Editor's Note: Early detection and treatment of HIV play a crucial role in AIDS prevention and control. A critical battlefield is emerging with increasing importance—the timely detection of acute HIV infection (AHI). AHI refers to the period from the entry of the HIV virus into the body until antibodies become detectable, typically occurring within a few weeks to a few months after infection. During this period, the virus replicates rapidly within the body, leading to a sharp increase in viral load, reaching its peak concentration. Consequently, individuals with AHI are at high risk of transmitting HIV and are a key focus for controlling the spread of the virus. At the 25th International AIDS Conference (AIDS2024), Infectious Diseases Frontier(IIDF) invited Dr. Eduard Sanders from the Aurum Institute in Johannesburg, South Africa, and Dr. Hugo Xi, Senior Medical Director of Scientific and Clinical Affairs at Abbott, to discuss the strategic importance and urgency of AHI detection. They emphasized the immense potential of innovative fourth-generation rapid HIV screening tests in identifying highly infectious individuals. Faced with challenges such as high testing costs, limited data, and false positives, they call for increased public awareness of AHI and advocate for policy adjustments and technological advancements to ensure more people benefit from this crucial testing.

01

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?

Eduard 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?

Hugo 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

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.

Hugo Xi: The new generation (fourth-generation) HIV test kits show significant importance and multiple advantages over previous technologies, which can be analyzed in the following three aspects:

1. Integration of Tradition and Innovation The fourth-generation test kits have achieved innovation and development while retaining the advantages of traditional cyclic antibody detection. Not only do they inherit the best features from the third-generation test kits, but they also skillfully incorporate new detection capabilities, ensuring the accuracy and reliability of the results. This strategy of blending tradition with innovation allows the fourth-generation kits to maintain high sensitivity while further enhancing detection efficiency and accuracy.

2. Combined Antigen-Antibody Detection, Enhanced Identification Capability By introducing antigen detection components, the fourth-generation test kits effectively identify newly infected patients. This technological breakthrough enables the timely detection of patients who test positive for both antigen and antibody, significantly shortening the detection window period. According to the latest research data and clinical practice, the accuracy rate of identifying HIV-infected individuals using fourth-generation kits, where both antigen and antibody are positive, reaches 100%. This result undoubtedly provides patients with a more definitive and reliable diagnostic basis.

3. Aligning with Critical Detection Time Points, Accelerating Intervention Process As Professor Sanders pointed out, the 2-3 week period following HIV infection is a critical time when viral load increases sharply and the infectiousness is at its peak. The introduction of fourth-generation kits enables us to quickly identify new infections within this crucial time frame, thereby accelerating the treatment and management process for patients. Through timely intervention and treatment, we can effectively reduce the patient’s viral load, decrease their infectiousness, and thus curb the spread of the HIV epidemic.

Eduard Sanders: Additionally, it’s important to highlight a key time point discovered during our in-depth exploration of HIV infection dynamics: around two weeks after HIV infection, the presence of the p24 antigen can be detected, although this period is relatively short. During this time, patients often exhibit flu-like or malaria-like symptoms, such as sore throat, muscle aches, fever, etc. However, due to the non-specific nature of these symptoms, patients are often misdiagnosed with other illnesses and do not receive timely HIV-related diagnoses.

Based on this observation, we emphasize the importance of the fourth-generation HIV test kits. Unlike the third-generation kits, the fourth-generation kits not only retain the traditional antibody detection function but also add the ability to detect antigens like p24. This technological innovation enables us to accurately identify acute HIV infection (AHI) during the early symptomatic stage, thereby preventing treatment delays caused by misdiagnosis.

03

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?

Eduard 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?

Hugo 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

IIDF: What are the highlights of this Congress for you? Is there some research or poster that has triggered your interest?

Hugo Xi: My personal impression is that long-term PrEP (pre-exposure prophylaxis) has garnered widespread attention and considerable interest. This is a great development. It’s not just about the affordability and accessibility of PrEP, but also about long-term outcomes—how to ensure that people can consistently take PrEP over the long term, and how to conduct related testing, diagnosis, and monitoring. This is a comprehensive set of issues that we need to fully consider. Currently, we are in an exciting time. For AIDS patients, we have made significant progress over the past 40 years. We have advanced technologies and strong determination. If everyone works together with a united effort, I am confident that we can achieve remarkable results.

Eduard Sanders: Every time I attend the AIDS conference, I feel an immense sense of energy and optimism, which always reinforces my belief that we can achieve the goal of eliminating the threat of AIDS. However, in the current context, HIV is spreading among key populations, particularly those who are disadvantaged and from impoverished areas, who are often overlooked. This means we still have a lot of work to do. We need to develop new strategies. In summary, we are still facing daunting challenges, and much more effort is required.