HIV antibody therapy may teach the immune system to control the virus for years, study finds

An HIV antibody treatment tested in a small international trial appears to do more than temporarily suppress the virus: it may be training patients' own immune systems to keep controlling HIV long after the drug itself has cleared the body, according to a new analysis published this week in Nature Medicine.

The finding comes from a deeper look at data from the RIO trial, a randomized, placebo-controlled study run jointly by Rockefeller University, Imperial College London and the University of Oxford. Researchers led by Marcilio Fumagalli and Michel C. Nussenzweig at Rockefeller's Laboratory of Molecular Immunology found that people who already carried their own HIV-neutralizing antibodies before treatment kept the virus in check for months longer than those who did not — even after the infused antibodies had disappeared from their blood.

What the trial found

The 68 men enrolled in RIO had all started standard daily antiretroviral therapy (ART) soon after infection. In the trial's active arm, they instead received one or two infusions of two long-acting broadly neutralizing antibodies, known as bNAbs, and then paused their daily pills under close monitoring — a "treatment interruption" that would normally let HIV rebound within two to four weeks.

Instead, according to results reported by Imperial College London earlier this year in The Lancet HIV, roughly three-quarters of participants who got the antibodies stayed off ART for at least 20 weeks. Half were still virally undetectable at 48 weeks, and about a third remained off daily medication at 72 weeks — more than a year after their last antibody dose.

The new Nature Medicine paper digs into why some people did so much better than others. Participants who already had measurable neutralizing antibodies of their own against HIV before the trial began stayed off treatment for an average of 108 weeks before needing to restart, compared with just 27.5 weeks for those without such antibodies. One participant has now gone 160 weeks — more than three years — without daily medication, despite the infused antibodies having long since washed out of his system. The researchers also found that the pool of dormant, "intact" HIV hiding in resting immune cells shrank far faster after antibody treatment, with an estimated half-life of about 36 weeks, compared with four to seven years typically seen under standard ART alone.

How researchers got here

Broadly neutralizing antibodies were not invented in a lab from scratch. Nussenzweig's group pioneered techniques over the past two decades to isolate and clone them from "elite controllers" — the rare 1 to 2 percent of people with HIV whose immune systems naturally suppress the virus without any medication. Only a larger minority, roughly 5 to 10 percent of people with HIV, eventually develop their own weaker neutralizing antibodies naturally, usually years into infection, according to reporting by the HIV information service aidsmap. Manufactured versions of these antibodies have been tested in HIV therapy trials for more than a decade, but earlier studies mostly showed short-lived viral suppression that faded once the antibodies cleared.

Standard antiretroviral therapy already keeps HIV levels undetectable in most patients who take it daily, but it cannot touch the so-called viral reservoir: a small population of resting immune cells carrying dormant, replication-ready copies of the virus that reawaken almost immediately if medication stops. Eliminating or shrinking that reservoir has long been considered essential to any real HIV cure, which is what makes the reservoir-shrinkage finding in the new paper notable alongside the immune-training result.

Who this could affect

An estimated 40.8 million people were living with HIV worldwide in 2024, according to the U.N. agency UNAIDS, and about 32 million of them were on antiretroviral therapy by the end of 2025 — most taking daily pills indefinitely. A therapy that could let some patients go months or years between treatments, without losing viral control, would mark a significant change for a population that currently faces lifelong medication, potential side effects and the logistical burden of consistent daily access to drugs, particularly in lower-income countries.

The RIO results are still early. The trial enrolled only men who began treatment shortly after infection, a population whose reservoirs tend to be smaller and easier to influence than those of people who have lived with untreated HIV for years. Whether the same antibody-training effect would hold in women, in people who started ART late, or in larger populations remains untested.

What researchers are saying

"The antibodies appear to be teaching the immune system to control HIV," said Michel C. Nussenzweig, head of Rockefeller's Laboratory of Molecular Immunology and senior author of the study.

Nussenzweig described the effect as if the participants' own immune activity had become "a second component" working alongside the infused antibodies, rather than the antibodies acting alone. Fumagalli, a postdoctoral associate in the lab, pointed to the trial's most striking outlier: a participant who has now gone more than three years without antiretroviral therapy even though the therapeutic antibodies have been fully cleared from his blood for most of that time.

Outside commentators have been cautiously optimistic. Sarah Fidler, an Imperial College London professor and the trial's chief investigator, has called the sustained viral control "the first time a long-acting immune-based therapy has shown sustained viral control in multiple participants," while HIV community advocates who have tracked the trial, such as Simon Collins, have welcomed how many participants have been able to stay off daily pills for extended stretches without their virus rebounding.

What happens next

Nussenzweig said the next challenge is figuring out how to reproduce the strongest responses more consistently. "What we are now looking for are ways to make good outcomes more general," he said, pointing to strategies such as therapeutic vaccination that might boost a patient's own antibody production before or alongside a bNAb infusion. The RIO collaboration has already opened a new study arm testing different dosing schedules to see whether timing the antibody infusions differently can extend viral control further.

None of this amounts to a cure, and the researchers have been careful not to call it one. But by showing that an antibody infusion can apparently nudge a patient's own immune system into taking over some of the work of virus control — and can meaningfully shrink the hidden reservoir that has frustrated cure efforts for decades — the RIO findings give HIV researchers a more concrete mechanism to chase, rather than simply a longer-lasting drug.