Three Novel Immune-based Therapies for HIV Cure Launch Clinical Trial

Although antiretroviral treatment (ART) can help manage the impact of the Human Immunodeficiency Virus (HIV), it is not a cure. People living with HIV need to take the treatment for their entire lives to suppress viral replication and protect their immune systems.

To address this clinical need, ACTG, a global clinical trials network focused on HIV and other infectious diseases, today announced the opening of A5374, a phase 1/2a study evaluating the safety, tolerability, and antiviral effect of a novel combination regimen that includes therapeutic T-cell vaccines, two broadly neutralizing antibodies (3BNC117-LS, 10-1074-LS), and an immune-system boosting treatment among people living with HIV who started ART during acute HIV infection.

This study hypothesizes that this combination regimen will be safe and result in a more extended period of viral control during a closely monitored pause in ART (known as an analytic treatment interruption) compared to placebo.

The approach being studied in A5374 is part of a potential path toward enabling the immune system to manage HIV in the absence of ART for weeks or months.

“We expect that controlling HIV in the absence of ART will require a combination of novel treatments to decrease the number of cells harboring HIV and simultaneously stimulate the immune system to keep the virus from replicating,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California Los Angeles in a press release.

“A5374 is a pivotal trial, and we hope it will provide us with important insights into how to boost the immune system to control HIV.”

ACTG says carefully monitored analytic treatment interruptions are an essential part of HIV cure clinical trials. They can help determine whether a research intervention can reduce latent HIV (HIV that is “hidden” in different cells and tissues but not replicating) or increase immune function and delay or prevent latent HIV from actively replicating.

While there are no U.S. FDA-approved HIV prevention vaccines today, clinical development accelerated in 2023, with vaccine candidates utilizing innovative technologies such as mRNA.