Very early ART enables ART-free remission in children

In the IMPAACT* P1115 study presented at CROI 2024, four children who received antiretroviral therapy (ART) for HIV very early in life remained free of detectable HIV for over a year after a break in their ART regimen.

“[We sought] to evaluate whether very early ART for newborns would limit HIV-1 reservoirs sufficiently to observe at least one case of ART-free remission,” said lead study virologist Professor Deborah Persaud from Johns Hopkins University School of Medicine, Baltimore, Maryland, US, at CROI 2024. “[In our study,] four of the six very early treated children with durable virologic suppression achieved ART-free remission with no viraemic rebound for ≥48 weeks.”

The six participants had confirmed in-utero HIV-1 and were all from sub-Saharan Africa. They received very early ART** within 48 hours of life and discontinued for analytic treatment interruption (ATI). Median age at ATI was 5.5 years; four were girls. ART-free remission was defined as having no confirmed plasma HIV-1 RNA above the limit of detection of the assay for ≥48 weeks off ART. [CROI 2024, abstract 184]

One patient had acute retroviral syndrome (ARS) after 80 weeks of ART-free remission; another patient developed ARS after 8 weeks of ART discontinuation. Another participant achieved asymptomatic viral rebound after 3 weeks of ART discontinuation. All were resuppressed to undetectable plasma viral loads between 6.7 and 20 weeks, noted Persaud.

The lack of quantifiable lopinavir confirms ART discontinuation, while the lack of quantifiable lopinavir in the blood post ATI with sustained aviraemia confirms ART-free remission in very early-treated IMPAACT P1115 participants, Persaud explained.

Although both ARS cases resolved, Persaud underscored that “the occurrence of ARS with rebound viraemia, which is very uncommon in children, warrants careful clinical oversight during ATI.”

Groundbreaking findings

“This is the first study to rigorously replicate and expand upon the outcomes observed in the Mississippi case report,” said Persaud in a news release. The ‘Mississippi Baby’ case pertains to an infant born with HIV in Mississippi who had very early ART (30 hours of age), was taken off ART at 18 months of age, and remained in remission with no evidence of detectable HIV for 27 months. [https://www.nih.gov/news-events/news-releases/children-surpass-year-hiv-remission-after-treatment-pause]

“This study provides proof-of-concept that very early ART in neonates with in-utero HIV-1 significantly curtailed viral reservoirs and enabled ART-free remission,” said Persaud. “These results are groundbreaking for HIV remission and cure research, and also point to the necessity of immediate neonatal testing and treatment initiation in healthcare settings for all infants potentially exposed to HIV in utero.”

A beacon for future research

NIAID*** Director Dr Jeanne Marrazzo noted in the news report that “[the] 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.”

“ART shifted the HIV care paradigm, but treatment is a long road, especially for children as lifetime HIV survivors,” commented Professor Adeodata Kekitiinwa from Baylor College of Medicine, Houston, Texas, US. “This trial takes us a step closer to realizing another paradigm shift in which our approach to ART could be so effective that it might be used for a season of life, rather than its entirety.”

This ongoing research is conducted by the IMPAACT Network and funded by the NIAID, a part of the National Institutes of Health (with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the National Institute of Mental Health).