Seven of ten people maintained low HIV levels for months after stopping antiretroviral drugs following an experimental triple therapy, according to research published December 1 in Nature.
The treatment combined three immunotherapy approaches: a vaccine to boost T cells targeting HIV, two broadly neutralizing antibodies plus an immune stimulant, and a second antibody dose before stopping medications. One participant showed no virus rebound for over 18 months.
T Cells Poised Like Hunting Cats
The key to success appeared in how participants’ immune systems responded when virus levels began rising again after treatment stopped. Those who controlled the virus showed something unexpected: their CD8+ T cells expanded dramatically when encountering HIV.
“It turns out the controllers had T cells that were able to expand dramatically once they ran into the virus. It’s like they were hanging out waiting for their target, kind of like a cat getting ready to pounce on a mouse.”
That description comes from Rachel Rutishauser, associate professor in UCSF’s Division of Experimental Medicine and co-senior author. The T cells expressed high levels of TCF-1, a protein associated with memory cells that can continuously generate new virus-fighting cells.
In contrast, three participants experienced rapid viral rebound similar to what typically happens when people stop antiretroviral therapy without intervention. Their T cells didn’t show the same robust expansion response.
Slower Viral Rebound Than Controllers
The research team measured how quickly HIV levels increased after treatment interruption. Even among the three participants who didn’t achieve long-term control, virus rebounded more slowly than in a comparison group of people who stopped treatment without intervention.
The viral rebound slope reached 0.06 log copies per milliliter per day for the six viremic controllers in the study. That compared to 0.12 for natural controllers (people who spontaneously control HIV before starting treatment) and 0.27 for non-controllers in the observational study.
Before restarting treatment, the seven controllers maintained viral loads significantly lower than their levels before originally starting antiretroviral therapy: a median of 651 copies per milliliter compared to 14,477 copies per milliliter.
The study enrolled participants who had started antiretroviral therapy soon after HIV infection, preserving their immune response. Most had very low levels of intact HIV DNA in their cells. The participant who showed no rebound had started treatment within days of infection and had among the lowest HIV reservoir measurements in the cohort.
Michael Peluso, assistant professor at UCSF and first author, cautioned that the approach needs refinement.
“This is not the end game, but it proves we can push progress on a challenge we often frame as unsolvable.”
The trial was made possible by amfAR’s $20 million partnership with UCSF launched in 2015, with additional support from the National Institutes of Health.
Nature: 10.1038/s41586-025-09929-5
ScienceBlog.com has no paywalls, no sponsored content, and no agenda beyond getting the science right. Every story here is written to inform, not to impress an advertiser or push a point of view.
Good science journalism takes time — reading the papers, checking the claims, finding researchers who can put findings in context. We do that work because we think it matters.
If you find this site useful, consider supporting it with a donation. Even a few dollars a month helps keep the coverage independent and free for everyone.