Can babies infected with HIV be cured?

More than a decade ago, a Mississippi baby who tested positive for HIV at birth almost immediately started to receive antiretroviral treatment (ART). When a pediatrician saw the girl shortly before her second birthday, she was off the drugs but oddly had no virus detected on standard tests. The so called “Mississippi baby” became an international news story about a potential strategy to cure HIV infections.

Pediatrician Deborah Persaud of the Johns Hopkins Children’s Center led the team that reported the Mississippi baby case. At a meeting yesterday, she described similar success with four more children. No one is claiming that the children have been cured—nor was the Mississippi baby, as it turned out. But the finding raises hopes that some babies who are born with the virus might benefit from this approach, and that closely studying their blood over time may inform cure strategies for older children and adults alike.

Speaking at the Conference on Retroviruses and Opportunistic Infections (CROI), the largest annual HIV/AIDS meeting held in the United States, Persaud described how her team followed 54 infected newborns from 11 countries who began to receive standard anti-HIV drugs within 2 days of birth. Six of the children, all living in sub-Saharan African countries, had the best responses to the HIV drugs. All had no detectable virus for at least 4 years, and after consultations with physicians, their parents or guardians agreed to have them stop taking the drugs. In two the virus returned within weeks, as it usually does. Those children are back on medication and doing fine. But four of the kids remained in remission—defined as having no detectable virus with the most sensitive tests—for at least 48 weeks. One remained in remission for 80 weeks before signs of the virus were again detected and the girl was put back on drugs.

Still, those in the field are impressed. “This is the first time through a planned approach that researchers have demonstrated kids can come off ART and stay virus free,” says pediatrician George Siberry, chief medical officer for the HIV/AIDS branch of the U.S. Agency for International Development. “It’s a game changer.”

Persaud stresses that her team is not claiming these results are cures, but they are heartening. “This is the proof of concept that very early therapy in the Mississippi baby was not a one-off,” she says. Below, Science delves into the implications of the new work.

How many babies are born each year infected with HIV?

Cases of mother-to-child transmission of HIV have plummeted because of the advent of ART drugs. Pregnant people who are living with HIV and taking ART that fully suppresses the virus rarely, if ever, transmit to their babies. Those same drugs, even if only administered when a person is in labor and then given to the baby after birth, prevent many other newborn infections. Still, some pregnant people do not know they are infected or cannot access the drugs. In 2023, an estimated 130,000 babies worldwide were born with the virus, according to the United Nations Programme on HIV/AIDS.

What happened with the Mississippi baby?

The baby began treatment at 31 hours after birth, but, for unclear reasons, stopped receiving the medications at 18 months. Three months later, a pediatrician in Mississippi saw the baby and discovered she did not have antibodies against HIV or evidence of the virus on standard tests. Persaud’s team studied blood samples and only found genetic traces of the virus in certain tissues, areas dubbed HIV reservoirs. At the time, the Mississippi baby would have only been the second documented person to be cured—the first, an adult with leukemia, had received a bone marrow transplant of cells that were highly resistant to HIV infection. But after 27 months of ART-free remission—researchers no longer use the freighted word “cure” —the virus returned to the child. “She’s doing very well, but is on antiretroviral treatment,” Persaud says.

Why does the virus eventually return?

HIV infects CD4 white blood cells and weaves a DNA copy of its genes—the provirus—into human chromosomes. ART works so powerfully that it virtually shuts down the ability of these integrated viral genes to make new HIVs, but some of the infected CD4 cells remain in various tissues—the reservoirs. When treatment stops, their latent infections can quickly become active again.

How might early treatment lead to sustained remission and even a cure?

When adults stop ART, the virus routinely roars back within weeks. A small percent of adults have stopped ART and remained virus free for years on standard tests, but these “elite controllers” all still have evidence of reservoirs with low levels of the virus.

Immediate treatment after an infection theoretically has a better chance of shrinking viral reservoirs. With adults, people rarely know with precision when they became infected, but the timeline is clearer for babies infected in utero. Once treatment has depleted the reservoirs, they should be easier for the immune system to contain. Over time, in theory, it could destroy all HIV-infected cells, or at least all the cells capable of producing virus.

Why did only six children in this study stop treatment?

In the study, which was funded by the National Institutes of Health, children were eligible to cease ART only if they had no detectable virus for at least 48 weeks, healthy immune systems, no HIV antibodies, and no evidence of proviral infection in massive numbers of their white blood cells. Only six of the 54 children—who were from Uganda, Tanzania, and Zimbabwe—met these strict criteria. The children stayed on ART until they were between 5.3 and 5.7 years old, when treatment was stopped.

The study began 9 years ago. Might newer HIV treatments work better?

Several more safe and effective ART options have become available since 2015. “We started with an ‘n’ of one, and we’ve gone to four with a suboptimal antiretroviral treatment regimen, so we can probably do better,” Persaud says.

What are the benefits and harms to children who go off treatment and rebound?

Each child who rebounded with signs of HIV in their blood responded well to restarting ART, and Persaud says there is at least a psychological benefit to taking what some call a drug holiday. “When you ask the moms and guardians, ‘Why are you doing this?’ for them, even not having [their kids] take meds for a couple of days is liberating.”

Have other researchers reported similar findings?

Yes. A report in 2015 described a girl in France who had stopped ART at 6 years old and 12 years later still had no HIV detectable on standard blood tests, but had evidence of the virus in some cells. Two years later, South African researchers reported a case of a child who was off ART for 8.5 years and also only had low viral levels in reservoirs. At CROI this week, pediatrician Gabriela Cromhout from the University of KwaZulu-Natal described a study that has followed 309 mother-child pairs, both living with HIV, since 2015. As first reported in July 2023, they found that five boys who stopped treatment “for social reasons” had no viral rebound for up to 10 months. The study is now incorporating planned ART interruptions. Cromhout told Science that four children now have had ART-free remissions for longer than 6 months and one is out 29 months. “It’s fantastic that this is a way that we can see whether children can in fact, control the virus,” Cromhout says.