Summary: Scientists tested a multi-step immune-based therapy designed to retrain the body to control HIV without continuous antiviral treatment. After stopping standard HIV drugs, seven out of ten participants maintained low viral levels for extended periods, and one showed no viral rebound at all.
The therapy worked by stimulating powerful virus-targeting T cells while simultaneously lowering viral reservoirs with antibodies. The findings provide rare proof that long-term drug-free HIV control may be achievable and could reshape future cure strategies.
Key Facts
- Sustained Control: 70% of participants kept HIV at low levels after stopping daily medication.
- Immune Reprogramming: A vaccine plus antibody therapy trained immune cells to suppress the virus.
- Delayed Rebound: Only three participants showed the rapid viral return typically seen after stopping treatment.
Source: UCSF
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).
Key Questions Answered:
A: In this small clinical trial, most participants maintained low virus levels for months after stopping standard HIV medication.
A: A combination of therapeutic vaccination and targeted antibodies retrained the immune system to suppress the virus.
A: It’s not a cure yet, but it offers strong proof that long-term drug-free control may be possible.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this HIV and immunotherapy research news
Author: Laura Kurtzman
Source: UCSF
Contact: Laura Kurtzman – UCSF
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Correlates of HIV-1 control after combination immunotherapy” by Steven Deeks et al. Nature
Abstract
Correlates of HIV-1 control after combination immunotherapy
The identification of therapeutic strategies to induce sustained antiretroviral therapy (ART)-free control of HIV infection is a major priority.
Combination immunotherapy including HIV vaccination, immune stimulation/latency reversal, and passive transfer of broadly neutralizing antibodies (bNAbs) has shown promise in non-human primate models, but few studies have translated such approaches into people.
We performed a single-arm, proof-of-concept study in ten people with HIV on ART combining the following three approaches: (1) therapeutic vaccination with an HIV/Gag conserved element (CE)-targeted DNA+IL-12 prime/MVA boost regimen followed by (2) administration of two bNAbs (10-1074, VRC07-523LS) and a toll-like receptor 9 agonist (lefitolimod) during ART suppression, followed by (3) repeat bNAb administration at the time of ART interruption (NCT04357821).
Seven of the ten participants exhibited post-intervention control after stopping ART, independent of residual bNAb plasma levels. Robust expansion of activated CD8+ T cells early in response to rebounding virus correlated with lower median viral load following peak viremia off ART.
These data suggest that combination immunotherapy approaches might prove effective to induce sustained control of HIV by slowing rebound and improving CD8+ T cell responses, and that these approaches should continue to be optimized.
