Can HIV-infected babies be cured? 

Can HIV-infected babies be cured? New research shows that functional cure may be possible with immediate treatment after birth.

According to the United Nations AIDS Program, an estimated 130,000 babies were born with HIV in 2023.

With the advent of antiretroviral drugs, cases of mother-to-child transmission of HIV have declined significantly. Pregnant women who are infected with HIV and receive antiretroviral therapy (ART) that fully suppresses the virus are very unlikely to transmit the virus to their babies.

Even if used only during childbirth, or given to babies after birth, ART can prevent many other newborn infections. However, some pregnant women do not know they are infected with HIV, or do not have access to medication.

The World Health Organization (WHO) says that HIV-positive pregnant women who do not receive ART have a 15% to 45% chance of transmitting the virus during pregnancy, childbirth, or breastfeeding.

In 2010, a baby girl born in Mississippi was born to a mother who tested positive for HIV during childbirth. The baby girl was born before her mother could receive ART, and she also tested positive for HIV.

The baby girl started ART 30 hours after birth, and was tested at 6, 11, and 19 days after birth, all three tests were positive for HIV; at 29 days, she was tested again and found to have HIV levels below the detectable level.

At 18 months old, the baby girl’s HIV levels were still below the detectable level. Her mother then stopped the baby girl’s ART; at 23 months old, the baby was tested again and her HIV levels were still below the detectable level.

At the time, doctors believed the baby girl had been cured of HIV, and it made headlines around the world. Around the same time, the “Berlin patient” was also declared cured of HIV. However, 27 months after stopping ART, the “Mississippi baby” had HIV rebound.

Before news of the viral rebound in the “Mississippi baby” broke, the U.S. National Institutes of Health had planned a global study (using 17 U.S. hospitals and hospitals in 11 other countries) to treat 54 HIV-positive babies with ART within 48 hours of birth, hoping to replicate the success of the “Mississippi baby”.

Recently, at the Conference on Retroviruses and Opportunistic Infections (CROI 2024) in Denver, Colorado, Deborah Persaud, a pediatrician at Johns Hopkins Children’s Center, presented the results of the study (IMPAACT P1115 (NCT02140255)) and revisited the “Mississippi baby”. She had reported the case of the “Mississippi baby” at CROI in 2013.

She described how the team tracked 54 infected newborns from 11 countries who started ART within 48 hours of birth. The study began in 2015.

A group of 34 babies (23 girls and 11 boys) born to mothers who did not receive ART during pregnancy started treatment with three drugs: Retrovir or Ziagen, Epivir and Viramune; a second group of 20 babies (10 girls and 10 boys) whose mothers received treatment during pregnancy started a similar regimen shortly after birth. A fourth drug, the boosted Kaletra, was added for all babies who had a positive HIV test at about 14 days. Babies with two consecutive undetectable viral load tests stopped Viramune treatment.

Of these, six children (now about 5.5 years old) were enrolled and followed up in sub-Saharan Africa, and according to the study criteria, they were eligible to stop HIV medication and be closely monitored to prevent any potential health and safety problems.

The results showed that four children had remission, which is defined as HIV levels being undetectable for at least 48 weeks after treatment. The virus in one girl rebounded to detectable levels after 80 weeks; the other three children had sustained remission for 48, 52, and 64 weeks, respectively.

In the two children who did not achieve remission, HIV was detected within 3 and 8 weeks of ART interruption, respectively, and mild acute retroviral syndrome (ARS) occurred at 8 and 80 weeks, respectively, with symptoms including headache, fever, rash, swollen lymph nodes, tonsillitis, diarrhea, nausea and vomiting. One child had a significant decrease in white blood cells in a very short period of time. ARS and leukopenia resolved quickly before or after ART was restarted. The children with HIV rebound restarted ART and had their virus controlled to undetectable levels and associated symptoms alleviated after 7-20 weeks.

At the 2024 Conference on Retroviruses and Opportunistic Infections (CROI), researchers from the University of KwaZulu-Natal in South Africa presented findings from a study that followed 309 HIV-positive mothers and their babies since 2015. The researchers found that five of the boys in the study were able to stop antiretroviral therapy (ART) for up to 10 months without experiencing a viral rebound. The study is currently enrolling participants in a planned ART interruption.

Why does the virus eventually come back?

HIV infects CD4 white blood cells and integrates a DNA copy of its genes (the provirus) into human chromosomes. While ART can suppress HIV replication indefinitely, the virus inserts its genetic blueprint into the DNA of human cells early in the course of infection, establishing a long-term reservoir that is inaccessible to antiretroviral drugs and often invisible to the immune system. When treatment is stopped, these latent infections can quickly reactivate.

In adults, the virus typically rebounds within weeks of stopping ART. A small number of adults have been able to stop ART and remain virus-free for years on standard tests, the so-called “elite controllers,” but they still have low levels of HIV in their bodies.

In 2015, an international AIDS conference in Vancouver, Canada, heard about a French girl who stopped ART at age 6 and 12 years later still had no detectable HIV on standard blood tests, but evidence of the virus was found in some cells; in 2017, South African researchers reported the case of a child who had been off ART for 8.5 years and also had low levels of virus in the body’s reservoirs.

These findings support earlier research that suggested that very early treatment can limit the size of the HIV reservoir, making a functional cure possible.

What’s next?

It’s important to note that the research Deborah Persaud reported at CROI 2024 began nine years ago. And since 2015, there have been several new, safer and more effective ART regimens. “We started with one regimen, then we went to a suboptimal antiretroviral regimen, and now we’re on our fourth regimen, so we can probably do even better,” she said.

Efforts to eliminate pediatric HIV

Efforts to find a cure for HIV are ongoing, and there is a global effort to eliminate pediatric HIV by 2030. In 2022, during the International AIDS Conference in Montreal, a new global coalition was launched by the UNAIDS, UNICEF, and WHO. The coalition aims to accelerate progress towards the elimination of pediatric HIV by 2030.