First human study of new HIV antibody therapy shows promise
“This is an early study, but it’s a study with some impressive results,” says Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases.
By James McIntosh
A study trialing a new generation of broadly neutralizing antibodies in humans for the first time has shown promise as a treatment for HIV, according to researchers.
The results of the clinical trial, published in Nature, have been more successful than previous HIV antibody tests in humans, with the researchers finding that their experimental therapy can reduce the amount of virus present in a patient’s blood significantly.
“What’s special about these antibodies is that they have activity against over 80 percent of HIV strains and they are extremely potent,” says co-first author Marina Caskey, an assistant professor of clinical investigation in the Nussenzweig Laboratory of Molecular Immunology at the Rockefeller University, New York, NY.
The antibody in question is 3BNC117, and it has shown activity against 195 of the 237 HIV strains. 3BNC117 works by targeting the CD4 binding site of the HIV viral envelope; the CD4 receptor is the main site of attachment of HIV to host cells.
Around 10-30 percent of humans with HIV naturally produce broadly neutralizing anti-bodies, but these only tend to develop several years after infection. During this time, the virus is able to evolve, changing shape to protect itself from the antibodies.
Isolating and cloning these antibodies allows the researchers to deliver them instead as therapeutic agents, administering them against HIV infections before the virus is able to evolve. This process is known as passive immunization.
The antibody showed success when used in mouse and non-human primate models of HIV, leading the team to commence human trials.
For the study, the researchers tested four different doses of 3BNC117 on a total of 29 participants. Each was given a single dose of the antibody and monitored for the next 56 days. Of these participants, 17 had HIV and 15 of these participants did not take any antiretroviral medication for the duration of the study.
Among the eight participants that received the highest dose of the antibody – 30 mg per kg of weight – the researchers found
that the amount of virus in the blood was reduced by 8-250 times for a period of 28 days.
It is likely 3BNC117 will need to be used in combination with other antibodies or drugs
A single dose of the antibody was well tolerated by each participant and was successful at temporarily reducing viral loads. The viral loads of some participants remained below starting levels even at the end
of the study period.
However, the researchers noted that in two of the participants receiving the highest dose of 3BNC117, the antibody became approximately 80 percent less effective in neutralizing the virus after 28 days of treatment. This reduction may have been due to the virus evolving in order to evade the anti-body.
“One antibody alone, like one drug alone, will not be sufficient to suppress viral load for a long time because resistance will arise,” says Caskey. Like many other antiretroviral drugs, it is likely that 3BNC117 will need to be utilized in combination with other antibodies or drugs.
The research group have developed a second HIV antibody and plan to test it both alone and in combination with 3BNC117 in the future. “The goal is a once-a-year shot for prevention and a combination approach for cure,” states lead author Michel Nussenzweig, an infectious disease physician and immunologist at the Rockefeller University.
In addition to these findings, the study also raises hopes for a future HIV vaccine. By inducing an uninfected individual’s immune system to create these kinds of antibodies, researchers could prevent HIV infections before they take hold.
“In contrast to conventional antiretroviral therapy, anti-body-mediated therapy can also engage the patient’s immune cells, which can help to better neutralize the virus,” says co-first author Florian Klein, also an assistant professor of clinical investigation in the Nussenzweig laboratory.
Recently, Medical News Today reported on a study from the University College London in the UK in which experts have created a new model for HIV progression, noting that the method by which HIV spreads through the body is akin to the spread of Internet malware.