• Children with HIV who were considered for treatment interruption did so to see if they could achieve HIV remission (no detectable virus for at least 48 weeks).
  • Four out of six children experienced HIV remission
  • One child went into remission for 80 weeks before the HIV infection rose again to detectable levels
  • Relying less on “bad drugs” to control HIV is a “tremendous improvement” for families’ quality of life

Newswise – Four children who were infected with HIV in utero have remained free of detectable HIV for more than a year, according to new findings presented today, March 6, at the Conference on Retroviruses and Opportunistic Infections (CROI) in Denver, Colorado.

The study is part of ongoing, multinational research led in part by scientists at Northwestern University Feinberg School of Medicine and the Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital in Chicago.

If a child becomes infected with HIV in utero, during birth, or through breast milk, he or she must receive lifelong antiretroviral therapy (ART) to control the virus’s ability to replicate and thus prevent life-threatening complications. ART medications – taken in liquid form for children – place a huge burden on families because they have a rancid taste (often referred to as “the nasty medicine”) and must be taken on a regular, strict schedule to keep the virus in Keeping chess is expensive and can have many unpleasant side effects.

“Moving away from reliance on daily ART for HIV control would be a huge improvement in the quality of life of these children,” said the study protocol director Dr. Ellen ChadwickProfessor of Pediatric Infectious Diseases at Feinberg and former Director of the Division of Pediatric, Adolescent and Maternal HIV Infections at Lurie Children’s.

The children in the study received ART within the first 48 hours of life and were closely monitored for drug safety and HIV viral suppression. At the age of five years, ART was stopped in those eligible for an ART break under close health and safety monitoring to see if they could achieve HIV remission (the absence of detectable virus for at least 48 weeks without ART).

This is the first study of its kind in the United States and worldwide, Chadwick said.

Breakdown of findings

Of the 54 children originally enrolled in the study – most of whom were international children – six children were eligible for ART interruption. Among these six, HIV remained completely undetected in four children for 48 weeks or longer; Of these, three children will be observed in remission for 48, 52 and 64 weeks, respectively. The fourth child experienced remission for 80 weeks before the HIV infection rose again to detectable levels.

“This remission lasted much longer than we expected,” Chadwick said. “We won’t be surprised or devastated if they go back up because that’s what usually happens when the medication is stopped. If we can get the virus down to such a low level that we can potentially use some newer, innovative treatments to prevent them from needing medication every day, then we are setting them up for success with long-term virologic control. “

In the two children who did not experience remission, HIV became detectable within three and eight weeks of ART interruption, respectively. The two children, whose HIV returned at 8 and 80 weeks, suffered from mild acute retroviral syndrome (ARS) with symptoms including headache, fever, rash, swollen lymph nodes, tonsillitis, diarrhea, nausea and vomiting. One child’s white blood cells (a type of immune cell) were significantly low for a very short period of time. Both ARS and white blood deficiency disappeared either before or shortly after resumption of ART. The three children who experienced viral rebound had HIV suppression returned to undetected levels within 6, 8, and 20 weeks after resuming ART.

Previous ART research that led to current findings

Previous research has suggested that very early ART initiation may limit the ability of HIV to establish reservoirs of dormant viruses in infants. In the United States, babies born to people at high risk of HIV transmission typically receive three medications as part of the ART protocol in the first hours of life.

“Very early treatment also relies on testing at birth, which is not done everywhere,” he said Jennifer Jao, protocol co-chair and professor of pediatric infectious diseases at Feinberg and researcher and physician at Lurie Children’s. “The idea that we are doing this in newborns is very new. We are pursuing the idea of ​​giving ART to the babies so early that we can try to contain the virus so that it drops to such a low level and a reservoir of almost zero is achieved.”

The insights build an earlier phase of the study by Chadwick and Jaopublished in December 2023 in The Lancet HIVIt found that children who started ART within 48 hours of birth had biomarkers by the age of two that may make them eligible for testing for drug-free remission.

Although scientists don’t know the reason for the remission, they have hypotheses.

“We don’t know exactly why they did so well, but we think it’s because we reduced the reservoir to such a low level that the virus didn’t resurface in the same way that it would in someone with it “A larger, more established reservoir would be the case,” Chadwick said.

The next steps in this research include even earlier ART interruption (at age 2), the use of better tolerated and more effective drugs, and the addition of a line of research that involves broadly neutralizing antibodies that will serve as an additional fight against the virus.

“The Mississippi Baby”

Typically, stopping treatment quickly leads to a resumption of HIV replication and detectable virus in the blood within a few weeks, the scientists said. However, in 2013, a case report titled “The Mississippi Baby” described an infant born with HIV in Mississippi who started treatment at 30 hours of life, was taken off ART at 18 months of age, and had no symptoms When the disease was in remission, detectable HIV remained detectable for 27 months.

“This is the first study to rigorously replicate and extend the results observed in the Mississippi case report,” said lead study virologist Dr. Deborah Persaud, who reported on the Mississippi case. She is a professor of pediatrics at the Johns Hopkins University School of Medicine and director of the Division of Pediatric Infectious Diseases at the Johns Hopkins Children’s Center.

“These results are groundbreaking for HIV remission and cure research and also point to the need for immediate testing of newborns and initiation of healthcare treatment for all infants who may be exposed to HIV in utero,” said Persaud, who led the Results announced on Wednesday were her conference presentation, “ART-free HIV-1 remission in very early-treated children: Results from IMPAACT P1115.”

This ongoing research is being conducted by International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT), a research network funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, with co-funding from Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH).

This study, called IMPAACT P1115, was funded by the IMPAACT network as a Phase 1 and 2 proof-of-concept study of very early ART in infants, conducted in Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand and Uganda was carried out in the United States, Zambia and Zimbabwe.

Overall support for IMPAACT was provided by NIAID with co-funding from NICHD and NIMH, all components of the National Institutes of Health (NIH), under grant numbers UM1AI068632-15 (IMPAACT LOC), UM1AI068616-15 (IMPAACT SDMC), and UM1AI106716-09 ( IMPAACT LC) and by NICHD contract number HHSN275201800001I. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Research at Ann & Robert H. Lurie Children’s Hospital of Chicago is conducted by the Stanley Manne Children’s Research Institute, whose focus is improving children’s health, transforming pediatric medicine and ensuring a healthier future through the relentless pursuit of knowledge. Lurie Children’s is a nonprofit organization dedicated to ensuring every child has access to exceptional care. It is ranked as one of the best children’s hospitals in the country US News and World Report. Lurie Children’s is the pediatric training campus of Northwestern University Feinberg School of Medicine.

By admin

Leave a Reply

Your email address will not be published. Required fields are marked *