乙肝治疗，应避免干扰素和核苷类药物同时服用

StephenW

回复 lifflefield 的帖子

1引起病毒变异 - 正确的，但是这也包括抗病毒药物. 但病毒变异可以被高基因屏障(high genetic barrier)打败.

2肝细胞死亡 - 这就是为什么干扰素是不适合所有患者.

乙人救星

不要当教条主义，可以因人而异联用。

咬牙硬挺

看到一个新文章似乎联用效果更好

StephenW

[Is this article a beatup?]
http://www.ucsf.edu/news/2012/02/11598/fighting-infections-old-drug-reveals-new-tricks
Fighting Infections: Old Drug Reveals New Tricks                                                                                                                UCSF-led Study Shows How Interferon Works to Suppress Virus in Patients With HIV, Hepatitis                                                                                                                                                       

                                       
                                                                          

By [url=mailto:%[email protected]]Jason Bardi[/url] on February 29, 2012

    A drug once taken by people with HIV/AIDS, but long ago shelved after newer, modern antiretroviral therapies became available, has now shed light on how the human body uses its natural immunity to fight the virus — work that could help uncover new targets for drugs.
    Satish K. Pillai, PhD

In an article published online this month by the journal PNAS, a group of U.S. and Swiss researchers led by scientists at the University of California, San Francisco (UCSF) presented the first clinical assessment of how this drug fights infections in people. The drug, called interferon, is a biotechnology product based on a protein the body naturally produces to fight infections.
While purified interferon was given to people with HIV/AIDS in the early days of the epidemic because it alleviated many of the symptoms of the disease, its mode of action was always something of a black box.
"Nobody knew how it worked," said Satish K. Pillai, PhD, lead investigator and assistant professor of Medicine at UCSF and the UCSF-affiliated San Francisco VA Medical Center.
Experiments in the laboratory in recent years have shown how interferon may work to suppress HIV in vitro, but there was no clinical evidence until now showing how the drug attacks HIV in treated patients. The problem is that so few people actually take interferon for HIV any more. However, interferon is still used in combination with other drugs to treat hepatitis C, which gave the team the possibility to assess its effect on HIV.


30 Years of AIDS

Interferon is commonly used to treat people with hepatitis C virus, and Pillai and his colleagues were able to identify 20 people enrolled in the Swiss HIV Cohort Study, which began in 1988, who have both HIV and hepatitis C. All 20 were taking interferon to treat their hepatitis C, but none were receiving antiretroviral drugs to treat HIV. This allowed researchers to examine how interferon works to suppress the virus.
How Interferon WorksThe new work sheds further light on somewhat mysterious components of the immune system known as restriction factors, which are chemicals the human body produces to keep viruses like HIV in check and prevent them from infecting other cells.
These are just two fronts in the overall battle between HIV and the immune system — a battle in which the immune system seeks to destroy the virus while the virus constantly counters by undermining the immune system.
Unlike other parts of the immune system, where whole cells gobble up invading pathogens or attack other cells, the action of these restriction factors is more subtle and localized within the infected cell itself — one of the reasons scientists didn’t appreciate what they do until just a few years ago.
One of them, called APOBEC3, fights viruses by stealthily jumping onto new virus particles as they form. Therein, the APOBEC3 protein fouls up HIV’s genetic material by mutating it. When the virus tries to infect another cell, it no longer has the potency to replicate.
Another factor, called tetherin, takes an even more direct approach. It attaches to virus particles as they emerge from infected cells in the body and literally tethers them in place, preventing them from moving elsewhere in the body where they could infect new cells.
HIV has its own countermeasures to thwart these defenses. It produces a protein known as Vpu that neutralizes tetherin. Another HIV protein, called Vif, subverts APOBEC.
In the new study, Pillai and his colleagues showed that interferon combats HIV by mediating the action of both of these restriction factors. They collected samples from the 20 patients and measured the levels of APOBEC3 and tetherin before, during and after they took the drug interferon. The levels increased in response to interferon when the drug was in the bloodstream, and patients with the highest restriction factor levels showed the most precipitous drop in HIV viral load during interferon treatment.
While this insight does not immediately suggest new drugs or new ways of treating people with HIV, Pillai said scientists armed with this knowledge may one day figure out how to enhance this defense mechanism and specifically enhance the expression of restriction factors like tetherin and APOBEC3 in HIV-1–infected individuals.
If these factors can be induced to higher levels, their attack on the virus may become more potent — perhaps even overriding HIV’s countermeasures and helping flush the virus from infected cells.
The article, “Role of retroviral restriction factors in the interferon-α–mediated suppression of HIV-1 in vivo,” was written by Satish K. Pillai, Mohamed Abdel-Mohsen, John Guatelli, Mark Skasko, Alexander Monto, Katsuya Fujimoto, Steven Yukl, Warner C. Greene, Helen Kovari, Andri Rauch, Jacques Fellay, Manuel Battegay, Bernard Hirschel, Andrea Witteck, Enos Bernasconi, Bruno Ledergerber, Huldrych F. Günthard, Joseph K. Wong, and the Swiss HIV Cohort Study.
In addition to UCSF, the authors of this study are affiliated with the San Francisco VA Medical Center, the Veterans Affairs San Diego Healthcare System at the University of California at San Diego, the Gladstone Institute of Virology and Immunology, and the Swiss university hospitals of Zurich, Berne, Lausanne, Basel, Geneva, St. Gallen and Lugano.
This work was funded by the National Institutes of Health and through the American Recovery and Reinvestment Act. Additional support was provided by Swiss HIV Cohort Study Project 594; the Veterans Affairs Merit Review; and several Swiss National Science Foundation Grants. The Swiss HIV Cohort Study is supported by the Swiss National Science Foundation and the Swiss HIV Cohort Study Research Foundation.
UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.
   
  

负负得正

楼上的，翻译下，水平有限，看不懂。

StephenW

一次与艾滋病毒/艾滋病的人采取药物，但不久前搁置新的，现代的抗逆转录病毒疗法后成为可用的，对人体如何利用其天然的免疫力，对抗病毒现在已经摆脱光 - 工作可能有助于发现药物的新目标。
萨蒂什光皮莱博士

萨蒂什光皮莱博士

在网上公布期刊PNAS上，一组美国和瑞士的研究人员在加州大学旧金山分校（UCSF）的科学家领导的这个月的一篇文章中介绍了这种药物如何对抗人感染的临床评估。药物，干扰素，是一家生物技术产品上的一种蛋白质，人体自然产生抵抗感染。

虽然纯化干扰素与艾滋病毒/艾滋病的疫情初期的人，因为它缓解许多疾病的症状，其作用方式是一个黑盒子的东西。

“没有人知道它是如何工作的，说：”萨蒂什光皮莱博士，首席研究员和加州大学旧金山分校和加州大学旧金山分校下属的旧金山VA医学中心的医学助理教授。

近年来在实验室的实验表明干扰素如何工作，以抑制艾滋病毒在体外，但有没有临床证据，直至现在显示如何药物攻击艾滋病毒治疗的患者。问题是有这么几个人实际上采取任何艾滋病毒的干扰素。然而，干扰素仍用其他药物结合治疗丙型肝炎，这给球队的可能性，以评估其对艾滋病毒的效果。


艾滋病30年

通常使用干扰素治疗丙型肝炎病毒的人，皮莱和他的同事们能够确定20人参加在瑞士艾滋病队列研究，于1988年开始，那些艾滋病毒和丙型肝炎的所有20人服用干扰素对待自己的C型肝炎，但没有接受抗逆转录病毒药物治疗艾滋病。这使研究人员能够研究如何干扰素，抑制病毒。
干扰素工程

新的工作流，进一步光几分神秘色彩被称为制约因素，这是化学品对人体产生保持像HIV病毒检查，防止感染其他细胞免疫系统的组件。

这些只是两条战线中的艾滋病毒与免疫系统之间的整体战斗 - 战斗中的免疫系统，旨在摧毁，而由病毒破坏人体免疫系统的病毒不断柜台。

与其他部位的免疫系统，整个细胞吞噬病原体入侵或攻击其他细胞不同的是，这些制约因素的作用是更加微妙和局部感染的细胞本身内 - 的原因之一，科学家们并不欣赏他们做什么，直到仅仅几年前。

其中之一，称为APOBEC3，对抗病毒悄悄到新的病毒粒子，因为它们形成跳跃。其中，APOBEC3多达艾滋病毒的遗传物质，蛋白质犯规由变异。当病毒试图感染其他细胞，它不再具有效力复制。

另一个因素，称为tetherin，需要一个更直接的办法。它十分重视从被感染的细胞，因为他们出现在身体和字面上系绳到位，防止他们从其他地方，在那里他们可以感染新的细胞在体内的病毒粒子。

艾滋病毒有自己的对策，以阻止这些防御。它产生已知的蛋白质作为VPU抵消tetherin。另一种艾滋病毒的蛋白质，叫做VIF，颠覆APOBEC。

在新研究中，皮莱和他的同事发现了艾滋病毒，干扰素战斗调解这些制约因素的行动。他们收集了20例样本和测量APOBEC3和tetherin的前的水平，期间和之后他们把药物干扰素。增加干扰素的水平时，血液中的药物，限制因子水平最高的患者表现为在干扰素治疗过程中的艾滋病毒的病毒载量急剧下降。

虽然这种认识不立即建议新的药物或治疗艾滋病毒感染者的新途径，皮莱说，科学家用这些知识武装起来的，也许有一天弄清楚如何增强这种防御机制，并特别加强tetherin和APOBEC3在艾滋病毒的制约因素，如表达-1感染者。

如果这些因素可诱发较高水平，其对病毒的攻击可能会成为更有力 - 甚至覆盖艾滋病毒的对策，并帮助冲洗病毒感染的细胞。

文章认为，“在α-干扰素介导的体内抑制HIV-1逆转录病毒的制约因素的作用，”写，穆罕默德·阿卜杜勒·穆赫辛·萨蒂什光皮莱，约翰Guatelli，马克Skasko，亚历山大·蒙托，冈田克藤，安德里·劳赫海伦Kovari，史蒂芬Yukl，华纳C.格林，，Fellay雅克·曼努埃尔·Battegay，Hirschel伯纳德，Witteck安德烈，伊诺斯Bernasconi，布鲁诺Ledergerber，Huldrych楼Günthard黄，约瑟夫·K.，瑞士艾滋病队列研究。

除了加州大学旧金山分校，这项研究的作者是旧金山VA医学中心，退伍军人事务圣地亚哥医疗系统在美国加州大学圣迭戈，格莱斯顿病毒学和免疫学研究所，瑞士大学医院附属苏黎世，伯尔尼，洛桑，巴塞尔，日内瓦，圣加仑州和卢加诺。

这项工作是由国家卫生研究院和美国恢复和再投资法案通过。瑞士艾滋病队列研究项目594退伍军人事务部的优异审查;和瑞士国家科学基金会资助，提供额外的支持。瑞士艾滋病队列研究是由瑞士国家科学基金会和瑞士艾滋病队列研究研究基金会的支持。

加州大学旧金山分校是一家领先的大学，致力于通过先进的生物医学研究，在生命科学和卫生专业的研究生水平的教育，卓越的病人护理促进全球健康。

9病成医

既然同时用有争议,那就交替使用吗.

lifevendor

回复 lifflefield 的帖子

有没有用看效果，看实验数据，看事实。

baobao7676

回复 lifflefield 的帖子

许多人认为病毒的变异是药物的影响，其实这是大错特错的。病毒进入人体后， 体内所有的分子都会对他形成作用，要变异， 早就不知变成什么摸样了。一个药物进入体内， 不过相当于ppb的浓度， 在这个水平上可以认为对病毒的变异没有任何影响。但抗病毒药物确实可以影响病毒的变异方向，主要是选择性地抑制。无论如何， 停药后变异株急速消失表明变异株的复制能力远远落后于野生株。从这个意义上讲，即使变异了， 也比不治疗要好。

王震宇

楼主的论点是对的，论据是错的。

干扰素+核苷，帮不上什么忙，反而添不少乱，就像机枪上刺刀。