WWhen children with HIV are injected with neutralizing antibodies, the treatment can suppress cells that contain the virus and are able to reactivate, an early-stage study found.
Details of the process, documented in a study published Wednesday in Science Translational Medicine, show that broadly neutralizing antibodies can enhance the protective effects of antiretroviral drugs. This suggests that antibody drugs could be used as supplements or even as alternative treatments for HIV in children.
“It was very clear proof of the concept that we can use broadly neutralizing antibodies as an alternative therapy,” said study leader Roger Shapiro, a professor of immunology and infectious diseases at Harvard University’s T. H. Chan School of Public Health.
The trial was conducted in children living with HIV in Botswana. It is the first time that broadly neutralizing antibodies – in combination with antiretroviral drugs – have been tested against HIV in a pediatric population. “The conclusion of this study is that it’s feasible,” said Ann Chahroudi, an associate professor of pediatrics at Emory University School of Medicine, who was not involved in the study.
While researchers have administered neutralizing antibodies to treat HIV in patients in recent years, their focus has been on adults living with the infection. Chahrudi said the new trial is significant and showed that children are ideal candidates to benefit from combinations of neutralizing antibody treatments.
Worldwide, approximately 1.7 million babies and children are living with HIV. Children living with HIV must receive daily life-saving antiretroviral treatments for months. But taking the drugs can be complicated for many reasons. Pediatric formulations can be scarce. Caregivers of children receiving antiretroviral therapy often have difficulty preparing and administering the drugs effectively. And they take on challengessuch as financial burdens caused by transportation costs required to receive the drugs at hospitals and comply with follow-up.
Neutralizing antibodies may offer a new approach to addressing the challenges of HIV treatment, especially in children.
Shapiro and researchers at the Harvard AIDS Institute Partnership in Botswana recruited 25 children with HIV who received antiretroviral therapy from birth. They injected the children with monthly doses of two neutralizing antibodies known as VRC01LS and 10-1074. After eight weeks, the researchers stopped the antiviral treatments but continued to administer the antibody drug cocktail for 24 weeks.
Of the 25 infants, 11 continued to suppress the virus without the antiretroviral medication. “It turned out that almost half of the children were able to suppress the virus,” Shapiro said.
The researchers then performed genomic tests to measure the amount of HIV in blood samples collected from the children. They found that the children had lower viral loads in their DNA and smaller viral reservoirs in their immune cells. This means that children with HIV who receive the neutralizing antibodies are more likely to live a healthy life. The findings are similar to those in studies performed in adults with HIV.
The study was limited by its small size, and so may not be representative of other children living with HIV in general, the researchers said. Children already on antiviral treatments also have low viral reservoirs – where the virus hides and can be reactivated – making it difficult for researchers to measure. “It was very difficult for us to measure the impact on the [viral] reservoir to a greater extent,” Shapiro said.
Shapiro told STAT that researchers are currently enrolling all children in long-term studies for in-depth profiling of viral reservoir cells and immune responses.
While antibodies have been used to treat conditions including Covid-19, they are expensive to produce. And administering the neutralizing antibodies to children with HIV would not be an easy task. This would be particularly the case in low-income countries, where the burden of disease is highest.
But Shapiro is hopeful. “Research has to start somewhere,” he said. “We are only at the beginning of understanding what is biologically possible in the near future, even if it seems like an expensive, logistically challenging strategy.”