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Jonah Sacha, Ph.D.
Photo Credit: OHSU/Christine Torres Hicks
Scientific Frontline: Extended "At a Glance" Summary: Triple-Dose HIV Regimen for Newborns
The Core Concept: A one-time, three-part therapeutic regimen administered within 72 hours of birth that demonstrates the potential to permanently clear HIV infection in exposed newborns.
Key Distinction/Mechanism: Unlike standard treatments that only suppress the virus, this approach combines three distinct mechanisms to achieve clearance: antiretroviral therapy minimizes active viral replication, neutralizing antibodies corral circulating virus in the bloodstream, and the monoclonal antibody leronlimab blocks residual HIV from entering immune cells by sealing off the CCR5 surface receptor.
Major Frameworks/Components:
- Antiretroviral Therapy (ART): Standard treatment utilized to halt and minimize active viral replication.
- Broadly Neutralizing Antibodies: Immune proteins deployed to capture and reduce the volume of virus circulating within the blood supply.
- CCR5 Blockade: Application of leronlimab, an experimental monoclonal antibody, to inhibit HIV from accessing the CCR5 surface protein on immune cells.
- Critical Window of Efficacy: Treatment requires administration within a strict three-day (72-hour) window following initial viral exposure.
Branch of Science: Virology, Immunology, Pathobiology, and Neonatology.
Future Application: Immediate progression to human clinical trials to eliminate HIV in exposed newborns, with subsequent trials planned to evaluate efficacy in newly exposed adults.
Why It Matters: With over 120,000 newborns contracting HIV annually and requiring lifelong care, this combined regimen transitions neonatal intervention from chronic viral suppression to a potential permanent cure, offering a critical new tool to constrain the global epidemic.
Research from the lab of Jonah Sacha, PhD, at OHSU, has identified a one-time regimen of therapies for newborns with HIV that, if given within three days of birth, could permanently clear the virus. The research team hopes to use the animal model results to move into human clinical trials.
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 really exciting part is that it could go to clinical trials immediately to eliminate HIV infection in newborns,” said co-lead author Jonah Sacha, PhD, professor and chief of pathobiology and immunology at OHSU’s Oregon National Primate Research Center and Vaccine and Gene Therapy Institute. “The next step after that is to test if this can work in newly exposed adults.”
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.
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| Nancy L. Haigwood, Ph.D. Photo Credit: OHSU/Christine Torres Hicks |
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, PhD, thought combining existing therapies with leronlimab might be effective.
The study 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 for human use, 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 humans—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 humans.
“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 works 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 bloodstream.
- Sealing off: Leronlimab blocks what’s left of the virus from infecting immune cells—the equivalent of sealing off the room with a watertight 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 after 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?”
Funding: Supported by the National Institutes of Health under award numbers R01HD080459 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); R01AI154559, R01AI166969, and R01AI129703 from the National Institute of Allergy and Infectious Diseases (NIAID); K01OD036063 from the Office of the Director (OD), NIH; P51OD011092 and U42OD010426 from the Office of Research Infrastructure Programs (ORIP), NIH, to the Oregon National Primate Research Center; and P51OD011107 from ORIP, NIH, to the California National Primate Research Center.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Published in journal: Nature Microbiology
Authors: Jonah B. Sacha, Tracy Ordonez, Shilpi Pandey, Gabriela Webb, Philip Barnette, Cleiton Pessoa, Matthew C. Humkey, Jason Reed, Anden Morehead, Jennifer K. Watanabe, Jodie L. Usachenko, Shrivaas Vijayan, Altair Fazio, Heather Sidener, Anne D. Lewis, Gabrielle Pastenkos, Sohita Ojha, Aaron Barber-Axthelm, Bella Swan, Rachele Bochart, John R. Mascola, Amarendra Pegu, Emily J. Fray, Rachael M. Wolters, Janet D. Siliciano, Robert F. Siliciano, Scott G. Hansen, Koen K. A. Van Rompay, Ann J. Hessell, and Nancy L. Haigwood
Source/Credit: Oregon Health & Science University | Erik Robinson
Edited by: Scientific Frontline
Reference Number: vi081026_01
