性病毒的抑制作用、作用机制和临床效果等几个方面介绍了解决HIV耐药性问题的新化合物。     

抗艾滋病药物的研究进展

目的 了解目前世界上最新上市的抗艾滋病新药以及正在研究中的新化合物。方法 通过对大量有代表性的文献进行归纳，介绍了2000年以来上市的抗艾滋病新药以及各类处于临床和临床前研究的化合物。结果 发现抗艾滋病药物在近年来有突破性进展，除了传统的蛋白酶抑制剂，逆转录酶抑制剂外，最新发展的融合抑制剂类药物已上市，并且还有很多具有新型作用机制的化舍物以及具有抗HIV-1活性的先导天然化合物正处于研究阶段。结论 抗艾滋病药物的发展前景广阔。     

喹啉酮酸类HIV-1整合酶抑制剂的研究进展

整合酶是人类免疫缺陷病毒(HIV)进入宿主细胞复制过程中必不可少的一种酶,而人体组织中无此酶,因此,此酶成为高效、低毒的抗HIV药物研发的理想靶标.简介HIV-1整合酶及其抑制剂的作用机制,分类综述具有二酮酸药效团类似结构的喹啉酮酸类HIV-1整合酶抑制剂的研究进展.     

26-51 HIV-1整合酶抑制剂Phenalenones

逆转录酶抑制剂和蛋白酶抑制剂联用可抑制HIV-1复制，降低病毒载量并减少发病率和病死率，而由于耐药突变病毒株的出现，有时使治疗失败。为了克服这一情况需寻找作用于病毒复制过程中不同位点的高效且毒副作用小的抗HIV-1药物。HIV-1复制过程中有3种必需酶即逆转录酶、蛋白酶和整合酶。整合酶是HIV DNA进入宿主基因中进行特殊的DNA重组反应的关键酶，对整合过程中的3’末端过程和链转移过程起重要的催化作用。     

抗艾滋病药物的现状与展望

艾滋病（AIDs）的肆意传播对人类生存和发展提出了严峻挑战,迫切需要开发出新的药物来遏制AIDS的泛滥。笔者全面综述了已上市的五大类抗AIDS药物,包括核苷类逆转录酶抑制剂（NRTIs）、非核苷类逆转录酶抑制剂（NNRTIs）、蛋白酶抑制剂（PIs）、进入抑制剂（entry inhibitors）、整合酶抑制剂（integrase inhibitors）的作用机制、特点及ADR情况,并探讨了一些有可能成为新的抗AIDS药物的研究进展,以期为AIDS的药物治疗提供参考。     

Ongoing trials in HIV protease inhibitors

The development of antiretrovirals has led to a revolution in the care of patients infected with HIV. What was once a uniformly fatal syndrome has become a more treatable, chronic, infectious disease. Central to this revolution have been the protease inhibitors, a class of drugs with potent antiretroviral activity. The first member of this class was approved for use in 1995 and there are now five protease inhibitors approved by the US Food and Drug Administration (FDA): amprenavir, indinavir, nelfinavir, ritonavir and saquinavir. As a result of the magnitude of the HIV pandemic coupled with the clinically proven efficacy of protease inhibitors, there are currently hundreds of ongoing clinical trials with these agents. Trial designs include comparisons between the various licensed protease inhibitors, comparisons of protease inhibitors to other classes of potent antiretroviral drugs, investigations with new protease inhibitors, investigations of protease inhibitor-related toxicities and attempts at simplifying current dosing regimens.     

Ongoing trials in HIV protease inhibitors

The development of antiretrovirals has led to a revolution in the care of patients infected with HIV. What was once a uniformly fatal syndrome has become a more treatable, chronic, infectious disease. Central to this revolution have been the protease inhibitors, a class of drugs with potent antiretroviral activity. The first member of this class was approved for use in 1995 and there are now five protease inhibitors approved by the US Food and Drug Administration (FDA): amprenavir, indinavir, nelfinavir, ritonavir and saquinavir. As a result of the magnitude of the HIV pandemic coupled with the clinically proven efficacy of protease inhibitors, there are currently hundreds of ongoing clinical trials with these agents. Trial designs include comparisons between the various licensed protease inhibitors, comparisons of protease inhibitors to other classes of potent antiretroviral drugs, investigations with new protease inhibitors, investigations of protease inhibitor-related toxicities and attempts at simplifying current dosing regimens.     

HIV蛋白酶抑制剂的临床应用进展

自从1996年蛋白酶抑制剂（PI）被使用到高效抗逆转录病毒治疗（HAART）中以来,HIV携带者的发病率和艾滋病患者的死亡率被大大降低。至今经美国FDA批准上市的蛋白酶抑制剂已有11种,其中多种药物被列为美国和欧洲HIV治疗指南的一线治疗方案。然而我国在这方面的报道还不足,因此,本文对HAART,蛋白酶抑制剂的发展史和海外临床应用现状作一综述。     

Linagliptin for the treatment of type 2 diabetes

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic agents that have been rapidly adopted since their introduction in 2006. There are now five agents in global use, with three approved for treatment of patients with type 2 diabetes (T2D) in the USA. The results of Phase III clinical trials for linagliptin, a new addition to this class of inhibitors (approved by the FDA on 2 May 2011), have now been published. We reported on a 24-week Phase III trial of linagliptin administered as monotherapy in patients with T2D. This agent is characterized by a pharmacokinetic and metabolic profile that may have important implications for the choice of treatment in certain patient populations.     

Clinical pharmacology of HIV protease inhibitors: focus on saquinavir, indinavir, and ritonavir

In this review the clinical pharmacology of HIV protease inhibitors, a new class of antiretroviral drugs, is discussed. After considering HIV protease function and structure, the development of inhibitors of HIV protease is presented. Three protease inhibitors are reviewed in more detail: saquinavir, indinavir, and ritonavir. Clinical trial results with these agents are evaluated. Furthermore, adverse effects, resistance, dosage and administration, clinical pharmacokinetics, pharmacokinetic-pharmacodynamic relationships, and drug interactions are discussed.     

Novel integrase inhibitors for HIV

Importance of the field: Integrase inhibitors are the newest class of antiretroviral agents developed to treat HIV-1 infection. Raltegravir (RAL), the only integrase inhibitor (INI) currently approved for the treatment of HIV-infected patients, has proven to be a potent and well-tolerated antiretroviral (ARV) agent. It is currently approved and used for the treatment of both ARV-experienced and ARV-naive patients. Nevertheless, the relatively low genetic barrier for resistance of RAL encourages the search for new INIs with different mechanisms of actions and resistance profiles.

Areas covered in this review: Here we review the data available about INI that are currently being tested in clinical trials or are in preclinical development: elvitegravir (EVG), S/GSK1349572, S/GSK1265744 and LEDGINs. We focus on their clinical efficacy, pharmacokinetic, safety and resistance profiles.

What the reader will gain: Up-to-date overview on the currently available, clinically relevant INIs and promising preclinical inhibitors at all phases of development.

Take home message: Integrase inhibitors represent the newest therapeutic class available to treat HIV-1 infection. There are a variety of compounds either available in the clinic (RAL), advancing to Phase III trials (EVG), or in earlier phases of development. Taken together, this class offers new treatment options for the HIV-infected individual.