A combination of two anti-HIV antibodies is capable of suppressing HIV for months at a time.
Antiretroviral therapy (ART) has come a long way, making an HIV diagnosis today a manageable condition. Although effective, ART is not a cure. In addition, there are barriers to correct usage. In order to maintain effective treatment, and keep the viral titer low, a patient must stick to a strict regimen of multiple pills every day.
New results from clinical trials suggest that a novel antibody-based treatment has the potential to target HIV, for both treatment and prevention. The results of testing this novel immunotherapy in humans are published in two papers titled “Combination therapy with anti-HIV-1 antibodies maintains viral suppression” published in Nature and a related paper in Nature Medicine titled “Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals.”
The work was a collaboration of Marina Caskey, M.D., early phase physician scientist and Michel Nussenzweig, M.D., Ph.D., Zanvil A. Cohn and Ralph M. Steinman professor, both at The Rockefeller University; and Florian Klein, M.D., M.Sc., professor and director, institute of virology at the University Hospital Cologne, Germany.
The work reports a Phase Ib clinical trial in which a combination of two potent monoclonal anti-HIV-1 broadly neutralizing antibodies (or bNAbs), 3BNC117 and 10-1074, that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption.
Participants in the trial stopped taking antiretroviral drugs and subsequently received three infusions of the two bNAbs over the course of six weeks (at 0, 3, and 6 weeks.) Among nine individuals who carried viruses that were sensitive to both antibodies, the treatment suppressed HIV for between 15 and 30 weeks, with an average of 21 weeks. In addition, patients with active viremia saw a significant reduction in viral titer for three months. Moreover, participants experienced no major side effects, the most significant reaction being mild fatigue in a small portion of patients.
The novel immunotherapy was shown to be capable of suppressing HIV for months at a time. Additionally, the drugs were found to be both safe and more effective than any previously tested antibody therapy.
The antibodies were first identified in people, referred to as “elite controllers” who produce natural antibodies that successfully fight off HIV infection without treatment. The idea behind using the bNAb therapy is to turn people into elite controllers, by administering the antibodies that fight off the virus.
Using two antibodies at the same time was done to combat the viruses inevitable mutations that could lead to resistance, rendering the therapy ineffective. Indeed, the researchers report that the patients receiving combination therapy did not develop resistance if their viruses were sensitive to the antibodies. In addition, the antibodies remain in the body longer than ART.
Although very promising, Dr. Caskey says that “These two antibodies are not going to work for everyone.” Dr. Nussenzweig adds that, over time, bNAb therapy could prompt the body to produce HIV-fighting antibodies on its own. “Like some anticancer antibodies, these drugs could interact with the host immune system to boost natural immunity,” he says.
Dr. Nussenzweig adds that continued research may lengthen the amount of time that these drugs are effective. Although four months is an impressively long time, this could potentially become even longer with new bNAb variants, revolutionizing how HIV is treated and prevented. “If future studies are similarly successful, bNAbs could really become a practical alternative to ART,” says Dr. Caskey, “an alternative that would be safe and wouldn't require a pill every day.” A long-acting HIV medication that is both a treatment and a prevention could alter the status of the HIV epidemic as we know it.
