New ACTG Trial Aims to Control HIV Without the use of ART

Judith Courrier, M.D., M.Sc.

The AIDS Clinical Trials Group (ACTG) announced Monday that a new clinical trial called A5374 has begun. The new trial aims to treat HIV patients with a combination of three therapies that include a therapeutic T-cell vaccines, two broadly neutralizing antibodies (3BNC117-LS, 10-1074-LS) and TLR7 agonists to boost the immune response. The goal of the trial is to improve the immune response so that HIV patients can successfully stop relying on ART for treatment.

ACTG Chair Judith Currier, M.D., M.Sc., spoke with Managed Healthcare Executive and explained what this trial may change for the future of HIV. Currier is a professor of medicine, Executive Vice Chair for Research and Co-Director of the Center for AIDS Research and Education Center (CARE) in the Department of Medicine at University of California, Los Angeles (UCLA). She has been treating HIV patients for over 30 years.

The ACTG is one of the largest HIV clinical trial organizations in the world and was founded in 1987.

Tell us about the new trial. How will it work?

It's for a very unique population of people who were identified right at the time they acquired HIV. There's a window where you can tell if somebody is in the process of developing antibodies to HIV.

It's thought that if you detect HIV and treat it really early, you might control the size of what's called the latent reservoir, so the virus doesn't get to set up housekeeping.

The goal is to see whether this approach delays the return of the virus or improves the immune response compared to what would have happened without it.

The way that we evaluate whether the intervention has done anything to improve the body's immune response is to stop their antiretroviral therapy and look for how long they can remain off treatment before the virus comes back.

If it works, it could be tested on people who had HIV that were identified later, not just in this very early stage.

Is this trial similar or different to previous HIV treatment trials? How so?

Normally, [the trials] test one thing at a time but combining these three things together looked promising in the nonhuman primate model. There are many different approaches to ART-free remission that have been explored to enhance the immune response, but this study is focused on trying to make it so that you can control HIV without medication. These components have all been tested individually in other settings and so it's time to bring them together.

It's putting three things together that are each experimental. I think the extra effort required will pay off because we need to be bold in our approaches and make progress. Taking little steps hasn't gotten us very far.

Where is this trial in the timeline to curing HIV?  Do you think we’re on course to curing HIV by 2030?

When they say they want to end HIV by 2030, it's ending new infections. There's a whole category of studies that are been focused on trying to “cure HIV.” The word cure has as a lot of connotations, so we use antiretroviral-free remission. We're looking at strategies that might make it possible for people with HIV to be off treatment and control the virus themselves. It's not decades away. I think it could be sooner than that.