South African Child Appears to Beat HIV Remission began after early treatment was halted

PARIS -- A 9-year-old girl, diagnosed with HIV when she was a month old and treated for a year with antiretroviral drugs, has been off therapy ever since without disease.
The girl had an extremely high HIV viral load when she was diagnosed and enrolled in a clinical trial of delayed therapy versus treatment on diagnosis for either 40 or 96 weeks, according to Avy Violari, MD, of the University of the Witwatersrand in Johannesburg.
Her case appears to be the first time deliberate treatment interruption of an infant has followed long-term control of HIV, Violari said at the International AIDS Society meeting on HIV Science.
But two previous cases of such post-treatment control in children have been reported:
The "Mississippi Baby" was born with HIV in 2010, received anti-HIV treatment beginning 30 hours after birth, stopped therapy around 18 months of age, and controlled the virus without drugs for 27 months before it reappeared in her blood.
In 2015, investigators reported the case of a French child who was born with HIV in 1996, started therapy at age 3 months, and stopped sometime between ages 5.5 and 7 years. She continues to control the virus without drugs more than 11 years later.
But most HIV-positive people, whether children or adults, see their virus rebound within a few weeks or at most months.
Tim Henrich, MD, of the University of California San Francisco, reported here on an adult patient first treated in the "hyperacute" phase -- within about 10 days of infection. After some 2 years of treatment, during which HIV was not detectable even using ultra-sensitive tests, the patient stopped therapy.
Unusually, the patient remained in remission for 224 days, or more than 7 months, Henrich reported. But then the HIV returned with a vengeance -- from plasma HIV RNA of 36 copies per mL to more than 56,000 copies within 6 days.
In other words, "there's a broad spectrum from when you stop therapy to when you rebound," commented Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), which was one of the sponsors of the study in which the South African child is enrolled.
"The exciting thing is: what is it that makes that difference?," he told reporters. "Is it an immunological response? Is it something about the virus? Is there immune activation in one individual that you don't see in another individual?"
He added that early treatment "seems to be a very important common denominator" because it reserves immune function and reduces the number of cells latently infected with HIV the reservoir that is responsible for rebound when treatment is stopped.
On the other hand, even a very small reservoir is not enough, Henrich noted: His group calculated that their patient had at most 200 such cells, but eventually one of them activated and began producing HIV again.
The South African child, whose case was reported here, was diagnosed with HIV infection in 2007 when she was 32 days old. She was enrolled in the Children with HIV Early Antiretroviral Therapy (CHER) clinical trial.
The infants in the trial were randomly assigned to get antiretroviral for 40 or 96 weeks, or to have their treatment deferred until their immune systems began to fail. The child in the current study was one of 143 assigned to get 40 weeks of treatment.
Before treatment, the child had a plasma viral load of more than 750,000 copies of HIV RNA per mL, but the therapy quickly suppressed that to undetectable levels. According to the study plan, the researchers stopped treatment after 40 weeks and have closely followed the child's health since.
Recent analysis of stored blood samples show that the child has maintained an undetectable level of HIV, Violari reported.
Lab and clinical studies have shown a small reservoir of virus but no other evidence of HIV infection. She has weak antibody and CD4-positive T cell responses to HIV and no detectable CD8-positive T cells responses. Also, her level of immune activation was low and si