A low-activity virus sensitive to the immune system: the case of 5 children who keep HIV controlled without antiretroviral treatment

According to the latest UNAIDS 2022 report, there were approximately 130,000 new HIV infections among children under five years old, most of them in low-income countries. The data also shows that worldwide, only 58% of children with HIV have access to antiretroviral treatment or the necessary structures to follow the treatment regimen correctly. For this reason, finding a definitive cure for children with HIV would represent a paradigm shift, and this goal is currently a clear priority for the scientific community.

Now, an international study led by the University of Oxford, with the participation of IrsiCaixa, has followed 284 newborns in South Africa who acquired HIV before birth but received antiretroviral treatment from the outset. Of all the children studied, 5 have shown exceptional control of HIV, as they maintain the virus undetectable in their blood despite having later stopped or intermittently taken antiretroviral treatment.

The study’s results link these children’s ability to control HIV to having a less replicative virus that is more sensitive to interferon—a molecule characteristic of the immune response against HIV. These factors, along with other features of the innate immune system, differ between males and females. This bias could explain why the 5 exceptional cases identified are male. Thus, the data suggests that in cases where antiretroviral treatment is initiated early after birth, some children may achieve spontaneous control of the virus, and this control may be linked to factors that differ between sexes.

Rapid initiation of antiretroviral treatment, a non-hyperactive immune system, and infection by a less aggressive virus are three factors that reduce the size of the HIV reservoir and increase the potential for a cure. "These three factors are common in infants, creating an ideal scenario for applying HIV cure strategies," says Javier Martínez-Picado, ICREA researcher at IrsiCaixa. "We wanted to know exactly which factors are relevant for enabling infants to control HIV in the absence of treatment, so we can use this information as a basis for future designs of cure strategies," he adds.

Receiving a virus with less replicative capacity

Of the 284 newborns included in the study, all born in the KwaZulu-Natal province of South Africa, the majority achieved an undetectable viral load in their blood thanks to antiretroviral treatment. By monitoring drug levels in their blood, researchers identified that those who didn’t reach undetectable viral loads were not taking the treatment properly. “Even so, we were surprised to find 5 cases in which, despite detecting little or no medication in the blood, the virus was fully controlled,” highlights Mari Carmen Puertas, senior researcher at IrsiCaixa.

The study’s results indicate that the virus transmitted from the mother in these 5 cases had a lower replicative capacity compared to the viruses in the other children in the cohort. Researchers suggest that this, along with the virus’s sensitivity to the immune response, could be two factors contributing to this exceptional control.

Differences in HIV infection between male and female newborns

Although 60% of the infants studied were female, all 5 of the exceptional cases were male. This led the research team to investigate the differences between the two sexes. On one hand, the study demonstrates that the viruses transmitted to male newborns are more sensitive to interferon, a molecule that triggers the entire immune response against HIV. This sensitivity makes the virus more vulnerable to the body’s defenses, which facilitates viral control even in the absence of treatment. On the other hand, viruses acquired by males typically have greater replicative capacity and, therefore, a higher ability to spread throughout the body. However, the 5 exceptional cases identified in the study deviated from this trend, providing these children with a second advantage.

“The study shows that it is essential to study HIV infection in infants separately by sex. This will allow us to better understand how the infection works, identify candidates for cure strategies, and design potential sex-specific approaches,” says Martínez-Picado.