A small, highly anticipated study shows a glimmer of hope in the long effort to control HIV without medication and search for a cure for a virus that attacks immune cells.
Researchers gave 10 people with HIV a complex regimen of experimental immunotherapies, then discontinued the daily pills that kept the virus at bay. In six participants, the virus rebounded slowly and stayed at a low level for months, and one person’s immune system kept the virus in check for more than a year and a half — giving scientists hope that they could optimize the approach to create a cure.
“It’s provocative, but I’ve been doing treatment interruption studies for 30 years, and this is unexpected and unparalleled,” said Steven Deeks, a professor of medicine at University of California at San Francisco and one of the leaders of the study. He and other scientists were quick to caution that this is a promising step forward, not a solution. The small study did not include a control group, so more studies will be needed to confirm and flesh out the exciting signal.
“I am very excited about the findings. The study, although small, will drive new directions in the field,” Sharon Lewin, director of the Doherty Institute at the University of Melbourne, wrote in an email. “This is something the field urgently needs.”
About 40 million people are living with HIV worldwide, according to the World Health Organization. Antiretroviral drugs that prevent HIV and keep it in check have been transformative, but a cure is a long-sought goal. Managing HIV with medications requires people to take drugs for their entire lives, which means they need consistent health care and access to medications.
Tom Perrault, 60, had been taking a daily pill since 2005. He participated in the UCSF trial and, after receiving a “kitchen sink” of immunotherapies, stopped taking his daily medication in early July 2021.
“It didn’t come back in July, didn’t come back in August, didn’t come back in September, didn’t come back in October,” Perrault recalled. “All of a sudden, I was like: ‘My body is suppressing it. I think it’s working. This is exceeding their expectations.’”
He was boarding a plane that November to fly home to spend Thanksgiving with family when he saw a missed call from doctors at UCSF. His heart sank. He called them when he landed in Virginia, only to learn that the virus had rebounded. Despite the setback, he says the study was a revelation.
“I was surprised by the level of emotion,” Perrault said. “All of a sudden, I dared hope. You want to hope. What a gift this will be for the world if and when this would work.”
A way to make immune cells ready to pounce
The new study published Monday in Nature, along with two others, highlight the paths scientists are pursuing toward finding an HIV cure.
Researchers in Germany detail a case study of the seventh-known person to go into long-term remission from HIV after receiving a bone marrow transplant. Since 2009, when the first “Berlin patient” was apparently cured of HIV after a transplant to treat leukemia, these cases have seized the world’s attention because they show what is possible. But bone marrow transplants are risky procedures, and a cure depends on donors who carry a rare mutation that blocks the HIV virus ability to enter immune cells.
Yet another paper focuses on untangling the biological reason that some people who have HIV, and take an experimental treatment that targets the virus, are able to control the virus long-term, without additional medication.
The trial led by Deeks was an intensive experiment, requiring about 60 clinic visits over two years, and the cooperation of multiple research groups and pharmaceutical companies. It pooled together three immunotherapy approaches — drugs that ignite and shape a person’s immune response.
“This has been a long-anticipated study, and it has kept the field watching closely,” said Javier Martinez-Picado, a research professor at IrsiCaixa, an HIV research institute based in Barcelona. In an email, he said the results were exciting and highly promising, because they are a proof of concept that can increase scientists’ understanding of what allows some people to control the virus after treatment is stopped.
First, people received an experimental vaccine aimed at triggering immune cells called T cells to fight the virus in their bodies. Then, they received two broadly neutralizing antibodies — drugs that target HIV and have been tested also for HIV prevention — plus a drug to activate the immune system. Then, they received another round of antibodies, and they stopped taking daily pills to keep the virus in check.
The approach was tested in a monkey study that showed the majority of animals controlled the simian version of HIV.
“The idea is that if you increase immunologic control of virus, then you might be able to prevent or slow viral rebound after you stop antiretroviral therapy,” said Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center. He led the primate study. His lab is also running a clinical trial testing combinations of immunotherapy in people, and expects to report results next year.
Barouch noted that because of the lack of control group, it was not conclusive that the rebound was slower in the six people in the San Francisco study. But he said what was most intriguing to him was that the researchers found that those patients who appeared to partially control the virus had an early response in a specific population of T cells.
“They were ready to pounce on the virus as it was coming out,” said Rachel Rutishauser, an immunologist and infectious-disease doctor at UCSF and a leader of the study. “We’re not advocating that this is the therapeutic regimen to take into the clinic. … We can start to learn and how can we make the T cells better.”
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