编者按：在HIV防治领域，广谱中和抗体（bnAbs）正展现出前所未有的潜力。在第25届国际艾滋病大会（AIDS2024）上，美国旧金山公共卫生部Bridge HIV临床研究医学主任Hyman Scott教授介绍关于bnAbs在HIV防治中的最新进展。《感染医线》非常荣幸地邀请到Scott教授进行了深度访谈，详细阐述了bnAbs在HIV预防和治疗中的重要作用。Scott教授指出，bnAbs以其每六个月仅需注射一次的便捷性和高效预防能力，为HIV感染高风险人群提供了全新选择。通过与现有抗逆转录病毒疗法的互补，bnAbs不仅丰富了预防手段，还为治疗HIV感染开辟了新路径。未来，随着HVTN/HPTN/IAVI合作框架下bnAbs临床开发的深入，我们有望见证这一创新疗法在全球范围内的广泛应用，为终结艾滋病流行带来新希望。

 

01

 

《感染医线》：教授您好，能否简要介绍一下广谱中和抗体（bnAbs）在HIV预防和治疗中的潜在作用及其重要性？

 

Scott教授：广谱中和抗体（bnAbs）在HIV感染的预防和治疗方面有多种潜力。我们目前已有很好的选择，但有时这些选择并不适合所有人，bnAbs可以为那些对暴露前预防（PrEP）用药有特定需求的人群提供另一种选择。bnAbs有诸多优点，其中之一是每六个月注射一次，无需每日服药或频繁就医。根据我们目前的研究，bnAbs作为预防措施使用时，显示出显著降低HIV感染风险的高效能和强大的预防能力。此外，bnAbs在HIV治疗中的应用正在探索当中。已有研究表明，bnAbs与其他抗逆转录病毒药物联合使用时，可能更有效地控制HIV感染。然而，该研究仍处于早期阶段。我们还需要做更多的工作，以确定可能有效用于HIV预防和治疗的联合方案。

 

IIDF: Professor Scott, could you briefly elaborate on the potential role and significance of bnAbs (broadly neutralizing antibodies) in HIV prevention and treatment?

 

Dr Scott: Broadly neutralizing antibodies, also known as bnAbs, have a potential for HIV prevention and treatment in a couple of different ways. One is that it would be an additional option for individuals who are interested in a form of PrEP (pre-exposure prophylaxis) that better fits what their needs might be. We have great options available, but sometimes those options don’t work for people, and we want to make sure we have additional choices that people can make for bnAbs. There are many things that might be good about bnAbs, including the fact it is possible to administer them every six months, so it doesn’t require a daily pill or frequent visits to a healthcare provider to receive them. It does appear, in the studies we are doing right now, they have a high potential for reducing HIV risk significantly with a really high efficacy and ability to prevent HIV when being used as prevention. There are also some smaller studies that are looking at the use of bnAbs for HIV treatment. It does appear that in combination, bnAbs do have the ability to control the HIV virus in the absence of treatment during the time periods of those studies. It is still in early phases of study. We have more work to do to identify bnAb combinations that might be effective for HIV prevention and HIV treatment.

 

02

 

《感染医线》：在HVTN/HPTN/IAVI的合作框架下，bnAbs的临床开发取得了哪些关键性的进展或突破？

 

Scott教授：bnAbs发展的关键进展主要体现在以下几个方面。首先，我们现在已经制定了一个蓝图，用于评估多种bnAbs组合在HIV预防中的效能。这一蓝图明确了实现HIV预防目标所需的具体目标以及bnAbs应具备的关键特性。抗逆转录病毒药物为基础的PrEP（如FTC/TDF）作为一种高效的口服HIV预防药物，为我们树立了标准，这也是我们期望bnAbs能够达到的效果。如今，我们对bnAbs所需达成的目标和功能有了更深入的理解，以确保它们能在HIV预防方面达到我们期望的水平。

 

此外，我们欣慰地发现，这些bnAbs是安全的，人们能够很好地耐受它们。患者在接受注射时不会感到不适，且无论是单独使用还是联合使用，我们尚未观察到与这些抗体相关的任何安全问题。

 

IIDF: Under the collaboration framework of HVTN/HPTN/IAVI, what are the key advancements or breakthroughs achieved in the clinical development of bnAbs?

 

Dr Scott: The key developments for the development of bnAbs have been around a couple of things. One is that we now have a blueprint for evaluating a combination of bnAbs for HIV prevention. We have identified what our targets need to be, what the characteristics of the bnAbs need to be in order to potentially achieve our goals of HIV prevention. What we have the ability to do with PrEP has sort of set the standard for what we want to achieve with the bnAbs. Antiretroviral-based PrEP like Truvada (tenofovir disoproxil fumarate) is an oral pill that has high efficacy for preventing HIV. There are now injectable forms of PrEP that also work really well for preventing HIV, and those are really the standard we are going to be comparing bnAbs to. Now that we have a better idea of what our targets need to be and how the bnAbs need to function in order to prevent HIV at the levels that we want it to prevent HIV. We are also finding that these are safe. People are able to tolerate them. They are able to receive the infusions and not get uncomfortable. And we haven’t seen any safety concerns with the antibodies individually or in combination.

 

03

 

《感染医线》：您认为bnAbs与现有的HIV治疗方法（如ART）相比，有哪些独特的优势或不足？

 

Scott教授：这是一个常被提及的问题，关于bnAbs如何与我们现有的预防手段，特别是用于预防的抗逆转录病毒疗法相结合。我认为bnAbs具有几个显著的优势或积极作用。首先，它提供了多样性选择。尽管我们目前已经为患者提供了一些选项，但在许多地区，这些选项并未被广泛采纳，这背后有多重原因。因此，我们致力于让患者能够真正做出自己的选择，而bnAbs在这方面做出了重要贡献。患者可以根据个人偏好选择最适合自己的预防手段。他们可能更倾向于选择像bnAb这样的蛋白质药物，而不是传统的抗逆转录病毒药物。又或者，他们可能更喜欢输液的形式，而非注射或口服药物。我们尊重患者的选择权，不替他们做决定，而是提供多样化的选项供他们选择。

 

此外，我们将持续努力确保bnAbs的给药方式既可行又便捷。我们的目标是使bnAbs的给药过程能够在诊所中顺利进行，无需增加过多的工作量，相比目前如注射用PrEP或其他医疗服务形式来说，更加高效和实用。

 

IIDF: How do you see the unique advantages or limitations of bnAbs compared to the existing HIV treatment methods, such as ART?

 

Dr Scott: That is an excellent question that we get asked frequently. How does this fit in with what we already have, particularly the antiretroviral therapies that are being used for prevention? I think there are a couple of advantages or positive around bnAbs. One is around choice. We have options available now for people, and we still haven’t seen tremendous uptake in many places. There are many reasons for that, but one of the things we do know from contraception is that when you give people choice, the more choices you give them, the more people pick something that works for them. We want to give people the options to make that choice in an authentic way, and we think bnAbs are an important contribution to that. People can decide. They might have a preference for something like a bnAb, which is a protein, over something like an antiretroviral. They may have a preference for an infusion rather than a shot or a pill. We don’t want to make that choice for them. We want to give them the option to make that choice. Some of the things we will continue to work on is making sure that when bnAbs are given, they are given in a way that is feasible, that they can be conducted and completed in a clinic without a tremendous amount of work over what is currently been done for, for example, injectable PrEP or other forms of healthcare services that are provided.

 

04

 

《感染医线》：未来，HVTN/HPTN/IAVI在bnAbs的临床开发和应用方面有哪些规划和展望？我们何时可以期待bnAbs成为HIV治疗的新选择？

 

Scott教授：展望未来，我们计划在接下来的一年内启动一项II期研究以评估bnAbs组合的疗效，预计在一年内将获得初步成果，随后启动大规模的疗效研究。II期研究将涵盖数百名参与者，而大规模研究则将涉及数千人。我们的目标是在未来两到三年内启动这项研究，并在接下来的两年内得出结果。进行这些研究是为了确保我们有确凿的证据来支持其在预防领域的应用。多年来，尽管我们已经批准了多个版本的PrEP，但对于许多社区而言，这些药物并未以易获取的方式提供。我们希望改变这种状况，为他们提供多样化的PrEP方案以供选择。

 

IIDF: Looking ahead, what are the plans and visions for the HVTN/HPTN/IAVI collaboration in the clinical development and application of bnAbs? When can we expect bnAbs to become a new standard for HIV treatment or prevention?

 

Dr Scott: Looking at where we are with the bnAbs and where we hope to be, in the next year, we will be started a phase II study that is going to be evaluating a combination of bnAbs that we would like to move into a larger efficacy study. We hope to have the initial results of that phase II study within a year or so, and then be able to start the large scale efficacy study. The smaller study will be with a couple of hundred people, and the larger study will be with a few thousand. The aim is having that study start in 2 or 3 years, and having a result within two years after that. We need to do the studies to make sure we have evidence about how this could be used in prevention, for example. I think if the trials show we have prevention of HIV among the study participants, then we can move forward through the process to make them available. We do want to make sure that if there is success in these trials that we are ready for that, and that we are able to provide this to the communities that can benefit from the bnAbs, and to ensure we don’t have significant delays. We have had approved versions of PrEP for many years that are really not available in an accessible way for a lot of our communities. We want to change that. We want to make sure that if something shows evidence of preventing HIV, we make it available in an accessible way for all of our communities globally.

 

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来源：《感染医线》

 

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