Research co-led by an investigator at Johns Hopkins Children’s Center shows that four children born with HIV who were safely removed from antiretroviral therapy (ART) continued to have undetectable levels of the virus for about a year or more without treatment. The children were among 54 newborns who were given very early treatment within the first 48 hours of life — rather than within weeks or months, as is typical.
Findings of the study, which was co-led by physician-scientist Deborah Persaud, M.D., and sponsored by the National Institutes of Health and the International Maternal Pediatric Adolescent AIDS Clinical Trials Network, were presented March 6 at the Conference on Retroviruses and Opportunistic Infections (CROI) in Denver, Colorado.
The study was conducted by the International Maternal Pediatric AIDS Clinical Trials Network at 30 clinical research sites in 11 countries, and was designed to replicate the case of the Mississippi baby, who is believed to be the first documented case of HIV remission in a child who was born with the virus and received very early HIV treatment at 30 hours of age. Persaud, who was part of the research team to report on the case in 2013 at CROI and is director of the Eudowood Division of Pediatric Infectious Diseases at the Children’s Center, says the study findings confirm the notion that ART-free remission is possible with very early effective antiretroviral treatment of newborns. She adds that standard treatment of babies with HIV typically starts weeks after birth, often due to delays in testing and getting results — particularly in countries outside of the U.S. where the burden of HIV is highest and ART drugs are less available.
Findings from the study reported in December in Lancet HIV showed that giving very early ART to newborns who acquire HIV in the womb safely suppressed the amount of HIV in the blood to undetectable levels through 2 years of age while they were still on the therapy.
In the latest phase of the trial, the findings of which were presented at this year’s CROI, six of the children, now about 5½ years old, who were all enrolled and followed in sub-Saharan Africa, became eligible based on study criteria to stop their HIV medication while being closely monitored for any potential health and safety concerns. Four of the children experienced remission, which was defined as undetectable HIV levels for at least 48 weeks off their treatment. For one of those children, the virus returned to detectable levels after 80 weeks. Three children have continued to remain in remission for 48, 52 and 64 weeks each. Two other children in the study did not experience HIV remission criteria because their HIV became detectable within three and eight weeks each. Two children whose HIV rebounded developed a mild acute retroviral syndrome, flu-like symptoms that are typically early signs of HIV in adults. The children whose HIV rebounded were restarted on ART, which controlled their virus to undetectable levels after seven to 20 weeks. Their symptoms also subsided.
“This is the first time we’ve been able to successfully recreate the case of the Mississippi baby — and in four children,” says Persaud, who is a professor of pediatrics at the Johns Hopkins University School of Medicine. “These results are an important first step to understanding how to curtail HIV reservoirs in children toward ART-free remission and cure for more children living with HIV, ultimately changing the treatment paradigm for this infection that currently afflicts 1.7 million children around the world.”
Persaud adds that additional research is needed to understand how very early ART specifically reduced HIV reservoirs to create ART-free remission.
