Triple-Dose Regimen May Permanently Clear HIV in Newborns, Primate Study Shows
核心洞察
A one-time triple combination of antiretroviral therapy, broadly neutralizing antibodies, and leronlimab cleared HIV (搜索) in newborn macaques when given within three days of infection.
The study, published in Nature Microbiology, showed the regimen prevented viral reservoir seeding—an outcome no single therapy had achieved alone.
Researchers at Oregon Health & Science University say the approach could move directly into clinical trials, initially in newly exposed adults, before testing in newborns.
More than 120,000 newborns worldwide contract HIV (搜索) each year, and for those who survive, the standard of care is lifelong antiretroviral therapy—assuming they have access and can afford it. Now, a study led by Oregon Health & Science University (OHSU) suggests a radically different possibility: a one-time, three-part regimen administered within days of birth that may permanently clear the virus.
Published in Nature Microbiology, the research demonstrates that combining standard antiretroviral therapy, broadly neutralizing antibodies (bNAbs), and the experimental monoclonal antibody leronlimab prevented the establishment of persistent HIV (搜索) infection in infant macaques. The findings remain preclinical, but the anatomical and immunological similarity between nonhuman primates and humans gives researchers confidence that the strategy could translate.
"The really exciting part is that it could go to clinical trials immediately to eliminate HIV (搜索) infection in newborns," said co-lead author Jonah Sacha, Ph.D., 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."
A layered attack on early infection
Each component of the regimen was designed to interrupt a different stage of HIV (搜索)'s spread. Antiretroviral drugs suppress viral replication by targeting enzymes required for production of new virus particles. Broadly neutralizing antibodies bind to vulnerable regions on the viral surface, blocking infection by multiple HIV variants and helping recruit immune cells to remove antibody-coated virus. Leronlimab adds a third layer by binding to CCR5 (搜索), the surface protein that many HIV strains use as a coreceptor to enter immune cells.
Nancy Haigwood, Ph.D., a virologist and immunologist who has specialized in HIV (搜索) antibody research for decades and served as co-author, described the combination using an analogy: antiretroviral therapy "turns off the faucet" by minimizing replication; neutralizing antibodies "mop up" circulating virus; and leronlimab "seals off" what remains by blocking viral entry into immune cells.
Each of the individual treatments had been tested previously and failed to permanently clear the virus. Sacha was not convinced combining them would work any better—but Haigwood thought otherwise. The study proved her correct.
"We were astounded and overjoyed, actually," Haigwood said. "It's a remarkable result."
The reservoir problem
The findings address a central obstacle in HIV (搜索) medicine: the virus can integrate its genetic material into the DNA of infected cells soon after exposure, creating latent reservoirs largely invisible to both the immune system and conventional antiretroviral drugs. Once established, stopping therapy allows the virus to rebound. Preventing or sharply reducing reservoir seeding during the earliest phase of infection could therefore be more effective than attempting to eliminate mature reservoirs later.
"For reasons we don't understand, HIV (搜索) really wants to use CCR5 (搜索) receptors to infect cells," Sacha said. "By blocking access, it's like you've kept fuel away from the fire."
Haigwood noted that the combination appears especially potent early in 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."
Open questions and next steps
The precise biological mechanism behind the apparent clearance is not yet fully understood. The investigators reported that the treatment prevented or greatly restricted reservoir seeding, but further work will be needed to determine whether all replication-competent virus was eliminated or whether residual virus remained below the limits of detection.
The timing question is especially critical for clinical use. Newborns exposed to HIV (搜索) may not be identified immediately, and the circumstances of exposure vary widely. "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?"
Antiretroviral therapy is already approved for human use, while bNAbs and leronlimab are being evaluated separately in clinical research. The researchers plan to investigate whether the combination can work when given one or two weeks after infection and whether the approach could benefit adults who have recently acquired HIV (搜索), when viral reservoirs may still be relatively limited.
The study was supported by multiple National Institutes of Health institutes, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, and the Office of Research Infrastructure Programs. OHSU disclosed that Sacha and co-author Scott Hansen, Ph.D., have significant financial interests in CytoDyn (搜索), a company that may have a commercial interest in the research and related technology.
HIV (搜索) continues to cause approximately 600,000 deaths worldwide each year, and access to lifelong treatment remains uneven. A safe, single-course intervention for newborns could substantially reduce the burden of pediatric HIV, particularly in settings where continuous treatment is difficult to maintain.