Next-Gen HIV Treatment

Antiretroviral therapy (ART) turned HIV from a death sentence into a manageable condition that allows most individuals to enjoy a typical lifespan. But achieving that longevity usually requires taking one or more medications every day for a lifetime.

Broadly neutralizing antibodies (bNAbs) could be one tool in the next frontier of HIV treatment and prevention, with the potential to provide yearlong protection using a single dose. But questions remain: How much should be given? How often? How does viral load affect dosing strategy?

A new study led by pharmacy researchers at the University at Buffalo takes a big step toward answering those questions, bringing these promising therapeutics closer to clinical use.

Some people with HIV can maintain undetectable viral loads and normal immunity without medication. “We call them elite controllers,” says Qing Ma, associate professor of pharmacy practice at UB and senior author of the study. When researchers studied the blood of some of these individuals, they found that it contained bNAbs. 

Over the years, these powerful antibodies have been engineered in the lab to give them even more potency, longevity and breadth of neutralization.

“BNAbs are highly engineered to recognize and remove HIV from the body,” explains Nicholas Smith, assistant professor of pharmacy practice and first author of the study. “Previous studies have shown they can reduce viral loads in patients, but researchers have struggled to understand exactly how to best utilize this type of medicine.” 

That dosing information is exactly what the UB-led study set out to learn, focusing on a particularly promising bNAb called VRC07-523-LS.

The team combined pharmacokinetic modeling with AI, specifically a genetic algorithm, to determine the impact of viral load on dosing. What they found was that the antibody is cleared from the body more slowly when HIV is suppressed, while it can be eliminated more than six times faster than normal at high viral loads.

In other words, people with an active HIV infection may need higher or more frequent dosing, while people who have well-controlled HIV might need less frequent treatment.

“The hope is that just one injection of future versions of these antibodies can be an additional tool to provide protection for more than a year for people who have well-controlled HIV or who are at risk for contracting HIV,” Smith says, noting that reducing the frequency of treatment would not only make it easier for patients and health providers to control the virus, but would serve as both a time- and a cost-saving measure.

 “This could be the future of HIV management.”