A new clinical trial shows that broadly neutralizing antibodies can suppress HIV for up to four months, far longer than currently available drugs. Though improvements in antiretroviral therapy, HIV is now a manageable condition. To remain healthy, people infected with HIV must therefore adhere to strict medication regimens, which typically involve ingesting pills every day for the rest of their lives.

New clinical trials from Rockefeller University researchers suggest that a novel immunotherapy, a combination of two anti-HIV antibodies, is capable of suppressing HIV for months at a time. The drugs, called broadly neutralizing antibodies or bNAbs (pronounced bee-nabbs), were found to be both safe and more effective than any previously tested antibody therapy. The results were published in Nature and Nature Medicine.

The power of antibodies

Antiretroviral therapy, the gold standard for HIV treatment, works almost perfectly in clinical trials. But in the real world, things are more complicated. Some patients neglect to take their meds, or lose access to healthcare. And inconsistency in treatment presents a risk not only to the person infected, but to the population at large: when the virus is not adequately controlled, the likelihood of transmission increases.

Nussenzweig, the Zanvil A. Cohn and Ralph M. Steinman Professor, initially identified the antibodies, known as 3BNC117 and 10-1074, while studying people whose bodies successfully combat HIV without the help of drugs. In these so-called "elite controllers," natural antibodies target proteins on the outside of the virus and recruit the body's immune system to combat infection.

The ultimate goal of bNAb therapy is to turn anyone taking the medication into an elite controller, effectively suppressing the virus through an enhanced immune response. These drugs have the added benefit of remaining in the body longer than antiretroviral drugs, and therefore should require less frequent administration.

As 3BNC117 and 10-1074 attack HIV from two different angles, the researchers suspected that administering the two drugs together might evade resistance — an approach first tested in animals. Following the success of these initial experiments, Nussenzweig and Caskey, an associate professor of clinical investigation, adapted the treatment for use in humans.

In their phase 1b clinical trial, published in Nature, participants stopped taking antiretroviral drugs and subsequently received three infusions of the two bNAbs over the course of six weeks. The researchers report that, among nine individuals who carried viruses that were sensitive to both antibodies, this treatment suppressed HIV for an average of 21 weeks and over 30 weeks in some patients.

The future of bNAbs

Caskey and Nussenzweig say that although combination therapy is very promising, bNAb treatments do have their limitations. The HIV virus comes in many varieties, not all of which respond to a given antibody.

"These two antibodies are not going to work for everyone," says Caskey. "But if we start to combine this therapy with other antibodies or with antiretroviral drugs, it could be effective in more people — and that's something we hope to look at in future studies."

The researchers believe that bNAbs have the potential to change not only how we treat HIV, but also how we prevent it. Currently, people at risk for contracting the virus can take preemptive antiretroviral medication. But that too requires daily dosing, and many people follow the regimen imperfectly. Like long-acting birth control, long-acting HIV medication would allow people to achieve the desired outcome without being perfect pill takers.

"If future studies are similarly successful, bNAbs could really become a practical alternative to ART," says Caskey, "an alternative that would be safe and wouldn't require a pill every day."