Keeping HIV at bay: New approach explores broadly neutralizing antibodies to treat infants

by Delthia Ricks, Medical Xpress

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In the ongoing effort to find new therapeutics for infants born infected with the human immunodeficiency virus, an international team of investigators has discovered that babies can tolerate treatment with anti-HIV antibodies.

While the first studies in adults involving anti-HIV antibodies were conducted in the late 1990s, it has taken until now for medical investigators to test the feasibility of an antibody strategy for babies as young as 12 weeks.

Conducting their research on three continents—North America, Africa and Asia—researchers hoped to cripple one of the worst aspects of the human immunodeficiency virus: its ability to become a dormant stowaway in key immune cells. This insidious trick allows the virus to remain thoroughly concealed—often for years. But it can unexpectedly reactivate and reboot the infection cycle.

"Despite advances in perinatal HIV prevention, 130,000 infants acquire HIV annually and 1.5 million children live with HIV globally," wrote Dr. Alka Khaitan, lead author of the study, which is published in the journal Science Translational Medicine.

"These children are committed to lifelong treatment with antiretroviral therapy because an HIV cure remains elusive. The rapid establishment of a viral reservoir in resting CD4 T cells is a major barrier to an HIV cure," added Khaitan, a pediatric virologist at Indiana University School of Medicine in Indianapolis, who worked with the far-flung team of collaborators.

Anti-HIV antibodies are monoclonal antibodies

The researchers conducted a clinical trial that combined antiretroviral drug therapy with broadly neutralizing antibodies, proteins designed to block HIV's key glycoprotein—gp120. The virus uses that glycoprotein to break into human cells.

Broadly neutralizing antibodies—bNAbs—target and block highly conserved regions on swiftly mutating viruses, hence their use against HIV. The bNAb used in the study zeros in on HIV's gp120. All bNAbs are monoclonal antibodies, which are made in a lab via cloning from a parent protein. All monoclonals are designed to home in on and bind to a specific target.

One of the biggest obstacles in the fight against HIV is the virus's ability to establish reservoirs in long-lived immune cells. Once inside these cells, HIV can remain dormant for years, effectively hiding from both the immune system and antiretroviral drugs.

Researchers have long wondered whether bNAbs could help eliminate some of these infected cells if administered early enough in life. Because the antibodies are engineered to recognize and attack a region of HIV that changes very little from strain to strain, they are attractive candidates for therapies designed to supplement conventional antiretroviral treatment.

Although bNAbs have been studied extensively in adults, far less is known about their use in infants, a population in which the viral reservoir becomes established early. To gather data on bNAb effectiveness in babies, researchers studied the clinical impact of a broadly neutralizing antibody called VRC01.

Multisite clinical trial

"In this study, we hypothesized that adding a bNAb at initiation of early HIV treatment in infants would facilitate clearance of HIV-infected cells, thereby lowering viral reservoir size," Khaitan asserted in the study.

"We conducted a multisite randomized trial of subcutaneous VRC01 injections within 14 days of antiretroviral therapy initiation in infants younger than 12 weeks of age living with HIV to examine the safety and antiviral effects of VRC01 combined with antiretroviral therapy versus antiretroviral therapy alone," Khaitan continued.

The experimental treatment proved safe and well tolerated. However, investigators found no significant overall difference in HIV DNA levels between infants who received VRC01 and those treated with antiretroviral therapy alone.

Of the 61 babies in the study, 31 received antiretroviral therapy alone, while the other 30 received antiretroviral therapy along with VRC01, which showed no safety concerns. Although there was no observed difference between the two groups in the decline of HIV viral DNA after 14 weeks, the team's analysis suggests that higher concentrations of VRC01 could lower viral DNA levels more effectively.

Further analysis offered clues as to why. Many infants harbored HIV strains that were already resistant to VRC01, and antibody concentrations in the bloodstream were often lower than researchers had predicted. Even so, infants who achieved higher concentrations of the antibody tended to experience larger declines in HIV DNA, suggesting that more potent antibodies or combinations of antibodies could produce stronger effects.

"Our study highlights that infants living with HIV are a unique population, and adult clinical trial results may not translate directly to infants," Khaitan and her colleagues concluded. They noted that further trials with more potent bNAbs, or cocktails with several bNAbs, will be necessary to determine how viable the approach is as a therapeutic strategy.

Written for you by our author Delthia Ricks, edited by Gaby Clark, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You'll get an ad-free account as a thank-you.

Publication details

Alka Khaitan et al, VRC01 with antiretroviral initiation in infants is well tolerated, and higher concentrations associate with greater HIV-1 DNA declines, Science Translational Medicine (2026). DOI: 10.1126/scitranslmed.adr4509

Journal information: Science Translational Medicine

Key medical concepts

HIVBroadly Neutralizing AntibodiesAntiretroviral Therapy

Clinical categories

PediatricsInfectious diseasesHIV & AIDSChildren's health Who's behind this story?

Delthia Ricks

Award-winning science writer published in Newsday and Discover Magazine. Author of four books. UCLA and Columbia graduate. Full profile →

Gaby Clark

MA in English, copy editor since 2021 with experience in higher education and health content. Dedicated to trustworthy science news. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

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