Scientists Train Immune System to Control HIV Without Daily Drugs, Raising Cure Hopes as US Funding Cuts Loom

SAN FRANCISCO — Scientists are making progress toward a goal that has eluded HIV researchers for more than four decades. In small trials, they have trained the body's immune system to keep the virus in check without daily medication.

Researchers at the University of California, San Francisco, and elsewhere have shown in early studies that combinations of immune-based therapies can prime the body to control HIV after patients stop taking antiretroviral drugs. The findings, highlighted in a Bloomberg feature published this week, point toward a possible functional cure, in which the virus stays suppressed without lifelong treatment.

The advances come at a difficult time for the field. Cuts to U.S. government funding threaten the research needed to build on the early results.

From crisis to control

Steven Deeks, a professor of medicine at UCSF and one of the world's leading HIV cure researchers, has worked on the disease since the early 1990s.

When he began working at Ward 86, the AIDS clinic at San Francisco General Hospital, in 1993, the epidemic was near its deadliest point in the city. Only a few HIV drugs were available, and none could reliably suppress the virus or stop the disease from progressing.

The arrival of combination antiretroviral therapy in the mid-1990s transformed HIV from a near-certain death sentence into a manageable chronic condition. Today, people with HIV who take daily medication can live near-normal lifespans, and those with suppressed virus cannot transmit it to sexual partners.

But the drugs do not cure the infection. HIV hides in a reservoir of long-lived immune cells, and if treatment stops, the virus usually comes back within weeks.

Retraining the immune system

Rather than trying to eliminate every infected cell, a goal that has proved extremely difficult, many researchers are now focused on helping the immune system control the virus on its own.

In a small study led by UCSF researchers and published late last year, participants received a combination immunotherapy designed to boost their immune response to HIV. The approach included a therapeutic vaccine, an immune-stimulating drug and broadly neutralizing antibodies, which can target many different strains of the virus.

After participants stopped their antiretroviral drugs, about 70% kept their virus at low levels for an extended period.

"The majority had some evidence of control, which we believe is unprecedented," Deeks said at the time.

The study was small and did not include a control group, so researchers cautioned that larger trials are needed. Still, the results stood out. Without any intervention, only about 4% of people who stop HIV treatment keep the virus under control after 84 days, according to a meta-analysis cited by researchers.

Promising results from cell therapy

Researchers are also testing a one-time cell therapy approach. In May, Deeks presented early data from a trial of a genetically engineered immune cell treatment known as duoCAR-T therapy, developed with the nonprofit Caring Cross.

The therapy modifies a patient's own immune cells so they can better recognize and attack HIV-infected cells.

In the trial, nine men received the treatment. Three of them simply stopped taking their HIV drugs afterward, and all three saw the virus rebound quickly.

The other six received a low dose of chemotherapy before stopping treatment, a step designed to help the engineered cells take hold. Two of those participants maintained undetectable or low levels of virus, one for nearly a year and the other for nearly two years. A third had intermittent control for almost three months.

"We are particularly interested in two individuals who have maintained control of HIV with undetectable viral loads for extended periods," Deeks said in a statement released by Caring Cross.

Researchers said people who started HIV treatment early in their infection appeared more likely to benefit, likely because their viral reservoirs are smaller and their immune systems healthier.

Caution about 'cures'

Deeks has stressed that the research is at an early stage and that experimental approaches carry risks.

"People need to understand that these so-called cures come at real cost and real risk," he said in an interview earlier this year.

Only a handful of people worldwide have been considered cured of HIV, most of them after stem cell transplants to treat cancer. Those procedures are too dangerous to be used widely for HIV alone.

Immune-based approaches, by contrast, could potentially be simpler and more scalable, though researchers say they must be refined and tested in larger, more diverse groups of people.

Funding threats

The progress comes as U.S. support for HIV research and global AIDS programs faces significant cuts. Reductions in federal research grants and in international HIV assistance have raised concerns among scientists and public health experts about the future of the field.

Deeks and colleagues have written this year that the HIV/AIDS response "as we knew it is over," reflecting concerns about shrinking funding and shifting priorities.

Researchers warn that cuts could slow or halt clinical trials at a moment when the science appears to be advancing.

A global challenge

About 40 million people worldwide are living with HIV, most of them in sub-Saharan Africa. While antiretroviral therapy has saved millions of lives, many people struggle to access daily treatment or to take medication consistently for life.

A therapy that allows people to stay healthy without daily drugs could transform care, particularly in regions with limited access to health services.

Researchers plan larger studies to confirm the early findings, identify which patients are most likely to benefit and make the treatments safer and easier to deliver. Several trials testing combinations of antibodies, vaccines and immune-modulating drugs are underway or planned.

While a widely available cure remains years away, scientists say the latest results offer the strongest evidence yet that the immune system can be trained to control HIV, if research funding holds.