After getting off to a disappointing start that ultimately resulted in clinical trial abandonment, a new human study has led to renewed hope for the use of antibodies to treat HIV infection. After providing patients with different doses of these potent molecules, scientists found that they were not only well tolerated, but that they can also significantly reduce the amount of virus present in the blood. Researchers are now optimistic that this therapy could represent a novel and effective way to manage HIV infection, and may ultimately lead to a new preventative measure. The study has been published in Nature.
HIV is renowned for its ability to rapidly mutate, allowing it to evolve ways to escape virtually everything we throw at it, whether that be antiviral drugs or antibodies produced by our own immune system. But researchers have identified a possible strategy to avoid this inevitable outcome: target essential bits of the virus that would be disadvantageous for the pathogen to alter. Since antibodies can be designed to stick to virtually anything, researchers started to target different parts of the virus with these molecules and then tested them in various different scenarios.
Despite promising early results that showed they were indeed capable of neutralizing HIV, both pre-clinical and clinical trials revealed that these antibodies were largely ineffective as they were specific to a limited number of viral strains. But not all hope was lost as scientists later discovered the possibility of using a different generation of antibodies, known as broadly neutralizing antibodies, which are capable of potently targeting a wide range of strains. These antibodies are produced in around 20% of people with HIV, and many can even prevent infection and suppress active infection in mice and monkeys.
Having proven to be effective in animals, scientists from Rockefeller University decided to take the next step and investigate how they fare in infected humans. They chose to study a molecule called 3BNC117, which targets an outer part of the virus that is used to stick to host cells, and thus is necessary for HIV entry. Importantly, this antibody is active against 195 out of 237 HIV strains.
For the study, scientists administered varying single doses of this virus to both infected and uninfected patients and monitored their response for 56 days. Not only was the antibody well tolerated, but the highest dose administered was found to dramatically decrease the amount of virus present in their blood, reducing it by up to 250 times the original amount for 28 days. Furthermore, half of these individuals maintained viral loads below starting levels at the end of the trial, and no resistance was observed.
In addition to directly neutralizing the circulating virus, the researchers believe that antibodies such as this could also help boost the ability of our own immune system to fight the virus, which could lead to better control of infection. Although they have yet to gather evidence to support this, the team also hopes that these antibodies could target dormant HIV, which evades detection by our immune systems and thus represents a major hurdle in treatment.
While these early results are promising, it is currently unknown whether these antibodies will produce lasting effects. Furthermore, the extremely high price tag that comes with this therapy limits the people that could benefit from it, which is problematic given that the majority of infected individuals live in developing countries.
[Via Nature, Nature and Rockefeller University]
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