Editor's note: Broad spectrum neutralizing antibodies (bnAbs) are showing unprecedented potential in the field of HIV prevention and treatment. At the 25th International AIDS Conference (AIDS2024), Professor Hyman Scott, medical director of Bridge HIV clinical research, San Francisco Department of Public Health, introduced the latest progress of bnAbs in HIV prevention and treatment. Infectious Disease Frontier（IIDF） is honored to invite Professor Scott for an in-depth interview, elaborating on the important role of bnAbs in HIV prevention and treatment. Professor Scott pointed out that bnAbs provides a new option for people at high risk of HIV infection due to its convenience and efficient prevention ability of only requiring one injection every six months. By complementing existing antiretroviral therapies, bnAbs not only enriches prevention methods, but also opens up new pathways for the treatment of HIV infection. In the future, with the deepening of clinical development of bnAbs under the framework of HVTN/HPTN/IAVI cooperation, we are expected to witness the widespread application of this innovative therapy worldwide, bringing new hope to end the AIDS epidemic.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.
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.
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.
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.
