HIV treatment research advance is published in Science

By Jordana Lenon
March 20, 2024

Findings from a highly collaborative preclinical nonhuman primate study were given the green light to advance to clinical trials for a potential new treatment for HIV. Researchers at multiple institutions, including the Wisconsin National Primate Research Center and led by James Whitney, a virologist at Boston College and Harvard University, published their results in the journal Science on Feb. 29, 2024.

The research team showed that a combination of two different therapies may potentially enable the immune system to control human immunodeficiency virus in people living with HIV without the need for daily antiretroviral treatment. The therapy involves an interleukin-15 superagonist therapy termed N-803 (trade name Anktiva) used together with broadly neutralizing antibodies (bNAbs).

Funded by the National Institutes of Health and the National Institute of Allergy and Infectious Diseases, this combination therapy led to durable viral remission after discontinuation of antiretrovial therapy (ART) in rhesus macaques infected with chimeric simian-human immunodeficiency virus AD8 (SHIV-AD8).

The monkeys involved in the study were at the Wisconsin National Primate Research Center. Study coauthors included WNPRC scientists, veterinarians and other specialized animal care staff. Anktiva was developed by ImmunityBio, Inc.

Microscopic view of HIV particles, or virions.
This thin-section transmission electron microscopic (TEM) image depicts the ultrastructural details of a number of human immunodeficiency virus (HIV) particles, or virions. A member of the genus Lentivirus, HIV is separated into two serotypes, HIV-1 and HIV-2, and is the cause for the disease known as acquired immunodeficiency syndrome, or AIDS.

At first, treatment with N-803 and bNAbs led to immune activation and transient viremia, but interestingly, only minor changes in the SHIV reservoir, Whitney said. Upon discontinuation of antiretroviral therapy, all animals experienced viral rebound. This was then followed by long-term virus control for up to 10 months in approximately 70 percent of those treated with N-803 plus bNAbs.

“The viral reservoir in people living with HIV is seeded within the first few days after infection and cannot be eliminated by the body’s immune system or currently available treatments, representing a significant obstacle in curing an established HIV infection,” Whitney explained. “When combined with broadly neutralizing antibodies, N-803 has the potential to provide immunologic control of virus without eradication of the existing viral reservoir. This further suggests that the complete eradication of this reservoir may not be required to induce sustained remission after discontinuing antiretroviral therapy.”

Because of these promising preclinical results in monkeys whose immune systems mirror our own, two clinical trials are already underway to investigate the ability of N-803 and bNAbs to reduce viral loads in HIV-infected humans on antiretroviral therapy, according to ImmunityBio news releases in early March. These Phase 1 human trials will include an analytical treatment interruption (ATI) to determine the effect of the immunotherapies on post therapy viral loads. They are clinical trials ACTG A5386, NCT04340596: and NCT05245292 at the Rockefeller University and are actively enrolling participants.

““These exciting findings provide proof-of-principle that immune-mediated control of HIV can be achieved after discontinuation of ART and predict succuss in clinical trials that may clear the way for widespread use of such therapies in HIV infected patients,” said Jon Levine, WNPRC director and University of Wisconsin–Madison professor of neuroscience. Levine has overseen the center’s research areas, including its Global Infectious Diseases Research Program, since 2010.