编者按：HIV的早期发现与早期治疗在艾滋病防控中占据着至关重要的地位。一个不容忽视的战场正逐渐显现其重要性——急性期HIV感染（acute HIV infection，AHI）的及时检测。AHI是指从HIV病毒进入人体到抗体可检测出来之前的阶段，通常发生在感染后的几周到几个月内。在此期间，病毒在体内迅速复制，导致病毒载量急剧上升，感染者体内病毒浓度达到高峰。因此，AHI感染者是HIV传播的主要风险群体，更是控制HIV传播的关键所在。在第25届国际艾滋病大会（AIDS2024）上，《感染医线》特邀请南非约翰内斯堡奥勒姆研究所Eduard Sanders教授与雅培科学与临床事务部高级医学总监Hugo Xi博士对话，深入探讨了AHI检测的战略意义及紧迫性，强调了创新第四代快速HIV筛查测试在识别高传染性感染者方面的巨大潜力。面对高昂的检测成本、数据有限及假阳性等挑战，他们呼吁提高公众对AHI的认知，并倡导通过政策调整和技术进步，让更多人受益于这一关键性检测。
01
《感染医线》：AHI的及时检测对控制HIV疫情的传播具有怎样的战略意义？为什么专家强调其检测的紧迫性？
Eduard Sanders
本次会议带来了一个积极的信号，即新增HIV感染人数正处于下降趋势，然而，这一下降速度尚未达到令人满意的水平。鉴于当前感染人数仍未达到预期的控制目标，并期望实现感染人数的显著减少，我们必须采取更加有效的新策略。在此背景下，早期检测被视为一个至关重要的新做法。
回顾过去的检测实践，我们意识到可能错过了关键的检测窗口。具体来说，个体在感染HIV后的七天内，即可通过检测手段识别其感染状态。尤为关键的是，在感染后的2-3周期间，感染者体内的病毒载量会急剧上升，达到一个非常高的水平。这一时期内的感染者，往往因尚未意识到自己的感染状况，而具有较高的传染性，从而成为病毒传播的主要风险源。这些未能及时进行检测的感染者，由于其高病毒载量，极有可能导致大量的持续感染事件。因此，早期检测的重要性不言而喻。通过尽早识别并确诊HIV感染者，我们可以迅速启动相应的治疗和管理措施，有效阻断病毒的进一步传播，从而加速HIV疫情的控制进程。
Hugo Xi
正如您所言，尽管新增HIV感染人数已经处于较低水平并持续减少，但总体病例数依然较高，这一现象引人深思。深入剖析其背后原因，我们发现急性期HIV感染（AHI）占据了新增感染病例的显著比例，高达50%至60%。这一发现凸显了AHI在HIV疫情持续传播中的核心作用。为了有效控制新增感染病例，我们必须直面并解决这一关键问题。此外，由于AHI感染者在感染初期病毒载量极高，如果未早期发现可能增加传播风险，这两个因素共同作用，使得AHI感染者成为HIV疫情传播的主要驱动力。因此，针对AHI感染者的早期检测、及时干预和治疗显得尤为重要。
IIDF: What is the strategic significance of timely detection of acute HIV infection in curbing the spread of the HIV epidemic? Why do experts stress the urgency of its detection?
Dr Sanders: New infections go down, which is the good news at this conference, but they don’t go down fast enough. If you look at the trend where infections are still not reaching target and you want to have much fewer infections, you need to do something differently. In doing something differently, we think about the early testing. What do we miss, or potentially miss? When somebody gets HIV, you can detect it seven days following acquisition. Two weeks following acquisition, and within three weeks, virus load is really high. People who do not know that at that moment are highly infectious, so the risk has changed, their viral load is high, and they can contribute to a number of ongoing infections if they are not tested. Would you agree, Dr Xi?
Dr Xi: That is absolutely right. I think on the question of why is it important, if you look at new infections being low and getting lower, then why are cases still consistent? The cause of this is acute HIV infection, or AHI, as you call it, which is contributing 50-60% of new infections. If we want to control new infections, we have to deal with what matters. And what matters most is AHI in a population, because of their high virus load, and because of their sexual behavior.
02
《感染医线》：请介绍一下创新的第四代快速HIV筛查测试相比之前的测试方法有哪些优势和新的可能性？特别是在识别高传染性急性HIV感染者方面。
Hugo Xi
新一代（第四代）HIV检测试剂相较于以往的技术，展现出了显著的重要性和多重优势，具体可从以下三个方面进行深入分析：
一、技术传承与创新融合
第四代试剂在保留传统循环抗体检测优势的基础上，实现了技术的创新与发展。它不仅继承了第三代试剂中表现最为出色的部分，还巧妙地融入了新的检测功能，确保了检测结果的准确性和可靠性。这种技术传承与创新融合的策略，使得第四代试剂在保持高敏感性的同时，进一步提升了检测效率和准确性。
二、抗原抗体联合检测，提升识别能力
通过引入抗原组分的检测，第四代试剂实现了对新感染患者的有效识别。这一技术突破使得那些抗原和抗体同时呈阳性的患者能够被及时检出，从而大大缩短了检测窗口期。根据最新的研究数据和临床实践，采用第四代试剂进行检测时，抗原抗体均为阳性的患者群体被确认为HIV感染者的准确率高达100%，这一结果无疑为患者提供了更为明确和可靠的诊断依据。
三、契合关键检测时间点，加速干预进程
正如Sanders教授所指出，HIV感染后的2-3周是病毒载量急剧上升的关键时期，也是传染性最强的阶段。第四代试剂的引入，使得我们能够在这一关键时间点内迅速识别出新的感染者，从而加速了对患者的治疗和管理进程。通过及时的干预和治疗，我们可以有效降低患者的病毒载量，减少其传染性，进而遏制HIV疫情的扩散。
Eduard Sanders
需要补充的一点是，我们在深入探究HIV感染的动态过程中发现一个关键的时间点：即在HIV感染后2周左右，就能检测到p24抗原的存在，尽管这一时间段相对短暂。在这一时期，感染者常会出现一系列类似流感或疟疾的症状，如喉咙痛、肌肉疼痛、发烧等。然而，由于这些症状的非特异性，感染者往往被误诊为其他疾病，而未能及时得到HIV相关的诊断。
正是基于这一观察，我们强调了第四代HIV检测试剂的重要性。与第三代试剂相比，第四代试剂不仅保留了传统的抗体检测功能，还新增了对抗原（如p24）的检测能力。这一技术革新使得我们能够在感染者出现症状的早期阶段，即能准确地识别出AHI（急性期HIV感染），从而避免了因误诊而导致的治疗延误。
IIDF: Please elaborate on the advantages and new possibilities offered by the fourth-generation rapid HIV screening test compared to previous testing methods, especially in the case-finding of highly infectious acute HIV individuals.
Dr Xi: Yes, I can take it first on this one. I can answer this question probably in three ways. Why does the new fourth-generation matter? First of all, the fourth generation has the traditional circulating antibody in it, so we are not losing anything, everything we gain is on top of that. So we still have the best performing third-generation embedded in the fourth-generation. The next is, for the antigen component, we will identify new patients. New patients come in as two groups. One of those is patients who are both antigen- and antibody-positive, and the fourth-generation detect antigen and antibody. For that population, from our data, and we have seen from Spain and Kenya today, who are both antigen- and antibody-positive, they are 100% confirmed as positive. That is the benefit for the patient of a confirmed result. The second group is that you identify patients who only have antigen. As Professor Sanders mentioned earlier, that fits into the 2-3 week timeframe, when we can identify new patients. Those are three benefits I can think of.
Dr Sanders: I can add onto that. If you look at the dynamics of HIV acquisition and two weeks later being able to detect the p24 antigen. That is only for a brief period. But what is interesting is that that is the period people often seek healthcare for symptoms - a sore throat, muscle pain, fever. They think they have a flu. Some others may think they have malaria. If the fourth-generation test can be offered rather than the third-generation test, we can detect an acute infection. That is why we want to have this change in thinking about when we can diagnose acute HIV.
03
《感染医线》：在推进急性HIV检测以阻止病毒传播、改善HIV患者预后以及提高HIV项目经济效率方面，目前面临的主要挑战是什么？
Eduard Sanders
在HIV检测领域，尽管第四代检测试剂具有诸多优势，但由于其价格昂贵，目前尚未得到广泛推广。除此之外，当前尚未全面推广第四代HIV检测的原因还包括：一是数据积累尚不充分，影响了对试剂性能的全面评估；二是存在假阳性的可能性，增加了误诊的风险；三是检测结果呈阳性后，需要进一步的确认检测，增加了患者的经济和心理负担。此外，改变现有的医疗行为和政策制定者的观念也是一个巨大的挑战。
Hugo Xi
正如前面我们所讨论的，提高大众对AHI的认知是解决这一问题的关键。只有当人们充分认识到AHI的危害性及其高传染性时，才会更加重视早期检测的重要性。值得欣慰的是，新版的艾滋病指南中多次提及AHI，这标志着AHI问题已经引起了广泛的关注和重视。
因此，我们需要进一步加强AHI相关知识的普及和教育，提高公众的认知水平。同时，积极探索降低第四代检测试剂成本的方法，以便让更多的人能够负担得起这一先进的检测手段。只有这样，我们才能实现尽早发现、尽早干预的目标，有效控制HIV疫情的传播。
IIDF: What are the primary challenges currently faced in advancing acute HIV testing to halt onward transmission, improve HIV patient outcomes, and increase the economic efficiency of HIV programs?
Dr Sanders: I think one of the challenges is that, in healthcare, we often want the Rolls Royce, and the Rolls Royce is a very expensive test that is laboratory-based, and is not accessible for a large number of people. The hesitation to not promote the fourth-generation test is perhaps based on that the data are limited, that there are false positives, and the need for confirmatory tests if someone is testing positive. Changing behavior is always difficult. Changing the thinking of policymakers is even more difficult. That is what we hope to do, isn’t it?
Dr Xi: Absolutely right. I think everything comes down to this. How much are people aware of acute HIV? In an earlier session today, Professor Sanders mentioned that for the first time ever, the new HIV Guidelines have AHI, acute HIV infection, mentioned twelve times. This was not happening before. We are getting there. Professor Sanders, you mentioned that we still don’t have a guideline on AHI itself. We are moving toward that goal, but it is about awareness. As Professor Sanders said, the solution revolves around a Rolls Royce test versus a point of care test that gives people some result that can be acted upon with follow-up testing and so on.
04
《感染医线》：最后，请两位教授分享一下本届大会的亮点以及感兴趣的研究？
Hugo Xi
我的个人印象是，长期PrEP（暴露前预防）已经引起了广泛的关注和浓厚的兴趣。这是一件极好的事情。它不仅关乎PrEP的可负担性和可获得性，还涉及到长期效果的问题，例如如何确保人们能够长期服用PrEP，以及如何进行相关的检测、诊断和监测。这是一整套需要我们全面考虑的事情。当前，我们正处于一个令人振奋的时期。对于艾滋病患者而言，在过去的40年里，我们已经取得了显著的进步。我们拥有先进的技术，我们有坚定的意愿。只要大家齐心协力，共同努力，我相信我们一定能够取得惊人的成果。
Eduard Sanders
每次参加AIDS大会，我都感受到无限充沛的活力和乐观情绪，这总是让我更加坚信我们能够实现消除艾滋病威胁的目标。然而，当前形势下HIV正在向关键人群扩散，特别是那些处于劣势、来自贫困地区的人们，他们往往容易被忽视。这意味着我们还有大量的工作需要做。因此，我们需要制定出新的计划。总而言之，我们仍然面临着艰巨的任务，需要付出更多的努力。
IIDF: What are the highlights of this Congress for you? Is there some research or poster that has triggered your interest?
Dr Xi: My personal impression is that long-term PrEP has generated a lot of awareness and a lot of interest. I think that is a great thing. That comes with affordability and accessibility, and comes with long-term outcomes. And there’s how to put people on long-term PrEP, the testing, diagnosis and how we monitor it. It is a whole thing. I think it is a very exciting period. For HIV patients, in 40 years, we have come a long way. I am even more excited today than in any time. We have the technology. We have the will. With everybody working together, we will have fantastic results.
Dr Sanders: I am always mindful when I am here where is so much energy and optimism, that we can achieve those goals. When you listen to the people talk and look at the data, you see that HIV is moving into key populations - people who are disadvantaged, people from poor backgrounds - that are harder to reach. There is a lot of work that still has to be done. That is why we get re-energized at conferences like this. You get new plans. But in reality, we still have to do a lot of work.