A First Human Trial Shows Promise for a New HIV-Fighting Antibody

HIV gets its power through adaptation. It's easy enough to hurt the virus, give it a wicked black eye, but to really do something about it means anticipating HIV's ability to mutate and adapt to new threats. Show up with a sword, and the next version of the virus will boast a suit of armor. And HIV is able to adapt faster than pretty much any other known form of life.

This week, researchers at Rockefeller University are unveiling results for the first human trials of a new generation of so-called broadly neutralizing antibodies. The results are published in the current edition ​of Nature.

A single HIV virus is capable of spawning billions of copies per day. It do​es this "sloppily," which means that a whole lot of those copies are in essence bad copies: mutations. Every mutation is an opportunity, however, to produce a version of the virus that's resistant to the antibodies produced by the body's own immune system and to any antibodies that we might introduce in drug form. This is why HIV is treated with what's known as a drug cocktail: The chances that the virus might become resistant to one drug are pretty good, but many drugs at once, not so much.

This basic principle has, since the advent of highly-active antiretroviral therapy (HAART) in the 1990s, saved many millions of lives. But it's hardly perfect.

A broadly neutralizing antibody is a bit what it sounds like: A single drug that hits HIV on multiple fronts at once by fighting many different strains. The basic idea is that the surface of a virus particle is set up with an array of different "binding sites," which are just spots on the virus capable of creating chemical bonds with target immune cells. These bonds are the first step in the process of immune cell hijacking, by which HIV particles turn healthy cells into new HIV factories. An antibody in this case works by binding to those sites itself, taking away the virus particle's ability to bind to an immune cell.

The antibody tested by the Rockefeller group, known as 3BNC117, hits the CD4 binding site. This is actually a capability the body's own immune system can develop, and 10 to 30 percent of patients actually do start making these antibodies naturally. But it takes several years to happen and, by then, it's too late to do as much good. 3BNC117 offers a head start.

Broadly neutralizing antibodies had already been successful in mouse and primate models, but this is the first test within human populations: 12 uninfected and 17 HIV-1-infected individuals. "3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics," the Nature study reports. The virus was suppressed for 28 days in the trial, meaning the antibody reduced the amount of HIV-1 in the blood.

"In contrast to conventional antiretroviral therapy, antibody-mediated therapy can also engage the patient's immune cells, which can help to better neutralize the virus," offered the study's co-first author, Florian Klein, in a separate statement.

The promise is not of a cure so much as a new treatment. Rather than the daily regimen of pills HIV patients are required to take now, something like 3BNC117, which has so far shown few side effects, might be effective if taken monthly. However, it would most likely need to be combined with other antibodies or drugs as using just one antibody could lead to resistance.

In addition to a treatment, it also hints at the promise of a vaccine: If 3BNC117 is already floating around in someone's system when HIV is first introduced, it might prevent the virus from ever getting a foothold.