Innovative Therapy Combination Shows Potential to Permanently Eliminate HIV in Newborns

More than 120,000 babies worldwide are diagnosed with HIV each year. A new study from Oregon Health & Science University (OHSU) reveals that a combination of therapies administered within three days of birth may lead to a permanent elimination of the virus. The research findings were published in Nature Microbiology.

According to co-lead author Jonah Sacha, Ph.D., who is a professor and chief of pathobiology and immunology at OHSU’s Oregon National Primate Research Center, the research is poised to move into clinical trials for newborns. “The really exciting part is that it could go to clinical trials immediately to eliminate HIV infection in newborns,” he stated, adding that the next step is to assess its effectiveness in recently exposed adults.

Research Methodology

The study involved collaboration among numerous researchers and included nonhuman primates at both OHSU and California’s national primate research centers. For several weeks, the team administered a combination of three therapies: neutralizing antibodies, standard antiretroviral therapy, and an experimental monoclonal antibody known as leronlimab.

Despite individual testing of these approaches not successfully clearing the virus before, the combination yielded unexpected results. Sacha initially doubted that simply combining them would enhance efficacy but acknowledged the possibility when longtime collaborator Nancy Haigwood, Ph.D., suggested pairing leronlimab with existing HIV therapies.

Haigwood expressed her excitement about the positive results: “We were astounded and overjoyed, actually. It’s a remarkable result.”

Path Forward for Human Trials

While standard antiretroviral therapy is already approved for human use, the newly identified three-part treatment must undergo human clinical trials before becoming available for newborns. The researchers predict that initial human studies will likely focus on adults recently exposed to HIV. If successful, this strategy aims to provide a new avenue to combat an ongoing epidemic that claims approximately 600,000 lives annually worldwide.

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

Mechanisms of Action

The exact reasons for the success of the combined treatment remain unclear. However, Sacha and Haigwood observed that the therapies appear to have a synergistic effect when used together. Leronlimab, which blocks a surface protein known as CCR5 that HIV utilizes to enter immune cells, may play a critical role in this efficacy.

Leronlimab’s blocking mechanism can be likened to “keeping fuel away from the fire,” according to Sacha. Haigwood offered another analogy for the three therapies: antiretroviral therapy acts like turning off a faucet to limit virus replication, neutralizing antibodies work to “mop up” circulating HIV, and leronlimab acts to “seal off” what remains of the virus from entering immune cells.

Timing of Treatment

Haigwood believes the treatment may be most effective when administered shortly after infection. She noted that the initial week of infection is more dynamic than previously understood, highlighting that a complex interaction occurs between the virus and antibodies during this period.

The researchers intend to explore the duration of this critical treatment window further, as the combined regimen was tested only within 72 hours post-infection. “We only tested out to three days,” Sacha explained. “Could it work a week after infection? Two weeks? How far can you go after infection, and still purge the virus?”

Understanding these parameters may broaden the potential benefits of the combined therapy for various individuals.

Research Funding

The study received support from the National Institutes of Health under several award numbers, including R01HD080459 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and multiple grants from the National Institute of Allergy and Infectious Diseases, among others. The findings reflect the independent research of the authors and do not necessarily represent the official views of the NIH.