(Press-News.org) A new study from UC San Francisco shows it may be possible to control HIV without long-term antiviral treatment — an advance that points the way toward a possible cure for a disease that affects 40 million people around the world.
Treatment with a combination of experimental immunotherapy agents enabled seven out of 10 participants to keep the virus at low levels for many months after going off antiretroviral therapy (ART).
The results appear on Dec. 1, World AIDS Day, in Nature.
The trial, which relied on a collaboration with nearly a dozen pharmaceutical companies and other partners in HIV research, offers a proof of concept that the approach could work. Although the study was small and did not include a control arm, investigators said the results are extremely encouraging.
“The majority had some evidence of control, which we believe is unprecedented,” said the paper’s co-senior author, Steven Deeks, MD, a professor of Medicine at UCSF who is in the Division of HIV, Infectious Diseases, and Global Medicine at Zuckerberg San Francisco General Hospital. “I do believe we are finally making real progress towards developing a therapy that may allow people to live a healthy life without the need of life-long medications.”
The trial was made possible by the Foundation for AIDS Research (amfAR)’s $20 million, five-year partnership with UCSF to advance AIDS cure research, launched in 2015. It was also supported by the National Institutes of Health (NIH).
Reprogramming the body’s immune system
Antiretroviral therapy (ART) was introduced in the 1990s and turned HIV infection from a death sentence into a chronic disease. But it is not a cure, and the virus stays in the body ready to reawaken as soon as someone stops taking ART.
The study was designed to test whether a triple combination of immunotherapies could reprogram the body’s immune system to control the virus after going off ART. Most of the participants had started ART soon after they acquired HIV, which helped preserve their immune response.
First, participants received a therapeutic vaccine to encourage their T cells — a part of the immune system that attacks viruses — to go after the latent HIV in their bodies. Then, they received an antibody cocktail to reduce the amount of HIV in the body. Finally, they were given another round of anti-HIV antibodies before being taken off ART.
Typically, when a person with HIV stops HIV medicines, the virus starts to rebound in about two weeks and then skyrockets. This time, only three of the 10 patients experienced the typical rapid rebound. Six maintained low levels of the virus for months, and one did not rebound at all.
The pouncing cat analogy
The investigators then examined the immune responses of those who controlled the virus to see how they did it.
“It turns out the controllers had T cells that were able to expand dramatically once they ran into the virus,” said Rachel Rutishauser, MD, PhD, an associate professor in UCSF’s Division of Experimental Medicine and co-senior author of the paper. “It’s like they were hanging out waiting for their target, kind of like a cat getting ready to pounce on a mouse.”
The treatment would need to be simplified and proved effective in much larger studies before it could replace standard HIV treatment.
“This is not the end game,” said Michael Peluso, MD, an assistant professor in UCSF’s Department of Medicine and the study’s first author. “But it proves we can push progress on a challenge we often frame as unsolvable.”
Authors: Additional UCSF co-first authors include Demi Sandel, PhD, Amelia Deitchman, PharmD, PhD, along with co-authors Steven Yukl, MD, Timothy Henrich, MD, Matthew Spitzer, PhD, David Glidden, PhD, Michiko Shimoda, PhD, Rebecca Hoh, Thomas Dalhusien, Hari Prabhath Tummala, PharmD, Sun Jin Kim, PhD, Gina Borgo, PhD, Rafael Tibúrcio, PhD, Lily Zemelko, Kaiti Schwartz, Monika Deswal, Meghan Williams, RN, and Mandana Khalili, MD.
Funding: The UCSF amfAR Combination Trial was funded by amfAR: The Foundation for AIDS Research (109301-59-RGRL). The prospective ATI study was funded by the Bill & Melinda Gates Foundation (INV-002707). Additional support was provided by the NIH (UM1AI164560), (K23AI157875), (K23AI162249), (R01AI170239), (P01AI178375), (P01AI16960), (T32GM136547), (T32AI060530), (K24AA022523), (R01DE032031008), (P30AI027763), (S101S10OD01804001), (P30AI152501), Cancer Research Institute award CR14437 and amfAR (110560-74-RPRL). This research was also supported in part by the Intramural Research Program of the NIH and the NIH’s National Center for Advancing Translational Sciences through UCSF CTSI (UL1 TR001872).
END
Long-term HIV control: Could this combination therapy be the key?
2025-12-01
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