艾滋病研究重点从控制转向治愈

华盛顿——国际艾滋病学会7月20日在《自然评论/免疫学》(Nature Reviews/Immunology)上在线发表了名为《以治愈艾滋病为目标的开创性全球科学战略》(The Inaugural Global Scientific Strategy Towards an HIV Cure)的7点计划，正式将其重点从控制HIV感染转向治愈HIV感染(vol. 12, pp. 607-14)。


Steven Deeks博士

参与撰写该计划的加州大学旧金山分校的Steven Deeks博士表示，该策略是寻找艾滋病治愈方法的第一步。抗病毒药物可控制HIV，但不能清除该病毒。2012年，已有20~25种药物可供应用，通过多种组合方式应用的疗效非常好，显著延长了艾滋病患者的生存时间。目前这些药物已经达到了预期所能达到的最高治疗程度，其应用受到多个方面的限制，如依从性问题、毒性、费用和许多国家缺乏实施治疗的基础服务机构等。日复一日地持续数十年向全球3,300万HIV感染者提供药物将是一个巨大的挑战。因此，目前需要开发安全、费用上可负担且可调整的治愈方法，从本质上能够完全清除HIV，或能够调节免疫系统使其能在不治疗的情况下控制病毒。

研究者发现，一位名为Timothy Brown的男性“柏林患者”在移植来自一位对HIV具有天然抵抗力的供体的骨髓后5年停用了所有药物，并且未再检出病毒。这一结果使人们对于开发治愈方法的可能性越发乐观。

这项战略书中描述的7个开发治愈方法的研究重点包括：

· 明确HIV持续感染得以维持的细胞和病毒机制。

· 在接受长期抗逆转录病毒治疗的患者中明确持续HIV感染的组织和细胞来源。

· 在接受抗逆转录病毒治疗的患者中明确免疫活化和炎症的来源，并明确HIV持续感染的后果。

· 明确控制感染但允许病毒持续存在的宿主和免疫机制。

· 研究、比较和验证用于评价持续感染的检测方法。

· 开发和检验能够清除接受抗逆转录病毒治疗者的潜伏感染的治疗药物或免疫策略。

· 开发和检验能够提高宿主控制病毒复制的应答能力的策略。

目前美国国立卫生研究院已启动了针对性的筹资计划，为研究HIV感染的治愈方法提供资金支持。法国、加拿大和英国的相关机构也正在增加这方面的资金投入。

Deeks博士声明从默沙东和吉利德公司获得资金支持，并曾为百时美施贵宝等公司担任顾问。

爱思唯尔  版权所有

By: MIRIAM E. TUCKER, Ob.Gyn. News Digital Network
WASHINGTON – The International AIDS Society has officially shifted its focus from controlling to curing HIV infection.

Their seven-point plan called "The Inaugural Global Scientific Strategy Towards an HIV Cure" will be published online July 20 in the August issue of Nature Reviews/Immunology (vol. 12, pp. 607-14), and is outlined in a commentary published in Nature (vol. 487, pp. 293-4).
 
Miriam E. Tucker/IMNG Medical Media

The strategy merely represents the first step toward finding an AIDS cure, Dr. Steven Deeks emphasized at a press conference announcing the strategy. "No one thinks it’s going to be easy. Many people don’t even think it’s going to be possible. But, it’s certainly worth the investment."

"[Antiretroviral] drugs control the virus; they don’t eliminate it. In 2012, we now have 20-25 drugs, [used in] multiple combinations. They work very well, and people are now living much, much longer. But now that we’ve achieved what I think is the best that we can achieve with these drugs, we’re realizing some limitations," said Dr. Deeks, professor of medicine at the University of California, San Francisco.

HIV therapy is limited by problems of adherence, toxicity, cost, and lack of infrastructure in many countries for delivering drugs, he said. "Delivering drugs to the 33 million HIV-infected individuals worldwide – day in, day out, for decades and decades – is going to be a major challenge. ... So, now that we’ve achieved what we can with the current strategies, the field has shifted to what we think is the optimal intervention, which is to come up with a safe, affordable scalable intervention that will essentially either eliminate the virus completely or modify the immune system so that it can control the virus in the absence of therapy – a cure."

Fueling optimism about the possibility of a cure is the so-called "Berlin Patient," a man named Timothy Brown who received bone marrow from a naturally HIV-resistant donor. The Berlin Patient is now off all drugs at 5 years post transplant and remains virus free. "I don’t think anyone would want to go through what he went through to get that cure, but [the process] proved it could be done. This has really, truly inspired the field," said Dr. Deeks, cochair of the 34-member scientific panel that developed the strategy.

The seven research priorities described in the strategy for the cure are as follows:

· Determine the cellular and viral mechanisms that maintain HIV persistence.
· Determine the tissue and cellular sources of persistent HIV in individuals on long-term antiretroviral therapy.
· Determine the origin of immune activation and inflammation in the presence of antiretroviral therapy and the consequences for HIV persistence.
· Determine host and immune mechanisms that control infection but allow viral persistence.
· Study, compare, and validate assays to measure persistent infection.
· Develop and test therapeutic agents or immunologic strategies to eliminate latent infection in individuals on antiretroviral therapy.
· Develop and test strategies to enhance the capacity of the host response to control viral replication.

The panel was convened by the International AIDS Society with endorsements from major HIV-related organizations and institutions worldwide including amfAR, UNAIDS, the University of Pennsylvania, the Fred Hutchinson Cancer Research Center, and Monash University. The National Institutes of Health has recently undertaken targeted funding initiatives, including the Martin Delaney Collaboratory, which provides grants for research on a cure for HIV infection.

Other groups also are increasing research funding for a cure, including the French National Agency for Research on AIDS and Viral Hepatitis, the Canadian Institutes of Health Research and the Medical Research Council in the United Kingdom. Moreover, many pharmaceutical companies that had invested heavily in developing antiretroviral drugs are now also allocating resources toward pursuing a cure, according to an International AIDS Society statement.

Dr. Deeks disclosed that he has received grant support from Merck and Gilead, and has consulted in the past for Bristol-Myers Squibb, Merck, GlaxoSmithKline, and Gilead.