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Anti-HIV antibody treatment promising in early experiments

[September 27, 2018] By Lisa Rapaport

(Reuters Health) - People living with HIV might someday be able to combat the virus with twice-a-year infusions of anti-HIV antibodies instead of daily antiretroviral pills, two preliminary experiments suggest.

The studies were extremely small - just seven patients in one, and nine in the other. And they only show that the anti-HIV antibodies have potential, not that they actually work. Larger, longer trials are needed to see whether this new treatment is safe and effective. Even then, it might take years for a new medicine to reach the market.

But the idea is tantalizing because daily pills that are currently the backbone of HIV treatment require a lifetime commitment. These pills stop working when patients stop taking them, which can happen when the medications are unaffordable, unavailable or cause serious side effects.

"If the larger trial with modified antibodies produces the expected results, they would be given once every six to nine months," said Dr. Michel Nussenzweig, senior author of both studies and a researcher at the Howard Hughes Medical Institute at Rockefeller University in New York City.

"This is helpful for people who forget to take their pills," Nussenzweig said by email. "In addition, the antibody is a natural product cloned from a human being and . . . so far it has few detectable side effects."

In the studies, scientists deployed two antibodies, called 3BNC117 and 10-1074, which had been identified by examining rare individuals whose bodies successfully combat HIV without the help of drugs. The two antibodies target proteins on the outside of the virus from two different angles, and recruit the body's immune system to combat infection.

Some cancer medicines use a similar approach to attack tumors by harnessing the immune system, but this approach hasn't yet been proven safe and effective for people with HIV.

For one of the experiments, nine HIV-positive patients stopped taking daily antiretroviral pills and then received three infusions of the two anti-HIV antibodies over the course of six weeks.

The duration of viral suppression ranged from 15 to more than 30 weeks, researchers report in Nature. In half of the patients, HIV was suppressed for at least 21 weeks.

Some patients reported mild fatigue, but there were no serious side effects.

One drawback of this experiment was that participants didn't have HIV circulating in their blood because they had been taking antiretroviral pills.

A second experiment focused on seven people who had been diagnosed with HIV but were not currently taking antiretrovirals, so the virus was circulating in their blood.

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Researchers included people who had variants of HIV that might respond to the anti-HIV antibodies. Participants received either a single infusion with both antibodies or three infusions of both antibodies across six weeks.

After treatment, participants had significantly reduced levels of HIV in their bloodstream for up to three months, researchers report in Nature Medicine.

One problem that has vexed HIV researchers is the potential for the virus to morph into drug-resistant versions when it's exposed to treatments. In the current experiment, none of the participants developed resistance to both antibodies.

As with other HIV treatments, however, it's still possible patients might stop responding to these antibodies in the future, noted Dr. Anthony Moody, a researcher at Duke University in Durham, North Carolina, who wasn't involved in the studies.

"Both antiretrovirals and the antibodies are only effective against HIV-1 strains that are susceptible, so if someone has resistance already, or comes into contact with resistant viruses, the medications may not be effective," Moody said by email.

Still, so-called broadly neutralizing antibodies like the ones tested in these two experiments have the potential to suppress the virus, which can currently be accomplished by daily antiretroviral pills, and also to clear virus-infected cells from the body, said Dr. Katharine Bar, a researcher at the University of Pennsylvania in Philadelphia who wasn't involved in the study.

"Antiretrovirals suppress HIV replication, but they aren't able to clear the virus-infected cells that remain hidden," Bar said by email. "Broadly neutralizing antibodies are able to target HIV-infected cells, and therefore have the potential to be a part of a cure strategy."

SOURCE: https://go.nature.com/2wx9QPa Nature and https://go.nature.com/2JURUUl Nature Medicine, online September 26, 2018.

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