Strong antibodies suppress HIV for months, could simplify treatment | Science

Anti-HIV drugs have prevented millions of AIDS-related premature deaths, but people need to take the pills every day for life. Now, two studies in a small number of people show for the first time that infusions of two potent anti-HIV antibodies can completely kill the virus for several months. If the results prove to be important in larger studies, they could simplify the treatment of people who have difficulty taking daily medications, reduce the risk of developing drug resistance and even drug resistance. reduce HIV transmission rates.

"It's a really exciting breakthrough," says Katharine Bar, a clinical virologist from the University of Pennsylvania who was not involved in this work. Bar is particularly encouraging because she conducted two similar studies with a single antibody that had only a lasting impact: resistant viruses quickly emerged. These failures, coupled with disappointing results in animal studies, led some on the ground to think that the strategy had no merit.

Immunologist Michel Nussenzweig of the Rockefeller University of New York asked if the antibodies needed more muscle. He and his colleagues administered infusions of two antibodies that contained more Wallop than Bar's unique antibody. As they show today in published studies in Nature and Medicine of nature, the strategy has been successful for most people in two trials.

Nussenzweig and colleagues have selected two antibodies that both have more potency than the one previously tested and can "neutralize" a wider range of HIV variants. These so-called largely neutralizing antibodies occur naturally in some HIV-infected people who have had uncontrolled infections for several years, but at this stage the antibodies have little control over the infection. The study published in Nature tested three infusions of antibodies on 11 people who suppressed their infections with antiretroviral drugs (ARVs) that paralyzed HIV and then stopped taking their medications. the Medicine of nature The article describes a trial involving seven people who were not on treatment and who had relatively high rates of virus in the beginning.

In the first study, nine of the eleven people who stopped antiretrovirals suppressed the virus below standard test detection levels for an average of 15 weeks before HIV rebounded. The analyzes showed that the two individuals whose virus had initially rebounded had HIV variants resistant to both antibodies at the start of the trial. Curiously, two of the participants remained without ARV for a year without the virus bouncing.

The antibodies were less effective in people who started having high levels of the virus, but four of the seven participants inhibited HIV for about three months. People who had not yet responded to the infusions had viruses that avoided antibodies. "In the end, it may not be good for everyone and it's expensive. But if you think about cancer, we have really made a big difference with immune therapies, "says Nussenzweig. "For HIV, there is no such thing."

Steven Deeks, who specializes in HIV cure research at the University of California at San Francisco, says he is particularly curious about the two trial participants who still have no ARV treatment. He points out that, for unexplained reasons, a small percentage of people stop ARVs and control their infections for years, and these two trial participants might just be part of this lucky group. Or it may be that the antibody treatment has an effect called "vaccine effect" that lasts much longer than the life of the antibodies.

Deeks points to an earlier study of monkeys with these antibodies that suggested a vaccine effect. In this experiment, conducted by virologist Malcolm Martin of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and co-authored by Nussenzweig, six animals infected with a monkey version of the AIDS virus controlled the disease. 39 infection for more than two years … much longer than the antibodies last. Researchers have shown that the virus comes back when they have depleted a type of T cell in monkeys, which helps the immune system to eliminate HIV-infected cells.

This suggested that when the antibodies became fixed on the virus, the immune system developed strong T-cell responses that persisted. In fact, the antibody treatment inadvertently provided long-term protection by suppressing the immune system. "That's the profile we all want to create in our patients right now, and that gives us a viable and testable strategy that could work for at least some people," says Deeks.

Nussenzweig says that there is still a lot of work to be done before the HIV treatment of HIV infection proves its value. In addition to improving people's ability to see who is most likely to respond to treatment, his group modifies the antibodies so that they last longer in the body. Nussenzweig predicts that it will soon have antibodies that will work for almost a year. "It's long, long," he says. Studies combining antibodies with a larger number of patients are being planned.