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Born HIV positive, children treated during their first two days of life were able to control HIV for more than a year after stopping antiretrovirals. Results which could change the care of children and which provide important clues for the development of a treatment leading to a cure for HIV.
Treated within 48 hours of birth, children born with HIV experienced one year of remission after stopping treatment. These results provide clues for tomorrow’s success in curing HIV, even if such early treatment remains difficult to access and if these interruptions can only be done under close monitoring.
Can we space out or stop treatment in children treated very early?
When a child contracts HIV in the womb, during childbirth or through breast milk, they must take antiretroviral therapy (ART) for life to control the virus’s ability to replicate, thereby avoiding life-threatening complications. Antiretroviral drugs – taken in liquid form for children – pose a huge burden on families because they taste rancid, must be taken on a frequent and rigid schedule to keep the virus under control. They are more expensive and can have many side effects.
In the light of previous results, a study wanted to know if treatment initiated in the first 48 hours of life subsequently made it possible to space out or even do without treatment. At age five, children who were deemed eligible for a drug break while being closely monitored for their health and safety had their ART stopped to see if they could achieve HIV remission (the absence of virus detectable for at least 48 weeks without ART). “No longer relying on daily ART to control HIV would be a considerable improvement in the quality of life of these children” said Dr. Ellen Chadwick, study leader and professor of pediatric infectious diseases at the Feinberg School of Medicine. This is the first study of its kind in the United States and worldwide.
Infection contained for more than a year
Of the 54 children initially enrolled in the study, six children were deemed eligible for ART interruption. Among these six children, HIV remained completely undetectable for 48 weeks or more in four children; among them, three children are still followed in remission for 48, 52 and 64 weeks respectively. The fourth child had been in remission for 80 weeks before his HIV rebounded to detectable levels. “This remission has been much longer than expected,” Chadwick said. “We are neither surprised nor disappointed that there is a rebound, as this is what usually happens when medications are stopped. If we can reduce the virus to levels so low that we might be able to use newer, innovative treatments to prevent them from needing medication every day, then we will set them up for success in controlling the virus on long term“.
In the two children who did not experience remission, their HIV became detectable three and eight weeks after ART interruption, respectively. The two children whose HIV recurred at 8 and 80 weeks had mild acute retroviral syndrome with symptoms including headache, fever, rash, swollen lymph nodes, tonsillitis, diarrhea, nausea and vomiting.
A child had a significantly low number of white blood cells (a type of immune cell) for a very brief period of time. The three children who experienced a viral rebound saw their viral load return to undetectable within 6, 8 and 20 weeks following resumption of treatment.
Previous research has found that starting these treatments very early could limit HIV’s ability to build up dormant virus reservoirs in infants (places where the virus remains “hidden” only to re-emerge when treatments end).
The results build on an earlier phase of the study by Chadwick and Jao, published in December 2023 in The Lancet HIV , which found that children who started ART within 48 hours of birth had biomarkers at age two that made them potentially eligible for drug testing. free remission.
Even if scientists don’t know the reason for this remission, they have hypotheses.
“We don’t know precisely why they were so successful, but we think it’s because we reduced the reservoir to such a low level that the virus didn’t re-emerge in the same way it would in someone. ‘one with a larger, well-established virus reservoir” said Chadwick.
The next steps in this research include stopping treatment earlier (at age 2), using drugs that are better tolerated and more active, and adding a research component incorporating broadly neutralizing antibodies, which will serve as an additional weapon against the virus.
A study based on the unique case of the “Mississippi baby”
Typically, stopping treatment will quickly lead to a resumption of HIV replication and detectable virus in the blood within a few weeks, the scientists said. However, in 2013, a case known as the “Mississippi baby” hit the headlines: an infant born with HIV in Mississippi who had started treatment at 30 hours of life, stopped treatment at age of 18 months and had remained in remission without any trace of detectable HIV for 27 months.
“This is the first study to rigorously replicate and expand on the findings observed in the Mississippi case report” said the study’s lead author, Dr. Deborah Persaud, who reported the Mississippi case.
“These findings are groundbreaking for HIV remission and cure research, and they also highlight the need for immediate neonatal testing and treatment initiation in health care settings for all infants potentially exposed to HIV in utero” said Dr. Persaud, during his presentation Wednesday at the Conference on Retroviruses and Opportunistic Infections (CROI) 2024 in Denver.