Children Achieve Over a Year of HIV Remission After Pausing Treatment

Promising outcomes with treatment started promptly after birth

Four children have remained free of detectable HIV for over a year after pausing their antiretroviral therapy (ART), as presented at the 2024 Conference on Retroviruses and Opportunistic Infections (CROI) in Denver. These children, who were born with HIV, participated in a National Institutes of Health-funded clinical trial where ART was initiated within 48 hours of birth. The trial monitored drug safety and HIV viral suppression, and the recent outcomes follow planned ART interruptions once the children met specific virological and immunological criteria.

Dr. Jeanne Marrazzo, Director of NIAID, highlighted the significance of these findings, stating, "These findings are clear evidence that very early treatment enables unique features of the neonatal immune system to limit HIV reservoir development, which increases the prospect of HIV remission. The promising signals from this study are a beacon for future HIV remission science and underscore the indispensable roles of the global network of clinicians and study staff who implement pediatric HIV research with the utmost care."

Advancements in ART have greatly reduced perinatal HIV transmission, which can occur in utero, during birth, or through breastfeeding. If transmission happens, children typically require lifelong ART to control the virus and protect their immune systems. Usually, stopping treatment leads to a rapid return of detectable HIV in the blood. However, a notable case in 2013 involved an infant born with HIV in Mississippi who started treatment at 30 hours old, paused ART at 18 months, and remained in remission for 27 months.

Building on this, researchers launched an early-stage proof-of-concept study of very early ART in infants across multiple countries, including Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand, Uganda, the United States, Zambia, and Zimbabwe. Prior publications from the study confirmed that ART initiated within hours of birth was both safe and effective in achieving and maintaining HIV suppression. A subset of children in the study met the criteria for ART interruption, which included sustained HIV suppression from 48 weeks of ART initiation, no detectable antibodies near ART interruption, and a CD4+ T-cell count comparable to a child without HIV. Eligible children were over 2 years old and had stopped breastfeeding.

At CROI, data on six children, all aged 5, eligible for ART interruption were presented. Four of these children achieved HIV remission, defined as the absence of replicating virus for at least 48 weeks off ART. One child experienced remission for 80 weeks before HIV became detectable again, while three others remained in remission for 48, 52, and 64 weeks, respectively. Two children did not achieve remission, with detectable HIV within three and eight weeks post-ART interruption. The two children who experienced viral rebound had mild acute retroviral syndrome (ARS) symptoms, which resolved either before or soon after restarting ART. The three children with viral rebound resumed HIV suppression within six, eight, and 20 weeks of restarting ART.

"This is the first study to rigorously replicate and expand upon the outcomes observed in the Mississippi case report," stated lead study virologist Deborah Persaud, M.D., professor of pediatrics at the Johns Hopkins University School of Medicine and director of the Division of Pediatric Infectious Diseases at Johns Hopkins Children's Center in Baltimore. "These results are groundbreaking for HIV remission and cure research and highlight the necessity of immediate neonatal testing and treatment initiation for all infants potentially exposed to HIV in utero in healthcare settings."

The latest findings indicate that very early initiation of ART can have varied but generally favorable outcomes in controlling HIV. While the cases of acute retroviral syndrome (ARS) were mild and resolved, the authors emphasized the need for close monitoring of this potential event in ongoing and future HIV remission research involving ART interruption. The children in this study were on ART regimens that have been part of standard first-line therapy for decades. Further research is planned or underway to explore how outcomes might differ in children receiving newer, more potent antiretroviral drugs and to identify biomarkers that could predict the likelihood of HIV remission or rebound after ART interruption. Additional studies are also needed to understand the mechanisms by which neonatal immunity and very early ART initiation limited HIV reservoir formation and contributed to the observed remission.

"ART revolutionized HIV care, but it’s a lifelong commitment, especially challenging for children who are lifetime survivors of HIV," said Adeodata Kekitiinwa, MBChB, MMed, emeritus clinical associate professor in the Department of Pediatrics at Baylor College of Medicine, study investigator of record, and clinical research site leader in Kampala, Uganda. "This trial brings us closer to another paradigm shift where ART could potentially be used for a season of life rather than its entirety."

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

The study was led by co-chairs Ellen Chadwick, M.D., professor of pediatrics at Northwestern University Feinberg School of Medicine, and Yvonne Bryson, M.D., professor of pediatrics at the David Geffen School of Medicine and Mattel Children's Hospital at UCLA, and director of the Los Angeles Brazil AIDS Consortium. Dr. Kekitiinwa, Boniface Njau, M.S., study coordinator at Kilimanjaro Christian Medical Centre in Tanzania, and Teacler Nematadzira, MBChB, site investigator at the University of Zimbabwe-University of California San Francisco Collaborative Research Program, continue to lead the teams overseeing the care of children who achieved HIV remission. Jennifer Jao, M.D., M.P.H., professor of pediatrics at Northwestern University Feinberg School of Medicine, has since taken on a co-chair role alongside Dr. Chadwick. The full IMPAACT P1115 study team comprises hundreds of staff across 30 NIAID- and NICHD-supported sites in 11 countries.