Every year, more than 120,000 newborns worldwide contract HIV, a global health burden that requires lifelong treatment for millions of people - assuming they have access and can afford it.

New research led by Oregon Health & Science University suggests another possibility: a one-time regimen of therapies given to newborns within three days of birth to permanently clear the virus.

The research was published today in the journal Nature Microbiology.

The really exciting part is that it could go to clinical trials immediately to eliminate HIV infection in newborns. The next step after that is to test if this can work in newly exposed adults."

Jonah Sacha, Ph.D., co-lead author, professor and chief of pathobiology and immunology at OHSU's Oregon National Primate Research Center and Vaccine and Gene Therapy Institute

The research involved many collaborators and nonhuman primates at both the Oregon and California national primate research centers.

Researchers tested three distinct treatments that were delivered for a few weeks: neutralizing antibodies, standard antiretroviral therapy, and an experimental monoclonal antibody known as leronlimab.

Each of the individual treatments has been tried previously and failed to permanently clear the virus - and Sacha wasn't convinced combining them would work any better. Sacha has worked for years to develop leronlimab, which is designed to block HIV from entering immune cells through a surface protein called CCR5. His longtime OHSU colleague and coauthor Nancy Haigwood, Ph.D., thought combining existing therapies with leronlimab might be effective.

The study that published today shows she was correct.

Haigwood, a former professor and ONPRC director, is a virologist and immunologist who has specialized in HIV antibody research for decades.

"We were astounded and overjoyed, actually," Haigwood said. "It's a remarkable result."

Antiretroviral therapy has already been approved in people, whereas broadly neutralizing antibodies and leronlimab are both being tested separately in clinical trials. This new discovery of a one-time, three-part regimen to clear the virus in newborn babies would first need to be tested in clinical trials in people - most likely in newly exposed adults initially - before it would be widely available to constrain an HIV epidemic that continues to kill 600,000 people worldwide each year.

Researchers say they are optimistic, given the anatomical similarity between nonhuman primates and people.

"There was no reason to think this would completely clear the virus," Sacha said. "It's one of those things where you test it and, holy cow, it works and you've discovered something new."

Exactly how this approach worked remains unclear, but Sacha and Haigwood said it appears that the combination of therapies is far more potent and effective than each therapy alone. The key appears to be leronlimab's ability to block HIV from entering immune cells through the surface protein CCR5.

"For reasons we don't understand, HIV really wants to use CCR5 receptors to infect cells," Sacha said. "By blocking access, it's like you've kept fuel away from the fire."

Haigwood uses a slightly different analogy:

• Turning off the faucet: Antiretroviral therapy doesn't eliminate HIV altogether, but it minimizes its ability to replicate.
• Mopping up: Neutralizing antibodies effectively corral HIV so there is less virus circulating in the body's blood supply.
• Sealing off: Leronlimab blocks what's left of the virus from infecting immune cells - the equivalent of sealing off the room with a water-tight valve.

Haigwood believes the combination appears to be especially potent early in the infection.

"There's a lot more going on during the first week of infection than we previously thought," she said. "From this experiment, it looks like there's a dynamic interaction between the virus and antibodies that takes place as the virus begins to spread."

Researchers are eager to see whether the combined regimen can be effective beyond 72 hours of the initial infection.

"We only tested out to three days," Sacha said. "Could it work a week after infection? Two weeks? How far can you go after infection, and still purge the virus?"