The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic.
The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic.
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DOI：
10.1016/j.antiviral.2009.10.002
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发表时间：
2010-01
影响因子：
7.6
通讯作者：
Broder S
中科院分区：
文献类型：
--
作者：
Broder S
在过去的25年里，导致获得性免疫缺陷综合症(艾滋病)的逆转录病毒HIV-1已经从一种“天生无法治愈”的感染性病原体转变为一种对一系列经批准的疗法非常敏感的病原体。在从20世纪80年代中期开始的五年时间里，我在国家癌症研究所的团队在第一代抗逆转录病毒药物的发现和开发中发挥了作用，从1985年开始，与Burroughs-Wellcome公司(现为葛兰素史克公司)的科学家合作，使用Retrovir®(齐多夫定，AZT)。我们专注于双脱氧核苷酸逆转录酶抑制剂(NRTI)家族中的AZT和相关同系物，将它们从实验室带到临床，以应对艾滋病的流行，艾滋病是一种可怕而致命的疾病。最重要的是，这些药物证明了艾滋病毒-1感染是可以治疗的，这种证据为来自许多来源的针对一系列病毒靶点的新疗法提供了动力，其速度在现代药物开发中很少能与之匹敌。抗逆转录病毒治疗使HIV-1感染的死亡率大幅下降，使其从一种快速致命性疾病转变为一种慢性可控疾病，符合非常长的生存时间。这在世界各地公共卫生的传统界限内具有特殊影响，但同时在某些区域也可能影响经济和国内不稳定的循环，在这种循环中，艾滋病毒-1/艾滋病既是原因也是结果。仍然存在许多挑战，包括1.)终生疗程；暴露前预防的最终作用(PrEP)；长期治疗的心脏代谢副作用或其他毒副作用；出现耐药性和病毒遗传多样性(非B亚型)；来自已建立的逆转录病毒宿主的新的跨物种传播的幽灵；以及东半球猴子；世界许多地区新感染艾滋病毒-1的速度继续加快。所有这些因素使精炼目前的治疗方法和开发新的治疗范例成为基本优先事项，本期《抗病毒研究》中的文章涵盖了这些主题。幸运的是，对HIV-1的生物学、它与细胞耐药因素的相互作用以及未来治疗的新攻击点有了令人兴奋的新见解。此外，从基础研究到世界各地的公共卫生福利，这是一段很短的旅程。当前的科学将导致新的治疗战略，对艾滋病毒-1/艾滋病大流行具有深远影响。本文是纪念抗逆转录病毒药物发现和开发25周年的《抗病毒研究》特刊的一部分，第85卷，2010年第1期。
In the last 25 years, HIV-1, the retrovirus responsible for the Acquired Immunodeficiency Syndrome (AIDS), has gone from being an “inherently untreatable” infectious agent to one eminently susceptible to a range of approved therapies. During a five-year period, starting in the mid-1980s, my group at the National Cancer Institute played a role in the discovery and development of the first generation of antiretroviral agents, starting in 1985 with Retrovir® (zidovudine, AZT) in a collaboration with scientists at the Burroughs-Wellcome Company (now GlaxoSmithKline). We focused on AZT and related congeners in the dideoxynucleoside family of nucleoside reverse transcriptase inhibitors (NRTIs), taking them from the laboratory to the clinic in response to the pandemic of AIDS, then a terrifying and lethal disease. These drugs proved, above all else, that HIV-1 infection is treatable, and such proof provided momentum for new therapies from many sources, directed at a range of viral targets, at a pace that has rarely if ever been matched in modern drug development. Antiretroviral therapy has brought about a substantial decrease in the death rate due to HIV-1 infection, changing it from a rapidly lethal disease into a chronic manageable condition, compatible with very long survival. This has special implications within the classic boundaries of public health around the world, but at the same time in certain regions may also affect a cycle of economic and civil instability in which HIV-1/AIDS is both cause and consequence. Many challenges remain, including 1.) the life-long duration of therapy; 2.) the ultimate role of pre-exposure prophylaxis (PrEP); 3.) the cardiometabolic side effects or other toxicities of long-term therapy; 4.) the emergence of drug-resistance and viral genetic diversity (non-B subtypes); 5.) the specter of new cross-species transmissions from established retroviral reservoirs in apes and Old World monkeys; and 6.) the continued pace of new HIV-1 infections in many parts of the world. All of these factors make refining current therapies and developing new therapeutic paradigms essential priorities, topics covered in articles within this special issue of Antiviral Research. Fortunately, there are exciting new insights into the biology of HIV-1, its interaction with cellular resistance factors, and novel points of attack for future therapies. Moreover, it is a short journey from basic research to public health benefit around the world. The current science will lead to new therapeutic strategies with far-reaching implications in the HIV-1/AIDS pandemic. This article forms part of a special issue of Antiviral Research marking the 25th anniversary of antiretroviral drug discovery and development, Vol 85, issue 1, 2010.
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影响因子：
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作者：
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影响因子：
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